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Sample records for enhance arsenic trioxide-induced

  1. Arsenic trioxide sensitizes glioblastoma to a myc inhibitor.

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    Yayoi Yoshimura

    Full Text Available Glioblastoma multiforme (GBM is associated with high mortality due to infiltrative growth and recurrence. Median survival of the patients is less than 15 months, increasing requirements for new therapies. We found that both arsenic trioxide and 10058F4, an inhibitor of Myc, induced differentiation of cancer stem-like cells (CSC of GBM and that arsenic trioxide drastically enhanced the anti-proliferative effect of 10058F4 but not apoptotic effects. EGFR-driven genetically engineered GBM mouse model showed that this cooperative effect is higher in EGFRvIII-expressing INK4a/Arf-/- neural stem cells (NSCs than in control wild type NSCs. In addition, treatment of GBM CSC xenografts with arsenic trioxide and 10058F4 resulted in significant decrease in tumor growth and increased differentiation with concomitant decrease of proneural and mesenchymal GBM CSCs in vivo. Our study was the first to evaluate arsenic trioxide and 10058F4 interaction in GBM CSC differentiation and to assess new opportunities for arsenic trioxide and 10058F4 combination as a promising approach for future differentiation therapy of GBM.

  2. Studying arsenic trioxide-induced apoptosis of Colo-16 cells with ...

    African Journals Online (AJOL)

    Jane

    2011-10-05

    Oct 5, 2011 ... induced apoptosis at the single cell level. Key words: Two-photon laser scanning microscopy, confocal laser scanning microscopy, human skin squamous carcinoma cells (Colo-16 cells), arsenic trioxide, apoptosis. INTRODUCTION. Although arsenic is poisonous and chronic arsenic exposure from ...

  3. Blockage of JNK pathway enhances arsenic trioxide-induced apoptosis in human keratinocytes

    International Nuclear Information System (INIS)

    Huang, H.-S.; Liu, Z.-M.; Hong, D.-Y.

    2010-01-01

    Arsenic is well known as a carcinogen predisposing humans to some severe diseases and also as an effective medicine for treating acute promyelocytic leukemia, syphilis, and psoriasis. Multiple active mechanisms, including cell cycle arrest and apoptosis, have been proposed in therapy; however, the opposing effects of arsenic remain controversial. Our previous study found that arsenic trioxide (ATO)-induced activation of p21 WAF1/CIP1 (p21) led to A431 cell death through the antagonistic effects of the signaling of ERK1/2 and JNK1. In the current study, the inhibitory effects of JNK1 on ATO-induced p21 expression were explored. Over-expression of JNK1 in A431 cells could inhibit p21 expression, which was associated with HDAC1 and TGIF. Using the GST pull-down assay and fluorescence resonance energy transfer analysis, N-terminal domain (amino acids 1-108) of TGIF, critical to its binding with c-Jun, was found. Using reporter assays, requirement of the C-terminal domain (amino acids 138-272) of TGIF to suppress ATO-induced p21 expression was observed. Thus, the domains of TGIF that carried out its inhibitory effects on p21 were identified. Finally, treatment with JNK inhibitor SP600125 could enhance ATO-induced apoptosis of HaCaT keratinocytes by using flow cytometry.

  4. Arsenic speciation in saliva of acute promyelocytic leukemia patients undergoing arsenic trioxide treatment

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    Chen, Baowei; Cao, Fenglin; Yuan, Chungang; Lu, Xiufen; Shen, Shengwen; Zhou, Jin; Le, X. Chris

    2013-01-01

    Arsenic trioxide has been successfully used as a therapeutic in the treatment of acute promyelocytic leukemia (APL). Detailed monitoring of the therapeutic arsenic and its metabolites in various accessible specimens of APL patients can contribute to improving treatment efficacy and minimizing arsenic-induced side effects. This article focuses on the determination of arsenic species in saliva samples from APL patients undergoing arsenic treatment. Saliva samples were collected from nine APL pa...

  5. Arsenic trioxide mediates HAPI microglia inflammatory response and subsequent neuron apoptosis through p38/JNK MAPK/STAT3 pathway

    International Nuclear Information System (INIS)

    Mao, Jiamin; Yang, Jianbing; Zhang, Yan; Li, Ting; Wang, Cheng; Xu, Lingfei; Hu, Qiaoyun; Wang, Xiaoke; Jiang, Shengyang; Nie, Xiaoke; Chen, Gang

    2016-01-01

    Arsenic is a widely distributed toxic metalloid all over the world. Inorganic arsenic species are supposed to affect astrocytic functions and to cause neuron apoptosis in CNS. Microglias are the key cell type involved in innate immune responses in CNS, and microglia activation has been linked to inflammation and neurotoxicity. In this study, using ELISA, we showed that Arsenic trioxide up-regulated the expression and secretion of IL-1β in a dose-dependent manner and a time-dependent manner in cultured HAPI microglia cells. The secretion of IL-1β caused the apoptosis of SH-SY5Y. These pro-inflammatory responses were inhibited by the STAT3 blocker, AG490 and P38/JNK MAPK blockers SB202190, SP600125. Further, Arsenic trioxide exposure could induce phosphorylation and activation of STAT3, and the translocation of STAT3 from the cytosol to the nucleus in this HAPI microglia cell line. Thus, the STAT3 signaling pathway can be activated after Arsenic trioxide treatment. However, P38/JNK MAPK blockers SB202190, SP600125 also obviously attenuated STAT3 activation and transnuclear transport induced by Arsenic trioxide. In concert with these results, we highlighted that the secretion of IL-1β and STAT3 activation induced by Arsenic trioxide can be mediated by elevation of P38/JNK MAPK in HAPI microglia cells and then induced the toxicity of neurons. - Highlights: • Arsenic trioxide exposure induced expression of IL-β in HAPI microglia. • Arsenic trioxide exposure induced activation of MAPK pathways in HAPI microglia. • Arsenic trioxide exposure induced activation of STAT3 pathways in HAPI microglia. • The expression of IL-β though P38/JNK MAPK/STAT3 pathways in HAPI microglia.

  6. Arsenic trioxide mediates HAPI microglia inflammatory response and subsequent neuron apoptosis through p38/JNK MAPK/STAT3 pathway

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    Mao, Jiamin [Department of Environmental Health, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Yang, Jianbing [Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001 (China); Zhang, Yan [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Li, Ting [Department of Environmental Health, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Wang, Cheng [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Xu, Lingfei; Hu, Qiaoyun; Wang, Xiaoke; Jiang, Shengyang [Department of Environmental Health, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Nie, Xiaoke [Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China); Chen, Gang, E-mail: chengang@ntu.edu.cn [Department of Environmental Health, School of Public Health, Nantong University, Nantong, Jiangsu 226001 (China)

    2016-07-15

    Arsenic is a widely distributed toxic metalloid all over the world. Inorganic arsenic species are supposed to affect astrocytic functions and to cause neuron apoptosis in CNS. Microglias are the key cell type involved in innate immune responses in CNS, and microglia activation has been linked to inflammation and neurotoxicity. In this study, using ELISA, we showed that Arsenic trioxide up-regulated the expression and secretion of IL-1β in a dose-dependent manner and a time-dependent manner in cultured HAPI microglia cells. The secretion of IL-1β caused the apoptosis of SH-SY5Y. These pro-inflammatory responses were inhibited by the STAT3 blocker, AG490 and P38/JNK MAPK blockers SB202190, SP600125. Further, Arsenic trioxide exposure could induce phosphorylation and activation of STAT3, and the translocation of STAT3 from the cytosol to the nucleus in this HAPI microglia cell line. Thus, the STAT3 signaling pathway can be activated after Arsenic trioxide treatment. However, P38/JNK MAPK blockers SB202190, SP600125 also obviously attenuated STAT3 activation and transnuclear transport induced by Arsenic trioxide. In concert with these results, we highlighted that the secretion of IL-1β and STAT3 activation induced by Arsenic trioxide can be mediated by elevation of P38/JNK MAPK in HAPI microglia cells and then induced the toxicity of neurons. - Highlights: • Arsenic trioxide exposure induced expression of IL-β in HAPI microglia. • Arsenic trioxide exposure induced activation of MAPK pathways in HAPI microglia. • Arsenic trioxide exposure induced activation of STAT3 pathways in HAPI microglia. • The expression of IL-β though P38/JNK MAPK/STAT3 pathways in HAPI microglia.

  7. Arsenic Trioxide Injection

    Science.gov (United States)

    ... people who have not been helped by other types of chemotherapy or whose condition has improved but then worsened following treatment with other types of chemotherapy. Arsenic trioxide is in a class of medications ...

  8. Development of an arsenic trioxide vapor and arsine sampling train

    International Nuclear Information System (INIS)

    Crecelius, E.A.; Sanders, R.W.

    1980-01-01

    A sampling train was evaluated using 76 As tracer for the measurement of particulate arsenic, arsine, and arsenic trioxide vapor in air and industrial process gas streams. In this train, a demister was used to remove droplets of water and oil, and particulates were removed by a filter. Vapor arsenic trioxide was collected in an impinger solution, and arsine gas was collected on silvered quartz beads. Hydrogen sulfide gas did not reduce the arsine trapping efficiency of the silvered beads, and charcoal proved to be an effective trap for both arsine and arsenic trioxide vapor. 1 figure, 2 tables

  9. Knockdown of TWIST1 enhances arsenic trioxide- and ionizing radiation-induced cell death in lung cancer cells by promoting mitochondrial dysfunction

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    Seo, Sung-Keum; Kim, Jae-Hee; Choi, Ha-Na [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Choe, Tae-Boo [Department of Microbiological Engineering, Kon-Kuk University, Gwangjin-gu, Seoul (Korea, Republic of); Hong, Seok-Il [Department of Laboratory Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Yi, Jae-Youn [Laboratory of Modulation of Radiobiological Responses, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of); Lee, Hyun-Gyu [Department of Microbiology and Immunology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Lee, Yun-Han, E-mail: yhlee87@yuhs.ac [Department of Radiation Oncology, College of Medicine, Yonsei University, 250 Seongsan-no, Seodaemun-gu, Seoul (Korea, Republic of); Park, In-Chul, E-mail: parkic@kcch.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, 215-4 Gongneung-dong, Nowon-gu, Seoul (Korea, Republic of)

    2014-07-11

    Highlights: • Knockdown of TWIST1 enhanced ATO- and IR-induced cell death in NSCLCs. • Intracellular ROS levels were increased in cells treated with TWIST1 siRNA. • TWIST1 siRNA induced MMP loss and mitochondrial fragmentation. • TWIST1 siRNA upregulated the fission-related proteins FIS1 and DRP1. - Abstract: TWIST1 is implicated in the process of epithelial mesenchymal transition, metastasis, stemness, and drug resistance in cancer cells, and therefore is a potential target for cancer therapy. In the present study, we found that knockdown of TWIST1 by small interfering RNA (siRNA) enhanced arsenic trioxide (ATO)- and ionizing radiation (IR)-induced cell death in non-small-cell lung cancer cells. Interestingly, intracellular reactive oxygen species levels were increased in cells treated with TWIST1 siRNA and further increased by co-treatment with ATO or IR. Pretreatment of lung cancer cells with the antioxidant N-acetyl-cysteine markedly suppressed the cell death induced by combined treatment with TWIST1 siRNA and ATO or IR. Moreover, treatment of cells with TWIST1 siRNA induced mitochondrial membrane depolarization and significantly increased mitochondrial fragmentation (fission) and upregulated the fission-related proteins FIS1 and DRP1. Collectively, our results demonstrate that siRNA-mediated TWIST1 knockdown induces mitochondrial dysfunction and enhances IR- and ATO-induced cell death in lung cancer cells.

  10. Ambient pressure hydrometallurgical conversion of arsenic trioxide to crystalline scorodite

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    Debekaussen, R. [Corus Consulting and Technical Services, Delft (Netherlands); Droppert, D. [Solumet Inc., Montreal, PQ (Canada); Demopoulos, G. P. [McGill Univ., Dept. of Metallurgical Enginering, Montreal, PQ (Canada)

    2001-06-01

    Development of a novel process for the ambient pressure conversion of arsenic trioxide, a common, but extremely toxic by-product of the non-ferrous smelting industry, is described. The process consists of three main stages; (1) dissolution of arsenic trioxide, (2) oxidation of trivalent arsenic with the addition of hydrogen peroxide at 95 degree C, to pentavalent arsenic, and (3) step-wise precipitation of crystalline scorodite from highly concentrated arsenic containing solutions, by operating below a characteristics induction pH in the presence of seed material. The technical feasibility of the process has been confirmed by bench-scale testing of industrial flue dust material or acid plant effluents. 30 refs., 2 tabs., 5 figs.

  11. Arsenic trioxide induced rhabdomyolysis, a rare but severe side effect, in an APL patient: a case report.

    Science.gov (United States)

    He, Haiyan; An, Ran; Hou, Jian; Fu, Weijun

    2017-06-01

    Arsenic trioxide (ATO), a component of the traditional Chinese medicine arsenic sublimate, promotes apoptosis and induces leukemic cell differentiation. Combined with all-trans-retinotic acid (ATRA), ATO has become the first-line induction therapy in treating acute promyelocytic leukemia (APL). The most common side effects of ATO include hepatotoxicity, gastrointestinal symptoms, water-sodium retention, and nervous system damage. In this report, we present a rare side effect, rhabdomyolysis, in a 68-year-old female APL patient who was treated with ATO. After taking 10 mg ATO daily for 6 days, she presented shortness of breath, myodynia, elevated creatine kinase, and acute renal insufficiency. This report describes the first case of ATO-induced rhabdomyolysis.

  12. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    International Nuclear Information System (INIS)

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C.; Ballestas, Mary E.; Elmets, Craig A.; Robbins, David J.; Matalon, Sadis; Deshane, Jessy S.; Afaq, Farrukh; Bickers, David R.; Athar, Mohammad

    2013-01-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions

  13. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

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    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children' s of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Robbins, David J. [Department of Surgery, Molecular Oncology Program, Miller School of Medicine, University of Miami, Miami (United States); Matalon, Sadis [Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL (United States); Deshane, Jessy S. [Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Afaq, Farrukh [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Bickers, David R. [Department of Dermatology, Columbia University Medical Center, New York (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States)

    2013-11-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions.

  14. Expression of cyclin A in A549 cell line after treatment with arsenic trioxide

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    Agnieszka Żuryń

    2015-12-01

    Full Text Available Background: Arsenic trioxide (ATO is an effective drug used in acute promyelocytic leukemia (AML. Many reports suggest that ATO can also be applied as an anticancer agent for solid tumors in the future. The influence of arsenic trioxide on the expression of different cell cycle regulators is poorly recognized. The purpose of the current study is to investigate how arsenic trioxide affects cyclin A expression and localization in the A549 cell line.Materials and methods: Morphological and ultrastructural changes in A549 cells were observed using light and transmission electron microscopes. Cyclin A localization was determined by immunofluorescence. Image-based cytometry was applied to evaluate the effect of arsenic trioxide on apoptosis and the cell cycle. Expression of cyclin A mRNA was quantified by real-time PCR.Results: After treatment with arsenic trioxide, increased numbers of cells with cytoplasmic localization of cyclin A were observed. The doses of 10 and 15 μM ATO slightly reduced expression of cyclin A mRNA. The apoptotic phenotype of cells was poorly represented, and the Tali imagebased cytometry analysis showed low percentages of apoptotic cells. The A549 population displayed an enriched fraction of cells in G0/G1 phase in the presence of 5μM ATO, whereas starting from the higher concentrations of the drug, i.e. 10 and 15 μM ATO, the G2/M fraction was on the increase.Discussion: Low expression of cyclin A in the A549 cell line may constitute a potential factor determining arsenic trioxide resistance. It could be hypothesized that the observed alterations in cyclin A expression/distribution may correlate well with changes in cell cycle regulation in our model, which in turn determines the outcome of the treatment.

  15. Sumoylation of the Tumor Suppressor Promyelocytic Leukemia Protein Regulates Arsenic Trioxide-Induced Collagen Synthesis in Osteoblasts.

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    Xu, Wen-Xiao; Liu, Sheng-Zhi; Wu, Di; Qiao, Guo-Fen; Yan, Jinglong

    2015-01-01

    Promyelocytic leukemia (PML) protein is a tumor suppressor that fuses with retinoic acid receptor-α (PML-RARα) to contribute to the initiation of acute promyelocytic leukemia (APL). Arsenic trioxide (ATO) upregulates expression of TGF-β1, promoting collagen synthesis in osteoblasts, and ATO binds directly to PML to induce oligomerization, sumoylation, and ubiquitination. However, how ATO upregulates TGF-β1 expression is uncertain. Thus, we suggested that PML sumoylation is responsible for regulation of TGF-β1 protein expression. Kunming mice were treated with ATO, and osteoblasts were counted under scanning electron microscopy. Masson's staining was used to quantify collagen content. hFOB1.19 cells were transfected with siRNA against UBC9 or RNF4, and then treated with ATO or FBS. TGF-β1, PML expression, and sumoylation were quantified with Western blot, and collagen quantified via immunocytochemistry. ATO enhanced osteoblast accumulation, collagen synthesis, and PML-NB formation in vivo. Knocking down UBC9 in hFOB1.19 cells inhibited ATO- and FBS-induced PML sumoylation, TGF-β1 expression, and collagen synthesis. Conversely, knocking down RNF4 enhanced ATO- and FBS-induced PML sumoylation, TGF-β1 expression, and collagen synthesis. These data suggest that PML sumoylation is required for ATO-induced collagen synthesis in osteoblasts. © 2015 S. Karger AG, Basel.

  16. Relapsed acute promyelocytic leukemia in a hemodialysis-dependent patient treated with arsenic trioxide: a case report

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    Emmons Gregory S

    2012-10-01

    Full Text Available Abstract Introduction In the relapsed setting, arsenic trioxide remains the backbone of treatment. Scant literature exists regarding treatment of relapsed acute promyelocytic leukemia in patients with renal failure. To the best of our knowledge we are the first to report a safe and effective means of treatment for relapsed acute promyelocytic leukemia in the setting of advanced renal failure, employing titration of arsenic trioxide based on clinical parameters rather than arsenic trioxide levels. Case presentation A 33-year-old Caucasian man with a history of acute promyelocytic leukemia in remission for 3 years, as well as dialysis-dependent chronic renal failure secondary to a solitary kidney and focal segmental glomerulosclerosis and human immunodeficiency virus infection, receiving highly active antiretroviral therapy presented to our hospital with bone marrow biopsy-confirmed relapsed acute promyelocytic leukemia. Arsenic trioxide was begun at a low dose with dose escalation based only on side effect profile monitoring and not laboratory testing for induction as well as maintenance without undue toxicity. Our patient achieved and remains in complete hematologic and molecular remission as of this writing. Conclusion Arsenic trioxide can be used safely and effectively to treat acute promyelocytic leukemia in patients with advanced renal failure using careful monitoring of side effects rather than blood levels of arsenic to guide therapeutic dosing.

  17. The antitumor effect of arsenic trioxide on hepatocellular carcinoma is enhanced by andrographolide.

    Science.gov (United States)

    Duan, Xuhua; Li, Tengfei; Han, Xinwei; Ren, Jianzhuang; Chen, Pengfei; Li, Hao; Gong, Shaojun

    2017-10-31

    High concentrations of arsenic trioxide (As 2 O 3 ) are used to treat acute promyelocytic leukemia and solid tumors, with negative side effects to normal cells. Andrographolide is a traditional Chinese medicine that exerts anti-cancer, anti-inflammatory, anti-virus, and anti-diabetic effects. Here, we tested the effects of combined andrographolide with As 2 O 3 against hepatocellular carcinoma (HCC). We found that by increasing apoptosis, andrographolide synergistically enhanced the anti-tumor effects of As2O3 in HepG2 cells in vitro and in vivo . Furthermore, results from our microarray assays and experiments with mouse xenografts showed that EphB4 was downregulated by the combination of As 2 O 3 plus andrographolide. These findings suggest that the combination of andrographolide and As 2 O 3 could yield therapeutic benefits in the treatment of HCC.

  18. Study of arsenic trioxide-induced vascular shutdown and enhancement with radiation in solid tumor

    International Nuclear Information System (INIS)

    Monzen, Hajime; Griffin, R.J.; Williams, B.W.; Amamo, Morikazu; Ando, Satoshi; Hasegawa, Takeo

    2004-01-01

    Arsenic trioxide (ATO) has been reported to be an effective chemotherapeutic agent for acute promyelocytic leukemia (APL), and, recently, anti-tumor effect has been demonstrated in solid tumors. However, little is known about the mechanism of action of the ATO effect on solid tumor. We investigated the anti-vascular effect of ATO and the potential of combining ATO with radiation therapy. We studied the anti-vascular effect of ATO and radiosensitization of squamous cell carcinoma (SCC) VII murine tumors of C3H mice. The anti-vascular effect was examined using magnetic resonance imaging (MRI), and radiosensitivity was studied by clonogenic assay and tumor growth delay. Histopathological changes of the tumors after various treatments were also observed with hematoxylin and eosin (H and E) staining. Necrosis and blood flow changes in the central region of tumors in the hind limbs of the animals were observed on T2-weighted imaging after an intraperitoneal (i.p.) injection of 8 mg/kg of ATO alone. ATO exposure followed by radiation decreased the clonogenic survival of SCC VII cells compared with either treatment alone. Tumor growth delay after 10-20 Gy of radiation alone was increased slightly compared with control tumors, but the combination of ATO injection 2 hours before exposure to 20 Gy of radiation significantly prolonged tumor growth delay by almost 20 days. The results suggest that ATO and radiation can enhance the radiosensitivity of solid tumor. (author)

  19. Antimony trioxide-induced apoptosis is dependent on SEK1/JNK signaling.

    Science.gov (United States)

    Mann, Koren K; Davison, Kelly; Colombo, Myrian; Colosimo, April L; Diaz, Zuanel; Padovani, Alessandra M S; Guo, Qi; Scrivens, P James; Gao, Wenli; Mader, Sylvie; Miller, Wilson H

    2006-01-05

    Very little is known concerning the toxicity of antimony, despite its commercial use as a flame retardant and medical use as a treatment for parasitic infections. Our previous studies show that antimony trioxide (Sb(2)O(3)) induces growth inhibition in patient-derived acute promyelocytic leukemia (APL) cell lines, a disease in which a related metal, arsenic trioxide (As(2)O(3)), is used clinically. However, signaling pathways initiated by Sb(2)O(3) treatment remain undefined. Here, we show that Sb(2)O(3) treatment of APL cells is associated with increased apoptosis as well as differentiation markers. Sb(2)O(3)-induced reactive oxygen species (ROS) correlated with increased apoptosis. In addition, when we decreased the buffering capacity of the cell by depleting glutathione, ROS production and apoptosis was enhanced. Arsenic-resistant APL cells with increased glutathione levels exhibited increased cross-resistance to Sb(2)O(3). Based on studies implicating c-jun kinase (JNK) in the mediation of the response to As(2)O(3), we investigated the role for JNK in Sb(2)O(3)-induced apoptosis. Sb(2)O(3) activates JNK and its downstream target, AP-1. In fibroblasts with a genetic deletion in SEK1, an upstream regulator of JNK, Sb(2)O(3)-induced growth inhibition as well as JNK activation was decreased. These data suggest roles for ROS and the SEK1/JNK pathway in the cytotoxicity associated with Sb(2)O(3) exposure.

  20. Dose- and Time-Dependent Response of Human Leukemia (HL-60 Cells to Arsenic Trioxide Treatment

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    Paul B. Tchounwou

    2006-06-01

    Full Text Available The treatment of acute promyelocytic leukemia (APL has been based on the administration of all-trans retinoic acid plus anthracycline chemotherapy, which is very effective as first line therapy; however 25 to 30% of patients will relapse with their disease becoming refractory to conventional therapy. Recently, studies have shown arsenic trioxide to be effective in the treatment of acute promyelocytic leukemia. In this study, we used the human leukemia (HL-60 cell line as a model to evaluate the cytoxicity of arsenic trioxide based on the MTT assay. Data obtained from this assay indicated that arsenic trioxide significantly reduced the viability of HL-60 cells, showing LD50 values of 14.26 + 0.5μg/mL, 12.54 + 0.3μg/mL, and 6.4 + 0.6μg/mL upon 6, 12, and 24 hours of exposure, respectively; indicating a dose- and time-dependent response relationship. Findings from the present study indicate that arsenic trioxide is highly cytotoxic to human leukemia (HL-60 cells, supporting its use as an effective therapeutic agent in the management of acute promyelocytic leukemia.

  1. Comparative investigations of sodium arsenite, arsenic trioxide and cadmium sulphate in combination with gamma-radiation on apoptosis, micronuclei induction and DNA damage in a human lymphoblastoid cell line

    International Nuclear Information System (INIS)

    Hornhardt, Sabine; Gomolka, Maria; Walsh, Linda; Jung, Thomas

    2006-01-01

    In the field of radiation protection the combined exposure to radiation and other toxic agents is recognised as an important research area. To elucidate the basic mechanisms of simultaneous exposure, the interaction of the carcinogens and environmental toxicants cadmium and two arsenic compounds, arsenite and arsenic trioxide, in combination with gamma-radiation in human lymphoblastoid cells (TK6) were investigated. Gamma-radiation induced significant genotoxic effects such as micronuclei formation, DNA damage and apoptosis, whereas arsenic and cadmium had no significant effect on these indicators of cellular damage at non-toxic concentrations. However, in combination with gamma-radiation arsenic trioxide induced a more than additive apoptotic rate compared to the sum of the single effects. Here, the level of apoptotic cells was increased, in a dose-dependent way, up to two-fold compared to the irradiated control cells. Arsenite did not induce a significant additive effect at any of the concentrations or radiation doses tested. On the other hand, arsenic trioxide was less effective than arsenite in the induction of DNA protein cross-links. These data indicate that the two arsenic compounds interact through different pathways in the cell. Cadmium sulphate, like arsenite, had no significant effect on apoptosis in combination with gamma-radiation at low concentrations and, at high concentrations, even reduced the radiation-induced apoptosis. An additive effect on micronuclei induction was observed with 1 μM cadmium sulphate with an increase of up to 80% compared to the irradiated control cells. Toxic concentrations of cadmium and arsenic trioxide seemed to reduce micronuclei induction. The results presented here indicate that relatively low concentrations of arsenic and cadmium, close to those occurring in nature, may interfere with radiation effects. Differences in action of the two arsenic compounds were identified

  2. Nrf2 activation ameliorates cytotoxic effects of arsenic trioxide in acute promyelocytic leukemia cells through increased glutathione levels and arsenic efflux from cells

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    Nishimoto, Shoichi; Suzuki, Toshihiro; Koike, Shin [Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588 (Japan); Yuan, Bo; Takagi, Norio [Department of Applied Biochemistry, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392 (Japan); Ogasawara, Yuki, E-mail: yo@my-pharm.ac.jp [Department of Analytical Biochemistry, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588 (Japan)

    2016-08-15

    Carnosic acid (CA), a phenolic diterpene isolated from Rosmarinus officinalis, has been shown to activate nuclear transcription factor E2-related factor 2 (Nrf2), which plays a central role in cytoprotective responses to oxidative and electrophilic stress. Recently, the Nrf2-Kelch ECH associating protein 1 (Keap1) pathway has been associated with cancer drug resistance attributable to modulation of the expression and activation of antioxidant and detoxification enzymes. However, the exact mechanisms by which Nrf2 activation results in chemoresistance are insufficiently understood to date. This study investigated the mechanisms by which the cytotoxic effects of arsenic trioxide (ATO), an anticancer drug, were decreased in acute promyelocytic leukemia cells treated with CA, a typical activator of Nrf2 used to stimulate the Nrf2/Keap1 system. Our findings suggest that arsenic is non-enzymatically incorporated into NB4 cells and forms complexes that are dependent on intracellular glutathione (GSH) concentrations. In addition, the arsenic complexes are recognized as substrates by multidrug resistance proteins and subsequently excreted from the cells. Therefore, Nrf2-associated activation of the GSH biosynthetic pathway, followed by increased levels of intracellular GSH, are key mechanisms underlying accelerated arsenic efflux and attenuation of the cytotoxic effects of ATO. - Highlights: • Nrf2 activation attenuates the effect of arsenic trioxide to acute promyelocytic leukemia cells. • The sensitivity of arsenic trioxide to NB4 cells was dependent on efflux rate of arsenic. • Activation of the GSH biosynthesis is essential in Nrf2-regulated responses for arsenic efflux.

  3. Enhanced suppression of tumor growth by concomitant treatment of human lung cancer cells with suberoylanilide hydroxamic acid and arsenic trioxide

    International Nuclear Information System (INIS)

    Chien, Chia-Wen; Yao, Ju-Hsien; Chang, Shih-Yu; Lee, Pei-Chih; Lee, Te-Chang

    2011-01-01

    The efficacy of arsenic trioxide (ATO) against acute promyelocytic leukemia (APL) and relapsed APL has been well documented. ATO may cause DNA damage by generating reactive oxygen intermediates. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, modulates gene and protein expression via histone-dependent or -independent pathways that may result in chromatin decondensation, cell cycle arrest, differentiation, and apoptosis. We investigated whether ATO and SAHA act synergistically to enhance the death of cancer cells. Our current findings showed that combined treatment with ATO and SAHA resulted in enhanced suppression of non-small-cell lung carcinoma in vitro in H1299 cells and in vivo in a xenograft mouse model. Flow cytometric analysis of annexin V+ cells showed that apoptotic cell death was significantly enhanced after combined treatment with ATO and SAHA. At the doses used, ATO did not interfere with cell cycle progression, but SAHA induced p21 expression and led to G1 arrest. A Comet assay demonstrated that ATO, but not SAHA, induced DNA strand breaks in H1299 cells; however, co-treatment with SAHA significantly increased ATO-induced DNA damage. Moreover, SAHA enhanced acetylation of histone H3 and sensitized genomic DNA to DNase I digestion. Our results suggest that SAHA may cause chromatin relaxation and increase cellular susceptibility to ATO-induced DNA damage. Combined administration of SAHA and ATO may be an effective approach to the treatment of lung cancer. -- Highlights: ► ATO and SAHA are therapeutic agents with different action modes. ► Combination of ATO and SAHA synergistically inhibits tumor cell growth. ► SAHA loosens chromatin structure resulting in increased sensitivity to DNase I. ► ATO-induced DNA damage and apoptosis are enhanced by co-treatment with SAHA.

  4. Arsenic trioxide: impact on the growth and differentiation of cancer cells and possible use in cancer therapy

    Directory of Open Access Journals (Sweden)

    Ewelina Hoffman

    2013-08-01

    Full Text Available Arsenic trioxide (As2O3 has recently been identified as an effective drug in different types of cancer therapy. It is a useful pharmacological agent in acute promyelocytic leukemia (APL treatment, especially the form that is resistant to conventional chemotherapy with all-trans retinoic acid (ATRA. What is more, laboratory data suggest that As2O3 is also active when it comes to several solid tumor cell lines. However, the mechanism of action is not fully understood. As2O3 in high doses triggers apoptosis, while in lower concentrations it induces partial differentiation. The As2O3 mechanism of action involves effects on mitochondrial transmembrane potential which lead to apoptosis. It also acts on the activity of JNK kinase, glutathione, caspases, NF-ĸB nuclear factor or pro- and antiapoptotic proteins. This publication presents the current knowledge about the influence of arsenic trioxide in cancer cells.

  5. Arsenic species excretion after dimercaptopropanesulfonic acid (DMPS) treatment of an acute arsenic trioxide poisoning

    Energy Technology Data Exchange (ETDEWEB)

    Heinrich-Ramm, R. [Ordinariat fuer Arbeitsmedizin der Universitaet Hamburg und Zentralinstitut fuer Arbeitsmedizin, Hamburg (Germany); Schaller, K.H.; Angerer, J. [Institut und Poliklinik fuer Arbeits-, Sozial- und Umweltmedizin der Universitaet Erlangen-Nuernberg, Schillerstr. 25, 91054 Erlangen (Germany); Horn, J. [Medizinische Klinik II, Toxikologische-internistische Intensivstation, Klinikum Nuernberg, Nuernberg (Germany)

    2003-02-01

    We studied the urinary excretion of the different arsenic species in urine samples from a young man who tried to commit suicide by ingesting about 0.6 g arsenic trioxide. He received immediate therapy with dimercaptopropanesulfonic acid (DMPS) after his delivery into the hospital. We assessed urinary arsenite (inorganic trivalent arsenic), arsenate (inorganic pentavalent arsenic), pentavalent dimethylarsinic acid (DMA) and pentavalent monomethylarsonic acid (MMA) in urine with ion-exchange chromatography and on-line hydride-technique atomic absorption spectrometry. The predominant amount of the excreted arsenic was unchanged trivalent inorganic arsenic (37.4%), followed by pentavalent inorganic arsenic (2.6%), MMA (2.1%), DMA (0.2%) and one unidentified arsenic species (0.7%, if calculated as DMA). In the first urine voiding in the clinic, the total arsenic concentration was 215 mg/l, which fell 1000-fold after 8 days of DMPS therapy. A most striking finding was the almost complete inhibition of the second methylation step in arsenic metabolism. As mechanisms for the reduced methylation efficiency, the saturation of the enzymatic process of arsenic methylation, the high dosage of antidote DMPS, which might inhibit the activity of the methyl transferases, and analytical reasons are discussed. The high dosage of DMPS is the most likely explanation. The patient left the hospital after a 12-day treatment with antidote. (orig.)

  6. Arsenic speciation in hair and nails of acute promyelocytic leukemia (APL) patients undergoing arsenic trioxide treatment.

    Science.gov (United States)

    Chen, Baowei; Cao, Fenglin; Lu, Xiufen; Shen, Shengwen; Zhou, Jin; Le, X Chris

    2018-07-01

    Arsenic in hair and nails has been used to assess chronic exposure of humans to environmental arsenic. However, it remains to be seen whether it is appropriate to evaluate acute exposure to sub-lethal doses of arsenic typically used in therapeutics. In this study, hair, fingernail and toenail samples were collected from nine acute promyelocytic leukemia (APL) patients who were administered intravenously the daily dose of 10 mg arsenic trioxide (7.5 mg arsenic) for up to 54 days. These hair and nail samples were analyzed for arsenic species using high performance liquid chromatography separation and inductively coupled plasma mass spectrometry detection (HPLC-ICPMS). Inorganic arsenite was the predominant form among water-extractable arsenicals. Dimethylarsinic acid (DMA V ), monomethylarsonic acid (MMA V ), monomethylarsonous acid (MMA III ), monomethylmonothioarsonic acid (MMMTA V ), and dimethylmonothioarsinic acid (DMMTA V ) were also detected in both hair and nail samples. This is the first report of the detection of MMA III and MMMTA V as metabolites of arsenic in hair and nails of APL patients. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Vorinostat enhances chemosensitivity to arsenic trioxide in K562 cell line

    Directory of Open Access Journals (Sweden)

    Nainong Li

    2015-05-01

    Full Text Available Objective. This study aimed to investigate the chemosensitive augmentation effect and mechanism of HDAC inhibitor Vorinostat (SAHA in combination with arsenic trioxide (ATO on proliferation and apoptosis of K562 cells.Methods. The CCK-8 assay was used to compare proliferation of the cells. Annexin-V and PI staining by flow cytometry and acridine orange/ethidium bromide stains were used to detect and quantify apoptosis. Western blot was used to detect expression of p21, Akt, pAkt, p210, Acetyl-Histone H3, and Acetyl-Histone H4 proteins.Results. SAHA and ATO inhibited proliferation of K562 cells in an additive and time- and dose-dependent manner. SAHA in combination with ATO showed significant apoptosis of K562 cells in comparison to the single drugs alone (p < 0.01. Both SAHA and ATO alone and in combination showed lower levels of p210 expression. SAHA and SAHA and ATO combined treatment showed increased levels of Acetyl-Histone H3 and Acetyl-Histone H4 protein expression. SAHA alone showed increased expression of p21, while ATO alone and in combination with SAHA showed no significant change. SAHA and ATO combined therapy showed lower levels of Akt and pAkt protein expression than SAHA or ATO alone.Conclusion. SAHA and ATO combined treatment inhibited proliferation, induced apoptosis, and showed a chemosensitive augmentation effect on K562 cells. The mechanism might be associated with increasing histone acetylation levels as well as regulating the Akt signaling pathway.

  8. TG-interacting factor transcriptionally induced by AKT/FOXO3A is a negative regulator that antagonizes arsenic trioxide-induced cancer cell apoptosis

    International Nuclear Information System (INIS)

    Liu, Zi-Miao; Tseng, Hong-Yu; Cheng, Ya-Ling; Yeh, Bi-Wen; Wu, Wen-Jeng; Huang, Huei-Sheng

    2015-01-01

    Arsenic trioxide (ATO) is a multi-target drug approved by the Food and Drug Administration as the first-line chemotherapeutic agent for the treatment of acute promyelocytic leukemia. In addition, several clinical trials are being conducted with arsenic-based drugs for the treatment of other hematological malignancies and solid tumors. However, ATO's modest clinical efficacy on some cancers, and potential toxic effects on humans have been reported. Determining how best to reduce these adverse effects while increasing its therapeutic efficacy is obviously a critical issue. Previously, we demonstrated that the JNK-induced complex formation of phosphorylated c-Jun and TG-interacting factor (TGIF) antagonizes ERK-induced cyclin-dependent kinase inhibitor CDKN1A (p21 WAF1/CIP1 ) expression and resultant apoptosis in response to ATO in A431 cells. Surprisingly, at low-concentrations (0.1–0.2 μM), ATO increased cellular proliferation, migration and invasion, involving TGIF expression, however, at high-concentrations (5–20 μM), ATO induced cell apoptosis. Using a promoter analysis, TGIF was transcriptionally regulated by ATO at the FOXO3A binding site (− 1486 to − 1479 bp) via the c-Src/EGFR/AKT pathway. Stable overexpression of TGIF promoted advancing the cell cycle into the S phase, and attenuated 20 μM ATO-induced apoptosis. Furthermore, blockage of the AKT pathway enhanced ATO-induced CDKN1A expression and resultant apoptosis in cancer cells, but overexpression of AKT1 inhibited CDKN1A expression. Therefore, we suggest that TGIF is transcriptionally regulated by the c-Src/EGFR/AKT pathway, which plays a role as a negative regulator in antagonizing ATO-induced CDKN1A expression and resultant apoptosis. Suppression of these antagonistic effects might be a promising therapeutic strategy toward improving clinical efficacy of ATO. - Highlights: • ATO-induced biphasic survival responses of cancer cells depend on low- or high-concentrations. • TGIF mediates

  9. TG-interacting factor transcriptionally induced by AKT/FOXO3A is a negative regulator that antagonizes arsenic trioxide-induced cancer cell apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zi-Miao; Tseng, Hong-Yu; Cheng, Ya-Ling [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Yeh, Bi-Wen [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China); Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Wu, Wen-Jeng [Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan (China); Huang, Huei-Sheng, E-mail: huanghs@mail.ncku.edu.tw [Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan (China)

    2015-05-15

    Arsenic trioxide (ATO) is a multi-target drug approved by the Food and Drug Administration as the first-line chemotherapeutic agent for the treatment of acute promyelocytic leukemia. In addition, several clinical trials are being conducted with arsenic-based drugs for the treatment of other hematological malignancies and solid tumors. However, ATO's modest clinical efficacy on some cancers, and potential toxic effects on humans have been reported. Determining how best to reduce these adverse effects while increasing its therapeutic efficacy is obviously a critical issue. Previously, we demonstrated that the JNK-induced complex formation of phosphorylated c-Jun and TG-interacting factor (TGIF) antagonizes ERK-induced cyclin-dependent kinase inhibitor CDKN1A (p21{sup WAF1/CIP1}) expression and resultant apoptosis in response to ATO in A431 cells. Surprisingly, at low-concentrations (0.1–0.2 μM), ATO increased cellular proliferation, migration and invasion, involving TGIF expression, however, at high-concentrations (5–20 μM), ATO induced cell apoptosis. Using a promoter analysis, TGIF was transcriptionally regulated by ATO at the FOXO3A binding site (− 1486 to − 1479 bp) via the c-Src/EGFR/AKT pathway. Stable overexpression of TGIF promoted advancing the cell cycle into the S phase, and attenuated 20 μM ATO-induced apoptosis. Furthermore, blockage of the AKT pathway enhanced ATO-induced CDKN1A expression and resultant apoptosis in cancer cells, but overexpression of AKT1 inhibited CDKN1A expression. Therefore, we suggest that TGIF is transcriptionally regulated by the c-Src/EGFR/AKT pathway, which plays a role as a negative regulator in antagonizing ATO-induced CDKN1A expression and resultant apoptosis. Suppression of these antagonistic effects might be a promising therapeutic strategy toward improving clinical efficacy of ATO. - Highlights: • ATO-induced biphasic survival responses of cancer cells depend on low- or high-concentrations. • TGIF

  10. Addition of Arsenic Trioxide into Induction Regimens Could Not Accelerate Recovery of Abnormality of Coagulation and Fibrinolysis in Patients with Acute Promyelocytic Leukemia.

    Directory of Open Access Journals (Sweden)

    Ye Zhang

    Full Text Available All-trans retinoic acid combined to anthracycline-based chemotherapy is the standard regimen of acute promyelocytic leukemia. The advent of arsenic trioxide has contributed to improve the anti-leukemic efficacy in acute promyelocytic leukemia. The objectives of the current study were to evaluate if dual induction by all-trans retinoic acid and arsenic trioxide could accelerate the recovery of abnormality of coagulation and fibrinolysis in patients with acute promyelocytic leukemia.Retrospective analysis was performed in 103 newly-diagnosed patients with acute promyelocytic leukemia. Hemostatic variables and the consumption of component blood were comparably analyzed among patients treated by different induction regimen with or without arsenic trioxide.Compared to patients with other subtypes of de novo acute myeloid leukemia, patients with acute promyelocytic leukemia had lower platelet counts and fibrinogen levels, significantly prolonged prothrombin time and elevated D-dimers (P<0.001. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification presented lower initial fibrinogen level than that of low-risk group (P<0.05. After induction treatment, abnormal coagulation and fibrinolysis of patients with acute promyelocytic leukemia was significantly improved before day 10. The recovery of abnormal hemostatic variables (platelet, prothrombin time, fibrinogen and D-dimer was not significantly accelerated after adding arsenic trioxide in induction regimens; and the consumption of transfused component blood (platelet and plasma did not dramatically change either. Acute promyelocytic leukemia patients with high or intermediate risk prognostic stratification had higher platelet transfusion demands than that of low-risk group (P<0.05.Unexpectedly, adding arsenic trioxide could not accelerate the recovery of abnormality of coagulation and fibrinolysis in acute promyelocytic leukemia patients who received all

  11. Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Ritesh K.; Li, Changzhao [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Wang, Yong [Department of Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Weng, Zhiping; Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Harrod, Kevin S. [Department of Anesthesiology and Perioperative Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Deshane, Jessy S., E-mail: treena@uab.edu [Department of Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States)

    2016-10-01

    Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4{sup +/+} wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4{sup +/−} heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca{sup ++} homeostasis. ATO induces Ca{sup ++}-dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca{sup ++} homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic. - Highlights: • ATF4 regulates arsenic-mediated impairment in macrophage functions. • Arsenic-mediated alterations in pulmonary macrophage are diminished in ATF4{sup +/−} mice

  12. Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions

    International Nuclear Information System (INIS)

    Srivastava, Ritesh K.; Li, Changzhao; Wang, Yong; Weng, Zhiping; Elmets, Craig A.; Harrod, Kevin S.; Deshane, Jessy S.; Athar, Mohammad

    2016-01-01

    Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4 +/+ wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4 +/− heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca ++ homeostasis. ATO induces Ca ++ -dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca ++ homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic. - Highlights: • ATF4 regulates arsenic-mediated impairment in macrophage functions. • Arsenic-mediated alterations in pulmonary macrophage are diminished in ATF4 +/− mice. • Changes in macrophage

  13. ETME, a novel β-elemene derivative, synergizes with arsenic trioxide in inducing apoptosis and cell cycle arrest in hepatocarcinoma cells via a p53-dependent pathway

    Directory of Open Access Journals (Sweden)

    Zhiying Yu

    2014-12-01

    Full Text Available Arsenic trioxide (ATO has been identified as an effective treatment for acute promyelocytic leukemia (APL but is much less effective against solid tumors such as hepatocellular carcinoma (HCC. In the search for ways to enhance its therapeutic efficacy against solid tumors, we have examined its use in combination with a novel derivative of β-elemene, N-(β-elemene-13-yltryptophan methyl ester (ETME. Here we report the effects of the combination on cell viability, apoptosis, the cell cycle and mitochondria membrane potential (MMP in HCC SMMC-7721 cells. We found that the two compounds acted synergistically to enhance antiproliferative activity and apoptosis. The combination also decreased the MMP, down-regulated Bcl-2 and pro-proteins of the caspase family, and up-regulated Bax and BID, all of which were reversed by the p53 inhibitor, pifithrin-α. In addition, the combination induced cell cycle arrest at the G2/M phase and reduced tumor volume and weight in an xenograft model of nude mice. Overall, the results suggest that ETME in combination with ATO may be useful in the treatment of HCC patients particularly those unresponsive to ATO alone.

  14. Berberine enhances inhibition of glioma tumor cell migration and invasiveness mediated by arsenic trioxide

    International Nuclear Information System (INIS)

    Lin, Tseng-Hsi; Kuo, Hsing-Chun; Chou, Fen-Pi; Lu, Fung-Jou

    2008-01-01

    Arsenic trioxide (As 2 O 3 ) exhibits promising anticarcinogenic activity in acute promyelocytic leukemic patients and induces apoptosis in various tumor cells in vitro. Here, we investigated the effect of the natural alkaloid berberine on As 2 O 3 -mediated inhibition of cancer cell migration using rat and human glioma cell lines. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to determine the viability of rat C6 and human U-87 glioma cells after treatment with As 2 O 3 or berberine, and after co-treatment with As 2 O 3 and berberine. The wound scratch and Boyden chamber assays were applied to determine the effect of As 2 O 3 and berberine on the migration capacity and invasiveness of glioma cancer cells. Zymography and Western blot analyses provided information on the effect of As 2 O 3 and berberine on the intracellular translocation and activation of protein kinase C (PKC), and some PKC-related downstream factors. Most assays were performed three times, independently, and data were analyzed using ANOVA. The cell viability studies demonstrated that berberine enhances As 2 O 3 -mediated inhibition of glioma cell growth after 24 h incubation. Untreated control cells formed a confluent layer, the formation of which was inhibited upon incubation with 5 μM As 2 O 3 . The latter effect was even more pronounced in the presence of 10 μM berberine. The As 2 O 3 -mediated reduction in motility and invasion of glioma cells was enhanced upon co-treatment with berberine. Furthermore, it has been reported that PKC isoforms influence the morphology of the actin cytoskeleton, as well as the activation of metalloproteases MT1-MMP and MMP-2, reported to be involved in cancer cell migration. Treatment of glioma cells with As 2 O 3 and berberine significantly decreased the activation of PKC α and ε and led to actin cytoskeleton rearrangements. The levels of two downstream transcription factors, myc and jun, and MT1-MMP and MMP-2 were also

  15. Serum Acetyl Cholinesterase as a Biomarker of Arsenic Induced Neurotoxicity in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Paul B. Tchounwou

    2005-04-01

    Full Text Available Arsenic is an environmental toxicant, and one of the major mechanisms by which it exerts its toxic effect is through an impairment of cellular respiration by inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Most toxicity of arsenic results from its ability to interact with sulfhydryl groups of proteins and enzymes, and to substitute phosphorus in a variety of biochemical reactions. Recent studies have pointed out that arsenic toxicity is associated with the formation of reactive oxygen species, which may cause severe injury/damage to the nervous system. The main objective of this study was to conduct biochemical analysis to determine the effect of arsenic trioxide on the activity of acetyl cholinesterase; a critical important nervous system enzyme that hydrolyzes the neurotransmitter acetylcholine. Four groups of six male rats each weighing an average 60 + 2 g were used in this study. Arsenic trioxide was intraperitoneally administered to the rats at the doses of 5, 10, 15, 20mg/kg body weight (BW, one dose per 24 hour given for five days. A control group was also made of 6 animals injected with distilled water without chemical. Following anaesthesia, blood specimens were immediately collected using heparinized syringes, and acetyl cholinesterase detection and quantification were performed in serum samples by spectrophotometry. Arsenic trioxide exposure significantly decreased the activity of cholinesterase in the Sprague-Dawley rats. Acetyl cholinesterase activities of 6895 + 822, 5697 + 468, 5069 + 624, 4054 + 980, and 3158 + 648 U/L were recorded for 0, 5, 10, 15, and 20 mg/kg, respectively; indicating a gradual decrease in acetyl cholinesterase activity with increasing doses of arsenic. These findings indicate that acetyl

  16. Establishment and characterization of arsenic trioxide resistant KB/ATO cells.

    Science.gov (United States)

    Zhang, Yun-Kai; Dai, Chunling; Yuan, Chun-Gang; Wu, Hsiang-Chun; Xiao, Zhijie; Lei, Zi-Ning; Yang, Dong-Hua; Le, X Chris; Fu, Liwu; Chen, Zhe-Sheng

    2017-09-01

    Arsenic trioxide (ATO) is used as a chemotherapeutic agent for the treatment of acute promyelocytic leukemia. However, increasing drug resistance is reducing its efficacy. Therefore, a better understanding of ATO resistance mechanism is required. In this study, we established an ATO-resistant human epidermoid carcinoma cell line, KB/ATO, from its parental KB-3-1 cells. In addition to ATO, KB/ATO cells also exhibited cross-resistance to other anticancer drugs such as cisplatin, antimony potassium tartrate, and 6-mercaptopurine. The arsenic accumulation in KB/ATO cells was significantly lower than that in KB-3-1 cells. Further analysis indicated that neither application of P-glycoprotein inhibitor, breast cancer resistant protein (BCRP) inhibitor, or multidrug resistance protein 1 (MRP1) inhibitor could eliminate ATO resistance. We found that the expression level of ABCB6 was increased in KB/ATO cells. In conclusion, ABCB6 could be an important factor for ATO resistance in KB/ATO cells. The ABCB6 level may serve as a predictive biomarker for the effectiveness of ATO therapy.

  17. Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lei; Hitron, John Andrew [Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Wise, James T.F. [Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Son, Young-Ok; Roy, Ram Vinod [Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Kim, Donghern; Dai, Jin [Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Pratheeshkumar, Poyil [Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Zhang, Zhuo [Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Xu, Mei; Luo, Jia [Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin, E-mail: xshi5@uky.edu [Center for Research on Environmental Disease, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States); Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536 (United States)

    2015-10-15

    Arsenic is a known carcinogen to humans, and chronic exposure to environmental arsenic is a worldwide health concern. As a dietary factor, ethanol carries a well-established risk for malignancies, but the effects of co-exposure to arsenic and ethanol on tumor development are not well understood. In the present study, we hypothesized that ethanol would enhance the function of an environmental carcinogen such as arsenic through increase in COX-2 expression. Our in vitro results show that ethanol enhanced arsenic-induced COX-2 expression. We also show that the increased COX-2 expression associates with intracellular ROS generation, up-regulated AKT signaling, with activation of both NFAT and NF-κB pathways. We demonstrate that antioxidant enzymes have an inhibitory effect on arsenic/ethanol-induced COX-2 expression, indicating that the responsive signaling pathways from co-exposure to arsenic and ethanol relate to ROS generation. In vivo results also show that co-exposure to arsenic and ethanol increased COX-2 expression in mice. We conclude that ethanol enhances arsenic-induced COX-2 expression in colorectal cancer cells via both the NFAT and NF-κB pathways. These results imply that, as a common dietary factor, ethanol ingestion may be a compounding risk factor for arsenic-induced carcinogenesis/cancer development. - Highlights: • Arsenic is able to induce Cox-2 expression in colorectal cancer cells. • Ethanol, a diet nutritional factor, could enhance arsenic-induced Cox-2. • The up-regulation of Cox-2 via both NFAT and NF-κB activities.

  18. Ethanol enhances arsenic-induced cyclooxygenase-2 expression via both NFAT and NF-κB signalings in colorectal cancer cells

    International Nuclear Information System (INIS)

    Wang, Lei; Hitron, John Andrew; Wise, James T.F.; Son, Young-Ok; Roy, Ram Vinod; Kim, Donghern; Dai, Jin; Pratheeshkumar, Poyil; Zhang, Zhuo; Xu, Mei; Luo, Jia; Shi, Xianglin

    2015-01-01

    Arsenic is a known carcinogen to humans, and chronic exposure to environmental arsenic is a worldwide health concern. As a dietary factor, ethanol carries a well-established risk for malignancies, but the effects of co-exposure to arsenic and ethanol on tumor development are not well understood. In the present study, we hypothesized that ethanol would enhance the function of an environmental carcinogen such as arsenic through increase in COX-2 expression. Our in vitro results show that ethanol enhanced arsenic-induced COX-2 expression. We also show that the increased COX-2 expression associates with intracellular ROS generation, up-regulated AKT signaling, with activation of both NFAT and NF-κB pathways. We demonstrate that antioxidant enzymes have an inhibitory effect on arsenic/ethanol-induced COX-2 expression, indicating that the responsive signaling pathways from co-exposure to arsenic and ethanol relate to ROS generation. In vivo results also show that co-exposure to arsenic and ethanol increased COX-2 expression in mice. We conclude that ethanol enhances arsenic-induced COX-2 expression in colorectal cancer cells via both the NFAT and NF-κB pathways. These results imply that, as a common dietary factor, ethanol ingestion may be a compounding risk factor for arsenic-induced carcinogenesis/cancer development. - Highlights: • Arsenic is able to induce Cox-2 expression in colorectal cancer cells. • Ethanol, a diet nutritional factor, could enhance arsenic-induced Cox-2. • The up-regulation of Cox-2 via both NFAT and NF-κB activities.

  19. Arsenic trioxide decreases the amount and inhibits the function of regulatory T cells, which may contribute to its efficacy in the treatment of acute promyelocytic leukemia.

    Science.gov (United States)

    Xu, Wen; Li, Xiaoxia; Quan, Lina; Yao, Jiying; Mu, Guannan; Guo, Jingjie; Wang, Yitong

    2018-03-01

    Arsenic trioxide (ATO) exhibits substantial clinical efficacy in the treatment of acute promyelocytic leukemia (APL). Here, we investigated whether ATO exerts its efficacy by affecting regulatory T (Treg) cells. We determined whether ATO treatment influenced the amount and function of purified Treg cells. We also examined the effect of ATO treatment on Treg cells from APL patients. ATO treatment induced apoptosis in purified Treg cells and dampened the inhibition of effector T (Teff) cells proliferation and the secretion of cytokine by Treg cells. Treg cell levels in the peripheral blood and serum IL-10 levels were dramatically decreased in APL patients after single ATO treatment. In summary, our results show that ATO decreases the amount and inhibits the function of Treg cells, thereby enhancing Teff cell function and overall anti-tumor immunity.

  20. Experimental study on effect of arsenic trioxide on vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Lu Qin; An Yanli; Niu Huanzhang; Teng Gaojun; Wang Zihao; Zhang Dongsheng; Fang Juanjuan

    2007-01-01

    Objective: To investigate the effect of arsenic trioxide (As 2 O 3 ) nanoparticles on rabbit vascular smooth muscle cells in vitro in comparison with normal form As 2 O 3 . Methods: The rabbit vascular smooth muscle cells were cultured in vitro. Nano and normal forms of As 2 O 3 with drug concentrations of 3 μmol/L were added into the cells. Cell proliferation curve was drawn according to the light absorption values of MTT test. Flow cytometry was applied to observe the apoptosis. DNA was extracted and underwent electrophoresis. Results: Cell proliferation treated with the 3 μmol/L concentration of As 2 O 3 was inhibited. Cell growth was inhibited markedly with increased treatment time, and the inhibition effect of nano drug form seemed stronger than that of normal form. MTT light absorption values of cells treated at 24, 48 and 72 h showed statistically significant difference (H=10.934, 15.039, 15.539, P 2 O 3 , normal drug form of As 2 O 3 and control group of cells without As 2 O 3 were 44.97%, 58.54%, 74.02% respectively. The early apoptosis rates were 16.89%, 11.27%, 11.20%, late apoptosis rates were 26.56%, 23.60%, 12.46%, and necrosis rates were 11.58%, 6.59%, 2.32% respectively. Agarose gel electrophoresis showed 'ladder' strand of DNA, with more strands and obscurity for nano drug form treated cells. Conclusion: Arsenic trioxide may inhibit the growth of rabbit vascular smooth muscle cells. The nano drug form showed stronger inhibition effect than that of the normal drug form. (authors)

  1. Dose-adjusted arsenic trioxide for acute promyelocytic leukaemia in chronic renal failure.

    Science.gov (United States)

    Firkin, Frank; Roncolato, Fernando; Ho, Wai Khoon

    2015-10-01

    To determine the potential for arsenic trioxide (ATO) to be safely and effectively incorporated into induction therapy of newly diagnosed acute promyelocytic leukaemia (APL) in patients with severe chronic renal failure (CRF) by reduction of the ATO dosage to compensate for reduced renal elimination of arsenic in CRF. Two of the four CRF patients with APL in the study were dialysis-dependent, and two had eGFRs of 18 and 19 mL/min/1.73 m(2) . ATO dosage schedules were adjusted to obtain comparable whole-blood arsenic levels to those in APL patients with normal renal function who achieved molecular remission (MR) while receiving 10 mg ATO daily for 28 d. Average ATO administered per day in CRF patients ranged from 36 to 50% of the ATO administered to APL patients with normal renal function. No clinically significant cardiac, hepatic or other toxicities were detected. RT-PCR-negative MR was achieved after one treatment course in two patients and after two courses in the others. Relapse-free survival is 155, 60, 43 and 5 months. The observations in this pilot study have demonstrated whole-blood arsenic levels can provide a guide to adjustments of ATO dosage schedules that permit safe and effective therapeutic outcomes in APL patients with severely compromised renal function. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Assessing the efficiency of aluminium phosphide and arsenic trioxide in controlling the Indian crested porcupine (hystrix indica) in an irrigated forest plantation or Punjab, Pakistan

    International Nuclear Information System (INIS)

    Khan, A.A.

    2010-01-01

    The Indian crested porcupine, Hystrix indica, is widely distributed in the irrigated forests of Punjab, Pakistan and causes serious damage to trees, nursery stocking, field crops and vegetables. Field trials were conducted to determine the efficacy of aluminium phosphide (Phostoxin, 3g tablets) and arsenic trioxide bait (at 2.5g per apple) against the porcupine in a forest plantation. For fumigation with phostoxin, tablets were used at the rate of four, five, six and seven tablets per den. Observations showed that four tablets were ineffective, five and six tablets provided partial control, while seven tablets provided complete control of porcupines. Baiting with arsenic trioxide also resulted in 89 % reduction of the porcupine population occupying the treated dens. (author)

  3. Ammonium and arsenic trioxide are potent facilitators of oligonucleotide function when delivered by gymnosis

    Science.gov (United States)

    Zhang, Xiaowei; Castanotto, Daniela; Liu, Xueli; Shemi, Amotz; Stein, Cy A

    2018-01-01

    Abstract Oligonucleotide (ON) concentrations employed for therapeutic applications vary widely, but in general are high enough to raise significant concerns for off target effects and cellular toxicity. However, lowering ON concentrations reduces the chances of a therapeutic response, since typically relatively small amounts of ON are taken up by targeted cells in tissue culture. It is therefore imperative to identify new strategies to improve the concentration dependence of ON function. In this work, we have identified ammonium ion (NH4+) as a non-toxic potent enhancer of ON activity in the nucleus and cytoplasm following delivery by gymnosis. NH4+ is a metabolite that has been extensively employed as diuretic, expectorant, for the treatment of renal calculi and in a variety of other diseases. Enhancement of function can be found in attached and suspension cells, including in difficult-to-transfect Jurkat T and CEM T cells. We have also demonstrated that NH4+ can synergistically interact with arsenic trioxide (arsenite) to further promote ON function without producing any apparent increased cellular toxicity. These small, inexpensive, widely distributed molecules could be useful not only in laboratory experiments but potentially in therapeutic ON-based combinatorial strategy for clinical applications. PMID:29522198

  4. Subchronic Arsenic Exposure Induces Anxiety-Like Behaviors in Normal Mice and Enhances Depression-Like Behaviors in the Chemically Induced Mouse Model of Depression

    Directory of Open Access Journals (Sweden)

    Chia-Yu Chang

    2015-01-01

    Full Text Available Accumulating evidence implicates that subchronic arsenic exposure causes cerebral neurodegeneration leading to behavioral disturbances relevant to psychiatric disorders. However, there is still little information regarding the influence of subchronic exposure to arsenic-contaminated drinking water on mood disorders and its underlying mechanisms in the cerebral prefrontal cortex. The aim of this study is to assess the effects of subchronic arsenic exposure (10 mg/LAs2O3 in drinking water on the anxiety- and depression-like behaviors in normal mice and in the chemically induced mouse model of depression by reserpine pretreatment. Our findings demonstrated that 4 weeks of arsenic exposure enhance anxiety-like behaviors on elevated plus maze (EPM and open field test (OFT in normal mice, and 8 weeks of arsenic exposure augment depression-like behaviors on tail suspension test (TST and forced swimming test (FST in the reserpine pretreated mice. In summary, in this present study, we demonstrated that subchronic arsenic exposure induces only the anxiety-like behaviors in normal mice and enhances the depression-like behaviors in the reserpine induced mouse model of depression, in which the cerebral prefrontal cortex BDNF-TrkB signaling pathway is involved. We also found that eight weeks of subchronic arsenic exposure are needed to enhance the depression-like behaviors in the mouse model of depression. These findings imply that arsenic could be an enhancer of depressive symptoms for those patients who already had the attribute of depression.

  5. Neurotoxicity induced by arsenic in Gallus Gallus: Regulation of oxidative stress and heat shock protein response.

    Science.gov (United States)

    Zhao, Panpan; Guo, Ying; Zhang, Wen; Chai, Hongliang; Xing, Houjuan; Xing, Mingwei

    2017-01-01

    Arsenic, a naturally occurring heavy metal pollutant, is one of the functioning risk factors for neurological toxicity in humans. However, little is known about the effects of arsenic on the nervous system of Gallus Gallus. To investigate whether arsenic induce neurotoxicity and influence the oxidative stress and heat shock proteins (Hsps) response in chickens, seventy-two 1-day-old male Hy-line chickens were treated with different doses of arsenic trioxide (As 2 O 3 ). The histological changes, antioxidant enzyme activity, and the expressions of Hsps were detected. Results showed slightly histology changes were obvious in the brain tissues exposure to arsenic. The activities of Glutathione peroxidase (GSH-Px) and catalase (CAT) were decreased compared to the control, whereas the malondialdehyde (MDA) content was increased gradually along with increase in diet-arsenic. The mRNA levels of Hsps and protein expressions of Hsp60 and Hsp70 were up-regulated. These results suggested that sub-chronic exposure to arsenic induced neurotoxicity in chickens. Arsenic exposure disturbed the balance of oxidants and antioxidants. Increased heat shock response tried to protect chicken brain tissues from tissues damage caused by oxidative stress. The mechanisms of neurotoxicity induced by arsenic include oxidative stress and heat shock protein response in chicken brain tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Arsenic transformation predisposes human skin keratinocytes to UV-induced DNA damage yet enhances their survival apparently by diminishing oxidant response

    International Nuclear Information System (INIS)

    Sun Yang; Kojima, Chikara; Chignell, Colin; Mason, Ronald; Waalkes, Michael P.

    2011-01-01

    Inorganic arsenic and UV, both human skin carcinogens, may act together as skin co-carcinogens. We find human skin keratinocytes (HaCaT cells) are malignantly transformed by low-level arsenite (100 nM, 30 weeks; termed As-TM cells) and with transformation concurrently undergo full adaptation to arsenic toxicity involving reduced apoptosis and oxidative stress response to high arsenite concentrations. Oxidative DNA damage (ODD) is a possible mechanism in arsenic carcinogenesis and a hallmark of UV-induced skin cancer. In the current work, inorganic arsenite exposure (100 nM) did not induce ODD during the 30 weeks required for malignant transformation. Although acute UV-treatment (UVA, 25 J/cm 2 ) increased ODD in passage-matched control cells, once transformed by arsenic to As-TM cells, acute UV actually further increased ODD (> 50%). Despite enhanced ODD, As-TM cells were resistant to UV-induced apoptosis. The response of apoptotic factors and oxidative stress genes was strongly mitigated in As-TM cells after UV exposure including increased Bcl2/Bax ratio and reduced Caspase-3, Nrf2, and Keap1 expression. Several Nrf2-related genes (HO-1, GCLs, SOD) showed diminished responses in As-TM cells after UV exposure consistent with reduced oxidant stress response. UV-exposed As-TM cells showed increased expression of cyclin D1 (proliferation gene) and decreased p16 (tumor suppressor). UV exposure enhanced the malignant phenotype of As-TM cells. Thus, the co-carcinogenicity between UV and arsenic in skin cancer might involve adaptation to chronic arsenic exposure generally mitigating the oxidative stress response, allowing apoptotic by-pass after UV and enhanced cell survival even in the face of increased UV-induced oxidative stress and increased ODD. - Highlights: → Arsenic transformation adapted to UV-induced apoptosis. → Arsenic transformation diminished oxidant response. → Arsenic transformation enhanced UV-induced DNA damage.

  7. Arsenic trioxide (AT) is a novel human neutrophil pro-apoptotic agent: effects of catalase on AT-induced apoptosis, degradation of cytoskeletal proteins and de novo protein synthesis.

    Science.gov (United States)

    Binet, François; Cavalli, Hélène; Moisan, Eliane; Girard, Denis

    2006-02-01

    The anti-cancer drug arsenic trioxide (AT) induces apoptosis in a variety of transformed or proliferating cells. However, little is known regarding its ability to induce apoptosis in terminally differentiated cells, such as neutrophils. Because neutropenia has been reported in some cancer patients after AT treatment, we hypothesised that AT could induce neutrophil apoptosis, an issue that has never been investigated. Herein, we found that AT-induced neutrophil apoptosis and gelsolin degradation via caspases. AT did not increase neutrophil superoxide production and did not induce mitochondrial generation of reactive oxygen species. AT-induced apoptosis in PLB-985 and X-linked chronic granulomatous disease (CGD) cells (PLB-985 cells deficient in gp91(phox) mimicking CGD) at the same potency. Addition of catalase, an inhibitor of H2O2, reversed AT-induced apoptosis and degradation of the cytoskeletal proteins gelsolin, alpha-tubulin and lamin B1. Unexpectedly, AT-induced de novo protein synthesis, which was reversed by catalase. Cycloheximide partially reversed AT-induced apoptosis. We conclude that AT induces neutrophil apoptosis by a caspase-dependent mechanism and via de novo protein synthesis. H2O2 is of major importance in AT-induced neutrophil apoptosis but its production does not originate from nicotinamide adenine dinucleotide phosphate dehydrogenase activation and mitochondria. Cytoskeletal structures other than microtubules can now be considered as novel targets of AT.

  8. Negligible expression of arsenic in some commercially available brands of Portland cement and mineral trioxide aggregate.

    Science.gov (United States)

    De-Deus, Gustavo; de Souza, Maria Claudia Brandão; Sergio Fidel, Rivail Antonio; Fidel, Sandra Rivera; de Campos, Reinaldo Calixto; Luna, Aderval S

    2009-06-01

    This study was designed aiming to determine and compare the amount of arsenic in some brands of mineral trioxide aggregate (MTA) and Portland cement. In the present study, arsenic species (As[III], As[V], and dimethylarsinic acid) were separated by high-performance liquid chromatography (HPLC) using a strong anion exchange column and converted into arsines by online HG. The instrumental coupling, HPLC-HG-AFS, was applied to 0.2 g of each cement that was prior digested in a solution of HCl, HNO(3), and HBF(4). Data were expressed as a part per million, and the preliminary analysis of the raw pooled data revealed a bell-shaped distribution. Statistical analysis was performed using one-way analysis of variance for multiple comparisons. In all chromatograms obtained, only type III arsenic could be detected. The minimum amount of arsenic was detected in samples of white MTA ProRoot (3.3 x 10-4) and the maximum in the samples MTA Bio Angelus (Angelus, Londrina, PR, Brazil) (8.6 x 10-4). In the Gray MTA (Angelus), gray ProRoot MTA (Tulsa/Dentsply, Tulsa, OK) and CP Juntalider (Brasilatex Ltda, Diadema, SP, Brazil) did not detect any trace of arsenic. The values of arsenic found in CP Irajazinho (Votorantim Cimentos, Rio Branco, SP, Brazil) and white MTA Angelus were intermediaries to minimum and maximum values. The nonparametric test Kruskal-Wallis showed statistically similar results among all cements tested (p > 0.5). Overall, the present study showed that all cements showed insignificant amounts of type III arsenic as well as no trace of arsenic DMA and type V could be detected.

  9. Use of arsenic trioxide in remission induction and consolidation therapy for acute promyelocytic leukaemia in the Australasian Leukaemia and Lymphoma Group (ALLG) APML4 study: a non-randomised phase 2 trial.

    Science.gov (United States)

    Iland, Harry J; Collins, Marnie; Bradstock, Ken; Supple, Shane G; Catalano, Alberto; Hertzberg, Mark; Browett, Peter; Grigg, Andrew; Firkin, Frank; Campbell, Lynda J; Hugman, Amanda; Reynolds, John; Di Iulio, Juliana; Tiley, Campbell; Taylor, Kerry; Filshie, Robin; Seldon, Michael; Taper, John; Szer, Jeff; Moore, John; Bashford, John; Seymour, John F

    2015-09-01

    Initial treatment of acute promyelocytic leukaemia traditionally involves tretinoin (all-trans retinoic acid) combined with anthracycline-based risk-adapted chemotherapy, with arsenic trioxide being the treatment of choice at relapse. To try to reduce the relapse rate, we combined arsenic trioxide with tretinoin and idarubicin in induction therapy, and used arsenic trioxide with tretinoin as consolidation therapy. Patients with previously untreated genetically confirmed acute promyelocytic leukaemia were eligible for this study. Eligibilty also required Eastern Cooperative Oncology Group performance status 0-3, age older than 1 year, normal left ventricular ejection fraction, Q-Tc interval less than 500 ms, absence of serious comorbidity, and written informed consent. Patients with genetic variants of acute promyelocytic leukaemia (fusion of genes other than PML with RARA) were ineligible. Induction comprised 45 mg/m(2) oral tretinoin in four divided doses daily on days 1-36, 6-12 mg/m(2) intravenous idarubicin on days 2, 4, 6, and 8, adjusted for age, and 0·15 mg/kg intravenous arsenic trioxide once daily on days 9-36. Supportive therapy included blood products for protocol-specified haemostatic targets, and 1 mg/kg prednisone daily as prophylaxis against differentiation syndrome. Two consolidation cycles with tretinoin and arsenic trioxide were followed by maintenance therapy with oral tretinoin, 6-mercaptopurine, and methotrexate for 2 years. The primary endpoints of the study were freedom from relapse and early death (within 36 days of treatment start) and we assessed improvement compared with the 2 year interim results. To assess durability of remission we compared the primary endpoints and disease-free and overall survival at 5 years in APML4 with the 2 year interim APML4 data and the APML3 treatment protocol that excluded arsenic trioxide. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12605000070639. 124

  10. Retinoic acid and arsenic trioxide in the treatment of acute promyelocytic leukemia: current perspectives

    Directory of Open Access Journals (Sweden)

    McCulloch D

    2017-03-01

    Full Text Available Derek McCulloch, Christina Brown, Harry Iland Institute of Hematology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia Abstract: Acute promyelocytic leukemia (APL is a distinct subtype of acute myeloid leukemia (AML with a unique morphological appearance, associated coagulopathy and canonical balanced translocation of genetic material between chromosomes 15 and 17. APL was first described as a distinct subtype of AML in 1957 by Dr Leif Hillestad who recognized the pattern of an acute leukemia associated with fibrinolysis, hypofibrinogenemia and catastrophic hemorrhage. In the intervening years, the characteristic morphology of APL has been described fully with both classical hypergranular and variant microgranular forms. Both are characterized by a balanced translocation between the long arms of chromosomes 15 and 17, [t(15;17(q24;q21], giving rise to a unique fusion gene PML-RARA and an abnormal chimeric transcription factor (PML-RARA, which disrupts normal myeloid differentiation programs. The success of current treatments for APL is in marked contrast to the vast majority of patients with non-promyelocytic AML. The overall prognosis in non-promyelocytic AML is poor, and although there has been an improvement in overall survival in patients aged <60 years, only 30%–40% of younger patients are still alive 5 years after diagnosis. APL therapy has diverged from standard AML therapy through the empirical discovery of two agents that directly target the molecular basis of the disease. The evolution of treatment over the last 4 decades to include all-trans retinoic acid and arsenic trioxide, with chemotherapy limited to patients with high-risk disease, has led to complete remission in 90%–100% of patients in trials and rates of overall survival between 86% and 97%. Keywords: acute promyelocytic leukemia, ATRA, arsenic trioxide

  11. Polyphenol-rich apple (Malus domestica L.) peel extract attenuates arsenic trioxide induced cardiotoxicity in H9c2 cells via its antioxidant activity.

    Science.gov (United States)

    Vineetha, Vadavanath Prabhakaran; Girija, Seetharaman; Soumya, Rema Sreenivasan; Raghu, Kozhiparambil Gopalan

    2014-03-01

    Evidences suggest that apple peel has a wide range of polyphenols having antioxidant activity and its consumption has been linked with improved health benefits. Arsenic trioxide (ATO) is a very effective drug for the treatment of acute promyelocytic leukemia (APL) but it leads to cardiotoxicity mediated through alterations in various cardiac ion channels and by increasing the intracellular calcium level and reactive oxygen species (ROS). The aim of the present investigation was to study the effect of methanolic extract of apple peel (APME) and aqueous extract of apple peel (APAE) on ATO (5 μM) induced toxicity in the H9c2 cardiac myoblast cell line. We estimated the cellular status of innate antioxidant enzymes, level of ROS, mitochondrial superoxide, glutathione and intracellular calcium with ATO and apple peel extracts. Prior to the cell line based study, we had evaluated the antioxidant potential of apple peel extract by 1,1-diphenyl-2-picrylhydrazyl (DPPH), total reducing power (TRP), superoxide anion and hydroxyl radical scavenging activity, in addition to quantifying total phenolic and flavonoid content. Both the extracts showed considerable antioxidant activity in cell-free chemical assays. In addition, both APME and APAE prevented the alteration in antioxidant status induced by ATO in H9c2 cells. Significant differential alterations had been observed in the activity of lactate dehydrogenase, superoxide dismutase, catalase, glutathione, glutathione peroxidase, thioredoxin reductase, xanthine oxidase, calcium overload and caspase 3 activity with ATO. The overall result revealed the protective property of polyphenol-rich apple peel extract against ATO induced cardiac toxicity via its antioxidant activity.

  12. Bone marrow necrosis in a patient with acute promyelocytic leukemia during re-induction therapy with arsenic trioxide.

    Science.gov (United States)

    Ishitsuka, Kenji; Shirahashi, Akihiko; Iwao, Yasuhiro; Shishime, Mikiko; Takamatsu, Yasushi; Takatsuka, Yoshifusa; Utsunomiya, Atae; Suzumiya, Junji; Hara, Syuji; Tamura, Kazuo

    2004-04-01

    Arsenic trioxide (As2O3) therapy at a daily dose of 0.15 mg/kg was given to a 60-yr-old Japanese male with refractory acute promyelocytic leukemia. White blood cell (WBC) of 6.6 x 10(3)/microl increased to 134 x 10(3)/microl following the administration of As2O3. Daily hydroxyurea (HU), and 6-mercaptopurine (6-MP) were added on days 7 and 19, respectively. Both HU and 6-MP were discontinued on day 28, when WBC declined to 54.0 x 10(3)/microl. He developed unexplained fever and profound cytopenia requiring multiple blood products transfusions. Bone marrow examination on day 42 revealed massive necrosis. Pharmacokinetics confirmed a mean maximum plasma arsenic concentration (Cpmax) and a half-life time (t1/2) of 6.9 microm and 3.2 h, respectively, in the therapeutic range. This is the first case of bone marrow necrosis after standard-dose As2O3 therapy.

  13. Sulfate and glutathione enhanced arsenic accumulation by arsenic hyperaccumulator Pteris vittata L

    International Nuclear Information System (INIS)

    Wei Shuhe; Ma, Lena Q.; Saha, Uttam; Mathews, Shiny; Sundaram, Sabarinath; Rathinasabapathi, Bala; Zhou Qixing

    2010-01-01

    This experiment examined the effects of sulfate (S) and reduced glutathione (GSH) on arsenic uptake by arsenic hyperaccumulator Pteris vittata after exposing to arsenate (0, 15 or 30 mg As L -1 ) with sulfate (6.4, 12.8 or 25.6 mg S L -1 ) or GSH (0, 0.4 or 0.8 mM) for 2-wk. Total arsenic, S and GSH concentrations in plant biomass and arsenic speciation in the growth media and plant biomass were determined. While both S (18-85%) and GSH (77-89%) significantly increased arsenic uptake in P. vittata, GSH also increased arsenic translocation by 61-85% at 0.4 mM (p < 0.05). Sulfate and GSH did not impact plant biomass or arsenic speciation in the media and biomass. The S-induced arsenic accumulation by P. vittata was partially attributed to increased plant GSH (21-31%), an important non-enzymatic antioxidant countering oxidative stress. This experiment demonstrated that S and GSH can effectively enhance arsenic uptake and translocation by P. vittata. - Sulfate and glutathione increased arsenic uptake and translocation in Pteris vittata.

  14. Resveratrol and arsenic trioxide act synergistically to kill tumor cells in vitro and in vivo.

    Directory of Open Access Journals (Sweden)

    Xiao-Yan Zhao

    Full Text Available BACKGROUND AND AIMS: Arsenic trioxide (As2O3, which used as an effective agent in the treatment of leukaemia and other solid tumors, is largely limited by its toxicity. QT prolongation, torsades de pointes and sudden heart death have been implicated in the cardiotoxicity of As2O3. The present study was designed to explore whether the combination of As2O3 and resveratrol could generate a more powerful anti-cancer effect both in vitro and in vivo. MATERIALS AND METHODS: MTT assay was performed to assess the proliferation of Hela, MCF-7 and NB4 cells. Isobolographic analysis was used to evaluate combination index values from cell viability data. The apoptosis and the cellular reactive oxygen species (ROS level were assessed by fluorescent microscopy and flow cytometry separately in vitro. The effect of As2O3, alone and in combination with resveratrol on Hela tumor growth in an orthotopic nude mouse model was also investigated. The tumor volume and the immunohistochemical analysis of CD31, CD34 and VEGF were determined. RESULTS: Resveratrol dramatically enhanced the anti-cancer effect induced by As2O3 in vitro. In addition, isobolographic analysis further demonstrated that As2O3 and resveratrol generated a synergistic action. More apoptosis and ROS generation were observed in the combination treatment group. Similar synergistic effects were found in nude mice in vivo. The combination of As2O3 and resveratrol dramatically suppressed both tumor growth and angiogenesis in nude mice. CONCLUSIONS: Combining As2O3 with resveratrol would be a novel strategy to treat cancer in clinical practice.

  15. Nicotinamide enhances repair of arsenic and ultraviolet radiation-induced DNA damage in HaCaT keratinocytes and ex vivo human skin.

    Directory of Open Access Journals (Sweden)

    Benjamin C Thompson

    Full Text Available Arsenic-induced skin cancer is a significant global health burden. In areas with arsenic contamination of water sources, such as China, Pakistan, Myanmar, Cambodia and especially Bangladesh and West Bengal, large populations are at risk of arsenic-induced skin cancer. Arsenic acts as a co-carcinogen with ultraviolet (UV radiation and affects DNA damage and repair. Nicotinamide (vitamin B3 reduces premalignant keratoses in sun-damaged skin, likely by prevention of UV-induced cellular energy depletion and enhancement of DNA repair. We investigated whether nicotinamide modifies DNA repair following exposure to UV radiation and sodium arsenite. HaCaT keratinocytes and ex vivo human skin were exposed to 2μM sodium arsenite and low dose (2J/cm2 solar-simulated UV, with and without nicotinamide supplementation. DNA photolesions in the form of 8-oxo-7,8-dihydro-2'-deoxyguanosine and cyclobutane pyrimidine dimers were detected by immunofluorescence. Arsenic exposure significantly increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in irradiated cells. Nicotinamide reduced both types of photolesions in HaCaT keratinocytes and in ex vivo human skin, likely by enhancing DNA repair. These results demonstrate a reduction of two different photolesions over time in two different models in UV and arsenic exposed cells. Nicotinamide is a nontoxic, inexpensive agent with potential for chemoprevention of arsenic induced skin cancer.

  16. Mineral trioxide aggregate induces osteoblastogenesis via Atf6

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    Toyonobu Maeda

    2015-06-01

    Full Text Available Mineral trioxide aggregate (MTA has been recommended for various uses in endodontics. To understand the effects of MTA on alveolar bone, we examined whether MTA induces osteoblastic differentiation using MC3T3-E1 cells. MTA enhanced mineralization concomitant with alkaline phosphatase activity in a dose- and time-dependent manner. MTA increased production of collagens (Type I and Type III and matrix metalloproteinases (MMP-9 and MMP-13, suggesting that MTA affects bone matrix remodeling. MTA also induced Bglap (osteocalcin but not Bmp2 (bone morphogenetic protein-2 mRNA expression. We observed induction of Atf6 (activating transcription factor 6, an endoplasmic reticulum (ER stress response transcription factor mRNA expression and activation of Atf6 by MTA treatment. Forced expression of p50Atf6 (active form of Atf6 markedly enhanced Bglap mRNA expression. Chromatin immunoprecipitation assay was performed to investigate the increase in p50Atf6 binding to the Bglap promoter region by MTA treatment. Furthermore, knockdown of Atf6 gene expression by introduction of Tet-on Atf6 shRNA expression vector abrogated MTA-induced mineralization. These results suggest that MTA induces in vitro osteoblastogenesis through the Atf6–osteocalcin axis as ER stress signaling. Therefore, MTA in endodontic treatment may affect alveolar bone healing in the resorbed region caused by pulpal infection.

  17. Acute and chronic arsenic toxicity

    OpenAIRE

    Ratnaike, R

    2003-01-01

    Arsenic toxicity is a global health problem affecting many millions of people. Contamination is caused by arsenic from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Arsenic is present as a contaminant in many traditional remedies. Arsenic trioxide is now used to treat acute promyelocytic leukaemia. Absorption occurs predominantly from ingestion from the small intestine, though minimal absorption o...

  18. Refractory acute promyelocytic leukemia successfully treated with combination therapy of arsenic trioxide and tamibarotene: A case report

    Directory of Open Access Journals (Sweden)

    Minoru Kojima

    2016-01-01

    Full Text Available A 40-year-old male developed refractory acute promyelocytic leukemia (APL after various treatments including all-trans retinoic acid, tamibarotene, arsenic trioxide (As2O3, conventional chemotherapy, and autologous peripheral blood stem cell transplantation. We attempted to use both tamibarotene and As2O3 as a combination therapy, and he achieved molecular complete remission. Grade 2 prolongation of the QTc interval on the electrocardiogram was observed during the therapy. The combination therapy of As2O3 and tamibarotene may be effective and tolerable for treating refractory APL cases who have no treatment options, even when they have previously been treated with tamibarotene and As2O3 as a single agent.

  19. Enhanced protective activity of nano formulated andrographolide against arsenic induced liver damage.

    Science.gov (United States)

    Das, Sujata; Pradhan, Goutam Kumar; Das, Subhadip; Nath, Debjani; Das Saha, Krishna

    2015-12-05

    Chronic exposure to arsenic over a period of time induces toxicity, primarily in liver but gradually in all systems of the body. Andrographolide (AG), a major diterpene lactone of Andrographis paniculata, shows a wide array of physiological functions including hepatoprotection. Therapeutic applications of AG are however seriously constrained because of its insolubility, poor bioavailability, and short plasma half-life. Nanoparticulation of AG is a possible solution to these problems. In the present study we investigated the effectiveness of polylactide co-glycolide (PLGA) nanocapsulated andrographolide (NA) against arsenic induced liver damage in mice. NA of average diameter 65.8 nm and encapsulation efficiency of 64% were prepared. Sodium arsenite at a dose of 40 mg/L supplied via drinking water in mice significantly raised the serum level of liver function markers such as AST, ALT, and ALP, and caused arsenic deposition in liver and ROS generation, though it did not show any lethality up to 30 days of exposure. However, even liver toxicity was not observed when mice were given AG and NA orally at doses up to 100 mg/kg bwt and 20 mg/kg bwt respectively on alternate days for one month. Treatment of non-toxic doses of AG or NA on alternate days along with arsenic significantly decreased the arsenic induced elevation of the serum level of ALT, AST and ALP, and arsenic deposition in liver. AG and NA increased the level of hepatic antioxidant enzymes such as superoxide dismutase (SOD), and catalase (CAT), and the level of reduced glutathione (GSH). Also, the ROS level was lowered in mice exposed to arsenic but treated with AG or NA. Protective efficiency of NA is about five times more than that of AG. Administration of NA to arsenic-treated mice caused signs of improvement in liver tissue architecture. In conclusion, the results of this study suggest that NA could be beneficial against arsenic-induced liver toxicity. Copyright © 2015 Elsevier Ireland Ltd. All rights

  20. Leukemia-associated gene MLAA-34 reduces arsenic trioxide-induced apoptosis in HeLa cells via activation of the Wnt/β-catenin signaling pathway.

    Science.gov (United States)

    Zhang, Pengyu; Zhao, Xuan; Zhang, Wenjuan; He, Aili; Lei, Bo; Zhang, Wanggang; Chen, Yinxia

    2017-01-01

    Our laboratory previously used the SEREX method in U937 cells and identified a novel leukemia-associated gene MLAA-34, a novel splice variant of CAB39L associated with acute monocytic leukemia, that exhibited anti-apoptotic activities in U937 cells. Whether MLAA-34 has an anti-apoptotic role in other tumor cells has not yet been reported. We explored whether MLAA-34 exhibited anti-apoptotic effects in HeLa cervical cancer cells and the possible mechanism of action. We generated a HeLa cell line stably expressing MLAA-34 and found that MLAA-34 overexpression had no effect on the growth, apoptosis and cell cycle of HeLa cells. However, upon treatment with arsenic trioxide (ATO) to induce apoptosis, the cell viability and colony formation ability of ATO-treated MLAA-34 stable HeLa cells were significantly higher than that of ATO-treated controls, and the apoptosis rate and proportion of G2/M cells also decreased. We found that ATO treatment of HeLa cells resulted in significant decreases in the expression of β-catenin mRNA and protein and the downstream target factors c-Myc, cyclin B1, and cyclin D1 in the Wnt signaling pathway. Notably, ATO-treated MLAA-34 stable HeLa cells showed a significant reduction in the ATO-mediated downregulation of these factors. In addition, MLAA-34 overexpression significantly increased the expression of nuclear β-catenin protein in ATO-treated cells compared with HeLa cells treated only with ATO. Thus, here we have found that the Wnt/β-catenin signaling pathway is involved in ATO-induced apoptosis in HeLa cells. MLAA-34 reduces ATO-induced apoptosis and G2/M arrest, and the anti-apoptotic effect may be achieved by activating the Wnt/β-catenin signaling pathway in HeLa cells.

  1. Effects of Arsenic Trioxide on Radiofrequency Ablation of VX2 Liver Tumor: Intraarterial versus Intravenous Administration

    International Nuclear Information System (INIS)

    Seong, Nak Jong; Yoon, Chang Jin; Kang, Sung Gwon; Chung, Jin Wook; Kim, Hyo Cheol; Park, Jae Hyung

    2012-01-01

    Arsenic trioxide (As 2 O 3 ) can be used as a possible pharmaceutical alternative that augments radiofrequency (RF) ablation by reducing tumor blood flow. The aim of this study was to assess the effect of intraarterial and intravenous administration of As 2 O 3 on RF-induced ablation in an experimentally induced liver tumor. VX2 carcinoma was grown in the livers of 30 rabbits. As 2 O 3 (1 mg/kg) was administered through the hepatic artery (n = 10, group A) or ear vein (n = 10, group B), 30 minutes before RF ablation (125 mA ± 35; 90 ± 5 degrees Celsius). As a control group, 10 rabbits were treated with RF ablation alone (group C). RF was intentionally applied to the peripheral margin of the tumor so that ablation can cover the tumor and adjacent hepatic parenchyma. Ablation areas of the tumor and adjacent parenchymal changes among three groups were compared by the Kruskal-Wallis and Mann-Whitney U test. The overall ablation areas were 156 ± 28.9 mm 2 (group A), 119 ± 31.7 (group B), and 92 ± 17.4 (group C, p 2 ) than both group B (50 ± 19.4, p = 0.02) and group C (28 ± 2.2, p 2 O 3 . The intraarterial administration of As 2 O 3 seems to be helpful for the selective ablation of the tumor.

  2. Nine-month Angiographic and Two-year Clinical Follow-up of Novel Biodegradable-polymer Arsenic Trioxide-eluting Stent Versus Durable-polymer Sirolimus-eluting Stent For Coronary Artery Disease

    Directory of Open Access Journals (Sweden)

    Li Shen

    2015-01-01

    Full Text Available Background: Despite great reduction of in-stent restenosis, first-generation drug-eluting stents (DESs have increased the risk of late stent thrombosis due to delayed endothelialization. Arsenic trioxide, a natural substance that could inhibit cell proliferation and induce cell apoptosis, seems to be a promising surrogate of sirolimus to improve DES performance. This randomized controlled trial was to evaluate the efficacy and safety of a novel arsenic trioxide-eluting stent (AES, compared with traditional sirolimus-eluting stent (SES. Methods: Patients with symptoms of angina pectoris were enrolled and randomized to AES or SES group. The primary endpoint was target vessel failure (TVF, and the second endpoint includes rates of all-cause death, cardiac death or myocardial infarction, target lesion revascularization (TLR by telephone visit and late luminal loss (LLL at 9-month by angiographic follow-up. Results: From July 2007 to 2009, 212 patients were enrolled and randomized 1:1 to receive either AES or SES. At 2 years of follow-up, TVF rate was similar between AES and SES group (6.67% vs. 5.83%, P = 0.980. Frequency of all-cause death was significantly lower in AES group (0 vs. 4.85%, P = 0.028. There was no significant difference between AES and SES in frequency of TLR and in-stent restenosis, but greater in-stent LLL was observed for AES group (0.29 ± 0.52 mm vs. 0.10 ± 0.25 mm, P = 0.008. Conclusions: After 2 years of follow-up, AES demonstrated comparable efficacy and safety to SES for the treatment of de novo coronary artery lesions.

  3. α-Lipoic Acid Mitigates Arsenic-Induced Hematological Abnormalities in Adult Male Rats

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    Sonali Ghosh

    2017-05-01

    Full Text Available Background: Arsenic toxicity is a major global health problem and exposure via contaminated drinking water has been associated with hematological and other systemic disorders. The present investigation has been conducted in adult male rats to evaluate the protective ability of α-lipoic acid (ALA against such hematological disorders. Methods: Twenty-four adult male Wister rats (b.wt.130±10g were grouped and accordingly group I (control received the normal diet, group II (treated was given arsenic orally for 28 consecutive days as arsenic trioxide (3 mg/kgbw/rat/day whereas group III (supplemented received the same dose of arsenic along with ALA (25 mg/kgbw/rat/day as oral supplement. Hematological profile, plasma oxidant/antioxidant status, and erythrocyte morphology were assessed. Statistical analysis was done by one-way ANOVA using SPSS software (version 16.0. Results: Arsenic exposure caused reduction of erythrocyte (P=0.021, leucocyte (P<0.001, and hemoglobin (P=0.031 associated with echinocytic transformation as evidenced by light and scanning electron microscopic studies. The other significantly altered parameters include increased mean corpuscular volume (P=0.041 and lymphocytopenia (P<0.001 with insignificant neutropenia and eosinophilia. Altered serum oxidative balance as evidenced by decreased TAS (P<0.001 and increased TOS (P<0.001 with OSI (P<0.001 was also noted. The dietary supplementation of ALA has a beneficial effect against the observed (P<0.05 arsenic toxicities. It brings about the protection by restoring the hematological redox and inflammatory status near normal in treated rats. Arsenic-induced morphological alteration of erythrocytes was also partially attenuated by ALA supplementation. Conclusion: It is concluded that arsenicosis is associated with hematological alterations and ALA co-supplementation can partially alleviate these changes in an experimental male rat model.

  4. Arsenic trioxide (As2O3) induced calcium signals and cytotoxicity in two human cell lines: SY-5Y neuroblastoma and 293 embryonic kidney (HEK)

    International Nuclear Information System (INIS)

    Florea, Ana-Maria; Splettstoesser, Frank; Buesselberg, Dietrich

    2007-01-01

    Arsenic trioxide (As 2 O 3 ) has anticancer properties; however, its use also leads to neuro-, hepato- or nephro-toxicity, and therefore, it is important to understand the mechanism of As 2 O 3 toxicity. We studied As 2 O 3 influence on intracellular calcium ([Ca 2+ ] i ) homeostasis of human neuroblastoma SY-5Y and embryonic kidney cells (HEK 293).We also relate the As 2 O 3 induced [Ca 2+ ] i modifications with cytotoxicity. We used Ca 2+ sensitive dyes (fluo-4 and rhod-2) combined with laser scanning microscopy or fluorescence activated cell sorting to measure Ca 2+ changes during the application of As 2 O 3 and we approach evaluation of cytotoxicity. As 2 O 3 (1 μM) increased [Ca 2+ ] i in SY-5Y and HEK 293 cells. Three forms of [Ca 2+ ] i -elevations were found: (1) steady-state increases (2) transient [Ca 2+ ] i -elevations and (3) Ca 2+ -spikes. [Ca 2+ ] i modifications were independent from extracellular Ca 2+ but dependent on internal calcium stores. The effect was not reversible. Inositol triphosphate (IP 3 ) and ryanodine (Ry) receptors are involved in regulation of signals induced by As 2 O 3 . 2-APB and dantrolene significantly reduced the [Ca 2+ ] i -rise (p 2+ ] i -elevation or spiking. This indicates that other Ca 2+ regulating mechanisms are involved. In cytotoxicity tests As 2 O 3 significantly reduced cell viability in both cell types. Staining with Hoechst 33342 showed occurrence of apoptosis and DNA damage. Our data suggest that [Ca 2+ ] i is an important messenger in As 2 O 3 induced cell death

  5. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Pranay [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Yadav, Rajesh S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Department of Crimnology and Forensic Science, Harisingh Gour University, Sagar 470 003 (India); Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Dwivedi, Hari N. [Babu Banarasi Das University, BBD City, Faizabad Road, Lucknow 227 015 (India); Pant, Aditiya B. [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India); Khanna, Vinay K., E-mail: vkkhanna1@gmail.com [CSIR-Indian Institute of Toxicology Research, Post Box 80, MG Marg, Lucknow 226 001 (India)

    2014-09-15

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  6. Unraveling the mechanism of neuroprotection of curcumin in arsenic induced cholinergic dysfunctions in rats

    International Nuclear Information System (INIS)

    Srivastava, Pranay; Yadav, Rajesh S.; Chandravanshi, Lalit P.; Shukla, Rajendra K.; Dhuriya, Yogesh K.; Chauhan, Lalit K.S.; Dwivedi, Hari N.; Pant, Aditiya B.; Khanna, Vinay K.

    2014-01-01

    Earlier, we found that arsenic induced cholinergic deficits in rat brain could be protected by curcumin. In continuation to this, the present study is focused to unravel the molecular mechanisms associated with the protective efficacy of curcumin in arsenic induced cholinergic deficits. Exposure to arsenic (20 mg/kg body weight, p.o) for 28 days in rats resulted to decrease the expression of CHRM2 receptor gene associated with mitochondrial dysfunctions as evident by decrease in the mitochondrial membrane potential, activity of mitochondrial complexes and enhanced apoptosis both in the frontal cortex and hippocampus in comparison to controls. The ultrastructural images of arsenic exposed rats, assessed by transmission electron microscope, exhibited loss of myelin sheath and distorted cristae in the mitochondria both in the frontal cortex and hippocampus as compared to controls. Simultaneous treatment with arsenic (20 mg/kg body weight, p.o) and curcumin (100 mg/kg body weight, p.o) for 28 days in rats was found to protect arsenic induced changes in the mitochondrial membrane potential and activity of mitochondrial complexes both in frontal cortex and hippocampus. Alterations in the expression of pro- and anti-apoptotic proteins and ultrastructural damage in the frontal cortex and hippocampus following arsenic exposure were also protected in rats simultaneously treated with arsenic and curcumin. The data of the present study reveal that curcumin could protect arsenic induced cholinergic deficits by modulating the expression of pro- and anti-apoptotic proteins in the brain. More interestingly, arsenic induced functional and ultrastructural changes in the brain mitochondria were also protected by curcumin. - Highlights: • Neuroprotective mechanism of curcumin in arsenic induced cholinergic deficits studied • Curcumin protected arsenic induced enhanced expression of stress markers in rat brain • Arsenic compromised mitochondrial electron transport chain protected

  7. Arsenic trioxide inhibits Ewing's sarcoma cell invasiveness by targeting p38(MAPK) and c-Jun N-terminal kinase.

    Science.gov (United States)

    Zhang, Shuai; Guo, Wei; Ren, Ting-Ting; Lu, Xin-Chang; Tang, Guo-Qing; Zhao, Fu-Long

    2012-01-01

    Ewing's sarcoma is the second most frequent primary malignant bone tumor, mainly affecting children and young adults. The notorious metastatic capability of this tumor aggravates patient mortality and remains a problem to be overcome. We investigated the effect of arsenic trioxide (As₂O₃) on the metastasis capability of Ewing's sarcoma cells. We performed 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-2H-tetrazolium bromide assays to choose appropriate concentrations of As₂O₃ for the experiments. Migration, invasion, and adhesion assays were performed to assess the effect of As₂O₃ on the metastasis of Ewing's sarcoma. Immunofluorescent staining was used to observe cytoskeleton reorganization in Ewing's sarcoma cells treated with As₂O₃. Changes in matrix metalloproteinase-9 expression and the mitogen-activated protein kinase (MAPK) pathway were investigated using western blot. Inhibitors of p38(MAPK) (sb202190) and c-Jun NH₂-terminal kinase (JNK, sp600125) were used in invasion assays to determine the effect of p38(MAPK) and JNK. We found that As₂O₃ may markedly inhibit the migration and invasion capacity of Ewing's sarcoma cells with structural rearrangements of the actin cytoskeleton. The expressions of matrix metalloproteinase-9, phosphor-p38(MAPK), and phosphor-JNK were suppressed by As₂O₃ treatment in a dose-dependent manner. The inhibitors of p38(MAPK) (sb202190) and JNK (sp600125) enhanced the inhibition induced by As₂O₃, which was counteracted by anisomycin, an activating agent of p38(MAPK) and JNK. Taken together, our results demonstrate that As₂O₃ can inhibit the metastasis capability of RD-ES and A-673 cells and may have new therapeutic value for Ewing's sarcoma.

  8. Resveratrol, a Natural Antioxidant, Has a Protective Effect on Liver Injury Induced by Inorganic Arsenic Exposure

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    Zhigang Zhang

    2014-01-01

    Full Text Available Resveratrol (Rev can ameliorate cytotoxic chemotherapy-induced toxicity and oxidative stress. Arsenic trioxide (As2O3 is a known cytotoxic environmental toxicant and a potent chemotherapeutic agent. However, the mechanisms by which resveratrol protects the liver against the cytotoxic effects of As2O3 are not known. Therefore, in the present study we investigated the mechanisms involved in the action of resveratrol using a cat model in which hepatotoxicity was induced by means of As2O3 treatment. We found that pretreatment with resveratrol, administered using a clinically comparable dose regimen, reversed changes in As2O3-induced morphological and liver parameters and resulted in a significant improvement in hepatic function. Resveratrol treatment also improved the activities of antioxidant enzymes and attenuated As2O3-induced increases in reactive oxygen species and malondialdehyde production. In addition, resveratrol attenuated the As2O3-induced reduction in the ratio of reduced glutathione to oxidized glutathione and the retention of arsenic in liver tissue. These findings provide a better understanding of the mechanisms whereby resveratrol modulates As2O3-induced changes in liver function and tissue morphology. They also provide a stronger rationale for the clinical utilization of resveratrol for the reduction of As2O3-induced hepatotoxicity.

  9. Immunotoxicity and biodistribution analysis of arsenic trioxide in C57Bl/6 mice following a 2-week inhalation exposure

    International Nuclear Information System (INIS)

    Burchiel, Scott W.; Mitchell, Leah A.; Lauer, Fredine T.; Sun Xi; McDonald, Jacob D.; Hudson, Laurie G.; Liu Kejian

    2009-01-01

    In these studies the immunotoxicity of arsenic trioxide (ATO, As 2 O 3 ) was evaluated in mice following 14 days of inhalation exposures (nose only, 3 h per day) at concentrations of 50 μg/m 3 and 1 mg/m 3 . A biodistribution analysis performed immediately after inhalation exposures revealed highest levels of arsenic in the kidneys, bladder, liver, and lung. Spleen cell levels were comparable to those found in the blood, with the highest concentration of arsenic detected in the spleen being 150 μg/g tissue following the 1 mg/m 3 exposures. No spleen cell cytotoxicity was observed at either of the two exposure levels. There were no changes in spleen cell surface marker expression for B cells, T cells, macrophages, and natural killer (NK) cells. There were also no changes detected in the B cell (LPS-stimulated) and T cell (Con A-stimulated) proliferative responses of spleen cells, and no changes were found in the NK-mediated lysis of Yac-1 target cells. The primary T-dependent antibody response was, however, found to be highly susceptible to ATO suppression. Both the 50 μg/m 3 and 1 mg/m 3 exposures produced greater than 70% suppression of the humoral immune response to sheep red blood cells. Thus, the primary finding of this study is that the T-dependent humoral immune response is extremely sensitive to suppression by ATO and assessment of humoral immune responses should be considered in evaluating the health effects of arsenic containing agents.

  10. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    International Nuclear Information System (INIS)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy; Pillai, Ayyappan Harikrishna; Harikumar, Sankaran Kutty; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2014-01-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  11. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  12. Bioscorodite: biological crystallization of scorodite for arsenic removal

    NARCIS (Netherlands)

    Gonzalez-Contreras, P.A.

    2012-01-01

    The use of arsenic is banned for most applications, leading to its accumulation as arsenic trioxide and ferric arsenate sludge. The aim of this thesis was to develop a controlled process for biological crystallization of scorodite from metallurgical streams. In this thesis, the proof of

  13. Inhibition of early T cell cytokine production by arsenic trioxide occurs independently of Nrf2.

    Directory of Open Access Journals (Sweden)

    Kelly R VanDenBerg

    Full Text Available Nuclear factor erythroid 2-related factor 2 (Nrf2 is a stress-activated transcription factor that induces a variety of cytoprotective genes. Nrf2 also mediates immunosuppressive effects in multiple inflammatory models. Upon activation, Nrf2 dissociates from its repressor protein, Keap1, and translocates to the nucleus where it induces Nrf2 target genes. The Nrf2-Keap1 interaction is disrupted by the environmental toxicant and chemotherapeutic agent arsenic trioxide (ATO. The purpose of the present study was to determine the effects of ATO on early events of T cell activation and the role of Nrf2 in those effects. The Nrf2 target genes Hmox-1, Nqo-1, and Gclc were all upregulated by ATO (1-2 μM in splenocytes derived from wild-type, but not Nrf2-null, mice, suggesting that Nrf2 is activated by ATO in splenocytes. ATO also inhibited IFNγ, IL-2, and GM-CSF mRNA and protein production in wild-type splenocytes activated with the T cell activator, anti-CD3/anti-CD28. However, ATO also decreased production of these cytokines in activated splenocytes from Nrf2-null mice, suggesting the inhibition is independent of Nrf2. Interestingly, ATO inhibited TNFα protein secretion, but not mRNA expression, in activated splenocytes suggesting the inhibition is due to post-transcriptional modification. In addition, c-Fos DNA binding was significantly diminished by ATO in wild-type and Nrf2-null splenocytes activated with anti-CD3/anti-CD28, consistent with the observed inhibition of cytokine production by ATO. Collectively, this study suggests that although ATO activates Nrf2 in splenocytes, inhibition of early T cell cytokine production by ATO occurs independently of Nrf2 and may instead be due to impaired AP-1 DNA binding.

  14. Identification of Arsenic Direct-Binding Proteins in Acute Promyelocytic Leukaemia Cells

    Directory of Open Access Journals (Sweden)

    Tao Zhang

    2015-11-01

    Full Text Available The identification of arsenic direct-binding proteins is essential for determining the mechanism by which arsenic trioxide achieves its chemotherapeutic effects. At least two cysteines close together in the amino acid sequence are crucial to the binding of arsenic and essential to the identification of arsenic-binding proteins. In the present study, arsenic binding proteins were pulled down with streptavidin and identified using a liquid chromatograph-mass spectrometer (LC-MS/MS. More than 40 arsenic-binding proteins were separated, and redox-related proteins, glutathione S-transferase P1 (GSTP1, heat shock 70 kDa protein 9 (HSPA9 and pyruvate kinase M2 (PKM2, were further studied using binding assays in vitro. Notably, PKM2 has a high affinity for arsenic. In contrast to PKM2, GSTP1and HSPA9 did not combine with arsenic directly in vitro. These observations suggest that arsenic-mediated acute promyelocytic leukaemia (APL suppressive effects involve PKM2. In summary, we identified several arsenic binding proteins in APL cells and investigated the therapeutic mechanisms of arsenic trioxide for APL. Further investigation into specific signal pathways by which PKM2 mediates APL developments may lead to a better understanding of arsenic effects on APL.

  15. Alterations in glutathione levels and apoptotic regulators are associated with acquisition of arsenic trioxide resistance in multiple myeloma.

    Directory of Open Access Journals (Sweden)

    Shannon M Matulis

    Full Text Available Arsenic trioxide (ATO has been tested in relapsed/refractory multiple myeloma with limited success. In order to better understand drug mechanism and resistance pathways in myeloma we generated an ATO-resistant cell line, 8226/S-ATOR05, with an IC50 that is 2-3-fold higher than control cell lines and significantly higher than clinically achievable concentrations. Interestingly we found two parallel pathways governing resistance to ATO in 8226/S-ATOR05, and the relevance of these pathways appears to be linked to the concentration of ATO used. We found changes in the expression of Bcl-2 family proteins Bfl-1 and Noxa as well as an increase in cellular glutathione (GSH levels. At low, clinically achievable concentrations, resistance was primarily associated with an increase in expression of the anti-apoptotic protein Bfl-1 and a decrease in expression of the pro-apoptotic protein Noxa. However, as the concentration of ATO increased, elevated levels of intracellular GSH in 8226/S-ATOR05 became the primary mechanism of ATO resistance. Removal of arsenic selection resulted in a loss of the resistance phenotype, with cells becoming sensitive to high concentrations of ATO within 7 days following drug removal, indicating changes associated with high level resistance (elevated GSH are dependent upon the presence of arsenic. Conversely, not until 50 days without arsenic did cells once again become sensitive to clinically relevant doses of ATO, coinciding with a decrease in the expression of Bfl-1. In addition we found cross-resistance to melphalan and doxorubicin in 8226/S-ATOR05, suggesting ATO-resistance pathways may also be involved in resistance to other chemotherapeutic agents used in the treatment of multiple myeloma.

  16. Accumulation and suppressive function of regulatory T cells in malignant ascites: Reducing their suppressive function using arsenic trioxide in vitro.

    Science.gov (United States)

    Hu, Zilong; Hu, Shidong; Wu, Youjun; Li, Songyan; He, Changzheng; Xing, Xiaowei; Wang, Yufeng; Du, Xiaohui

    2018-04-01

    Although adoptive cell therapy (ACT) has demonstrated effective and remarkable clinical responses in several studies, this approach does not lead to objective clinical responses in all cases. The function of ACT is often compromised by various tumor escape mechanisms, including the accumulation of immunoregulatory cells. As a result of peritoneal metastasis in the terminal stage, malignant ascites fluid lacks effectiveness and is a poor prognostic factor for gastric cancer. The present study assessed T-cell subsets in lymphocytes derived from malignant ascites, and investigated the effects of arsenic trioxide (As 2 O 3 ) on regulatory T cells (Tregs) and ascites-derived tumor-infiltrating lymphocytes (TILs) in vitro . In this study, lymphocytes were separated from malignant ascites and T-cell subsets were detected via flow cytometry. Forkhead box P3 (FoxP3) expression was assessed by immunohistochemistry and reverse transcription-quantitative polymerase chain reaction. In addition, cytokines, including interleukin-10 (IL-10), transforming growth factor-β (TGF-β), and interferon-γ (IFN-γ), were measured by enzyme-linked immunosorbent assay (ELISA). Abundant Tregs were observed in ascites lymphocytes, which and exhibited a significantly increased frequency compared with that in the peripheral blood of patients. Furthermore, As 2 O 3 treatment significantly reduced Treg numbers and Foxp3 mRNA levels in vitro (P<0.05). IFN-γ levels in the supernatant of ascites-derived TILs were increased by As 2 O 3 , whereas IL-10 and TGF-β levels were significantly reduced (P<0.05). As 2 O 3 may induce selective depletion and inhibit immunosuppressive function of Tregs, and may enhance the cytotoxic activity of ascites-derived TILs.

  17. Combined application of arsenic trioxide and lithium chloride augments viability reduction and apoptosis induction in human rhabdomyosarcoma cell lines.

    Directory of Open Access Journals (Sweden)

    Sabine B Schleicher

    Full Text Available Rhabdomyosarcomas (RMS are the most prevalent soft tissue sarcomas affecting children and adolescents. Despite intensive treatment consisting of multimodal chemotherapy and surgery RMS patients diagnosed with metastatic disease expect long term survival rates of only 20%. Often multidrug resistance arises upon initial response emphasizing the need for new therapeutic drugs to improve treatment efficiency. Previously, we demonstrated the efficacy of the FDA approved drug arsenic trioxide (ATO specifically inhibiting viability and clonal growth as well as inducing cell death in human RMS cell lines of different subtypes. In this study, we combined low dose ATO with lithium chloride (LiCl, which is approved as mood stabilizer for the treatment of bipolar disorder, but also inhibits growth and survival of different cancer cell types in pre-clinical research. Indeed, we could show additive effects of LiCl and ATO on viability reduction, decrease of colony formation as well as cell death induction. In the course of this, LiCl induced inhibitory glycogen synthase kinase-3β (GSK-3β serine 9 phosphorylation, whereas glioma associated oncogene family 1 (GLI1 protein expression was particularly reduced by combined ATO and LiCl treatment in RD and RH-30 cell lines, showing high rates of apoptotic cell death. These results imply that combination of ATO with LiCl or another drug targeting GSK-3 is a promising strategy to enforce the treatment efficiency in resistant and recurrent RMS.

  18. Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells

    International Nuclear Information System (INIS)

    Wang, Hongtao; Gao, Peng; Zheng, Jie

    2014-01-01

    Highlights: • As 2 O 3 inhibits growth of cervical cancer cells and expression of HPV oncogenes in these cells. • HPV-negative cervical cancer cells are more sensitive to As 2 O 3 than HPV-positive cervical cancer cells. • HPV-18 positive cervical cancer cells are more sensitive to As 2 O 3 than HPV-16 positive cancer cells. • Down-regulation of HPV oncogenes by As 2 O 3 is partially due to the diminished AP-1 binding. - Abstract: Arsenic trioxide (As 2 O 3 ) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As 2 O 3 induced apoptosis of human papillomavirus (HPV) 16 DNA-immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As 2 O 3 on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV-negative C33A cells were more sensitive to growth inhibition induced by As 2 O 3 than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As 2 O 3 than HPV 16-positive CaSki and SiHa cells. After As 2 O 3 treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As 2 O 3 is a potential anticancer drug for cervical cancer

  19. Arsenic trioxide inhibits cell proliferation and human papillomavirus oncogene expression in cervical cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hongtao [Department of Pathology, School of Medicine, Southeast University, Nanjing 210009 (China); Gao, Peng [Department of Internal Medicine, University of Iowa, Iowa City, IA 52242 (United States); Zheng, Jie, E-mail: jiezheng54@126.com [Department of Pathology, School of Medicine, Southeast University, Nanjing 210009 (China)

    2014-09-05

    Highlights: • As{sub 2}O{sub 3} inhibits growth of cervical cancer cells and expression of HPV oncogenes in these cells. • HPV-negative cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-positive cervical cancer cells. • HPV-18 positive cervical cancer cells are more sensitive to As{sub 2}O{sub 3} than HPV-16 positive cancer cells. • Down-regulation of HPV oncogenes by As{sub 2}O{sub 3} is partially due to the diminished AP-1 binding. - Abstract: Arsenic trioxide (As{sub 2}O{sub 3}) has shown therapeutic effects in some leukemias and solid cancers. However, the molecular mechanisms of its anticancer efficacy have not been clearly elucidated, particularly in solid cancers. Our previous data showed that As{sub 2}O{sub 3} induced apoptosis of human papillomavirus (HPV) 16 DNA-immortalized human cervical epithelial cells and cervical cancer cells and inhibited the expression of HPV oncogenes in these cells. In the present study, we systemically examined the effects of As{sub 2}O{sub 3} on five human cervical cancer cell lines and explored the possible molecular mechanisms. MTT assay showed that HPV-negative C33A cells were more sensitive to growth inhibition induced by As{sub 2}O{sub 3} than HPV-positive cervical cancer cells, and HPV 18-positive HeLa and C4-I cells were more sensitive to As{sub 2}O{sub 3} than HPV 16-positive CaSki and SiHa cells. After As{sub 2}O{sub 3} treatment, both mRNA and protein levels of HPV E6 and E7 obviously decreased in all HPV positive cell lines. In contrast, p53 and Rb protein levels increased in all tested cell lines. Transcription factor AP-1 protein expression decreased significantly in HeLa, CaSki and C33A cells with ELISA method. These results suggest that As{sub 2}O{sub 3} is a potential anticancer drug for cervical cancer.

  20. Unfolded Protein Response Signaling and MAP Kinase Pathways Underlie Pathogenesis of Arsenic-induced Cutaneous Inflammation

    OpenAIRE

    Li, Changzhao; Xu, Jianmin; Li, Fugui; Chaudhary, Sandeep C.; Weng, Zhiping; Wen, Jianming; Elmets, Craig A.; Ahsan, Habibul; Athar, Mohammad

    2011-01-01

    Arsenic exposure through drinking water is a major global public health problem and is associated with an enhanced risk of various cancers including skin cancer. In human skin, arsenic induces precancerous melanosis and keratosis, which may progress to basal cell and squamous cell carcinoma. However, the mechanism by which these pathophysiological alterations occur remains elusive. In this study, we showed that sub-chronic arsenic exposure to SKH-1 mice induced unfolded protein response (UPR)...

  1. Effects of Arsenic Trioxide on Radiofrequency Ablation of VX2 Liver Tumor: Intraarterial versus Intravenous Administration

    Energy Technology Data Exchange (ETDEWEB)

    Seong, Nak Jong; Yoon, Chang Jin; Kang, Sung Gwon [Seoul National University Bundang Hospital, Seongnam (Korea, Republic of); Chung, Jin Wook; Kim, Hyo Cheol; Park, Jae Hyung [Seoul National University Hospital, Seoul (Korea, Republic of)

    2012-03-15

    Arsenic trioxide (As{sub 2}O{sub 3}) can be used as a possible pharmaceutical alternative that augments radiofrequency (RF) ablation by reducing tumor blood flow. The aim of this study was to assess the effect of intraarterial and intravenous administration of As{sub 2}O{sub 3} on RF-induced ablation in an experimentally induced liver tumor. VX2 carcinoma was grown in the livers of 30 rabbits. As{sub 2}O{sub 3} (1 mg/kg) was administered through the hepatic artery (n = 10, group A) or ear vein (n = 10, group B), 30 minutes before RF ablation (125 mA {+-} 35; 90 {+-} 5 degrees Celsius). As a control group, 10 rabbits were treated with RF ablation alone (group C). RF was intentionally applied to the peripheral margin of the tumor so that ablation can cover the tumor and adjacent hepatic parenchyma. Ablation areas of the tumor and adjacent parenchymal changes among three groups were compared by the Kruskal-Wallis and Mann-Whitney U test. The overall ablation areas were 156 {+-} 28.9 mm{sup 2} (group A), 119 {+-} 31.7 (group B), and 92 {+-} 17.4 (group C, p < 0.04). The ablation area of the tumor was significantly larger in group A (73 {+-} 19.7 mm{sup 2}) than both group B (50 {+-} 19.4, p = 0.02) and group C (28 {+-} 2.2, p < 0.01). The ratios of the tumoral ablation area to the overall ablation area were larger in group A (47 {+-} 10.5%) than that of the other groups (42 {+-} 7.3% in group B and 32 {+-} 5.6% in group C) (p < 0.03). Radiofrequency-induced ablation area can be increased with intraarterial or intravenous administration of As{sub 2}O{sub 3}. The intraarterial administration of As{sub 2}O{sub 3} seems to be helpful for the selective ablation of the tumor.

  2. Targeting Hsp90 by 17-AAG in leukemia cells: mechanisms for synergistic and antagonistic drug combinations with arsenic trioxide and Ara-C.

    Science.gov (United States)

    Pelicano, H; Carew, J S; McQueen, T J; Andreeff, M; Plunkett, W; Keating, M J; Huang, P

    2006-04-01

    17-Allylamino-17-demethoxygeldanamycin (17-AAG) is a new anticancer agent currently in clinical trials. The ability of 17-AAG to abrogate the function of heat-shock protein Hsp90 and modulate cellular sensitivity to anticancer agents has prompted recent research to use this compound in drug combination therapy. Here we report that 17-AAG has striking opposite effects on the activity of arsenic trioxide (ATO) and ara-C. Combination of 17-AAG with ATO exhibited a synergistic effect in leukemia cells, whereas coincubation of 17-AAG and ara-C showed antagonistic activity. Mechanistic studies revealed that ATO exerted cytotoxic action by reactive oxygen species generation, and activated Akt survival pathway. 17-AAG abrogated Akt activation and enhanced the activity of ATO. In contrast, treatment of leukemia cells with 17-AAG caused a G1 arrest, a decrease in DNA synthesis and reduced ara-C incorporation into DNA, leading to antagonism. The ability of 17-AAG to enhance the antileukemia activity of ATO was further demonstrated in primary leukemia cells isolated from patients with acute myeloid leukemia and chronic lymphocytic leukemia, including cells from refractory patients. Our data suggest that combination of 17-AAG and ATO may be an effective therapeutic regimen. Caution should be exercised in using 17-AAG together with ara-C, as their combination effects are schedule dependent.

  3. Successful Control of Disseminated Intravascular Coagulation by Recombinant Thrombomodulin during Arsenic Trioxide Treatment in Relapsed Patient with Acute Promyelocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Motohiro Shindo

    2012-01-01

    Full Text Available Disseminated intravascular coagulation (DIC frequently occurs in patients with acute promyelocytic leukemia (APL. With the induction of therapy in APL using all-trans retinoic acid (ATRA, DIC can be controlled in most cases as ATRA usually shows immediate improvement of the APL. However, arsenic trioxide (ATO which has been used for the treatment of relapse in APL patients has shown to take time to suppress APL cells, therefore the control of DIC in APL with ATO treatment is a major problem. Recently, the recombinant soluble thrombomodulin fragment has received a lot of attention as the novel drug for the treatment of DIC with high efficacy. Here, we present a relapsed patient with APL in whom DIC was successfully and safely controlled by rTM during treatment with ATO.

  4. Arsenic-induced biochemical and genotoxic effects and distribution in tissues of Sprague-Dawley rats

    Science.gov (United States)

    Patlolla, Anita K.; Todorov, Todor I.; Tchounwou, Paul B.; van der Voet, Gijsbert; Centeno, Jose A.

    2012-01-01

    Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague–Dawley rats. Four groups of six male rats, each weighing approximately 60 ± 2 g, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15, 20 mg/kg BW of arsenic trioxide. A control group was also made of 6 animals injected with distilled water. Following anaesthetization, blood was collected and enzyme analysis was performed by spectrophotometry following standard protocols. At the end of experimentation, the animals were sacrificed, and the lung, liver, brain and kidney were collected 24 h after the fifth day treatment. Chromosome and micronuclei preparation was obtained from bone marrow cells. Arsenic exposure significantly increased (p < 0.05) the activities of plasma alanine aminotransferase–glutamate pyruvate transaminase (ALT/GPT), and aspartate aminotransferase–glutamate oxaloacetate transaminase (AST/GOT), as well as the number of structural chromosomal aberrations (SCA) and frequency of micronuclei (MN) in the bone marrow cells. In contrast, the mitotic index in these cells was significantly reduced (p < 0.05). These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also demonstrate that As has a strong genotoxic potential, as measured by the bone marrow SCA and MN tests in Sprague–Dawley rats. Total arsenic concentrations in tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl interference at mass 75, in the measurement of total As. Total As doses in tissues tended to correlate with specific exposure levels.

  5. Tracking the transformation and transport of arsenic sulfide pigments in paints: synchrotron-based X-ray micro-analyses

    NARCIS (Netherlands)

    Keune, K.; Mass, J.; Meirer, F.; Pottasch, C.; van Loon, A.; Hull, A.; Church, J.; Pouyet, E.; Cotte, M.; Mehta, A.

    2015-01-01

    Realgar and orpiment, arsenic sulfide pigments used in historic paints, degrade under the influence of light, resulting in transparent, whitish, friable and/or crumbling paints. So far, para-realgar and arsenic trioxide have been identified as the main oxidation products of arsenic sulfide pigments.

  6. Tracking the transformation and transport of arsenic sulfide pigments in paints : synchrotron-based X-ray micro-analyses

    NARCIS (Netherlands)

    Keune, Katrien; Mass, Jennifer; Meirer, Florian; Pottasch, Carol; van Loon, Annelies; Hull, Alyssa; Church, Jonathan; Pouyet, Emeline; Cotte, Marine; Mehta, Apurva

    2015-01-01

    Realgar and orpiment, arsenic sulfide pigments used in historic paints, degrade under the influence of light, resulting in transparent, whitish, friable and/or crumbling paints. So far, para-realgar and arsenic trioxide have been identified as the main oxidation products of arsenic sulfide pigments.

  7. Arsenic mediated disruption of promyelocytic leukemia protein nuclear bodies induces ganciclovir susceptibility in Epstein-Barr positive epithelial cells

    International Nuclear Information System (INIS)

    Sides, Mark D.; Block, Gregory J.; Shan, Bin; Esteves, Kyle C.; Lin, Zhen; Flemington, Erik K.; Lasky, Joseph A.

    2011-01-01

    Promyelocytic leukemia protein nuclear bodies (PML NBs) have been implicated in host immune response to viral infection. PML NBs are targeted for degradation during reactivation of herpes viruses, suggesting that disruption of PML NB function supports this aspect of the viral life cycle. The Epstein-Barr virus (EBV) Latent Membrane Protein 1 (LMP1) has been shown to suppress EBV reactivation. Our finding that LMP1 induces PML NB immunofluorescence intensity led to the hypothesis that LMP1 may modulate PML NBs as a means of maintaining EBV latency. Increased PML protein and morphometric changes in PML NBs were observed in EBV infected alveolar epithelial cells and nasopharyngeal carcinoma cells. Treatment with low dose arsenic trioxide disrupted PML NBs, induced expression of EBV lytic proteins, and conferred ganciclovir susceptibility. This study introduces an effective modality to induce susceptibility to ganciclovir in epithelial cells with implications for the treatment of EBV associated pathologies.

  8. Indomethacin-Enhanced Anticancer Effect of Arsenic Trioxide in A549 Cell Line: Involvement of Apoptosis and Phospho-ERK and p38 MAPK Pathways

    Directory of Open Access Journals (Sweden)

    Ali Mandegary

    2013-01-01

    Full Text Available Background. Focusing on novel drug combinations that target different pathways especially apoptosis and MAPK could be a rationale for combination therapy in successful treatment of lung cancer. Concurrent use of cyclooxygenase (COX inhibitors with arsenic trioxide (ATO might be a possible treatment option. Methods. Cytotoxicity of ATO, dexamethasone (Dex, celecoxib (Cel, and Indomethacin (Indo individually or in combination was determined at 24, 48, and 72 hrs in A549 lung cancer cells. The COX-2 gene and protein expression, MAPK pathway proteins, and caspase-3 activity were studied for the most cytotoxic combinations. Results. The IC50s of ATO and Indo were 68.7 μmol/L and 396.5 μmol/L, respectively. Treatment of cells with combinations of clinically relevant concentrations of ATO and Indo resulted in greater growth inhibition and apoptosis induction than did either agent alone. Caspase-3 activity was considerably high in the presence of ATO and Indo but showed no difference in single or combination use. Phosphorylation of p38 and ERK1/2 was remarkable in the concurrent presence of both drugs. Conclusions. Combination therapy with ATO and Indo exerted a very potent in vitro cytotoxic effect against A549 lung cancer cells. Activation of ERK and p38 pathways might be the mechanism of higher cytotoxic effect of ATO-Indo combination.

  9. Dissimilatory antimonate reduction and production of antimony trioxide microcrystals by a novel microorganism.

    Science.gov (United States)

    Abin, Christopher A; Hollibaugh, James T

    2014-01-01

    Antimony (Sb) is a metalloid that has been exploited by humans since the beginning of modern civilization. The importance of Sb to such diverse industries as nanotechnology and health is underscored by the fact that it is currently the ninth-most mined metal worldwide. Although its toxicity mirrors that of its Group 15 neighbor arsenic, its environmental chemistry is very different, and, unlike arsenic, relatively little is known about the fate and transport of Sb, especially with regard to biologically mediated redox reactions. To further our understanding of the interactions between microorganisms and Sb, we have isolated a bacterium that is capable of using antimonate [Sb(V)] as a terminal electron acceptor for anaerobic respiration, resulting in the precipitation of antimonite [Sb(III)] as microcrystals of antimony trioxide. The bacterium, designated strain MLFW-2, is a sporulating member of a deeply branching lineage within the order Bacillales (phylum Firmicutes). This report provides the first unequivocal evidence that a bacterium is capable of conserving energy for growth and reproduction from the reduction of antimonate. Moreover, microbiological antimonate reduction may serve as a novel route for the production of antimony trioxide microcrystals of commercial significance to the nanotechnology industry.

  10. Combination of Bifunctional Alkylating Agent and Arsenic Trioxide Synergistically Suppresses the Growth of Drug-Resistant Tumor Cells

    Directory of Open Access Journals (Sweden)

    Pei-Chih Lee

    2010-05-01

    Full Text Available Drug resistance is a crucial factor in the failure of cancer chemotherapy. In this study, we explored the effect of combining alkylating agents and arsenic trioxide (ATO on the suppression of tumor cells with inherited or acquired resistance to therapeutic agents. Our results showed that combining ATO and a synthetic derivative of 3a-aza-cyclopenta[a]indenes (BO-1012, a bifunctional alkylating agent causing DNA interstrand cross-links, was more effective in killing human cancer cell lines (H460, H1299, and PC3 than combining ATO and melphalan or thiotepa. We further demonstrated that the combination treatment of H460 cells with BO-1012 and ATO resulted in severe G2/M arrest and apoptosis. In a xenograft mouse model, the combination treatment with BO-1012 and ATO synergistically reduced tumor volumes in nude mice inoculated with H460 cells. Similarly, the combination of BO-1012 and ATO effectively reduced the growth of cisplatin-resistant NTUB1/P human bladder carcinoma cells. Furthermore, the repair of BO-1012-induced DNA interstrand cross-links was significantly inhibited by ATO, and consequently, γH2AX was remarkably increased and formed nuclear foci in H460 cells treated with this drug combination. In addition, Rad51 was activated by translocating and forming foci in nuclei on treatment with BO-1012, whereas its activation was significantly suppressed by ATO. We further revealed that ATO might mediate through the suppression of AKT activity to inactivate Rad51. Taken together, the present study reveals that a combination of bifunctional alkylating agents and ATO may be a rational strategy for treating cancers with inherited or acquired drug resistance.

  11. Protective effect of nitric oxide against arsenic-induced oxidative ...

    African Journals Online (AJOL)

    The effects of NO on alleviating arsenic-induced oxidative damage in tall fescue leaves were investigated. Arsenic (25 M) treatment induced significantly accumulation of reactive oxygen species (ROS) and led to serious lipid peroxidation in tall fescue leaves and the application of 100 M SNP before arsenic stress resulted ...

  12. Mineral trioxide aggregate enhances the odonto/osteogenic capacity of stem cells from inflammatory dental pulps via NF-κB pathway.

    Science.gov (United States)

    Wang, Y; Yan, M; Fan, Z; Ma, L; Yu, Y; Yu, J

    2014-10-01

    This study was designed to investigate the effects of mineral trioxide aggregate (MTA) on the osteo/odontogenic differentiation of inflammatory dental pulp stem cells (iDPSCs). inflammatory DPSCs were isolated from the inflammatory pulps of rat incisors and cocultured with MTA-conditioned medium. MTT assay and flow cytometry were performed to evaluate the proliferation of iDPSCs. Alkaline phosphatase (ALP) activity, alizarin red staining, real-time RT-PCR, and Western blot assay were used to investigate the differentiation capacity as well as the involvement of NF-κB pathway in iDPSCs. Mineral trioxide aggregate-treated iDPSCs demonstrated the higher ALP activity and formed more mineralized nodules than the untreated group. The odonto/osteoblastic markers (Alp, Runx2/RUNX2, Osx/OSX, Ocn/OCN, and Dspp/DSP, respectively) in MTA-treated iDPSCs were significantly upregulated as compared with untreated iDPSCs. Mechanistically, cytoplastic phos-P65 and nuclear P65 in MTA-treated iDPSCs were significantly increased in a time-dependent manner. Moreover, the inhibition of NF-κB pathway suppressed the MTA-induced odonto/osteoblastic differentiation of iDPSCs, as indicated by decreased ALP levels, weakened mineralization capacity and downregulated levels of odonto/osteoblastic genes (Osx, Ocn, and Dspp). Mineral trioxide aggregate enhances the odonto/osteogenic capacity of DPSCs from inflammatory sites via activating the NF-κB pathway. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Arsenic-Induced Genotoxicity and Genetic Susceptibility to Arsenic-Related Pathologies

    Directory of Open Access Journals (Sweden)

    Fabrizio Bianchi

    2013-04-01

    Full Text Available The arsenic (As exposure represents an important problem in many parts of the World. Indeed, it is estimated that over 100 million individuals are exposed to arsenic, mainly through a contamination of groundwaters. Chronic exposure to As is associated with adverse effects on human health such as cancers, cardiovascular diseases, neurological diseases and the rate of morbidity and mortality in populations exposed is alarming. The purpose of this review is to summarize the genotoxic effects of As in the cells as well as to discuss the importance of signaling and repair of arsenic-induced DNA damage. The current knowledge of specific polymorphisms in candidate genes that confer susceptibility to arsenic exposure is also reviewed. We also discuss the perspectives offered by the determination of biological markers of early effect on health, incorporating genetic polymorphisms, with biomarkers for exposure to better evaluate exposure-response clinical relationships as well as to develop novel preventative strategies for arsenic- health effects.

  14. Analytical artefacts in the speciation of arsenic in clinical samples

    International Nuclear Information System (INIS)

    Slejkovec, Zdenka; Falnoga, Ingrid; Goessler, Walter; Elteren, Johannes T. van; Raml, Reingard; Podgornik, Helena; Cernelc, Peter

    2008-01-01

    Urine and blood samples of cancer patients, treated with high doses of arsenic trioxide were analysed for arsenic species using HPLC-HGAFS and, in some cases, HPLC-ICPMS. Total arsenic was determined with either flow injection-HGAFS in urine or radiochemical neutron activation analysis in blood fractions (in serum/plasma, blood cells). The total arsenic concentrations (during prolonged, daily/weekly arsenic trioxide therapy) were in the μg mL -1 range for urine and in the ng g -1 range for blood fractions. The main arsenic species found in urine were As(III), MA and DMA and in blood As(V), MA and DMA. With proper sample preparation and storage of urine (no preservation agents/storage in liquid nitrogen) no analytical artefacts were observed and absence of significant amounts of alleged trivalent metabolites was proven. On the contrary, in blood samples a certain amount of arsenic can get lost in the speciation procedure what was especially noticeable for the blood cells although also plasma/serum gave rise to some disappearance of arsenic. The latter losses may be attributed to precipitation of As(III)-containing proteins/peptides during the methanol/water extraction procedure whereas the former losses were due to loss of specific As(III)-complexing proteins/peptides (e.g. cysteine, metallothionein, reduced GSH, ferritin) on the column (Hamilton PRP-X100) during the separation procedure. Contemporary analytical protocols are not able to completely avoid artefacts due to losses from the sampling to the detection stage so that it is recommended to be careful with the explanation of results, particularly regarding metabolic and pharmacokinetic interpretations, and always aim to compare the sum of species with the total arsenic concentration determined independently

  15. Ameliorative effects of selenium on arsenic-induced cytotoxicity in PC12 cells via modulating autophagy/apoptosis.

    Science.gov (United States)

    Rahman, Md Mostafizur; Uson-Lopez, Rachael A; Sikder, Md Tajuddin; Tan, Gongxun; Hosokawa, Toshiyuki; Saito, Takeshi; Kurasaki, Masaaki

    2018-04-01

    Arsenic is well known toxicant responsible for human diseases including cancers. On the other hand, selenium is an essential trace element with significant chemopreventive effects, anticancer potentials and antioxidant properties. Although previous studies have reported antagonism/synergism between arsenic and selenium in biological systems, the biomolecular mechanism/s is still inconclusive. Therefore, to elucidate the molecular phenomena in cellular level, we hypothesized that co-exposure of selenium with arsenic may have suppressive effects on arsenic-induced cytotoxicity. We found that selenium in co-exposure with arsenic increases cell viability, and suppresses oxidative stress induced by arsenic in PC12 cells. Consequently, DNA fragmentation due to arsenic exposure was also reduced by arsenic and selenium co-exposure. Furthermore, western blot analyses revealed that simultaneous exposure of both metals significantly inhibited autophagy which further suppressed apoptosis through positively regulation of key proteins; p-mTOR, p-Akt, p-Foxo1A, p62, and expression of ubiquitin, Bax, Bcl2, NFкB, and caspases 3 and 9, although those are negatively regulated by arsenic. In addition, reverse transcriptase PCR analysis confirmed the involvement of caspase cascade in cell death process induced by arsenic and subsequent inhibition by co-exposure of selenium with arsenic. The cellular accumulation study of arsenic in presence/absence of selenium via inductively coupled plasma mass spectrometry confirmed that selenium effectively retarded the uptake of arsenic in PC12 cells. Finally, these findings imply that selenium is capable to modulate arsenic-induced intrinsic apoptosis pathway via enhancement of mTOR/Akt autophagy signaling pathway through employing antioxidant potentials and through inhibiting the cellular accumulation of arsenic in PC12 cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

    Energy Technology Data Exchange (ETDEWEB)

    Qu, Wei, E-mail: qu@niehs.nih.gov; Waalkes, Michael P.

    2015-02-01

    We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO{sub 2}) was less cytolethal over 24 h in WT cells (LC{sub 50} = 11.0 ± 1.3 μM; mean ± SEM) than in MT-null cells (LC{sub 50} = 5.6 ± 1.2 μM). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 μM; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GSTα2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. - Highlights: • Metallothionein blocks arsenic toxicity. • Metallothionein reduces arsenic-induced DNA damage. • Metallothionein may bind arsenic or radicals produced by arsenic.

  17. Removal of arsenic from contaminated water using coagulation enhanced microfiltration

    International Nuclear Information System (INIS)

    Volchek, K.; Velicogna, D.; Dumouchel, A.; Wong, W.P.; Brown, C.E.

    2002-01-01

    Results of an innovative arsenic removal process were presented. The process is based on a combination of coagulation and microfiltration processes. Coagulation-Enhanced Microfiltration (CEMF) may eventually become a full-scale commercial technology. This study focused on the process with respect to groundwater treatment because of the importance of arsenic contamination in drinking water. Most experiments were bench-scale using tap water spiked with arsenic. Ferric chloride, which is commonly used in arsenic removal processes was also added. In addition, some tests were conducted on actual arsenic-contaminated water from the effluent treatment plant of a former mining site in Ontario. Results indicate a high arsenic removal efficiency in both spiked and actual water solutions. The microfiltration significantly reduced the level of arsenic in the treatment. This paper described the characteristics of membrane separation. It also presented information regarding chemically enhanced membrane filtration and coagulation-enhanced microfiltration. Bench-scale tests were conducted with both tubular membranes and with immersed capillary membranes. The effect of iron to arsenic ratios on the effectiveness of the system was also tested. It was recommended that future research should include a field study of the process on a pilot-scale to optimize process parameters and to accurately determine the cost of the process. 16 refs., 8 tabs., 9 figs

  18. Enhancements of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) metabolism and carcinogenic risk via NNK/arsenic interaction

    International Nuclear Information System (INIS)

    Lee, H.-L.; Chang, Louis W.; Wu, J.-P.; Ueng, Y.-F.; Tsai, M.-H.; Hsieh, Dennis Paul Hsientang; Lin Pinpin

    2008-01-01

    Epidemiological studies indicated an enhancement of cigarette smoke-induced carcinogenicity, including hepatocellular carcinoma, by arsenic. We believe that arsenic will enhance the expression of hepatic CYP2A enzyme and NNK metabolism (a cigarette smoke component), thus its metabolites, and carcinogenic DNA adducts. Male ICR mice were exposed to NNK (0.5 mg/mouse) and sodium arsenite (0, 10, or 20 mg/kg) daily via gavaging for 10 days and their urine was collected at day 10 for NNK metabolite analysis. Liver samples were also obtained for CYP2A enzyme and DNA adducts evaluations. Both the cyp2a4/5 mRNA levels and the CYP2A enzyme activity were significantly elevated in arsenic-treated mice liver. Furthermore, urinary NNK metabolites in NNK/arsenic co-treated mice also increased compared to those treated with NNK alone. Concomitantly, DNA adducts (N 7 -methylguanine and O 6 -methylguanine) were significantly elevated in the livers of mice co-treated with NNK and arsenic. Our findings provide clear evidence that arsenic increased NNK metabolism by up-regulation of CYP2A expression and activity leading to an increased NNK metabolism and DNA adducts (N 7 -methylguanine and O 6 -methylguanine). These findings suggest that in the presence of arsenic, NNK could induce greater DNA adducts formation in hepatic tissues resulting in higher carcinogenic potential

  19. Poisoning of bees by industrial arsenic emissions

    Energy Technology Data Exchange (ETDEWEB)

    Jaroslav, S

    1962-01-01

    Massive poisoning of bees by industrial arsenic emissions in Czechoslovakia are reviewed. Arsenic emissions from an ore processing plant in Tesin were responsible for massive bee deaths after World War I. Massive death of bees was observed in 1938 in the Krompach region around a copper ore smelting plant which emitted arsenic. Other accidents were reported in 1954 and 1957 in areas around industrial plants and power plants using arsenopyrite-containing low-grade coal or lignite. Arsenic was emitted bound in fly-ash in the form of arsenic trioxide or, in the case of coals containing alkaline chlorides, in the form of arsenic trichloride. The arsenic contamination extended to areas within a radius of 3 to 7 km. Settled fly-ash contained 0.0004 to 0.75 percent arsenic, which was soluble in a citrate-hydrochloric acid solution of pH 3.9, which corresponds to the gastric acid of bees. The arsenic uptake by the bees from pollen was calculated to amount to 1 microgram daily, against a toxic dose of 0.37 microgram. The toxic effect of arsenic on bees can be abated by adding colloidal iron hydroxide to the sugar solution which they are fed.

  20. Poisoning of bees by industrial arsenic emissions

    Energy Technology Data Exchange (ETDEWEB)

    Svoboda, J

    1962-01-01

    Massive poisoning of bees by industrial arsenic emissions in Czechoslovakia are reviewed. Arsenic emissions from an ore processing plant in Tesin were responsible for massive bee deaths after World War I. Massive death of bees was observed in 1938 in the Krompach region around a copper ore smelting plant which emitted arsenic. Other accidents were reported in 1954 and 1957 in areas around industrial plants and power plants using arsenopyrite-containing low-grade coal or lignite. Arsenic was emitted bound in fly-ash in the form of arsenic trioxide or, in the case of coals containing alkaline chlorides, in the form of arsenic trichloride. The arsenic contamination extended to areas within a radius of 3-7 km. Settled fly-ash contained 0.0004-0.75% arsenic, which was soluble in a citrate-hydrochloric acid solution of pH 3.9, which corresponds to the gastric acid of bees. The arsenic uptake by the bees from pollen was calculated to amount to 1 microgram daily, against a toxic dose of 0.37 microgram. The toxic effect of arsenic on bees can be abated by adding colloidal iron hydroxide to the sugar solution which they are fed. 5 references.

  1. Matrix metalloproteinase-9 is involved in chronic lymphocytic leukemia cell response to fludarabine and arsenic trioxide.

    Directory of Open Access Journals (Sweden)

    Irene Amigo-Jiménez

    Full Text Available Matrix metalloproteinase-9 (MMP-9 contributes to chronic lymphocytic leukemia (CLL pathology by regulating cell migration and preventing spontaneous apoptosis. It is not known if MMP-9 is involved in CLL cell response to chemotherapy and we address this in the present study, using arsenic trioxide (ATO and fludarabine as examples of cytotoxic drugs.We used primary cells from the peripheral blood of CLL patients and MEC-1 cells stably transfected with an empty vector or a vector containing MMP-9. The effect of ATO and fludarabine was determined by flow cytometry and by the MTT assay. Expression of mRNA was measured by RT-PCR and qPCR. Secreted and cell-bound MMP-9 was analyzed by gelatin zymography and flow cytometry, respectively. Protein expression was analyzed by Western blotting and immunoprecipitation. Statistical analyses were performed using the two-tailed Student's t-test.In response to ATO or fludarabine, CLL cells transcriptionally upregulated MMP-9, preceding the onset of apoptosis. Upregulated MMP-9 primarily localized to the membrane of early apoptotic cells and blocking apoptosis with Z-VAD prevented MMP-9 upregulation, thus linking MMP-9 to the apoptotic process. Culturing CLL cells on MMP-9 or stromal cells induced drug resistance, which was overcome by anti-MMP-9 antibodies. Accordingly, MMP-9-MEC-1 transfectants showed higher viability upon drug treatment than Mock-MEC-1 cells, and this effect was blocked by silencing MMP-9 with specific siRNAs. Following drug exposure, expression of anti-apoptotic proteins (Mcl-1, Bcl-xL, Bcl-2 and the Mcl-1/Bim, Mcl-1/Noxa, Bcl-2/Bax ratios were higher in MMP-9-cells than in Mock-cells. Similar results were obtained upon culturing primary CLL cells on MMP-9.Our study describes for the first time that MMP-9 induces drug resistance by modulating proteins of the Bcl-2 family and upregulating the corresponding anti-apoptotic/pro-apoptotic ratios. This is a novel role for MMP-9 contributing to CLL

  2. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    International Nuclear Information System (INIS)

    Stueckle, Todd A.; Lu, Yongju; Davis, Mary E.; Wang, Liying; Jiang, Bing-Hua; Holaskova, Ida; Schafer, Rosana; Barnett, John B.; Rojanasakul, Yon

    2012-01-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As 2 O 3

  3. Chronic occupational exposure to arsenic induces carcinogenic gene signaling networks and neoplastic transformation in human lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Stueckle, Todd A., E-mail: tstueckle@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Lu, Yongju, E-mail: yongju6@hotmail.com [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States); Davis, Mary E., E-mail: mdavis@wvu.edu [Department of Physiology, West Virginia University, Morgantown, WV 26506 (United States); Wang, Liying, E-mail: lmw6@cdc.gov [Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505 (United States); Jiang, Bing-Hua, E-mail: bhjiang@jefferson.edu [Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Holaskova, Ida, E-mail: iholaskova@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Schafer, Rosana, E-mail: rschafer@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV 26506 (United States); Rojanasakul, Yon, E-mail: yrojan@hsc.wvu.edu [Department of Basic Pharmaceutical Sciences, West Virginia University, Morgantown, WV 26506 (United States)

    2012-06-01

    Chronic arsenic exposure remains a human health risk; however a clear mode of action to understand gene signaling-driven arsenic carcinogenesis is currently lacking. This study chronically exposed human lung epithelial BEAS-2B cells to low-dose arsenic trioxide to elucidate cancer promoting gene signaling networks associated with arsenic-transformed (B-As) cells. Following a 6 month exposure, exposed cells were assessed for enhanced cell proliferation, colony formation, invasion ability and in vivo tumor formation compared to control cell lines. Collected mRNA was subjected to whole genome expression microarray profiling followed by in silico Ingenuity Pathway Analysis (IPA) to identify lung carcinogenesis modes of action. B-As cells displayed significant increases in proliferation, colony formation and invasion ability compared to BEAS-2B cells. B-As injections into nude mice resulted in development of primary and secondary metastatic tumors. Arsenic exposure resulted in widespread up-regulation of genes associated with mitochondrial metabolism and increased reactive oxygen species protection suggesting mitochondrial dysfunction. Carcinogenic initiation via reactive oxygen species and epigenetic mechanisms was further supported by altered DNA repair, histone, and ROS-sensitive signaling. NF-κB, MAPK and NCOR1 signaling disrupted PPARα/δ-mediated lipid homeostasis. A ‘pro-cancer’ gene signaling network identified increased survival, proliferation, inflammation, metabolism, anti-apoptosis and mobility signaling. IPA-ranked signaling networks identified altered p21, EF1α, Akt, MAPK, and NF-κB signaling networks promoting genetic disorder, altered cell cycle, cancer and changes in nucleic acid and energy metabolism. In conclusion, transformed B-As cells with their whole genome expression profile provide an in vitro arsenic model for future lung cancer signaling research and data for chronic arsenic exposure risk assessment. Highlights: ► Chronic As{sub 2}O

  4. Identifying arsenic trioxide (ATO) functions in leukemia cells by using time series gene expression profiles.

    Science.gov (United States)

    Yang, Hong; Lin, Shan; Cui, Jingru

    2014-02-10

    Arsenic trioxide (ATO) is presently the most active single agent in the treatment of acute promyelocytic leukemia (APL). In order to explore the molecular mechanism of ATO in leukemia cells with time series, we adopted bioinformatics strategy to analyze expression changing patterns and changes in transcription regulation modules of time series genes filtered from Gene Expression Omnibus database (GSE24946). We totally screened out 1847 time series genes for subsequent analysis. The KEGG (Kyoto encyclopedia of genes and genomes) pathways enrichment analysis of these genes showed that oxidative phosphorylation and ribosome were the top 2 significantly enriched pathways. STEM software was employed to compare changing patterns of gene expression with assigned 50 expression patterns. We screened out 7 significantly enriched patterns and 4 tendency charts of time series genes. The result of Gene Ontology showed that functions of times series genes mainly distributed in profiles 41, 40, 39 and 38. Seven genes with positive regulation of cell adhesion function were enriched in profile 40, and presented the same first increased model then decreased model as profile 40. The transcription module analysis showed that they mainly involved in oxidative phosphorylation pathway and ribosome pathway. Overall, our data summarized the gene expression changes in ATO treated K562-r cell lines with time and suggested that time series genes mainly regulated cell adhesive. Furthermore, our result may provide theoretical basis of molecular biology in treating acute promyelocytic leukemia. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Enhanced urinary bladder and liver carcinogenesis in male CD1 mice exposed to transplacental inorganic arsenic and postnatal diethylstilbestrol or tamoxifen

    International Nuclear Information System (INIS)

    Waalkes, Michael P.; Liu Jie; Ward, Jerrold M.; Diwan, Bhalchandra A.

    2006-01-01

    Pregnant CD1 mice received 85 ppm arsenite in the drinking water from gestation day 8 to 18, groups (n = 35) of male offspring were subsequently injected on postpartum days 1 through 5 with diethylstilbestrol (DES; 2 μg/pup/day) or tamoxifen (TAM; 10 μg/pup/day), and tumor formation was assessed over 90 weeks. Arsenic alone increased hepatocellular carcinoma (14%), adenoma (23%) and total tumors (31%) compared to control (0, 2 and 2%, respectively). Arsenic alone also increased lung adenocarcinoma, adrenal cortical adenoma and renal cystic tubular hyperplasia compared to control. Compared to arsenic alone, arsenic plus DES increased liver tumor incidence in mice at risk 2.2-fold and increased liver tumor multiplicity (tumors/liver) 1.8-fold. The treatments alone did not impact urinary bladder carcinogenesis, but arsenic plus TAM significantly increased formation of urinary bladder transitional cell tumors (papilloma and carcinoma; 13%) compared to control (0%). Urinary bladder proliferative lesions (combined tumors and hyperplasia) were also increased by arsenic plus TAM (40%) or arsenic plus DES (43%) compared to control (0%) or the treatments alone. Urinary bladder proliferative lesions occurred in the absence of any evidence of uroepithelial cytotoxic lesions. Urinary bladder lesions and hepatocellular carcinoma induced by arsenic plus TAM and/or DES overexpressed estrogen receptor-α, indicating that aberrant estrogen signaling may have been a factor in the enhanced carcinogenic response. Thus, in male CD1 mice, gestational arsenic exposure alone induced liver adenoma and carcinoma, lung adenocarcinoma, adrenal adenoma and renal cystic hyperplasia. Furthermore, DES enhanced transplacental arsenic-induced hepatocarcinogenesis. In utero arsenic also initiated urinary bladder tumor formation when followed by postnatal TAM and uroepithelial proliferative lesions when followed by TAM or DES

  6. Effect of hexane extract of spinach in the removal of arsenic from rat

    Directory of Open Access Journals (Sweden)

    Badar Uddin Umar

    2007-03-01

    Full Text Available Extensive search is going on for a cheap, easily available and effective remedy of chronic arsenic poisoning. The present study was designed to find the effects of hexane extract of spinach in the removal of arsenic from arsenic treated rat. Rats were fed arsenic trioxide through Ryle’s tube for one month then they were fed on hexane extract (1-4% of spinach for another one month. Hexane extract of spinach decreased accumulated arsenic from rat liver, spleen, kidney, intestine, lungs and skin significantly. Besides, it reduced the oxidative stress caused by arsenic which was evident by decreased levels of malondialdehye (MDA in the above tissues. Hexane extract decreases both arsenic level and MDA level in rat tissues in dose dependent manner, which is more effective at lower doses.

  7. Effect of hexane extract of spinach in the removal of arsenic from rat

    Directory of Open Access Journals (Sweden)

    Badar Uddin Umar

    2007-06-01

    Full Text Available Extensive search is going on for a cheap, easily available and effective remedy of chronic arsenic poisoning. The present study was designed to find the effects of hexane extract of spinach in the removal of arsenic from arsenic treated rat. Rats were fed arsenic trioxide through Ryle’s tube for one month then they were fed on hexane extract (1-4% of spinach for another one month. Hexane extract of spinach decreased accumulated arsenic from rat liver, spleen, kidney, intestine, lungs and skin significantly. Besides, it reduced the oxidative stress caused by arsenic which was evident by decreased levels of malondialdehyde (MDA in the above tissues. Hexane extract decreases both arsenic level and MDA level in rat tissues in dose dependent manner, which is more effective at lower doses.

  8. Biomarkers of exposure, effect, and susceptibility of arsenic-induced health hazards in Taiwan

    International Nuclear Information System (INIS)

    Chen, C.-J.; Hsu, L.-I; Wang, C.-H.

    2005-01-01

    Long-term exposure to inorganic arsenic from drinking water has been documented to induce cancers and vascular diseases in a dose-response relationship. A series of molecular environmental epidemiological studies have been carried out to elucidate biomarkers of exposure, effect, and susceptibility for arsenic-related health hazards in Taiwan. Arsenic levels in urine, hair, and nail are biomarkers for short-term (<1 year) internal dose, skin hyperpigmentation and palmoplantar hyperkeratosis are for long-term (many years) internal dose, and percentage of monomethylarsonic acid in total metabolites of inorganic arsenic in urine may be considered as an exposure marker for biologically effective dose. The biomarkers of early biological effects of ingested inorganic arsenic included blood levels of reactive oxidants and anti-oxidant capacity, genetic expression of inflammatory molecules, as well as cytogenetic changes including sister chromatid exchange, micronuclei, and chromosome aberrations of peripheral lymphocytes. Both mutation type and hot spots of p53 gene were significantly different in arsenic-induced and non-arsenic-induced TCCs. The frequency of chromosomal imbalances analyzed by comparative genomic hybridization and the frequency of loss of heterozygosity were significantly higher in arsenic-induced TCC than non-arsenic-induced TCC at specific sites. Biomarkers of susceptibility to arsenic-induced health hazards included genetic polymorphisms of enzymes involved in xenobiotic metabolism, DNA repair, and oxidative stress, as well as serum level of carotenoids. Gene-gene and gene-environment interactions are involved in arsenic-induced health hazards through toxicological mechanisms including genomic instability and oxidative stress

  9. Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats

    International Nuclear Information System (INIS)

    Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen; Zhang, Jie; Shen, Heqing

    2017-01-01

    Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33 proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb cardiac contraction and relaxation, impair heart morphogenesis and development, and induce thrombosis in rats, which is mediated by the Akt/p38 MAPK signaling pathway. Overall, these findings will augment our knowledge of the involved mechanisms and develop useful biomarkers for cardiotoxicity induced by environmental arsenic exposure. - Highlights: • Arsenic exposure has been associated with a number of adverse health effects. • The molecular mechanisms involved in arsenic-induced cardiotoxicity remain unclear. • Differential proteins were identified in arsenic-exposed rat heart by proteomics. • Arsenic induces heart toxicity through the Akt/p38 MAPK signaling pathway. - Label-free quantitative proteomic analysis of rat heart reveals putative mechanisms and biomarkers for arsenic-induced cardiotoxicity.

  10. Carbon-enhanced inductively coupled plasma mass spectrometric detection of arsenic and selenium and its application to arsenic speciation

    DEFF Research Database (Denmark)

    Larsen, Erik Huusfeldt; Sturup, Stefan

    1994-01-01

    Addition of carbon as methanol or ammonium carbonate to the aqueous analyte solutions in combination with increased plasma power input enhanced the inductively coupled plasma mass spectrometry (ICP-MS) signal intensities of arsenic and selenium. In the presence of the optimum 3% v/v methanol...... (noise) was not increased. Therefore, the observed increase in analyte sensitivity led to a similar increase in signal-to-noise ratio. The addition of carbon as ammonium carbonate enhanced the arsenic signal by a similar factor but caused severe contamination of the ICP-MS instrument by carbon. In the 3....../nebulization efficiency. It is proposed that an increased population of carbon ions or carbon-containing ions in the plasma facilitates a more complete ionization of analytes lower in ionization energy than carbon itself. The enhanced detection power for arsenic was applied to arsenic speciation by high...

  11. Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

    International Nuclear Information System (INIS)

    Ren, Xuefeng; Gaile, Daniel P.; Gong, Zhihong; Qiu, Wenting; Ge, Yichen; Zhang, Chuanwu; Huang, Chenping; Yan, Hongtao; Olson, James R.; Kavanagh, Terrance J.; Wu, Hongmei

    2015-01-01

    Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is

  12. Arsenic responsive microRNAs in vivo and their potential involvement in arsenic-induced oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Xuefeng, E-mail: xuefengr@buffalo.edu [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Gaile, Daniel P. [Department of Biostatistics, School of Public Health and Health Professions, the State University of New York, Buffalo, NY 14214 (United States); Gong, Zhihong [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Qiu, Wenting [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Ge, Yichen [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Zhang, Chuanwu; Huang, Chenping; Yan, Hongtao [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Olson, James R. [Department of Epidemiology and Environmental Health, School of Public Health and Health Professions, The State University of New York, Buffalo, NY 14214 (United States); Department of Pharmacology and Toxicology, School of Biomedical Sciences, The State University of New York, Buffalo, NY 14214 (United States); Kavanagh, Terrance J. [Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98195 (United States); Wu, Hongmei, E-mail: hongmeiwwu@hotmail.com [School of Public Health, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China)

    2015-03-15

    Arsenic exposure is postulated to modify microRNA (miRNA) expression, leading to changes of gene expression and toxicities, but studies relating the responses of miRNAs to arsenic exposure are lacking, especially with respect to in vivo studies. We utilized high-throughput sequencing technology and generated miRNA expression profiles of liver tissues from Sprague Dawley (SD) rats exposed to various concentrations of sodium arsenite (0, 0.1, 1, 10 and 100 mg/L) for 60 days. Unsupervised hierarchical clustering analysis of the miRNA expression profiles clustered the SD rats into different groups based on the arsenic exposure status, indicating a highly significant association between arsenic exposure and cluster membership (p-value of 0.0012). Multiple miRNA expressions were altered by arsenic in an exposure concentration-dependent manner. Among the identified arsenic-responsive miRNAs, several are predicted to target Nfe2l2-regulated antioxidant genes, including glutamate–cysteine ligase (GCL) catalytic subunit (GCLC) and modifier subunit (GCLM) which are involved in glutathione (GSH) synthesis. Exposure to low concentrations of arsenic increased mRNA expression for Gclc and Gclm, while high concentrations significantly reduced their expression, which were correlated to changes in hepatic GCL activity and GSH level. Moreover, our data suggested that other mechanisms, e.g., miRNAs, rather than Nfe2l2-signaling pathway, could be involved in the regulation of mRNA expression of Gclc and Gclm post-arsenic exposure in vivo. Together, our findings show that arsenic exposure disrupts the genome-wide expression of miRNAs in vivo, which could lead to the biological consequence, such as an altered balance of antioxidant defense and oxidative stress. - Highlights: • Chronic arsenic exposure induces changes of hepatic miRNA expression profiles. • Hepatic GCL activity and GSH level in rats are altered following arsenic exposure. • Arsenic induced GCL expression change is

  13. Arsenic-induced cutaneous hyperplastic lesions are associated with the dysregulation of Yap, a Hippo signaling-related protein

    International Nuclear Information System (INIS)

    Li, Changzhao; Srivastava, Ritesh K.; Elmets, Craig A.; Afaq, Farrukh; Athar, Mohammad

    2013-01-01

    Highlights: •Arsenic activates canonical Hippo signaling pathway and up-regulates αCatenin in the skin. •Arsenic activates transcriptional activity of Yap by its nuclear translocation. •Yap is involved in the disruption of tight/adherens junctions in arsenic-exposed animals. -- Abstract: Arsenic exposure in humans causes a number of toxic manifestations in the skin including cutaneous neoplasm. However, the mechanism of these alterations remains elusive. Here, we provide novel observations that arsenic induced Hippo signaling pathway in the murine skin. This pathway plays crucial roles in determining organ size during the embryonic development and if aberrantly activated in adults, contributes to the pathogenesis of epithelial neoplasm. Arsenic treatment enhanced phosphorylation-dependent activation of LATS1 kinase and other Hippo signaling regulatory proteins Sav1 and MOB1. Phospho-LATS kinase is known to catalyze the inactivation of a transcriptional co-activator, Yap. However, in arsenic-treated epidermis, we did not observed its inactivation. Thus, as expected, unphosphorylated-Yap was translocated to the nucleus in arsenic-treated epidermis. Yap by binding to the transcription factors TEADs induces transcription of its target genes. Consistently, an up-regulation of Yap-dependent target genes Cyr61, Gli2, Ankrd1 and Ctgf was observed in the skin of arsenic-treated mice. Phosphorylated Yap is important in regulating tight and adherens junctions through its binding to αCatenin. We found disruption of these junctions in the arsenic-treated mouse skin despite an increase in αCatenin. These data provide evidence that arsenic-induced canonical Hippo signaling pathway and Yap-mediated disruption of tight and adherens junctions are independently regulated. These effects together may contribute to the carcinogenic effects of arsenic in the skin

  14. Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J., E-mail: tokare@niehs.nih.gov

    2015-07-01

    Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

  15. Reduction of arsenite-enhanced ultraviolet radiation-induced DNA damage by supplemental zinc

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, Karen L.; King, Brenee S.; Sandoval, Monica M.; Liu, Ke Jian; Hudson, Laurie G., E-mail: lhudson@salud.unm.edu

    2013-06-01

    Arsenic is a recognized human carcinogen and there is evidence that arsenic augments the carcinogenicity of DNA damaging agents such as ultraviolet radiation (UVR) thereby acting as a co-carcinogen. Inhibition of DNA repair is one proposed mechanism to account for the co-carcinogenic actions of arsenic. We and others find that arsenite interferes with the function of certain zinc finger DNA repair proteins. Furthermore, we reported that zinc reverses the effects of arsenite in cultured cells and a DNA repair target protein, poly (ADP-ribose) polymerase-1. In order to determine whether zinc ameliorates the effects of arsenite on UVR-induced DNA damage in human keratinocytes and in an in vivo model, normal human epidermal keratinocytes and SKH-1 hairless mice were exposed to arsenite, zinc or both before solar-simulated (ss) UVR exposure. Poly (ADP-ribose) polymerase activity, DNA damage and mutation frequencies at the Hprt locus were measured in each treatment group in normal human keratinocytes. DNA damage was assessed in vivo by immunohistochemical staining of skin sections isolated from SKH-1 hairless mice. Cell-based findings demonstrate that ssUVR-induced DNA damage and mutagenesis are enhanced by arsenite, and supplemental zinc partially reverses the arsenite effect. In vivo studies confirm that zinc supplementation decreases arsenite-enhanced DNA damage in response to ssUVR exposure. From these data we can conclude that zinc offsets the impact of arsenic on ssUVR-stimulated DNA damage in cells and in vivo suggesting that zinc supplementation may provide a strategy to improve DNA repair capacity in arsenic exposed human populations. - Highlights: • Low levels of arsenite enhance UV-induced DNA damage in human keratinocytes. • UV-initiated HPRT mutation frequency is enhanced by arsenite. • Zinc supplementation offsets DNA damage and mutation frequency enhanced by arsenite. • Zinc-dependent reduction of arsenite enhanced DNA damage is confirmed in vivo.

  16. Protective effect of nitric oxide against arsenic-induced oxidative ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-03-15

    Mar 15, 2010 ... 1Department of Soil and Water Science, College of Resources and Environment, ... alleviated arsenic-induced electrolyte leakage and malondiadehyde (MDA) content in ..... gene construct for environmental arsenic detection.

  17. Arsenic downregulates tight junction claudin proteins through p38 and NF-κB in intestinal epithelial cell line, HT-29

    International Nuclear Information System (INIS)

    Jeong, Chang Hee; Seok, Jin Sil; Petriello, Michael C.; Han, Sung Gu

    2017-01-01

    Arsenic is a naturally occurring metalloid that often is found in foods and drinking water. Human exposure to arsenic is associated with the development of gastrointestinal problems such as fluid loss, diarrhea and gastritis. Arsenic is also known to induce toxic responses including oxidative stress in cells of the gastrointestinal track. Tight junctions (TJs) regulate paracellular permeability and play a barrier role by inhibiting the movement of water, solutes and microorganisms in the paracellular space. Since oxidative stress and TJ damage are known to be associated, we examined whether arsenic produces TJ damage such as downregulation of claudins in the human colorectal cell line, HT-29. To confirm the importance of oxidative stress in arsenic-induced TJ damage, effects of the antioxidant compound (e.g., N-acetylcysteine (NAC)) were also determined in cells. HT-29 cells were treated with arsenic trioxide (40 μM, 12 h) to observe the modified expression of TJ proteins. Arsenic decreased expression of TJ proteins (i.e., claudin-1 and claudin-5) and transepithelial electrical resistance (TEER) whereas pretreatment of NAC (5–10 mM, 1 h) attenuated the observed claudins downregulation and TEER. Arsenic treatment produced cellular oxidative stress via superoxide generation and lowering glutathione (GSH) levels, while NAC restored cellular GSH levels and decreased oxidative stress. Arsenic increased phosphorylation of p38 and nuclear translocation of nuclear factor-kappa B (NF-κB) p65, while NAC attenuated these intracellular events. Results demonstrated that arsenic can damage intestinal epithelial cells by proinflammatory process (oxidative stress, p38 and NF-κB) which resulted in the downregulation of claudins and NAC can protect intestinal TJs from arsenic toxicity.

  18. Oligofructose protects against arsenic-induced liver injury in a model of environment/obesity interaction

    Energy Technology Data Exchange (ETDEWEB)

    Massey, Veronica L. [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Stocke, Kendall S. [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Schmidt, Robin H.; Tan, Min [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Ajami, Nadim [Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX (United States); Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX (United States); Neal, Rachel E. [Department of Environmental and Occupational Health Sciences, School of Public Health, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Petrosino, Joseph F. [Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX (United States); Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, TX (United States); Barve, Shirish [Department of Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States); Arteel, Gavin E., E-mail: gavin.arteel@louisville.edu [Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, KY 40292 (United States)

    2015-05-01

    Arsenic (As) tops the ATSDR list of hazardous environmental chemicals and is known to cause liver injury. Although the concentrations of As found in the US water supply are generally too low to directly damage the liver, subhepatotoxic doses of As sensitize the liver to experimental NAFLD. It is now suspected that GI microbiome dysbiosis plays an important role in development of NALFD. Importantly, arsenic has also been shown to alter the microbiome. The purpose of the current study was to test the hypothesis that the prebiotic oligofructose (OFC) protects against enhanced liver injury caused by As in experimental NAFLD. Male C57Bl6/J mice were fed low fat diet (LFD), high fat diet (HFD), or HFD containing oligofructose (OFC) during concomitant exposure to either tap water or As-containing water (4.9 ppm as sodium arsenite) for 10 weeks. HFD significantly increased body mass and caused fatty liver injury, as characterized by an increased liver weight-to-body weight ratio, histologic changes and transaminases. As observed previously, As enhanced HFD-induced liver damage, which was characterized by enhanced inflammation. OFC supplementation protected against the enhanced liver damage caused by As in the presence of HFD. Interestingly, arsenic, HFD and OFC all caused unique changes to the gut flora. These data support previous findings that low concentrations of As enhance liver damage caused by high fat diet. Furthermore, these results indicate that these effects of arsenic may be mediated, at least in part, by GI tract dysbiosis and that prebiotic supplementation may confer significant protective effects. - Highlights: • Arsenic (As) enhances liver damage caused by a high-fat (HFD) diet in mice. • Oligofructose protects against As-enhanced liver damage caused by HFD. • As causes dysbiosis in the GI tract and exacerbates the dysbiosis caused by HFD. • OFC prevents the dysbiosis caused by HFD and As, increasing commensal bacteria.

  19. Oligofructose protects against arsenic-induced liver injury in a model of environment/obesity interaction

    International Nuclear Information System (INIS)

    Massey, Veronica L.; Stocke, Kendall S.; Schmidt, Robin H.; Tan, Min; Ajami, Nadim; Neal, Rachel E.; Petrosino, Joseph F.; Barve, Shirish; Arteel, Gavin E.

    2015-01-01

    Arsenic (As) tops the ATSDR list of hazardous environmental chemicals and is known to cause liver injury. Although the concentrations of As found in the US water supply are generally too low to directly damage the liver, subhepatotoxic doses of As sensitize the liver to experimental NAFLD. It is now suspected that GI microbiome dysbiosis plays an important role in development of NALFD. Importantly, arsenic has also been shown to alter the microbiome. The purpose of the current study was to test the hypothesis that the prebiotic oligofructose (OFC) protects against enhanced liver injury caused by As in experimental NAFLD. Male C57Bl6/J mice were fed low fat diet (LFD), high fat diet (HFD), or HFD containing oligofructose (OFC) during concomitant exposure to either tap water or As-containing water (4.9 ppm as sodium arsenite) for 10 weeks. HFD significantly increased body mass and caused fatty liver injury, as characterized by an increased liver weight-to-body weight ratio, histologic changes and transaminases. As observed previously, As enhanced HFD-induced liver damage, which was characterized by enhanced inflammation. OFC supplementation protected against the enhanced liver damage caused by As in the presence of HFD. Interestingly, arsenic, HFD and OFC all caused unique changes to the gut flora. These data support previous findings that low concentrations of As enhance liver damage caused by high fat diet. Furthermore, these results indicate that these effects of arsenic may be mediated, at least in part, by GI tract dysbiosis and that prebiotic supplementation may confer significant protective effects. - Highlights: • Arsenic (As) enhances liver damage caused by a high-fat (HFD) diet in mice. • Oligofructose protects against As-enhanced liver damage caused by HFD. • As causes dysbiosis in the GI tract and exacerbates the dysbiosis caused by HFD. • OFC prevents the dysbiosis caused by HFD and As, increasing commensal bacteria

  20. Pathogenesis and treatment of leukemia: an Asian perspective.

    Science.gov (United States)

    Kwong, Yok-Lam

    2012-03-01

    Leukemias occur worldwide, but there are important geographic differences in incidences. Three leukemias with special Asian perspectives, acute promyelocytic leukemia (APL), T-cell large granular lymphocyte (T-LGL) leukemia and NK-cell leukemia. In APL, China has made contributions in discovering the efficacy of all-trans retinoic acid (ATRA) and arsenic trioxide. Some APL patients are potentially curable after treatment with ATRA or arsenic trioxide as a single agent. Combined treatment of APL with ATRA and arsenic trioxide induces remission with deeper molecular response. An oral formulation of arsenic trioxide is available, making outpatient treatment feasible. Future regimens for APL should examine how ATRA and arsenic trioxide can be optimally combined with other synergistic drugs. Asian patients with T-LGL leukemia present more frequently with pure red cell aplasia, but less frequently with neutropenia, recurrent infection, splenomegaly and rheumatoid arthritis as compared with Western patients. These differences have potential effects on treatment and disease pathogenesis. NK-cell leukemia is rapidly fatal and occurs almost exclusively in Asian and South American patients. Conventional anthracycline-based chemotherapy designed for B-cell lymphomas do not work in NK-cell leukemias. Novel therapeutic approaches targeting cellular signaling pathways or preferentially upregulated genes are needed to improve outcome.

  1. Specific histone modification responds to arsenic-induced oxidative stress

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Lu [Department of Toxicology, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou (China); Li, Jun [Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, Guizhou (China); Zhan, Zhengbao; Chen, Liping; Li, Daochuan; Bai, Qing; Gao, Chen; Li, Jie; Zeng, Xiaowen; He, Zhini; Wang, Shan; Xiao, Yongmei [Department of Toxicology, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou (China); Chen, Wen, E-mail: chenwen@mail.sysu.edu.cn [Department of Toxicology, Guangzhou Key Laboratory of Environmental Pollution and Health Risk Assessment, School of Public Health, Sun Yat-sen University, Guangzhou (China); Zhang, Aihua, E-mail: aihuagzykd@163.com [Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang, Guizhou (China)

    2016-07-01

    To explore whether specific histone modifications are associated with arsenic-induced oxidative damage, we recruited 138 arsenic-exposed and arsenicosis subjects from Jiaole Village, Xinren County of Guizhou province, China where the residents were exposed to arsenic from indoor coal burning. 77 villagers from Shang Batian Village that were not exposed to high arsenic coal served as the control group. The concentrations of urine and hair arsenic in the arsenic-exposure group were 2.4-fold and 2.1-fold (all P < 0.001) higher, respectively, than those of the control group. Global histone modifications in human peripheral lymphocytes (PBLCs) were examined by ELISA. The results showed that altered global levels of H3K18ac, H3K9me2, and H3K36me3 correlated with both urinary and hair-arsenic levels of the subjects. Notably, H3K36me3 and H3K18ac modifications were associated with urinary 8-OHdG (H3K36me3: β = 0.16; P = 0.042, H3K18ac: β = − 0.24; P = 0.001). We also found that the modifications of H3K18ac and H3K36me3 were enriched in the promoters of oxidative stress response (OSR) genes in human embryonic kidney (HEK) cells and HaCaT cells, providing evidence that H3K18ac and H3K36me3 modifications mediate transcriptional regulation of OSR genes in response to NaAsO{sub 2} treatment. Particularly, we found that reduced H3K18ac modification correlated with suppressed expression of OSR genes in HEK cells with long term arsenic treatment and in PBLCs of all the subjects. Taken together, we reveal a critical role for specific histone modification in response to arsenic-induced oxidative damage. - Highlights: • H3K18ac, H3K9me2 and H3K36me3 were associated with arsenic exposed levels. • H3K18ac and H3K36me3 were correlated with oxidative damage induced by arsenic. • H3K18ac and H3K36me3 might involve in transcriptional regulation of OSR genes. • Dysregulation of H3K18ac and H3K36me3 might be biomarkers of arsenic toxicity.

  2. Specific histone modification responds to arsenic-induced oxidative stress

    International Nuclear Information System (INIS)

    Ma, Lu; Li, Jun; Zhan, Zhengbao; Chen, Liping; Li, Daochuan; Bai, Qing; Gao, Chen; Li, Jie; Zeng, Xiaowen; He, Zhini; Wang, Shan; Xiao, Yongmei; Chen, Wen; Zhang, Aihua

    2016-01-01

    To explore whether specific histone modifications are associated with arsenic-induced oxidative damage, we recruited 138 arsenic-exposed and arsenicosis subjects from Jiaole Village, Xinren County of Guizhou province, China where the residents were exposed to arsenic from indoor coal burning. 77 villagers from Shang Batian Village that were not exposed to high arsenic coal served as the control group. The concentrations of urine and hair arsenic in the arsenic-exposure group were 2.4-fold and 2.1-fold (all P < 0.001) higher, respectively, than those of the control group. Global histone modifications in human peripheral lymphocytes (PBLCs) were examined by ELISA. The results showed that altered global levels of H3K18ac, H3K9me2, and H3K36me3 correlated with both urinary and hair-arsenic levels of the subjects. Notably, H3K36me3 and H3K18ac modifications were associated with urinary 8-OHdG (H3K36me3: β = 0.16; P = 0.042, H3K18ac: β = − 0.24; P = 0.001). We also found that the modifications of H3K18ac and H3K36me3 were enriched in the promoters of oxidative stress response (OSR) genes in human embryonic kidney (HEK) cells and HaCaT cells, providing evidence that H3K18ac and H3K36me3 modifications mediate transcriptional regulation of OSR genes in response to NaAsO 2 treatment. Particularly, we found that reduced H3K18ac modification correlated with suppressed expression of OSR genes in HEK cells with long term arsenic treatment and in PBLCs of all the subjects. Taken together, we reveal a critical role for specific histone modification in response to arsenic-induced oxidative damage. - Highlights: • H3K18ac, H3K9me2 and H3K36me3 were associated with arsenic exposed levels. • H3K18ac and H3K36me3 were correlated with oxidative damage induced by arsenic. • H3K18ac and H3K36me3 might involve in transcriptional regulation of OSR genes. • Dysregulation of H3K18ac and H3K36me3 might be biomarkers of arsenic toxicity.

  3. Airborne arsenic and urinary excretion of arsenic metabolites during boiler cleaning operations in a Slovak coal-fired power plant

    Energy Technology Data Exchange (ETDEWEB)

    Yager, J.W.; Hicks, J.B.; Fabianova, N. [EPRI, Palo Alto, CA (United States). Environment Group

    1997-08-01

    Little information is available on the relationship between occupational exposure to inorganic arsenic in coal fly ash and urinary excretion of arsenic metabolites. This study was undertaken in a coal-fired power plant in Slovakia during a routine maintenance outage. Arsenic was measured in the breathing zone of workers during 5 consecutive workdays, and urine samples were obtained for analysis of arsenic metabolites-inorganic arsenic (As), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) prior to the start of each shift. Results from a small number of cascade impacter air samples indicated that approximately 90% of total particle mass and arsenic was present in particle size fractions {ge} 3.5 {mu}m. The 8-hr time-weighted average (TWA) mean arsenic air concentration was 48.3 {mu}g/m{sup 3} (range 0.17-375.2) and the mean sum of urinary arsenic (Sigma As) metabolites was 16.9 {mu}g As/g creatinine (range 2.6-50.8). For an 8-hr TWA of 10 {mu}g/m{sup 3} arsenic from coal fly ash, the predicted mean concentration f the Sigma As urinary metabolites was 13.2 {mu}g As/g creatinine. Comparisons with previously published studies of exposure to arsenic trioxide vapors and dusts in copper smelters suggest that bioavailability of arsenic from airborne coal fly ash (as indicated by urinary excretion) is about one-third that seen in smelters and similar settings. Arsenic compound characteristics, matrix composition, and particle size distribution probably play major roles in determining actual uptake of airborne arsenic.

  4. IDENTIFICATION OF INTERSPECIES CONCORDANCE OF MECHANISMS OF ARSENIC INDUCED BLADDER CANCER BY GENE EXPRESSION.

    Science.gov (United States)

    Arsenic is a human carcinogen that induces urinary bladder cancer. Several mechanisms have been proposed for arsenic-induced cancer. Although inorganic arsenic (iAs) does not induce tumors in adult rodents, dimethylarsinic acid (DMA), a major metabolite of iAs, is a rat bladder c...

  5. Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism

    International Nuclear Information System (INIS)

    Dheer, Rishu; Patterson, Jena; Dudash, Mark; Stachler, Elyse N.; Bibby, Kyle J.; Stolz, Donna B.; Shiva, Sruti; Wang, Zeneng; Hazen, Stanley L.; Barchowsky, Aaron; Stolz, John F.

    2015-01-01

    Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogenesis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10 weeks to 0, 10 (low) or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes. - Highlights: • Arsenic exposure induces changes in host and host nitrogen metabolism that cause progresive change in the microbiome. • A polyphasic approach reveals changes

  6. Arsenic induces structural and compositional colonic microbiome change and promotes host nitrogen and amino acid metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Dheer, Rishu; Patterson, Jena; Dudash, Mark [Department of Biological Sciences, Duquesne University, Pittsburgh, PA 15282 (United States); Stachler, Elyse N.; Bibby, Kyle J. [Department of Civil and Environmental Engineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA 15261 (United States); Stolz, Donna B. [Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261 (United States); Shiva, Sruti [Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh 15261 (United States); Vascular Medicine Institute, University of Pittsburgh, Pittsburgh 15261 (United States); Wang, Zeneng; Hazen, Stanley L. [Department of Cellular and Molecular Medicine, Cleveland Clinic Lerner Research Institute, Cleveland, OH 44195 (United States); Barchowsky, Aaron, E-mail: aab20@pitt.edu [Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh 15261 (United States); Vascular Medicine Institute, University of Pittsburgh, Pittsburgh 15261 (United States); Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA 15219 (United States); Stolz, John F. [Department of Biological Sciences, Duquesne University, Pittsburgh, PA 15282 (United States)

    2015-12-15

    Chronic exposure to arsenic in drinking water causes cancer and non-cancer diseases. However, mechanisms for chronic arsenic-induced pathogenesis, especially in response to lower exposure levels, are unclear. In addition, the importance of health impacts from xeniobiotic-promoted microbiome changes is just being realized and effects of arsenic on the microbiome with relation to disease promotion are unknown. To investigate impact of arsenic exposure on both microbiome and host metabolism, the stucture and composition of colonic microbiota, their metabolic phenotype, and host tissue and plasma metabolite levels were compared in mice exposed for 2, 5, or 10 weeks to 0, 10 (low) or 250 (high) ppb arsenite (As(III)). Genotyping of colonic bacteria revealed time and arsenic concentration dependent shifts in community composition, particularly the Bacteroidetes and Firmicutes, relative to those seen in the time-matched controls. Arsenic-induced erosion of bacterial biofilms adjacent to the mucosal lining and changes in the diversity and abundance of morphologically distinct species indicated changes in microbial community structure. Bacterical spores increased in abundance and intracellular inclusions decreased with high dose arsenic. Interestingly, expression of arsenate reductase (arsA) and the As(III) exporter arsB, remained unchanged, while the dissimilatory nitrite reductase (nrfA) gene expression increased. In keeping with the change in nitrogen metabolism, colonic and liver nitrite and nitrate levels and ratios changed with time. In addition, there was a concomitant increase in pathogenic arginine metabolites in the mouse circulation. These data suggest that arsenic exposure impacts the microbiome and microbiome/host nitrogen metabolism to support disease enhancing pathogenic phenotypes. - Highlights: • Arsenic exposure induces changes in host and host nitrogen metabolism that cause progresive change in the microbiome. • A polyphasic approach reveals changes

  7. Arsenic toxicity induced endothelial dysfunction and dementia: Pharmacological interdiction by histone deacetylase and inducible nitric oxide synthase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Bhupesh, E-mail: drbhupeshresearch@gmail.com; Sharma, P.M.

    2013-11-15

    Arsenic toxicity has been reported to damage all the major organs including the brain and vasculature. Dementia including Alzheimer's disease (AD) and vascular dementia (VaD) are posing greater risk to the world population as it is now increasing at a faster rate. We have investigated the role of sodium butyrate, a selective histone deacetylase (HDAC) inhibitor and aminoguanidine, a selective inducible nitric oxide synthase (iNOS) inhibitor in pharmacological interdiction of arsenic toxicity induced vascular endothelial dysfunction and dementia in rats. Arsenic toxicity was done by administering arsenic drinking water to rats. Morris water-maze (MWM) test was used for assessment of learning and memory. Endothelial function was assessed using student physiograph. Oxidative stress (aortic superoxide anion, serum and brain thiobarbituric acid reactive species, brain glutathione) and nitric oxide levels (serum nitrite/nitrate) were also measured. Arsenic treated rats have shown impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate and brain GSH levels along with increase in serum and brain TBARS. Sodium butyrate as well as aminoguanidine significantly convalesce arsenic induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that arsenic induces endothelial dysfunction and dementia, whereas, sodium butyrate, a HDAC inhibitor as well as aminoguanidine, a selective iNOS inhibitor may be considered as potential agents for the management of arsenic induced endothelial dysfunction and dementia. - Highlights: • As has induced endothelial dysfunction (Edf) and vascular dementia (VaD). • As has increased oxidative stress, AChE activity and decreased serum NO. • Inhibitors of HDAC and iNOS have attenuated As induced Edf and VaD. • Both the inhibitors have attenuated As induced biochemical changes. • Inhibitor of HDAC and iNOS has shown good potential

  8. Arsenic toxicity induced endothelial dysfunction and dementia: Pharmacological interdiction by histone deacetylase and inducible nitric oxide synthase inhibitors

    International Nuclear Information System (INIS)

    Sharma, Bhupesh; Sharma, P.M.

    2013-01-01

    Arsenic toxicity has been reported to damage all the major organs including the brain and vasculature. Dementia including Alzheimer's disease (AD) and vascular dementia (VaD) are posing greater risk to the world population as it is now increasing at a faster rate. We have investigated the role of sodium butyrate, a selective histone deacetylase (HDAC) inhibitor and aminoguanidine, a selective inducible nitric oxide synthase (iNOS) inhibitor in pharmacological interdiction of arsenic toxicity induced vascular endothelial dysfunction and dementia in rats. Arsenic toxicity was done by administering arsenic drinking water to rats. Morris water-maze (MWM) test was used for assessment of learning and memory. Endothelial function was assessed using student physiograph. Oxidative stress (aortic superoxide anion, serum and brain thiobarbituric acid reactive species, brain glutathione) and nitric oxide levels (serum nitrite/nitrate) were also measured. Arsenic treated rats have shown impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate and brain GSH levels along with increase in serum and brain TBARS. Sodium butyrate as well as aminoguanidine significantly convalesce arsenic induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that arsenic induces endothelial dysfunction and dementia, whereas, sodium butyrate, a HDAC inhibitor as well as aminoguanidine, a selective iNOS inhibitor may be considered as potential agents for the management of arsenic induced endothelial dysfunction and dementia. - Highlights: • As has induced endothelial dysfunction (Edf) and vascular dementia (VaD). • As has increased oxidative stress, AChE activity and decreased serum NO. • Inhibitors of HDAC and iNOS have attenuated As induced Edf and VaD. • Both the inhibitors have attenuated As induced biochemical changes. • Inhibitor of HDAC and iNOS has shown good potential in

  9. The potential biological mechanisms of arsenic-induced diabetes mellitus

    International Nuclear Information System (INIS)

    Tseng, C.-H.

    2004-01-01

    Although epidemiologic studies carried out in Taiwan, Bangladesh, and Sweden have demonstrated a diabetogenic effect of arsenic, the mechanisms remain unclear and require further investigation. This paper reviewed the potential biological mechanisms of arsenic-induced diabetes mellitus based on the current knowledge of the biochemical properties of arsenic. Arsenate can substitute phosphate in the formation of adenosine triphosphate (ATP) and other phosphate intermediates involved in glucose metabolism, which could theoretically slow down the normal metabolism of glucose, interrupt the production of energy, and interfere with the ATP-dependent insulin secretion. However, the concentration of arsenate required for such reaction is high and not physiologically relevant, and these effects may only happen in acute intoxication and may not be effective in subjects chronically exposed to low-dose arsenic. On the other hand, arsenite has high affinity for sulfhydryl groups and thus can form covalent bonds with the disulfide bridges in the molecules of insulin, insulin receptors, glucose transporters (GLUTs), and enzymes involved in glucose metabolism (e.g., pyruvate dehydrogenase and α-ketoglutarate dehydrogenase). As a result, the normal functions of these molecules can be hampered. However, a direct effect on these molecules caused by arsenite at physiologically relevant concentrations seems unlikely. Recent evidence has shown that treatment of arsenite at lower and physiologically relevant concentrations can stimulate glucose transport, in contrary to an inhibitory effect exerted by phenylarsine oxide (PAO) or by higher doses of arsenite. Induction of oxidative stress and interferences in signal transduction or gene expression by arsenic or by its methylated metabolites are the most possible causes to arsenic-induced diabetes mellitus through mechanisms of induction of insulin resistance and β cell dysfunction. Recent studies have shown that, in subjects with chronic

  10. Neuroprotective efficacy of curcumin in arsenic induced cholinergic dysfunctions in rats.

    Science.gov (United States)

    Yadav, Rajesh S; Chandravanshi, Lalit P; Shukla, Rajendra K; Sankhwar, Madhu L; Ansari, Reyaz W; Shukla, Pradeep K; Pant, Aditya B; Khanna, Vinay K

    2011-12-01

    Our recent studies have shown that curcumin protects arsenic induced neurotoxicity by modulating oxidative stress, neurotransmitter levels and dopaminergic system in rats. As chronic exposure to arsenic has been associated with cognitive deficits in humans, the present study has been carried out to implore the neuroprotective potential of curcumin in arsenic induced cholinergic dysfunctions in rats. Rats treated with arsenic (sodium arsenite, 20mg/kg body weight, p.o., 28 days) exhibited a significant decrease in the learning activity, assessed by passive avoidance response associated with decreased binding of (3)H-QNB, known to label muscarinic-cholinergic receptors in hippocampus (54%) and frontal cortex (27%) as compared to controls. Decrease in the activity of acetylcholinesterase in hippocampus (46%) and frontal cortex (33%), staining of Nissl body, immunoreactivity of choline acetyltransferase (ChAT) and expression of ChAT protein in hippocampal region was also observed in arsenic treated rats as compared to controls. Simultaneous treatment with arsenic and curcumin (100mg/kg body weight, p.o., 28 days) increased learning and memory performance associated with increased binding of (3)H-QNB in hippocampus (54%), frontal cortex (25%) and activity of acetylcholinesterase in hippocampus (41%) and frontal cortex (29%) as compared to arsenic treated rats. Increase in the expression of ChAT protein, immunoreactivity of ChAT and staining of Nissl body in hippocampal region was also observed in rats simultaneously treated with arsenic and curcumin as compared to those treated with arsenic alone. The results of the present study suggest that curcumin significantly modulates arsenic induced cholinergic dysfunctions in brain and also exhibits neuroprotective efficacy of curcumin. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Combination of siRNA-directed Kras oncogene silencing and arsenic-induced apoptosis using a nanomedicine strategy for the effective treatment of pancreatic cancer.

    Science.gov (United States)

    Zeng, Linjuan; Li, Jingguo; Wang, Yong; Qian, Chenchen; Chen, Yinting; Zhang, Qiubo; Wu, Wei; Lin, Zhong; Liang, Jianzhong; Shuai, Xintao; Huang, Kaihong

    2014-02-01

    The synergetic inhibitory effects on human pancreatic cancer by nanoparticle-mediated siRNA and arsenic therapy were investigated both in vitro and in vivo. Poly(ethylene glycol)-block-poly(L-lysine) were prepared to form siRNA-complexed polyplex and poly(ethylene glycol)-block-poly(DL-lactide) were prepared to form arsenic-encapsulated vesicle, respectively. Down-regulation of the mutant Kras gene by siRNA caused defective abilities of proliferation, clonal formation, migration, and invasion of pancreatic cancer cells, as well as cell cycle arrest at the G0/G1 phase, which substantially enhanced the apoptosis-inducing effect of arsenic administration. Consequently, co-administration of the two nanomedicines encapsulating siRNA or arsenic showed ideal tumor growth inhibition both in vitro and in vivo as a result of synergistic effect of the siRNA-directed Kras oncogene silencing and arsenic-induced cell apoptosis. These results suggest that the combination of mutant Kras gene silencing and arsenic therapy using nanoparticle-mediated delivery strategy is promising for pancreatic cancer treatment. Treatment of pancreatic cancer remains a major challenge. These authors demonstrate a method that combines a siRNA-based Kras silencing with arsenic delivery to pancreatic cancer cells using nanoparticles, resulting in enhanced apoptosis induction in the treated cells. © 2013.

  12. Arsenic-induced oxidative myocardial injury: protective role of arjunolic acid

    Energy Technology Data Exchange (ETDEWEB)

    Manna, Prasenjit; Sinha, Mahua; Sil, Parames C. [Bose Institute, Department of Chemistry, Kolkata, West Bengal (India)

    2008-03-15

    Arsenic, one of the most harmful metalloids, is ubiquitous in the environment. The present study has been carried out to investigate the protective role of a triterpenoid saponin, arjunolic acid (AA) against arsenic-induced cardiac oxidative damage. In the study, NaAsO{sub 2} was chosen as the source of arsenic. The free radical scavenging activity and the effect of AA on the intracellular antioxidant power were determined from its 2,2-diphenyl-1-picryl hydrazyl radical scavenging ability and ferric reducing/antioxidant power assay, respectively. Oral administration of NaAsO{sub 2} at a dose of 10 mg/kg body weight for 2 days caused significant accumulation of arsenic in cardiac tissues of the experimental mice in association with the reduction in cardiac antioxidant enzymes activities, namely superoxide dismutase, catalase, glutathione-S-transferase, glutathione reductase and glutathione peroxidase. Arsenic intoxication also decreased the cardiac glutathione (GSH) and total thiol contents and increased the levels of oxidized glutathione (GSSG), lipid peroxidation end products and protein carbonyl content. Treatment with AA at a dose of 20 mg/kg body weight for 4 days prior to NaAsO{sub 2} intoxication protected the cardiac tissue from arsenic-induced oxidative impairment. In addition to oxidative stress, arsenic administration increased total cholesterol level as well as the reduced high-density lipoprotein cholesterol level in the sera of the experimental mice. AA pretreatment, however, could prevent this hyperlipidemia. Histological studies on the ultrastructural changes in cardiac tissue supported the protective activity of AA also. Combining all, results suggest that AA could protect cardiac tissues against arsenic-induced oxidative stress probably due to its antioxidant property. (orig.)

  13. Arsenic-induced alteration in intracellular calcium homeostasis induces head kidney macrophage apoptosis involving the activation of calpain-2 and ERK in Clarias batrachus

    International Nuclear Information System (INIS)

    Banerjee, Chaitali; Goswami, Ramansu; Datta, Soma; Rajagopal, R.; Mazumder, Shibnath

    2011-01-01

    We had earlier shown that exposure to arsenic (0.50 μM) caused caspase-3 mediated head kidney macrophage (HKM) apoptosis involving the p38-JNK pathway in Clarias batrachus. Here we examined the roles of calcium (Ca 2+ ) and extra-cellular signal-regulated protein kinase (ERK), the other member of MAPK-pathway on arsenic-induced HKM apoptosis. Arsenic-induced HKM apoptosis involved increased expression of ERK and calpain-2. Nifedipine, verapamil and EGTA pre-treatment inhibited the activation of calpain-2, ERK and reduced arsenic-induced HKM apoptosis as evidenced from reduced caspase-3 activity, Annexin V-FITC-propidium iodide and Hoechst 33342 staining. Pre-incubation with ERK inhibitor U 0126 inhibited the activation of calpain-2 and interfered with arsenic-induced HKM apoptosis. Additionally, pre-incubation with calpain-2 inhibitor also interfered with the activation of ERK and inhibited arsenic-induced HKM apoptosis. The NADPH oxidase inhibitor apocynin and diphenyleneiodonium chloride also inhibited ERK activation indicating activation of ERK in arsenic-exposed HKM also depends on signals from NADPH oxidase pathway. Our study demonstrates the critical role of Ca 2+ homeostasis on arsenic-induced HKM apoptosis. We suggest that arsenic-induced alteration in intracellular Ca 2+ levels initiates pro-apoptotic ERK and calpain-2; the two pathways influence each other positively and induce caspase-3 mediated HKM apoptosis. Besides, our study also indicates the role of ROS in the activation of ERK pathway in arsenic-induced HKM apoptosis in C. batrachus. - Highlights: → Altered Ca 2+ homeostasis leads to arsenic-induced HKM apoptosis. → Calpain-2 plays a critical role in the process. → ERK is pro-apoptotic in arsenic-induced HKM apoptosis. → Arsenic-induced HKM apoptosis involves cross talk between calpain-2 and ERK.

  14. Arsenic-induced nutrient uptake in As-hyperaccumulator Pteris vittata and their potential role to enhance plant growth.

    Science.gov (United States)

    Liu, Xue; Feng, Hua-Yuan; Fu, Jing-Wei; Chen, Yanshan; Liu, Yungen; Ma, Lena Q

    2018-05-01

    It is known that arsenic (As) promotes growth of As-hyperaccumulator Pteris vittata (PV), however, the associated mechanisms are unclear. Here we examined As-induced nutrient uptake in P. vittata and their potential role to enhance plant growth in sterile agar by excluding microbial effects. As-hyperaccumulator P. multifida (PM) and non-hyperaccumulator P. ensiformis (PE) belonging to the Pteris genus were used as comparisons. The results showed that, after 40 d of growth, As induced biomass increase in hyperaccumulators PV and PM by 5.2-9.4 fold whereas it caused 63% decline in PE. The data suggested that As played a beneficial role in promoting hyperaccumulator growth. In addition, hyperaccumulators PV and PM accumulated 7.5-13, 1.4-3.6, and 1.8-4.4 fold more As, Fe, and P than the non-hyperaccumulator PE. In addition, nutrient contents such as K and Zn were also increased while Ca, Mg, and Mn decreased or unaffected under As treatment. This study demonstrated that As promoted growth in hyperaccumulators and enhanced Fe, P, K, and Zn uptake. Different plant growth responses to As among hyperaccumulators PV and PM and non-hyperaccumulator PE may help to better understand why hyperaccumulators grow better under As-stress. Published by Elsevier Ltd.

  15. Arsenic-induced Aurora-A activation contributes to chromosome instability and tumorigenesis

    Science.gov (United States)

    Wu, Chin-Han; Tseng, Ya-Shih; Yang, Chao-Chun; Kao, Yu-Ting; Sheu, Hamm-Ming; Liu, Hsiao-Sheng

    2013-11-01

    Arsenic may cause serious environmental pollution and is a serious industrial problem. Depending on the dosage, arsenic may trigger the cells undergoing either proliferation or apoptosis-related cell death. Because of lack of the proper animal model to study arsenic induced tumorigenesis, the accurate risk level of arsenic exposure has not been determined. Arsenic shows genotoxic effect on human beings who uptake water contaminated by arsenic. Chromosome aberration is frequently detected in arsenic exposure-related diseases and is associated with increased oxidative stress and decreased DNA repairing activity, but the underlying mechanism remains elusive. Aurora-A is a mitotic kinase, over-expression of Aurora-A leads to centrosome amplification, chromosomal instability and cell transformation. We revealed that Aurora-A is over-expressed in the skin and bladder cancer patients from blackfoot-disease endemic areas. Our cell line studies reveal that arsenic exposure between 0.5 μM and 1 μM for 2-7 days are able to induce Aurora-A expression and activation based on promoter activity, RNA and protein analysis. Aurora-A overexpression further increases the frequency of unsymmetrical chromosome segregation through centrosome amplification followed by cell population accumulated at S phase in immortalized keratinocyte (HaCaT) and uroepithelial cells (E7). Furthermore, Aurora-A over-expression was sustained for 1-4 weeks by chronic treatment of immortalized bladder and skin cells with NaAsO2. Aurora-A promoter methylation and gene amplification was not detected in the long-term arsenic treated E7 cells. Furthermore, the expression level of E2F1 transcription factor (E2F1) is increased in the presence of arsenic, and arsenic-related Aurora-A over-expression is transcriptionally regulated by E2F1. We further demonstrated that overexpression of Aurora-A and mutant Ha-ras or Aurora-A and mutant p53 may act additively to trigger arsenic-related bladder and skin cancer

  16. Chronic subhepatotoxic exposure to arsenic enhances hepatic injury caused by high fat diet in mice

    International Nuclear Information System (INIS)

    Tan, Min; Schmidt, Robin H.; Beier, Juliane I.; Watson, Walter H.; Zhong, Hai; States, J. Christopher; Arteel, Gavin E.

    2011-01-01

    Arsenic is a ubiquitous contaminant in drinking water. Whereas arsenic can be directly hepatotoxic, the concentrations/doses required are generally higher than present in the US water supply. However, physiological/biochemical changes that are alone pathologically inert can enhance the hepatotoxic response to a subsequent stimulus. Such a ‘2-hit’ paradigm is best exemplified in chronic fatty liver diseases. Here, the hypothesis that low arsenic exposure sensitizes liver to hepatotoxicity in a mouse model of non-alcoholic fatty liver disease was tested. Accordingly, male C57Bl/6J mice were exposed to low fat diet (LFD; 13% calories as fat) or high fat diet (HFD; 42% calories as fat) and tap water or arsenic (4.9 ppm as sodium arsenite) for ten weeks. Biochemical and histologic indices of liver damage were determined. High fat diet (± arsenic) significantly increased body weight gain in mice compared with low-fat controls. HFD significantly increased liver to body weight ratios; this variable was unaffected by arsenic exposure. HFD caused steatohepatitis, as indicated by histological assessment and by increases in plasma ALT and AST. Although arsenic exposure had no effect on indices of liver damage in LFD-fed animals, it significantly increased the liver damage caused by HFD. This effect of arsenic correlated with enhanced inflammation and fibrin extracellular matrix (ECM) deposition. These data indicate that subhepatotoxic arsenic exposure enhances the toxicity of HFD. These results also suggest that arsenic exposure might be a risk factor for the development of fatty liver disease in human populations. -- Highlights: ► Characterizes a mouse model of arsenic enhanced NAFLD. ► Arsenic synergistically enhances experimental fatty liver disease at concentrations that cause no overt hepatotoxicity alone. ► This effect is associated with increased inflammation.

  17. Pomegranate protects against arsenic-induced p53-dependent ROS-mediated inflammation and apoptosis in liver cells.

    Science.gov (United States)

    Choudhury, Sreetama; Ghosh, Sayan; Mukherjee, Sudeshna; Gupta, Payal; Bhattacharya, Saurav; Adhikary, Arghya; Chattopadhyay, Sreya

    2016-12-01

    Molecular mechanisms involved in arsenic-induced toxicity are complex and elusive. Liver is one of the most favored organs for arsenic toxicity as methylation of arsenic occurs mostly in the liver. In this study, we have selected a range of environmentally relevant doses of arsenic to examine the basis of arsenic toxicity and the role of pomegranate fruit extract (PFE) in combating it. Male Swiss albino mice exposed to different doses of arsenic presented marked hepatic injury as evident from histological and electron microscopic studies. Increased activities of enzymes alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase and alkaline phosphatase corroborated extensive liver damage. It was further noted that arsenic exposure initiated reactive oxygen species (ROS)-dependent apoptosis in the hepatocytes involving loss of mitochondrial membrane potential. Arsenic significantly increased nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor-κB (NF-κB), coupled with increase in phosphorylated Iκ-B, possibly as adaptive cellular survival strategies. Arsenic-induced oxidative DNA damage to liver cells culminated in p53 activation and increased expression of p53 targets like miR-34a and Bax. Pomegranate polyphenols are known to possess remarkable antioxidant properties and are capable of protecting normal cells from various stimuli-induced oxidative stress and toxicities. We explored the protective role of PFE in ameliorating arsenic-induced hepatic damage. PFE was shown to reduce ROS generation in hepatocytes, thereby reducing arsenic-induced Nrf2 activation. PFE also inhibited arsenic-induced NF-κB-inflammatory pathway. Data revealed that PFE reversed arsenic-induced hepatotoxicity and apoptosis by modulating the ROS/Nrf2/p53-miR-34a axis. For the first time, we have mapped the possible signaling pathways associated with arsenic-induced hepatotoxicity and its rescue by pomegranate polyphenols. Copyright

  18. Fluoxetine treatment ameliorates depression induced by perinatal arsenic exposure via a neurogenic mechanism

    Science.gov (United States)

    Tyler, Christina R.; Solomon, Benjamin R.; Ulibarri, Adam L.; Allan, Andrea M.

    2014-01-01

    Several epidemiological studies have reported an association between arsenic exposure and increased rates of psychiatric disorders, including depression, in exposed populations. We have previously demonstrated that developmental exposure to low amounts of arsenic induces depression in adulthood along with several morphological and molecular aberrations, particularly associated with the hippocampus and the hypothalamic–pituitary–adrenal (HPA) axis. The extent and potential reversibility of this toxin-induced damage has not been characterized to date. In this study, we assessed the effects of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on adult animals exposed to arsenic during development. Perinatal arsenic exposure (PAE) induced depressive-like symptoms in a mild learned helplessness task and in the forced swim task after acute exposure to a predator odor (2,4,5-trimethylthiazoline, TMT). Chronic fluoxetine treatment prevented these behaviors in both tasks in arsenic-exposed animals and ameliorated arsenic-induced blunted stress responses, as measured by corticosterone (CORT) levels before and after TMT exposure. Morphologically, chronic fluoxetine treatment reversed deficits in adult hippocampal neurogenesis (AHN) after PAE, specifically differentiation and survival of neural progenitor cells. Protein expression of BDNF, CREB, the glucocorticoid receptor (GR), and HDAC2 was significantly increased in the dentate gyrus of arsenic animals after fluoxetine treatment. This study demonstrates that damage induced by perinatal arsenic exposure is reversible with chronic fluoxetine treatment resulting in restored resiliency to depression via a neurogenic mechanism. PMID:24952232

  19. Enhancement of the antimicrobial properties of orthorhombic molybdenum trioxide by thermal induced fracturing of the hydrates

    Energy Technology Data Exchange (ETDEWEB)

    Shafaei, Shahram; Van Opdenbosch, Daniel [Technische Universität München (TUM), Chair for Biogenic Polymers, Schulgasse 16, D-94315 Straubing (Germany); Fey, Tobias [Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Department of Materials Science and Engineering 3: Glass and Ceramics, Martensstraße 5, D-91058 Erlangen (Germany); Koch, Marcus; Kraus, Tobias [INM, Leibniz Institute for New Materials, Campus D2 2, D-66123 Saarbrücken (Germany); Guggenbichler, Josef Peter [AMiSTec GmbH & Co. KG, Leitweg 23, A-6345 Kössen (Austria); Zollfrank, Cordt, E-mail: cordt.zollfrank@tum.de [Technische Universität München (TUM), Chair for Biogenic Polymers, Schulgasse 16, D-94315 Straubing (Germany)

    2016-01-01

    The oxides of the transition metal molybdenum exhibit excellent antimicrobial properties. We present the preparation of molybdenum trioxide dihydrate (MoO{sub 3} × 2H{sub 2}O) by an acidification method and demonstrate the thermal phase development and morphological evolution during and after calcination from 25 °C to 600 °C. The thermal dehydration of the material was found to proceed in two steps. Microbiological roll-on tests using Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were performed and exceptional antimicrobial activities were determined for anhydrous samples with orthorhombic lattice symmetry and a large specific surface area. The increase in the specific surface area is due to crack formation and to the loss of the hydrate water after calcination at 300 °C. The results support the proposed antimicrobial mechanism for transition metal oxides, which based on a local acidity increase as a consequence of the augmented specific surface area. - Highlights: • Molybdenum trioxide dihydrate (MoO{sub 3} × 2H{sub 2}O) and anhydrous MoO{sub 3} after calcination exhibit exceptional antimicrobial activities • Especially the orthorhombic samples with a large specific surface area show excellent antimicrobial properties. • The increased specific surface area is due to crack formation and to loss of hydrate water after calcination at 300 °C. • Increased a local acidity as a consequence of the augmented surface area is related to the antimicrobial characteristics.

  20. Redistribution of cell cycle by arsenic trioxide is associated with demethylation and expression changes of cell cycle related genes in acute promyelocytic leukemia cell line (NB4).

    Science.gov (United States)

    Hassani, Saeed; Khaleghian, Ali; Ahmadian, Shahin; Alizadeh, Shaban; Alimoghaddam, Kamran; Ghavamzadeh, Ardeshir; Ghaffari, Seyed H

    2018-01-01

    PML-RARα perturbs the normal epigenetic setting, which is essential to oncogenic transformation in acute promyelocytic leukemia (APL). Transcription induction and recruitment of DNA methyltransferases (DNMTs) by PML-RARα and subsequent hypermethylation are components of this perturbation. Arsenic trioxide (ATO), an important drug in APL therapy, concurrent with degradation of PML-RARα induces cell cycle change and apoptosis. How ATO causes cell cycle alteration has remained largely unexplained. Here, we investigated DNA methylation patterns of cell cycle regulatory genes promoters, the effects of ATO on the methylated genes and cell cycle distribution in an APL cell line, NB4. Analysis of promoter methylation status of 22 cell cycle related genes in NB4 revealed that CCND1, CCNE1, CCNF, CDKN1A, GADD45α, and RBL1 genes were methylated 60.7, 84.6, 58.6, 8.7, 33.4, and 73.7%, respectively, that after treatment with 2 μM ATO for 48 h, turn into 0.6, 13.8, 0.1, 6.6, 10.7, and 54.5% methylated. ATO significantly reduced the expression of DNMT1, 3A, and 3B. ATO induced the expression of CCND1, CCNE1, and GADD45α genes, suppressed the expression of CCNF and CDKN1A genes, which were consistent with decreased number of cells in G1 and S phases and increased number of cells in G2/M phase. In conclusion, demethylation and alteration in the expression level of the cell cycle related genes may be possible mechanisms in ATO-induced cell cycle arrest in APL cells. It may suggest that ATO by demethylation of CCND1 and CCNE1 and their transcriptional activation accelerates G1 and S transition into the G2/M cell cycle arrest.

  1. Environmental Arsenic Exposure and Microbiota in Induced Sputum

    Directory of Open Access Journals (Sweden)

    Allison G. White

    2014-02-01

    Full Text Available Arsenic exposure from drinking water is associated with adverse respiratory outcomes, but it is unknown whether arsenic affects pulmonary microbiota. This exploratory study assessed the effect of exposure to arsenic in drinking water on bacterial diversity in the respiratory tract of non-smokers. Induced sputum was collected from 10 subjects with moderate mean household water arsenic concentration (21.1 ± 6.4 ppb and 10 subjects with low household water arsenic (2.4 ± 0.8 ppb. To assess microbiota in sputum, the V6 hypervariable region amplicons of bacterial 16s rRNA genes were sequenced using the Ion Torrent Personal Genome Machine. Microbial community differences between arsenic exposure groups were evaluated using QIIME and Metastats. A total of 3,920,441 sequence reads, ranging from 37,935 to 508,787 per sample for 316 chips after QIIME quality filtering, were taxonomically classified into 142 individual genera and five phyla. Firmicutes (22%, Proteobacteria (17% and Bacteriodetes (12% were the main phyla in all samples, with Neisseriaceae (15%, Prevotellaceae (12% and Veillonellacea (7% being most common at the genus level. Some genera, including Gemella, Lactobacillales, Streptococcus, Neisseria and Pasteurellaceae were elevated in the moderate arsenic exposure group, while Rothia, Prevotella, Prevotellaceae Fusobacterium and Neisseriaceae were decreased, although none of these differences was statistically significant. Future studies with more participants and a greater range of arsenic exposure are needed to further elucidate the effects of drinking water arsenic consumption on respiratory microbiota.

  2. Arsenic trioxide promotes mitochondrial DNA mutation and cell apoptosis in primary APL cells and NB4 cell line.

    Science.gov (United States)

    Meng, Ran; Zhou, Jin; Sui, Meng; Li, ZhiYong; Feng, GuoSheng; Yang, BaoFeng

    2010-01-01

    This study aimed to investigate the effects of arsenic trioxide (As(2)O(3)) on the mitochondrial DNA (mtDNA) of acute promyelocytic leukemia (APL) cells. The NB4 cell line was treated with 2.0 micromol/L As(2)O(3) in vitro, and the primary APL cells were treated with 2.0 micromol/L As(2)O(3) in vitro and 0.16 mg kg(-1) d(-1) As(2)O(3) in vivo. The mitochondrial DNA of all the cells above was amplified by PCR, directly sequenced and analyzed by Sequence Navigatore and Factura software. The apoptosis rates were assayed by flow cytometry. Mitochondrial DNA mutation in the D-loop region was found in NB4 and APL cells before As(2)O(3) use, but the mutation spots were remarkably increased after As(2)O(3) treatment, which was positively correlated to the rates of cellular apoptosis, the correlation coefficient: r (NB4-As2O3)=0.973818, and r (APL-As2O3)=0.934703. The mutation types include transition, transversion, codon insertion or deletion, and the mutation spots in all samples were not constant and regular. It is revealed that As(2)O(3) aggravates mtDNA mutation in the D-loop region of acute promyelocytic leukemia cells both in vitro and in vivo. Mitochondrial DNA might be one of the targets of As(2)O(3) in APL treatment.

  3. Neuroprotective effect of curcumin in arsenic-induced neurotoxicity in rats.

    Science.gov (United States)

    Yadav, Rajesh S; Shukla, Rajendra K; Sankhwar, Madhu Lata; Patel, Devendra K; Ansari, Reyaz W; Pant, Aditya B; Islam, Fakhrul; Khanna, Vinay K

    2010-09-01

    Our recent studies have shown that arsenic-induced neurobehavioral toxicity is protected by curcumin by modulating oxidative stress and dopaminergic functions in rats. In addition, the neuroprotective effect of curcumin has been investigated on arsenic-induced alterations in biogenic amines, their metabolites and nitric oxide (NO), which play an important role in neurotransmission process. Decrease in the levels of dopamine (DA, 28%), norepinephrine (NE, 54%), epinephrine (EPN, 46%), serotonin (5-HT, 44%), 3,4-dihydroxyphenylacetic acid (DOPAC, 20%) and homovanillic acid (HVA, 31%) in corpus striatum; DA (51%), NE (22%), EPN (47%), 5-HT (25%), DOPAC (34%) and HVA (41%) in frontal cortex and DA (35%), NE (35%), EPN (29%), 5-HT (54%), DOPAC (37%) and HVA (46%) in hippocampus, observed in arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) treated rats exhibited a trend of recovery in rats simultaneously treated with arsenic and curcumin (100 mg/kg body weight, p.o., 28 days). Increased levels of NO in corpus striatum (2.4-fold), frontal cortex (6.1-fold) and hippocampus (6.2-fold) in arsenic-treated rats were found decreased in rats simultaneously treated with arsenic and curcumin. It is evident that curcumin modulates levels of brain biogenic amines and NO in arsenic-exposed rats and these results further strengthen its neuroprotective efficacy. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Combination of arsenic and interferon-α inhibits expression of KSHV latent transcripts and synergistically improves survival of mice with primary effusion lymphomas.

    Science.gov (United States)

    El Hajj, Hiba; Ali, Jihane; Ghantous, Akram; Hodroj, Dana; Daher, Ahmad; Zibara, Kazem; Journo, Chloé; Otrock, Zaher; Zaatari, Ghazi; Mahieux, Renaud; El Sabban, Marwan; Bazarbachi, Ali; Abou Merhi, Raghida

    2013-01-01

    Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphomas (PEL). PEL cell lines infected with KSHV, but negative for Epstein-Barr virus have a tumorigenic potential in non-obese diabetic/severe combined immunodeficient mice and result in efficient engraftment and formation of malignant ascites with notable abdominal distension, consistent with the clinical manifestations of PEL in humans. Using this preclinical mouse model, we demonstrate that the combination of arsenic trioxide and interferon-alpha (IFN) inhibits proliferation, induces apoptosis and downregulates the latent viral transcripts LANA-1, v-FLIP and v-Cyc in PEL cells derived from malignant ascites. Furthermore, this combination decreases the peritoneal volume and synergistically increases survival of PEL mice. These results provide a promising rationale for the therapeutic use of arsenic/IFN in PEL patients.

  5. Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats.

    Science.gov (United States)

    Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen; Zhang, Jie; Shen, Heqing

    2017-10-01

    Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33 proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb cardiac contraction and relaxation, impair heart morphogenesis and development, and induce thrombosis in rats, which is mediated by the Akt/p38 MAPK signaling pathway. Overall, these findings will augment our knowledge of the involved mechanisms and develop useful biomarkers for cardiotoxicity induced by environmental arsenic exposure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Surface composition of carburized tungsten trioxide and its catalytic activity

    International Nuclear Information System (INIS)

    Nakazawa, M.; Okamoto, H.

    1985-01-01

    The surface composition and electronic structure of carburized tungsten trioxide are investigated using x-ray photoelectron spectroscopy (XPS). The relationship between the surface composition and the catalytic activity for methanol electro-oxidation is clarified. The tungsten carbide concentration in the surface layer increases with the carburization time. The formation of tungsten carbide enhances the catalytic activity. On the other hand, the presence of free carbon or tungsten trioxide in the surface layer reduces the activity remarkably. It is also shown that, the higher the electronic density of states near the Fermi level, the higher the catalytic activity

  7. The effects of arsenic or the combination of arsenic and radiation exposure is enhanced through the overexpression of the GSTO family member p28

    International Nuclear Information System (INIS)

    Giri, U.; Story, M.D.; Terry, N.H.A.; Giri, D.K.; Calkins, P.R.

    2003-01-01

    Full text: p28 is a member of the GST omega superfamily and has dehydroascorbate reductase, GST, and glutaredoxin activities. Furthermore, p28 is the rate-limiting enzyme in the bio-transformation of arsenic. The monomethyl arsenous reducatase activity of p28 produces dimethylarseniate, the most toxic form of arsenic. We investigated how p28 modulated arsenic cellular sensitivity in two mammalian models: 1) in LY-ar and LY-as cells where p28 is over-expressed and not expressed, respectively; and 2) in stably transfected A549 cells where p28 is over-expressed via a CMV promoter. The LY-ar mouse lymphoma cell line is radio and chemo-resistant and apoptosis refractory, whereas the parental cell line, LY-as, is radiosensitive and apoptotically permissive. In addition, we studied the effect of arsenic as a radiosensitizer in both cell systems. In LY-ar cells arsenic induced a dose- and time- dependent increase in apoptosis, which is comparable to that seen in LY-as cells. Arsenic plus 2.5Gy radiation induced apoptosis in LY-ar cells, which was more than additive. Survival in LY-ar cells was reduced to that of LY-as cells as well as p28 overexpression induced G2/M arrest in A549 cells and the combination of radiation with arsenic decreased the clonogenic survival of both the A549 and A549-p28 cells but the effect is more pronounced in the A549-P28 cell line. A549 and A549-p28 cells did not show a differential response to Taxol, which induces G2/M arrest and cell death via an inhibition of tubulin depolarization. Arsenic modulated the level of reduced GSH in both cell systems in a dose- and time- dependent manner, which correlated with survival outcome. This study illustrated that arsenic acts as a radiosensitizer and p28 augmented the potential of arsenic in inducing apoptosis, G2/M arrest, and radiosensitization. Further studies are underway to examine the bio-chemical pathways involved in arsenic-mediated cell death and the role of p28 therein

  8. Enhanced phytoremediation of arsenic contaminated land.

    Science.gov (United States)

    Jankong, P; Visoottiviseth, P; Khokiattiwong, S

    2007-08-01

    In an attempt to clean up arsenic (As) contaminated soil, the effects of phosphorus (P) fertilizer and rhizosphere microbes on arsenic accumulation by the silverback fern, Pityrogramma calomelanos, were investigated in both greenhouse and field experiments. Field experiments were conducted in Ron Phibun District, an As-contaminated area in Thailand. Soil (136-269 microg As g(-1)) was collected there and used in the greenhouse experiment. Rhizosphere microbes (bacteria and fungi) were isolated from roots of P. calomelanos growing in Ron Phibun District. The results showed that P-fertilizer significantly increased plant biomass and As accumulation of the experimental P. calomelanos. Rhizobacteria increased significantly the biomass and As content of the test plants. Thus, P-fertilizer and rhizosphere bacteria enhanced As-phytoextraction. In contrast, rhizofungi reduced significantly As concentration in plants but increased plant biomass. Therefore, rhizosphere fungi exerted their effects on phytostabilization.

  9. Arsenic-induced toxicity and the protective role of ascorbic acid in mouse testis

    International Nuclear Information System (INIS)

    Chang, Soo Im; Jin, Bohwan; Youn, Pilju; Park, Changbo; Park, Jung-Duck; Ryu, Doug-Young

    2007-01-01

    Oxidative stress has been suggested to be a major cause of male reproductive failure. Here, we investigated whether arsenic, which impairs male reproductive functions in rodent models, acts by inducing oxidative stress. Male 8-week-old ICR mice were given drinking water containing 20 or 40 mg/l sodium arsenite with or without 0.75 or 1.5 g/l of the antioxidant ascorbic acid for 5 weeks. The arsenic-treated mice showed decreased epididymidal sperm counts and testicular weights compared to untreated mice. These effects were reversed in mice that were co-treated with ascorbic acid. Similarly, arsenic treatment lowered the activities of testicular 3β-hydroxysteroid dehydrogenase (HSD) and 17β-HSD, which play important roles in steroidogenesis, and this was reversed by co-treatment with ascorbic acid. The testicles of arsenic-treated mice had decreased glutathione (GSH) levels (which correlate inversely with the degree of cellular oxidative stress) and elevated levels of protein carbonyl (a marker of oxidative damage to tissue proteins). Ascorbic acid co-treatment reversed both of these effects. Thus, ascorbic acid blocks both the adverse effects of arsenic on male reproductive functions and the arsenic-induced testicular oxidative changes. These observations support the notion that arsenic impairs male reproductive function by inducing oxidative stress

  10. Causes and prognostic factors for early death in patients with acute promyelocytic leukemia treated with single-agent arsenic trioxide.

    Science.gov (United States)

    Hou, Jinxiao; Wang, Shuye; Zhang, Yingmei; Fan, Dachuan; Li, Haitao; Yang, Yiju; Ge, Fei; Hou, Wenyi; Fu, Jinyue; Wang, Ping; Zhao, Hongli; Sun, Jiayue; Yang, Kunpeng; Zhou, Jin; Li, Xiaoxia

    2017-12-01

    Early death (ED) is one of the most critical issues involved in the current care of patients with acute promyelocytic leukemia (APL). Factors identified as independent predictors of ED varied among published studies. We retrospectively analyzed the incidence, causes, and prognostic factors of ED in a series of 216 patients with newly diagnosed APL who received arsenic trioxide (ATO) as induction therapy. Multivariate logistic regression analysis was used to determine the association of clinical factors with overall ED, hemorrhagic ED, death within 7 days, and death within 8-30 days. In total, 35 EDs (16.2%) occurred that were caused by hemorrhage, differentiation syndrome (DS), infection, and other causes, in order of prevalence. The independent prognostic factors for overall ED and death within 8-30 days were the same and included serum creatinine level, Eastern Cooperative Oncology Group (ECOG) score, sex, and fibrinogen level. The risk factors for hemorrhagic ED and death within 7 days were similar and included serum creatinine level, ECOG score, and white blood cell count, while hemorrhagic ED was also associated with D-dimer. Our findings revealed a high rate of ED, and the causes of ED were similar to those among patients who received ATRA-based therapy. Increased creatinine level was the most powerful predictor, and an ECOG score greater than 2 was another strong prognostic factor for all four types of ED.

  11. Induction of the mesenchymal to epithelial transition by demethylation-activated microRNA-125b is involved in the anti-migration/invasion effects of arsenic trioxide on human chondrosarcoma.

    Science.gov (United States)

    Bao, Xing; Ren, Tingting; Huang, Yi; Wang, Shidong; Zhang, Fan; Liu, Kuisheng; Zheng, Bingxin; Guo, Wei

    2016-08-30

    In addition to treating acute promyelocytic leukemia, arsenic trioxide (ATO) suppresses other solid tumors, including chondrosarcoma. However, the effects of ATO on metastasis in chondrosarcoma cells, and the underlying molecular mechanisms remain unclear. The effects of ATO on the migratory and invasive capacities of chondrosarcoma cells were investigated by Wound healing, Transwell and EMT assays. The expression of miR-125b in human chondrosarcoma tissues and cell lines was detected by real-time PCR analysis. Bisulfite sequencing analysis (BSP) was used to detect the effects of ATO on the expression of miR-125b. The gain-of-function and loss-of-function experiments were performed on chondrosarcoma cell lines to investigate the effects of miR-125b on chondrosarcoma invasion, and to determine whether signal transducer and activator of transcription 3(Stat3) mediates these effects. Dual-luciferase reporter assay was used to identify whether Stat3 is a direct target of miR-125b. MiR-125b was significantly downregulated in human metastatic chondrosarcoma tissues and cell lines but not in non-metastatic chondrosarcoma tissues. ATO up-regulates the expression of miR-125b by the demethylation of DNA. ATO induces MET and attenuates the invasive capacities of chondrosarcoma cells through miR-125b. Stat3 was verified as a direct target of miR-125b, which is involved in ATO regulating EMT-associated traits. These findings, for the first time, provides evidence that the miR-125b-mediated inhibition of Stat3 is involved in the ATO-induced attenuation of metastasis in chondrosarcoma cells.

  12. Arsenic induced apoptosis in rat liver following repeated 60 days exposure

    International Nuclear Information System (INIS)

    Bashir, Somia; Sharma, Yukti; Irshad, M.; Nag, T.C.; Tiwari, Monica; Kabra, M.; Dogra, T.D.

    2006-01-01

    Background: Accumulation of the wide spread environmental toxin arsenic in liver results in hepatotoxcity. Exposure to arsenite and other arsenicals has been previously shown to induce apoptosis in certain tumor cell lines at low (1-3 μM) concentration. Aim: The present study was focused to elucidate the role of free radicals in arsenic toxicity and to investigate the nature of in vivo sodium arsenite induced cell death in liver. Methods: Male wistar rats were exposed to arsenite at three different doses of 0.05, 2.5 and 5 mg/l for 60 days. Oxidative stress in liver was measured by estimating pro-oxidant and antioxidant activity in liver. Histopathological examination of liver was carried out by light and transmission electron microscopy. Analysis of DNA fragmentation by gel electrophoresis was used to identify apoptosis after the exposure. Terminal deoxy-nucleotidyl transferase mediated dUTP Nick end-labeling (TUNEL) assay was used to qualify and quantify apoptosis. Results: A significant increase in cytochrome-P450 and lipid peroxidation accompanied with a significant alteration in the activity of many of the antioxidants was observed, all suggestive of arsenic induced oxidative stress. Histopathological examination under light and transmission electron microscope suggested a combination of ongoing necrosis and apoptosis. DNA-TUNEL showed an increase in apoptotic cells in liver. Agarose gel electrophoresis of DNA of hepatocytes resulted in a characteristic ladder pattern. Conclusion: Chronic arsenic administration induces a specific pattern of apoptosis called post-mitotic apoptosis

  13. Modulatory role of dietary Chlorella vulgaris powder against arsenic-induced immunotoxicity and oxidative stress in Nile tilapia (Oreochromis niloticus).

    Science.gov (United States)

    Zahran, Eman; Risha, Engy

    2014-12-01

    Arsenic intoxicant have long been regarded as an impending carcinogenic, genotoxic, and immunotoxic heavy metal to human and animals as well. In this respect, we evaluated biomarkers of the innate immune response and oxidative stress metabolism in gills and liver of Nile tilapia (Oreochromis niloticus) after arsenic exposure, and the protective role of Chlorella vulgaris (Ch) dietary supplementation were elucidated. Protective role of C. vulgaris (Ch), as supplementary feeds (5% and 10% of the diet) was studied in Nile tilapia (O. niloticus) against arsenic induced toxicity (NaAsO2 at 7 ppm) for 21 days exposure period. A significant down-regulation in innate immune response; including, respiratory burst, lysozyme, and bactericidal activity followed due to deliberately As(+3) exposure. Similarly, oxidative stress response; like nitric oxide (NO), catalase (CAT), glutathione (GSH), glutathione peroxidase (GPx), malondialdehyde (MDA) and hydrogen peroxide (H2O2) levels were significantly decreased. Combined treatment of Ch and As(+3) significantly enhanced the innate immune response and antioxidant activity. Strikingly, Ch supplementation at 10% has been considered the optimum for Nile tilapia since it exhibited enhancement of innate immune response and antioxidant activity over the level 5%, and even better than that of control level. Thus, our results concluded that dietary Ch supplementation could protect Nile tilapia against arsenic induced immunosuppression and oxidative stresses. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    International Nuclear Information System (INIS)

    Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2014-01-01

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91 st day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E max of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced

  15. Atorvastatin restores arsenic-induced vascular dysfunction in rats: Modulation of nitric oxide signaling and inflammatory mediators

    Energy Technology Data Exchange (ETDEWEB)

    Kesavan, Manickam; Sarath, Thengumpallil Sasindran; Kannan, Kandasamy; Suresh, Subramaniyam; Gupta, Priyanka; Vijayakaran, Karunakaran; Sankar, Palanisamy; Kurade, Nitin Pandurang; Mishra, Santosh Kumar; Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com

    2014-10-01

    We evaluated whether atorvastatin, an extensively prescribed statin for reducing the risks of cardiovascular diseases, can reduce the risk of arsenic-induced vascular dysfunction and inflammation in rats and whether the modulation could be linked to improvement in vascular NO signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91{sup st} day, blood was collected for measuring serum C-reactive protein. Thoracic aorta was isolated for assessing reactivity to phenylephrine, sodium nitroprusside and acetylcholine; evaluating eNOS and iNOS mRNA expression and measuring NO production, while abdominal aorta was used for ELISA of cytokines, chemokine and vascular cell adhesion molecules. Histopathology was done in aortic arches. Arsenic did not alter phenylephrine-elicited contraction. Atorvastatin inhibited E{sub max} of phenylephrine, but it augmented the contractile response in aortic rings from arsenic-exposed animals. Sodium nitroprusside-induced relaxation was not altered with any treatment. However, arsenic reduced acetylcholine-induced relaxation and affected aortic eNOS at the levels of mRNA expression, protein concentration, phosphorylation and NO production. Further, it increased aortic iNOS mRNA expression, iNOS-derived NO synthesis, production of pro-inflammatory mediators (IL-1β, IL-6, MCP-1, VCAM, sICAM) and serum C-reactive protein and aortic vasculopathic lesions. Atorvastatin attenuated these arsenic-mediated functional, biochemical and structural alterations. Results show that atorvastatin has the potential to ameliorate arsenic-induced vascular dysfunction and inflammation by restoring endothelial function with improvement in NO signaling and attenuating production of pro-inflammatory mediators and cell adhesion molecules. - Highlights: • We evaluated if atorvastatin reduce arsenic-induced

  16. Combination of arsenic and interferon-α inhibits expression of KSHV latent transcripts and synergistically improves survival of mice with primary effusion lymphomas.

    Directory of Open Access Journals (Sweden)

    Hiba El Hajj

    Full Text Available BACKGROUND: Kaposi sarcoma-associated herpesvirus (KSHV is the etiologic agent of primary effusion lymphomas (PEL. PEL cell lines infected with KSHV, but negative for Epstein-Barr virus have a tumorigenic potential in non-obese diabetic/severe combined immunodeficient mice and result in efficient engraftment and formation of malignant ascites with notable abdominal distension, consistent with the clinical manifestations of PEL in humans. METHODOLOGY/PRINCIPAL FINDINGS: Using this preclinical mouse model, we demonstrate that the combination of arsenic trioxide and interferon-alpha (IFN inhibits proliferation, induces apoptosis and downregulates the latent viral transcripts LANA-1, v-FLIP and v-Cyc in PEL cells derived from malignant ascites. Furthermore, this combination decreases the peritoneal volume and synergistically increases survival of PEL mice. CONCLUSION/SIGNIFICANCE: These results provide a promising rationale for the therapeutic use of arsenic/IFN in PEL patients.

  17. Comparative proteomic analysis reveals heart toxicity induced by chronic arsenic exposure in rats

    DEFF Research Database (Denmark)

    Huang, Qingyu; Xi, Guochen; Alamdar, Ambreen

    2017-01-01

    Arsenic is a widespread metalloid in the environment, which poses a broad spectrum of adverse effects on human health. However, a global view of arsenic-induced heart toxicity is still lacking, and the underlying molecular mechanisms remain unclear. By performing a comparative quantitative...... proteomic analysis, the present study aims to investigate the alterations of proteome profile in rat heart after long-term exposure to arsenic. As a result, we found that the abundance of 81 proteins were significantly altered by arsenic treatment (35 up-regulated and 46 down-regulated). Among these, 33...... proteins were specifically associated with cardiovascular system development and function, including heart development, heart morphology, cardiac contraction and dilation, and other cardiovascular functions. It is further proposed that the aberrant regulation of 14 proteins induced by arsenic would disturb...

  18. Potential role of sodium-proton exchangers in the low concentration arsenic trioxide-increased intracellular pH and cell proliferation.

    Directory of Open Access Journals (Sweden)

    Carmen Aravena

    Full Text Available Arsenic main inorganic compound is arsenic trioxide (ATO presented in solution mainly as arsenite. ATO increases intracellular pH (pHi, cell proliferation and tumor growth. Sodium-proton exchangers (NHEs modulate the pHi, with NHE1 playing significant roles. Whether ATO-increased cell proliferation results from altered NHEs expression and activity is unknown. We hypothesize that ATO increases cell proliferation by altering pHi due to increased NHEs-like transport activity. Madin-Darby canine kidney (MDCK cells grown in 5 mmol/L D-glucose-containing DMEM were exposed to ATO (0.05, 0.5 or 5 µmol/L, 0-48 hours in the absence or presence of 5-N,N-hexamethylene amiloride (HMA, 5-100 µmol/L, NHEs inhibitor, PD-98059 (30 µmol/L, MAPK1/2 inhibitor, Gö6976 (10 µmol/L, PKCα, βI and μ inhibitor, or Schering 28080 (10 µmol/L, H(+/K(+ATPase inhibitor plus concanamycin (0.1 µmol/L, V type ATPases inhibitor. Incorporation of [(3H]thymidine was used to estimate cell proliferation, and counting cells with a hemocytometer to determine the cell number. The pHi was measured by fluorometry in 2,7-bicarboxyethyl-5,6-carboxyfluorescein loaded cells. The Na(+-dependent HMA-sensitive NHEs-like mediated proton transport kinetics, NHE1 protein abundance in the total, cytoplasm and plasma membrane protein fractions, and phosphorylated and total p42/44 mitogen-activated protein kinases (p42/44(mapk were also determined. Lowest ATO (0.05 µmol/L, ~0.01 ppm used in this study increased cell proliferation, pHi, NHEs-like transport and plasma membrane NHE1 protein abundance, effects blocked by HMA, PD-98059 or Gö6976. Cell-buffering capacity did not change by ATO. The results show that a low ATO concentration increases MDCK cells proliferation by NHEs (probably NHE1-like transport dependent-increased pHi requiring p42/44(mapk and PKCα, βI and/or μ activity. This finding could be crucial in diseases where uncontrolled cell growth occurs, such as tumor growth, and

  19. Analyses of heavy metals in mineral trioxide aggregate and Portland cement.

    Science.gov (United States)

    Schembri, Matthew; Peplow, George; Camilleri, Josette

    2010-07-01

    Portland cement is used in the construction industry as a binder in concrete. It is manufactured from chalk, limestone, and clay, which are clinkered at very high temperatures and ground with gypsum to form Portland cement. The raw materials and the manufacturing process can result in the inclusion of heavy metals in Portland cement. Portland cement with a four to one addition of bismuth oxide is marketed as mineral trioxide aggregate (MTA), which is used mainly as a dental material. Heavy metal inclusion can be of concern because MTA is in contact with hard and soft tissues. Measurements of arsenic, lead, and chromium in hydrated gray and white Portland cement, ProRoot MTA, and MTA Angelus were conducted with graphite furnace atomic absorption spectrophotometry after acid digestion on the hydrated material. The leaching of the metal ions from the solid material in water and simulated body fluid (SBF) was also determined. All cement types showed high relative values of leached chromium compared with arsenic and lead in both the total metal content and leached species. The gray Portland cement showed the highest total amount of metal. The white Portland and both MTAs had lower values for all the leached metal ions. Both MTAs released more arsenic than the amount specified in ISO 9917-1 (2007). Portland cements and MTAs showed evidence of heavy metals in the acid-soluble form as well as leaching in deionized water and SBF. MTA contained levels of arsenic higher than the safe limit specified by the ISO 9917-1 (2007). Copyright 2010 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  20. Differential effects of arsenic trioxide on chemosensitization in human hepatic tumor and stellate cell lines

    International Nuclear Information System (INIS)

    Rangwala, Fatima; Williams, Kevin P; Smith, Ginger R; Thomas, Zainab; Allensworth, Jennifer L; Lyerly, H Kim; Diehl, Anna Mae; Morse, Michael A; Devi, Gayathri R

    2012-01-01

    Crosstalk between malignant hepatocytes and the surrounding peritumoral stroma is a key modulator of hepatocarcinogenesis and therapeutic resistance. To examine the chemotherapy resistance of these two cellular compartments in vitro, we evaluated a well-established hepatic tumor cell line, HepG2, and an adult hepatic stellate cell line, LX2. The aim was to compare the chemosensitization potential of arsenic trioxide (ATO) in combination with sorafenib or fluorouracil (5-FU), in both hepatic tumor cells and stromal cells. Cytotoxicity of ATO, 5-FU, and sorafenib, alone and in combination against HepG2 cells and LX2 cells was measured by an automated high throughput cell-based proliferation assay. Changes in survival and apoptotic signaling pathways were analyzed by flow cytometry and western blot. Gene expression of the 5-FU metabolic enzyme, thymidylate synthase, was analyzed by real time PCR. Both HepG2 and LX2 cell lines were susceptible to single agent sorafenib and ATO at 24 hr (ATO IC 50 : 5.3 μM in LX2; 32.7 μM in HepG2; Sorafenib IC 50 : 11.8 μM in LX2; 9.9 μM in HepG2). In contrast, 5-FU cytotoxicity required higher concentrations and prolonged (48–72 hr) drug exposure. Concurrent ATO and 5-FU treatment of HepG2 cells was synergistic, leading to increased cytotoxicity due in part to modulation of thymidylate synthase levels by ATO. Concurrent ATO and sorafenib treatment showed a trend towards increased HepG2 cytotoxicity, possibly due to a significant decrease in MAPK activation in comparison to treatment with ATO alone. ATO differentially sensitizes hepatic tumor cells and adult hepatic stellate cells to 5-FU and sorafenib. Given the importance of both of these cell types in hepatocarcinogenesis, these data have implications for the rational development of anti-cancer therapy combinations for the treatment of hepatocellular carcinoma (HCC)

  1. Differential effects of arsenic trioxide on chemosensitization in human hepatic tumor and stellate cell lines

    Directory of Open Access Journals (Sweden)

    Rangwala Fatima

    2012-09-01

    Full Text Available Abstract Background Crosstalk between malignant hepatocytes and the surrounding peritumoral stroma is a key modulator of hepatocarcinogenesis and therapeutic resistance. To examine the chemotherapy resistance of these two cellular compartments in vitro, we evaluated a well-established hepatic tumor cell line, HepG2, and an adult hepatic stellate cell line, LX2. The aim was to compare the chemosensitization potential of arsenic trioxide (ATO in combination with sorafenib or fluorouracil (5-FU, in both hepatic tumor cells and stromal cells. Methods Cytotoxicity of ATO, 5-FU, and sorafenib, alone and in combination against HepG2 cells and LX2 cells was measured by an automated high throughput cell-based proliferation assay. Changes in survival and apoptotic signaling pathways were analyzed by flow cytometry and western blot. Gene expression of the 5-FU metabolic enzyme, thymidylate synthase, was analyzed by real time PCR. Results Both HepG2 and LX2 cell lines were susceptible to single agent sorafenib and ATO at 24 hr (ATO IC50: 5.3 μM in LX2; 32.7 μM in HepG2; Sorafenib IC50: 11.8 μM in LX2; 9.9 μM in HepG2. In contrast, 5-FU cytotoxicity required higher concentrations and prolonged (48–72 hr drug exposure. Concurrent ATO and 5-FU treatment of HepG2 cells was synergistic, leading to increased cytotoxicity due in part to modulation of thymidylate synthase levels by ATO. Concurrent ATO and sorafenib treatment showed a trend towards increased HepG2 cytotoxicity, possibly due to a significant decrease in MAPK activation in comparison to treatment with ATO alone. Conclusions ATO differentially sensitizes hepatic tumor cells and adult hepatic stellate cells to 5-FU and sorafenib. Given the importance of both of these cell types in hepatocarcinogenesis, these data have implications for the rational development of anti-cancer therapy combinations for the treatment of hepatocellular carcinoma (HCC.

  2. Study of arsenic accumulation in rice and evaluation of protective effects of Chorchorus olitorius leaves against arsenic contaminated rice induced toxicities in Wistar albino rats.

    Science.gov (United States)

    Hosen, Saeed Mohammed Imran; Das, Dipesh; Kobi, Rupkanowar; Chowdhury, Dil Umme Salma; Alam, Md Jibran; Rudra, Bashudev; Bakar, Muhammad Abu; Islam, Saiful; Rahman, Zillur; Al-Forkan, Mohammad

    2016-10-14

    In the present study, we investigated the arsenic accumulation in different parts of rice irrigated with arsenic contaminated water. Besides, we also evaluated the protective effects of Corchorus olitorius leaves against arsenic contaminated rice induced toxicities in animal model. A pot experiment was conducted with arsenic amended irrigation water (0.0, 25.0, 50.0 and 75.0 mg/L As) to investigate the arsenic accumulation in different parts of rice. In order to evaluate the protective effects of Corchorus olitorius leaves, twenty Wistar albino rats were divided into four different groups. The control group (Group-I) was supplied with normal laboratory pellets while groups II, III, and IV received normal laboratory pellets supplemented with arsenic contaminated rice, C. olitorius leaf powder (4 %), arsenic contaminated rice plus C. olitorius leaf powder (4 %) respectively. Different haematological parameters and serum indices were analyzed to evaluate the protective effects of Corchorus olitorius leaves against arsenic intoxication. To gather more supportive evidences of Corchorus olitorius potentiality against arsenic intoxication, histopathological analysis of liver, kidney, spleen and heart tissues was also performed. From the pot experiment, we have found a significant (p ≤ 0.05) increase of arsenic accumulation in different parts of rice with the increase of arsenic concentrations in irrigation water and the trend of accumulation was found as root > straw > husk > grain. Another part of the experiment revealed that supplementation of C. olitorius leaves with arsenic contaminated rice significantly (p rice induced toxicities. Arsenic accumulation in different parts of rice increased dose-dependently. Hence, for irrigation purpose arsenic contaminated water cannot be used. Furthermore, arsenic contaminated rice induced several toxicities in animal model, most of which could be minimized with the food supplementation of Corchorus olitorius

  3. Possible mechanisms for arsenic-induced proliferative diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wetterhahn, K.E.; Dudek, E.J.; Shumilla, J.A. [Dartmouth College and Medical School, Hanover, NH (United States)] [and others

    1996-12-31

    Possible mechanisms for cardiovascular diseases and cancers which have been observed on chronic exposure to arsenic have been investigated. We tested the hypothesis that nonlethal levels of arsenic are mitogenic, cause oxidative stress, increase nuclear translocation of trans-acting factors, and increase expression of genes involved in proliferation. Cultured porcine vascular (from aorta) endothelial cells were used as a model cell system to study the effects of arsenic on the target cells for cardiovascular diseases. Treatment of postconfluent cell cultures with nonovertly toxic concentrations of arsenite increased DNA synthesis, similar to the mitogenic response observed with hydrogen peroxide. Within 1 hour of adding noncytotoxic concentrations of arsenite, cellular levels of oxidants increased relative to control levels, indicating that arsenite promotes cellular oxidations. Arsenite treatment increased nuclear translocation of NF-{kappa}B, an oxidative stress-responsive transcription factor, in a manner similar to that observed with hydrogen peroxide. Pretreatment of intact cells with the antioxidants N-acetylcysteine and dimethylfumarate prevented the arsenite-induced increases in cellular oxidant formation and NF-KB translocation. Arsenite had little or no effect on binding of NF-KB to its DNA recognition sequence in vitro, indicating that it is unlikely that arsenite directly affects NF-KB. The steady-state mRNA levels of intracellular adhesion molecule and urokinase-like plasminogen activator, genes associated with the active endothelial phenotype in arteriosclerosis and cancer metastasis, were increased by nontoxic concentrations of arsenite. These data suggest that arsenite promotes proliferative diseases like heart disease and cancer by activating oxidant-sensitive endothelial cell signaling and gene expression. It is possible that antioxidant therapy would be useful in preventing arsenic-induced cardiovascular disease and cancer.

  4. Inhibition of insulin-dependent glucose uptake by trivalent arsenicals: possible mechanism of arsenic-induced diabetes

    International Nuclear Information System (INIS)

    Walton, Felecia S.; Harmon, Anne W.; Paul, David S.; Drobna, Zuzana; Patel, Yashomati M.; Styblo, Miroslav

    2004-01-01

    Chronic exposures to inorganic arsenic (iAs) have been associated with increased incidence of noninsulin (type-2)-dependent diabetes mellitus. Although mechanisms by which iAs induces diabetes have not been identified, the clinical symptoms of the disease indicate that iAs or its metabolites interfere with insulin-stimulated signal transduction pathway or with critical steps in glucose metabolism. We have examined effects of iAs and methylated arsenicals that contain trivalent or pentavalent arsenic on glucose uptake by 3T3-L1 adipocytes. Treatment with inorganic and methylated pentavalent arsenicals (up to 1 mM) had little or no effect on either basal or insulin-stimulated glucose uptake. In contrast, trivalent arsenicals, arsenite (iAs III ), methylarsine oxide (MAs III O), and iododimethylarsine (DMAs III O) inhibited insulin-stimulated glucose uptake in a concentration-dependent manner. Subtoxic concentrations of iAs III (20 μM), MAs III O (1 μM), or DMAs III I (2 μM) decreased insulin-stimulated glucose uptake by 35-45%. Basal glucose uptake was significantly inhibited only by cytotoxic concentrations of iAs III or MAs III O. Examination of the components of the insulin-stimulated signal transduction pathway showed that all trivalent arsenicals suppressed expression and possibly phosphorylation of protein kinase B (PKB/Akt). The concentration of an insulin-responsive glucose transporter (GLUT4) was significantly lower in the membrane region of 3T3-L1 adipocytes treated with trivalent arsenicals as compared with untreated cells. These results suggest that trivalent arsenicals inhibit insulin-stimulated glucose uptake by interfering with the PKB/Akt-dependent mobilization of GLUT4 transporters in adipocytes. This mechanism may be, in part, responsible for the development of type-2 diabetes in individuals chronically exposed to iAs

  5. Arsenic exposure induces the Warburg effect in cultured human cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Fei; Severson, Paul; Pacheco, Samantha; Futscher, Bernard W.; Klimecki, Walter T., E-mail: klimecki@pharmacy.arizona.edu

    2013-08-15

    Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect.

  6. Arsenic exposure induces the Warburg effect in cultured human cells

    International Nuclear Information System (INIS)

    Zhao, Fei; Severson, Paul; Pacheco, Samantha; Futscher, Bernard W.; Klimecki, Walter T.

    2013-01-01

    Understanding how arsenic exacts its diverse, global disease burden is hampered by a limited understanding of the particular biological pathways that are disrupted by arsenic and underlie pathogenesis. A reductionist view would predict that a small number of basic pathways are generally perturbed by arsenic, and manifest as diverse diseases. Following an initial observation that arsenite-exposed cells in culture acidify their media more rapidly than control cells, the report here shows that low level exposure to arsenite (75 ppb) is sufficient to induce aerobic glycolysis (the Warburg effect) as a generalized phenomenon in cultured human primary cells and cell lines. Expanded studies in one such cell line, the non-malignant pulmonary epithelial line, BEAS-2B, established that the arsenite-induced Warburg effect was associated with increased accumulation of intracellular and extracellular lactate, an increased rate of extracellular acidification, and inhibition by the non-metabolized glucose analog, 2-deoxy-D-glucose. Associated with the induction of aerobic glycolysis was a pathway-wide induction of glycolysis gene expression, as well as protein accumulation of an established glycolysis master-regulator, hypoxia-inducible factor 1A. Arsenite-induced alteration of energy production in human cells represents the type of fundamental perturbation that could extend to many tissue targets and diseases. - Highlights: • Chronic arsenite exposure induces aerobic glycolysis, dubbed the “Warburg effect”. • Arsenite-induced Warburg effect is a general phenomenon in cultured human cells. • HIF-1A may mediate arsenite induced Warburg effect

  7. Arsenic removal by using colloidal adsorption flotation utilizing Fe(OH)3 floc in a dissolved air flotation system

    International Nuclear Information System (INIS)

    Pavez, O.; Palacios, J. M.; Aguilar, C.

    2009-01-01

    In the present work, the influence of Fe/As ratio on the As removal, from aqueous solutions, applying flotation by colloidal adsorption was studied. Ferric chloride was used as coagulant and dodec il sulfate as collector, and arsenic trioxide was utilized to preparing the solutions. The obtained results show that the highest arsenic removal was accomplished in the range of pH between 4 and 5,5, and the increasing of the initial concentration of Fe(III), increases the removal of arsenic from the solution. However, with the decreasing of the initial concentration of arsenic in the solution, it is required a larger Fe/As ratio for its removal. For solutions containing: 13,73, 1,71 and 0,105 mg/L of arsenic, it was shown that to remove around 95% of the dissolved arsenic, a Fe/As ratios of approximately 6/1, 18/1 and 800/1, respectively, are required. (Author) 31 refs

  8. Study on the toxic effects induced by different arsenicals in primary cultured rat astroglia

    International Nuclear Information System (INIS)

    Jin Yaping; Sun Guifan; Li Xin; Li Gexin; Lu Chunwei; Qu Long

    2004-01-01

    Arsenic toxicity is a global health problem affecting millions of people. The objectives of this study were to determine if the toxic effects on primary cultured rat astroglia would be induced by different arsenicals. Based on alamarBlue assay and the single cell gel electrophoresis (SCGE, comet assay), the cell viability and DNA damage in the cells exposed to different arsenicals were evaluated. Treatment of astroglia with methylated arsenicals, that is, pentavalent monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV), resulted in no obvious changes in cell viability and DNA damage at micromolar concentrations. However, treatment of astroglia with inorganic arsenicals, that is, arsenite and arsenate, caused decreased cell viability and increased DNA damage at micromolar levels, and showing a dose-related decrease in mean alamarBlue reduced rate and a dose-related increase in mean comet length. Our study is therefore highly suggestive for a link between inorganic exposure and cellular toxicity or DNA damage. Based on the results of this study, the toxic effects induced by arsenite were stronger than those induced by arsenate

  9. Kinetic of martensitic transformations induced by hydrogen in the austenite

    International Nuclear Information System (INIS)

    Oliveira, Sergio P. de; Saavedra, A.; Miranda, P.E.V. de

    1986-01-01

    The X-ray diffractometry technique was used, with an automatic data acquisition system to determine the kinetics of hydrogen induced martensitic phase transformations in an AISI 304 austenitic stainless steel type, used in nuclear power plants. Hydrogenation was performed cathodically in a 1N sulfuric acid solution, containing 100 mg/l of arsenic trioxide, at 50 0 C, during 2 hours and with a current density of 200 A/m 2 . It was found that the microstructure of the steel plays a role on the generation of hydrogen induced martensitic phases and surface micro cracks. Both kinetics were slower on a pre-cold rolled steel. (Author) [pt

  10. Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration

    Energy Technology Data Exchange (ETDEWEB)

    Ngalame, Ntube N.O., E-mail: ngalamenn@niehs.nih.gov; Makia, Ngome L., E-mail: makianl@niehs.nih.gov; Waalkes, Michael P., E-mail: waalkes@niehs.nih.gov; Tokar, Erik J., E-mail: tokare@mail.nih.gov

    2016-12-01

    Inorganic arsenic, an environmental contaminant and a human carcinogen is associated with prostate cancer. Emerging evidence suggests that cancer stem cells (CSCs) are the driving force of carcinogenesis. Chronic arsenic exposure malignantly transforms the human normal prostate stem/progenitor cell (SC) line, WPE-stem to arsenic-cancer SCs (As-CSCs), through unknown mechanisms. MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the posttranscriptional level. In prior work, miR-143 was markedly downregulated in As-CSCs, suggesting a role in arsenic-induced malignant transformation. In the present study, we investigated whether loss of miR-143 expression is important in arsenic-induced transformation of prostate SCs. Restoration of miR-143 in As-CSCs was achieved by lentivirus-mediated miR-143 overexpression. Cells were assessed bi-weekly for up to 30 weeks to examine mitigation of cancer phenotype. Secreted matrix metalloproteinase (MMP) activity was increased by arsenic-induced malignant transformation, but miR-143 restoration decreased secreted MMP-2 and MMP-9 enzyme activities compared with scramble controls. Increased cell proliferation and apoptotic resistance, two hallmarks of cancer, were decreased upon miR-143 restoration. Increased apoptosis was associated with decreased BCL2 and BCL-XL expression. miR-143 restoration dysregulated the expression of SC/CSC self-renewal genes including NOTCH-1, BMI-1, OCT4 and ABCG2. The anticancer effects of miR-143 overexpression appeared to be mediated by targeting and inhibiting LIMK1 protein, and the phosphorylation of cofilin, a LIMK1 substrate. These findings clearly show that miR-143 restoration mitigated multiple cancer characteristics in the As-CSCs, suggesting a potential role in arsenic-induced transformation of prostate SCs. Thus, miR-143 is a potential biomarker and therapeutic target for arsenic-induced prostate cancer. - Highlights: • Chronic arsenic exposure

  11. Mitigation of arsenic-induced acquired cancer phenotype in prostate cancer stem cells by miR-143 restoration

    International Nuclear Information System (INIS)

    Ngalame, Ntube N.O.; Makia, Ngome L.; Waalkes, Michael P.; Tokar, Erik J.

    2016-01-01

    Inorganic arsenic, an environmental contaminant and a human carcinogen is associated with prostate cancer. Emerging evidence suggests that cancer stem cells (CSCs) are the driving force of carcinogenesis. Chronic arsenic exposure malignantly transforms the human normal prostate stem/progenitor cell (SC) line, WPE-stem to arsenic-cancer SCs (As-CSCs), through unknown mechanisms. MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the posttranscriptional level. In prior work, miR-143 was markedly downregulated in As-CSCs, suggesting a role in arsenic-induced malignant transformation. In the present study, we investigated whether loss of miR-143 expression is important in arsenic-induced transformation of prostate SCs. Restoration of miR-143 in As-CSCs was achieved by lentivirus-mediated miR-143 overexpression. Cells were assessed bi-weekly for up to 30 weeks to examine mitigation of cancer phenotype. Secreted matrix metalloproteinase (MMP) activity was increased by arsenic-induced malignant transformation, but miR-143 restoration decreased secreted MMP-2 and MMP-9 enzyme activities compared with scramble controls. Increased cell proliferation and apoptotic resistance, two hallmarks of cancer, were decreased upon miR-143 restoration. Increased apoptosis was associated with decreased BCL2 and BCL-XL expression. miR-143 restoration dysregulated the expression of SC/CSC self-renewal genes including NOTCH-1, BMI-1, OCT4 and ABCG2. The anticancer effects of miR-143 overexpression appeared to be mediated by targeting and inhibiting LIMK1 protein, and the phosphorylation of cofilin, a LIMK1 substrate. These findings clearly show that miR-143 restoration mitigated multiple cancer characteristics in the As-CSCs, suggesting a potential role in arsenic-induced transformation of prostate SCs. Thus, miR-143 is a potential biomarker and therapeutic target for arsenic-induced prostate cancer. - Highlights: • Chronic arsenic exposure

  12. Evaluation of DNA damage in patients with arsenic poisoning: urinary 8-hydroxydeoxyguanine

    International Nuclear Information System (INIS)

    Yamauchi, Hiroshi; Aminaka, Yoshito; Yoshida, Katsumi; Sun Guifan; Pi Jingbo; Waalkes, Michael P.

    2004-01-01

    The relationship between arsenic exposure and DNA damage in patients with acute or chronic arsenic poisoning was analyzed. Urinary 8-hydroxydeoxyguanine (8-OHdG) concentrations were measured as an indication of oxidative DNA damage. A remarkable increase in 8-OHdG in the urine was observed in 60% of 52 patients with acute arsenic poisoning from the accidental oral intake of the arsenic trioxide. This was two- to threefold higher than levels in normal healthy subjects (n = 248). There was a clear relationship between arsenic concentrations in urine after acute poisoning and elevated levels of 8-OHdG. Levels of urinary 8-OHdG returned to normal within 180 days after the acute arsenic poisoning event. In patients chronically poisoned by the consumption of well water with elevated levels of arsenate [As(V)], elevated 8-OHdG concentrations in urine were also observed. A significant correlation between the 8-OHdG levels and arsenic levels in the urine was observed in 82 patients with chronic poisoning. Thus, evidence of oxidative DNA damage occurred in acute arsenic poisoning by arsenite [As(III)] and in chronic arsenic poisoning by As(V). In chronic poisoning patients provided low-arsenic drinking water, evidence of DNA damage subsided between 9 months and 1 year after the high levels of arsenic intake were reduced. The initial level of arsenic exposure appeared to dictate the length of this recovery period. These data indicate that some aspects of chronic and acute arsenic poisoning may be reversible with the cessation of exposure. This knowledge may contribute to our understanding of the risk elevation from arsenic carcinogenesis and perhaps be used in a prospective fashion to assess individual risk

  13. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States); Kim, Donghern [Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536 (United States); Shi, Xianglin [Center for Research on Environmental Diseases, University of Kentucky, Lexington, KY 40536 (United States)

    2015-01-09

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H{sub 2}O{sub 2}) and superoxide dismutase 2 (SOD2, antioxidant against O{sub 2}{sup ·−}) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous

  14. Role of reactive oxygen species in arsenic-induced transformation of human lung bronchial epithelial (BEAS-2B) cells

    International Nuclear Information System (INIS)

    Zhang, Zhuo; Pratheeshkumar, Poyil; Budhraja, Amit; Son, Young-Ok; Kim, Donghern; Shi, Xianglin

    2015-01-01

    Highlights: • Short term exposure of cells to arsenic causes ROS generation. • Chronical exposure of cells to arsenic causes malignant cell transformation. • Inhibition of ROS generation reduces cell transformation by arsenic. • Arsenic-transformed cells exhibit reduced capacity of generating ROS. • Arsenic-transformed cells exhibit increased levels of antioxidants. - Abstract: Arsenic is an environmental carcinogen, its mechanisms of carcinogenesis remain to be investigated. Reactive oxygen species (ROS) are considered to be important. A previous study (Carpenter et al., 2011) has measured ROS level in human lung bronchial epithelial (BEAS-2B) cells and arsenic-transformed BEAS-2B cells and found that ROS levels were higher in transformed cells than that in parent normal cells. Based on these observations, the authors concluded that cell transformation induced by arsenic is mediated by increased cellular levels of ROS. This conclusion is problematic because this study only measured the basal ROS levels in transformed and parent cells and did not investigate the role of ROS in the process of arsenic-induced cell transformation. The levels of ROS in arsenic-transformed cells represent the result and not the cause of cell transformation. Thus question concerning whether ROS are important in arsenic-induced cell transformation remains to be answered. In the present study, we used expressions of catalase (antioxidant against H 2 O 2 ) and superoxide dismutase 2 (SOD2, antioxidant against O 2 ·− ) to decrease ROS level and investigated their role in the process of arsenic-induced cell transformation. Our results show that inhibition of ROS by antioxidant enzymes decreased arsenic-induced cell transformation, demonstrating that ROS are important in this process. We have also shown that in arsenic-transformed cells, ROS generation was lower and levels of antioxidants are higher than those in parent cells, in a disagreement with the previous report. The

  15. Exercise Prevents Memory Impairment Induced by Arsenic Exposure in Mice: Implication of Hippocampal BDNF and CREB.

    Directory of Open Access Journals (Sweden)

    Bao-Fei Sun

    Full Text Available High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g. was administered daily for 12 weeks. We found that arsenic at dosages of 1, 3, and 10 mg/kg decreased body weight and increased the arsenic content in the brain. The object recognition LTM (tested 24 h after training was disrupted by 3 mg/ kg and 10 mg/ kg, but not 1 mg/ kg arsenic exposure. Swimming exercise also prevented LTM impairment induced by 3 mg/ kg, but not with 10 mg/ kg, of arsenic exposure. The expression of brain-derived neurotrophic factor (BDNF and phosphorylated cAMP-response element binding protein (pCREB in the CA1 and dentate gyrus areas (DG of the dorsal hippocampus were decreased by 3 mg/ kg and 10 mg/ kg, but not by 1 mg/ kg, of arsenic exposure. The decrease in BDNF and pCREB in the CA1 and DG induced by 3 mg/ kg, but not 10 mg/ kg, of arsenic exposure were prevented by swimming exercise. Arsenic exposure did not affect the total CREB expression in the CA1 or DG. Taken together, these results indicated that swimming exercise prevented the impairment of object recognition LTM induced by arsenic exposure, which may be mediated by BDNF and CREB in the dorsal hippocampus.

  16. Cytogenetic insights into DNA damage and repair of lesions induced by a monomethylated trivalent arsenical

    Science.gov (United States)

    Arsenic is a human carcinogen, and only recently have animal models been developed that are useful in investigating its carcinogenic mode ofaction (MOA). However, how arsenic induces cancer is still an open question. In a previous paper, we proposed a model detailing how arsenic ...

  17. Atherosclerosis induced by arsenic in drinking water in rats through altering lipid metabolism

    International Nuclear Information System (INIS)

    Cheng, Tain-Junn; Chuu, Jiunn-Jye; Chang, Chia-Yu; Tsai, Wan-Chen; Chen, Kuan-Jung; Guo, How-Ran

    2011-01-01

    Arsenic in drinking water is a global environmental health problem, and the exposure may increase cardiovascular and cerebrovascular diseases mortalities, most likely through causing atherosclerosis. However, the mechanism of atherosclerosis formation after arsenic exposure is still unclear. To study the mechanism of atherosclerosis formation after arsenic exposure and explore the role of high cholesterol diet (HCD) in this process, we fed spontaneous hypertensive rats and Wistar Kyoto rats with basal diet or HCD and provided with them drinking water containing arsenic at different ages and orders for 20 consecutive weeks. We measured high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol, triglycerides, heat shock protein 70 (HSP 70), and high sensitive C-reactive protein (hs-CRP) at predetermined intervals and determined expressions of cholesteryl ester transfer protein-1 (CETP-1) and liver X receptor β (LXRβ) in the liver. Atherosclerosis was determined by examining the aorta with hematoxylin and eosin stain. After 20 weeks, we found arsenic, alone or combined with HCD, may promote atherosclerosis formation with transient increases in HSP 70 and hs-CRP. Early combination exposure decreased the HDL-C/LDL-C ratio without changing the levels of total cholesterol and triglyceride until 30 weeks old. Both CETP-1 and LXRβ activities were suppressed, most significantly in early combination exposure. In conclusion, arsenic exposure may induce atherosclerosis through modifying reverse cholesterol transport in cholesterol metabolism and suppressing LXRβ and CEPT-1 expressions. For decreasing atherosclerosis related mortality associated with arsenic, preventing exposure from environmental sources in early life is an important element. - Highlights: → Arsenic causes cardiovascular and cerebrovascular diseases through atherosclerosis. → Arsenic may promote atherosclerosis with transient increase in HSP 70 and hs

  18. Enhancing the efficacy of cisplatin in ovarian cancer treatment – could arsenic have a role

    Directory of Open Access Journals (Sweden)

    Helm C William

    2009-01-01

    Full Text Available Abstract Ovarian cancer affects more than 200,000 women each year around the world. Most women are not diagnosed until the disease has already metastasized from the ovaries with a resultant poor prognosis. Ovarian cancer is associated with an overall 5 year survival of little more than 50%. The mainstay of front-line therapy is cytoreductive surgery followed by chemotherapy. Traditionally, this has been by the intravenous route only but there is more interest in the delivery of intraperitoneal chemotherapy utilizing the pharmaco-therapeutic advantage of the peritoneal barrier. Despite three large, randomized clinical trials comparing intravenous with intraperitoneal chemotherapy showing improved outcomes for those receiving at least part of their chemotherapy by the intraperitoneal route. Cisplatin has been the most active drug for the treatment of ovarian cancer for the last 4 decades and the prognosis for women with ovarian cancer can be defined by the tumor response to cisplatin. Those whose tumors are innately platinum-resistant at the time of initial treatment have a very poor prognosis. Although the majority of patients with ovarian cancer respond to front-line platinum combination chemotherapy the majority will develop disease that becomes resistant to cisplatin and will ultimately succumb to the disease. Improving the efficacy of cisplatin could have a major impact in the fight against this disease. Arsenite is an exciting agent that not only has inherent single-agent tumoricidal activity against ovarian cancer cell lines but also multiple biochemical interactions that may enhance the cytotoxicity of cisplatin including inhibition of deoxyribose nucleic acid (DNA repair. In vitro studies suggest that arsenite may enhance the activity of cisplatin in other cell types. Arsenic trioxide is already used clinically to treat acute promyelocytic leukemia demonstrating its safety profile. Further research in ovarian cancer is warranted to define

  19. Arsenic induces apoptosis in mouse liver is mitochondria dependent and is abrogated by N-acetylcysteine

    International Nuclear Information System (INIS)

    Santra, Amal; Chowdhury, Abhijit; Ghatak, Subhadip; Biswas, Ayan; Dhali, Gopal Krishna

    2007-01-01

    Arsenicosis, caused by arsenic contamination of drinking water supplies, is a major public health problem in India and Bangladesh. Chronic liver disease, often with portal hypertension occurs in chronic arsenicosis, contributes to the morbidity and mortality. The early cellular events that initiate liver cell injury due to arsenicosis have not been studied. Our aim was to identify the possible mechanisms related to arsenic-induced liver injury in mice. Liver injury was induced in mice by arsenic treatment. The liver was used for mitochondrial oxidative stress, mitochondrial permeability transition (MPT). Evidence of apoptosis was sought by TUNEL test, caspase assay and histology. Pretreatment with N-acetyl-L-cysteine (NAC) was done to modulate hepatic GSH level. Arsenic treatment in mice caused liver injury associated with increased oxidative stress in liver mitochondria and alteration of MPT. Altered MPT facilitated cytochrome c release in the cytosol, activation of caspase 9 and caspase 3 activities and apoptotic cell death. Pretreatment of NAC to arsenic-treated mice abrogated all these alteration suggesting a glutathione (GSH)-dependent mechanism. Oxidative stress in mitochondria and inappropriate MPT are important in the pathogenesis of arsenic induced apoptotic liver cell injury. The phenomenon is GSH dependent and supplementation of NAC might have beneficial effects

  20. Arsenic and 17-β-estradiol bind to each other and neutralize each other’s signaling effects

    International Nuclear Information System (INIS)

    Kumar, Sukhdeep; Mukherjee, Tapan K.; Guptasarma, Purnananda

    2016-01-01

    We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each other’s independent cell signaling effects in respect of cell survival and proliferation/migration of breast cancer (MCF-7) cells. The possibility that this is due to binding of ATO to E2 was confirmed through difference absorption spectroscopy, chromatography-coupled voltammometry and 1-D 1 H and 13 C NMR spectroscopy. Binding leads to attenuation of E2’s hydroxyl 1 H peaks at its C17 and C3 carbon positions. The results suggest that ATO and E2 can titrate each other’s levels, potentially explaining why sustained arsenic exposure tends to be associated with delays in age of menarche, advanced age of menopause, poorer sperm quality, higher overall morbidity in men, and lower incidences of breast cancer in women in some arsenic-contaminated areas. - Highlights: • Difference absorption spectroscopy suggests that arsenic binds to estradiol. • Interaction with arsenic alters 1 H and 13 C NMR spectra of estradiol at positions C3 and C17. • Estradiol traps arsenic on C 18 reverse-phase columns. • Estradiol and arsenic neutralize each other’s ability to stimulate scratch wound healing. • Arsenic appears to form pnictogen bonds with hydroxyls on estradiol.

  1. Developmental and reproductive toxicity of inorganic arsenic: animal studies and human concerns.

    Science.gov (United States)

    Golub, M S; Macintosh, M S; Baumrind, N

    1998-01-01

    Information on the reproductive and developmental toxicity of inorganic arsenic is available primarily from studies in animals using arsenite and arsenate salts and arsenic trioxide. Inorganic arsenic has been extensively studied as a teratogen in animals. Data from animal studies demonstrate that arsenic can produce developmental toxicity, including malformation, death, and growth retardation, in four species (hamsters, mice, rats, rabbits). A characteristic pattern of malformations is produced, and the developmental toxicity effects are dependent on dose, route, and the day of gestation when exposure occurs. Studies with gavage and diet administration indicate that death and growth retardation are produced by oral arsenic exposure. Arsenic is readily transferred to the fetus and produces developmental toxicity in embryo culture. Animal studies have not identified an effect of arsenic on fertility in males or females. When females were dosed chronically for periods that included pregnancy, the primary effect of arsenic on reproduction was a dose-dependent increase in conceptus mortality and in postnatal growth retardation. Human data are limited to a few studies of populations exposed to arsenic from drinking water or from working at or living near smelters. Associations with spontaneous abortion and stillbirth have been reported in more than one of these studies, but interpretation of these studies is complicated because study populations were exposed to multiple chemicals. Thus, animal studies suggest that environmental arsenic exposures are primarily a risk to the developing fetus. In order to understand the implications for humans, attention must be given to comparative pharmacokinetics and metabolism, likely exposure scenarios, possible mechanisms of action, and the potential role of arsenic as an essential nutrient.

  2. Arsenic tolerant Trichoderma sp. reduces arsenic induced stress in chickpea (Cicer arietinum).

    Science.gov (United States)

    Tripathi, Pratibha; Singh, Poonam C; Mishra, Aradhana; Srivastava, Suchi; Chauhan, Reshu; Awasthi, Surabhi; Mishra, Seema; Dwivedi, Sanjay; Tripathi, Preeti; Kalra, Alok; Tripathi, Rudra D; Nautiyal, Chandra S

    2017-04-01

    Toxic metalloids including arsenic (As) can neither be eliminated nor destroyed from environment; however, they can be converted from toxic to less/non-toxic forms. The form of As species and their concentration determines its toxicity in plants. Therefore, the microbe mediated biotransformation of As is crucial for its plant uptake and toxicity. In the present study the role of As tolerant Trichoderma in modulating As toxicity in chickpea plants was explored. Chickpea plants grown in arsenate spiked soil under green house conditions were inoculated with two plant growth promoting Trichoderma strains, M-35 (As tolerant) and PPLF-28 (As sensitive). Total As concentration in chickpea tissue was comparable in both the Trichoderma treatments, however, differences in levels of organic and inorganic As (iAs) species were observed. The shift in iAs to organic As species ratio in tolerant Trichoderma treatment correlated with enhanced plant growth and nutrient content. Arsenic stress amelioration in tolerant Trichoderma treatment was also evident through rhizospheric microbial community and anatomical studies of the stem morphology. Down regulation of abiotic stress responsive genes (MIPS, PGIP, CGG) in tolerant Trichoderma + As treatment as compared to As alone and sensitive Trichoderma + As treatment also revealed that tolerant strain enhanced the plant's potential to cope with As stress as compared to sensitive one. Considering the bioremediation and plant growth promotion potential, the tolerant Trichoderma may appear promising for its utilization in As affected fields for enhancing agricultural productivity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Ground water pollution by arsenic and its effects on health. Involvement of metabolic methylation in arsenic-induced genetic damage and tumorigenesis; Muki hiso no mechiru ka taisha to idenshi shogaisei narabini shuyo yuhatsusei

    Energy Technology Data Exchange (ETDEWEB)

    Yamanaka, K. [Nihon Univ., Tokyo (Japan)] Okada, S. [Shizuoka Prefecture (Japan)

    1997-07-10

    Drinking water contamination has become a worldwide problem. It is pointed out that re-evaluation of genetic damage with carcinogen is considered as an important problem particularly arsenic`s effects on health. To explain the genetic damage development mechanism of arsenic compound, results of the research conducted on the action of arsenic compound which develops during metabolic methylation process and inorganic arsenic are explained in this paper. The results of the study are summarized as follows. Arsenic genetic damage mutation is caused by dimethyl arsenic in main metabolism than inorganic arsenic. Lung DNA damage is induced by the interaction of O2 and arsenic peroxide radical. Dimethyl arsenic shows very important effect on lung cancer formation process which is induced based on 4-nitroquinoline-1-oxide (4NQO). It not only promotes lung cancer but it also plays an important role in malignant tumor`s mutation. 25 refs., 2 figs.

  4. Risk of Erectile Dysfunction Induced by Arsenic Exposure through Well Water Consumption in Taiwan

    Science.gov (United States)

    Hsieh, Fang-I; Hwang, Ti-Sheng; Hsieh, Yi-Chen; Lo, Hsiu-Chiung; Su, Chien-Tien; Hsu, Hui-Shing; Chiou, Hung-Yi; Chen, Chien-Jen

    2008-01-01

    Background Erectile dysfunction (ED) has a profound impact on the quality of life of many men. Many risk factors are associated with ED, such as aging, sex hormone levels, hypertension, cardiovascular diseases, and diabetes mellitus. Arsenic exposure could damage peripheral vessels and increase the risk of cardiovascular disease. However, the relationship between arsenic exposure and ED has seldom been evaluated. Objectives In this study we aimed to investigate whether exposure to arsenic enhances the risk of ED. Methods We recruited 177 males ≥ 50 years of age through health examinations conducted in three hospitals in Taiwan. We used a questionnaire (International Index of Erectile Function-5) to measure the level of erectile function. Sex hormones, including total testosterone and sex hormone–binding globulin, were determined by radioimmunoassay. We used another standardized questionnaire to collect background and behavioral information (e.g., cigarette smoking; alcohol, tea, or coffee drinking; and physical activity). Results The prevalence of ED was greater in the arsenic-endemic area (83.3%) than in the non–arsenic-endemic area (66.7%). Subjects with arsenic exposure > 50 ppb had a significantly higher risk of developing ED than those with exposure ≤ 50 ppb, after adjusting for age, cigarette smoking, diabetes mellitus, hypertension, and cardiovascular disease [odds ratio (OR) = 3.4]. Results also showed that the risk of developing severe ED was drastically enhanced by arsenic exposure (OR = 7.5), after adjusting for free testosterone and traditional risk factors of ED. Conclusions Results suggested that chronic arsenic exposure has a negative impact on erectile function. PMID:18414639

  5. Red mud (RM)-Induced enhancement of iron plaque formation reduces arsenic and metal accumulation in two wetland plant species.

    Science.gov (United States)

    Yang, J X; Guo, Q J; Yang, J; Zhou, X Y; Ren, H Y; Zhang, H Z; Xu, R X; Wang, X D; Peters, M; Zhu, G X; Wei, R F; Tian, L Y; Han, X K

    2016-01-01

    Human activities have resulted in arsenic (As) and heavy metals accumulation in paddy soils in China. Phytoremediation has been suggested as an effective and low-cost method to clean up contaminated soils. A combined soil-sand pot experiment was conducted to investigate the influence of red mud (RM) supply on iron plaque formation and As and heavy metal accumulation in two wetland plant species (Cyperus alternifolius Rottb., Echinodorus amazonicus Rataj), using As and heavy metals polluted paddy soil combined with three rates of RM application (0, 2%, 5%). The results showed that RM supply significantly decreased As and heavy metals accumulation in shoots of the two plants due to the decrease of As and heavy metal availability and the enhancement of the formation of iron plaque on the root surface and in the rhizosphere. Both wetland plants supplied with RM tended to have more Fe plaque, higher As and heavy metals on roots and in their rhizospheres, and were more tolerant of As and heavy metal toxicity. The results suggest that RM-induced enhancement of the formation of iron plaque on the root surface and in the rhizosphere of wetland plants may be significant for remediation of soils contaminated with As and heavy metals.

  6. Microvascular dysfunction with increased vascular leakage response in mice systemically exposed to arsenic.

    Science.gov (United States)

    Chen, Shih-Chieh; Huang, Shin-Yin; Lu, Chi-Yu; Hsu, Ya-Hung; Wang, Dean-Chuan

    2014-09-01

    The mechanisms underlying cardiovascular disease induced by arsenic exposure are not completely understood. The objectives of this study were to investigate whether arsenic-fed mice have an increased vascular leakage response to vasoactive agents and whether enhanced type-2 protein phosphatase (PP2A) activity is involved in mustard oil-induced leakage. ICR mice were fed water or sodium arsenite (20 mg/kg) for 4 or 8 weeks. The leakage response to vasoactive agents was quantified using the Evans blue (EB) technique or vascular labeling with carbon particles. Increased EB leakage and high density of carbon-labeled microvessels were detected in arsenic-fed mice treated with mustard oil. Histamine induced significantly higher vascular leakage in arsenic-fed mice than in water-fed mice. Pretreatment with the PP2A inhibitor okadaic acid or the neurokinin 1 receptor (NK1R) blocker RP67580 significantly reduced mustard oil-induced vascular leakage in arsenic-fed mice. The protein levels of PP2Ac and NK1R were similar in both groups. PP2A activity was significantly higher in the arsenic-fed mice compared with the control group. These findings indicate that microvessels generally respond to vasoactive agents, and that the increased PP2A activity is involved in mustard oil-induced vascular leakage in arsenic-fed mice. Arsenic may initiate endothelial dysfunction, resulting in vascular leakage in response to vasoactive agents.

  7. Effect of precipitation route on the properties of antimony trioxide

    International Nuclear Information System (INIS)

    Abdullah, Abdul Halim; Noor, Nor Hayati Mohd; Ramli, Irmawati; Hashim, Mansor

    2008-01-01

    Antimony trioxide was prepared, using antimony potassium tartarate as starting material, via forward and reverse precipitation technique. The characteristics of the resulting antimony oxides were determined by BET surface area method, differential thermogravimetry analysis (DTG), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FT-IR) and SEM. The DTG curves for all uncalcined samples showed only a single endothermic peak which indicated that the sample is antimony trioxide. Unlike forward precipitation technique which resulted in a single antimony trioxide phase which is senarmontite, reverse precipitation technique produced antimony trioxide with both senarmontite and valentinite phase. Upon calcinations at 723 K, a small amount of Sb 2 O 4 with cervantite phase was formed at the expense of Sb 2 O 3 senarmontite phase as detected from the XRD pattern and infrared spectrum of RSb. The effect of preparation route on the properties of the antimony trioxide produced was clearly demonstrated

  8. Detection of trace amount of arsenic in groundwater by laser-induced breakdown spectroscopy and adsorption

    Science.gov (United States)

    Haider, A. F. M. Y.; Hedayet Ullah, M.; Khan, Z. H.; Kabir, Firoza; Abedin, K. M.

    2014-03-01

    LIBS technique coupled with adsorption has been applied for the efficient detection of arsenic in liquid. Several adsorbents like tea leaves, bamboo slice, charcoal and zinc oxide have been used to enable sensitive detection of arsenic presence in water using LIBS. Among these, zinc oxide and charcoal show the better results. The detection limits for arsenic in water were 1 ppm and 8 ppm, respectively, when ZnO and charcoal were used as adsorbents of arsenic. To date, the determination of 1 ppm of As in water is the lowest concentration of detected arsenic in water by the LIBS technique. The detection limit of As was lowered to even less than 100 ppb by a combination of LIBS technique, adsorption by ZnO and concentration enhancement technique. Using the combination of these three techniques the ultimate concentration of arsenic was found to be 0.083 ppm (83 ppb) for arsenic polluted water collected from a tube-well of Farajikandi union (longitude 90.64°, latitude 23.338° north) of Matlab Upozila of Chandpur district in Bangladesh. This result compares fairly well with the finding of arsenic concentration of 0.078 ppm in the sample by the AAS technique at the Bangladesh Council of Scientific and Industrial Research (BCSIR) lab. Such a low detection limit (1 ppm) of trace elements in liquid matrix has significantly enhanced the scope of LIBS as an analytical tool.

  9. Both Phosphorus Fertilizers and Indigenous Bacteria Enhance Arsenic Release into Groundwater in Arsenic-Contaminated Aquifers.

    Science.gov (United States)

    Lin, Tzu-Yu; Wei, Chia-Cheng; Huang, Chi-Wei; Chang, Chun-Han; Hsu, Fu-Lan; Liao, Vivian Hsiu-Chuan

    2016-03-23

    Arsenic (As) is a human carcinogen, and arsenic contamination in groundwater is a worldwide public health concern. Arsenic-affected areas are found in many places but are reported mostly in agricultural farmlands, yet the interaction of fertilizers, microorganisms, and arsenic mobilization in arsenic-contaminated aquifers remains uncharacterized. This study investigates the effects of fertilizers and bacteria on the mobilization of arsenic in two arsenic-contaminated aquifers. We performed microcosm experiments using arsenic-contaminated sediments and amended with inorganic nitrogenous or phosphorus fertilizers for 1 and 4 months under aerobic and anaerobic conditions. The results show that microcosms amended with 100 mg/L phosphorus fertilizers (dipotassium phosphate), but not nitrogenous fertilizers (ammonium sulfate), significantly increase aqueous As(III) release in arsenic-contaminated sediments under anaerobic condition. We also show that concentrations of iron, manganese, potassium, sodium, calcium, and magnesium are increased in the aqueous phase and that the addition of dipotassium phosphate causes a further increase in aqueous iron, potassium, and sodium, suggesting that multiple metal elements may take part in the arsenic release process. Furthermore, microbial analysis indicates that the dominant microbial phylum is shifted from α-proteobacteria to β- and γ-proteobacteria when the As(III) is increased and phosphate is added in the aquifer. Our results provide evidence that both phosphorus fertilizers and microorganisms can mediate the release of arsenic to groundwater in arsenic-contaminated sediments under anaerobic condition. Our study suggests that agricultural activity such as the use of fertilizers and monitoring phosphate concentration in groundwater should be taken into consideration for the management of arsenic in groundwater.

  10. Cortex and hippocampus DNA epigenetic response to a long-term arsenic exposure via drinking water.

    Science.gov (United States)

    Du, Xiaoyan; Tian, Meiping; Wang, Xiaoxue; Zhang, Jie; Huang, Qingyu; Liu, Liangpo; Shen, Heqing

    2018-03-01

    The neurotoxicity of arsenic is a serious health problem, especially for children. DNA epigenetic change may be an important pathogenic mechanism, but the molecular pathway remains obscure. In this study, the weaned male Sprague-Dawly (SD) rats were treated with arsenic trioxide via drinking water for 6 months, simulating real developmental exposure situation of children. Arsenic exposure impaired the cognitive abilities, and altered the expression of neuronal activity-regulated genes. Total arsenic concentrations of cortex and hippocampus tissues were significantly increased in a dose-dependent manner. The reduction in 5-methylcytosine (5 mC) and 5-hydroxymethylcytosine (5hmC) levels as well as the down-regulation of DNA methyltransferases (DNMTs) and ten-eleven translocations (TETs) expression suggested that DNA methylation/demethylation processes were significantly suppressed in brain tissues. S-adenosylmethionine (SAM) level wasn't changed, but the expression of the important indicators of oxidative/anti-oxidative balance and tricarboxylic acid (TCA) cycle was significantly deregulated. Overall, arsenic can disrupt oxidative/anti-oxidative balance, further inhibit TETs expression through TCA cycle and alpha-ketoglutarate (α-KG) pathway, and consequently cause DNA methylation/demethylation disruption. The present study implies oxidative stress but not SAM depletion may lead to DNA epigenetic alteration and arsenic neurotoxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Reactive oxygen species contribute to arsenic-induced EZH2 phosphorylation in human bronchial epithelial cells and lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Lingzhi; Qiu, Ping; Chen, Bailing; Lu, Yongju; Wu, Kai; Thakur, Chitra; Chang, Qingshan; Sun, Jiaying; Chen, Fei, E-mail: fchen@wayne.edu

    2014-05-01

    Our previous studies suggested that arsenic is able to induce serine 21 phosphorylation of the EZH2 protein through activation of JNK, STAT3, and Akt signaling pathways in the bronchial epithelial cell line, BEAS-2B. In the present report, we further demonstrated that reactive oxygen species (ROS) were involved in the arsenic-induced protein kinase activation that leads to EZH2 phosphorylation. Several lines of evidence supported this notion. First, the pretreatment of the cells with N-acetyl-L-cysteine (NAC), a potent antioxidant, abolishes arsenic-induced EZH2 phosphorylation along with the inhibition of JNK, STAT3, and Akt. Second, H{sub 2}O{sub 2}, the most important form of ROS in the cells in response to extracellular stress signals, can induce phosphorylation of the EZH2 protein and the activation of JNK, STAT3, and Akt. By ectopic expression of the myc-tagged EZH2, we additionally identified direct interaction and phosphorylation of the EZH2 protein by Akt in response to arsenic and H{sub 2}O{sub 2}. Furthermore, both arsenic and H{sub 2}O{sub 2} were able to induce the translocation of ectopically expressed or endogenous EZH2 from nucleus to cytoplasm. In summary, the data presented in this report indicate that oxidative stress due to ROS generation plays an important role in the arsenic-induced EZH2 phosphorylation. - Highlights:: • Arsenic (As{sup 3+}) induces EZH phosphorylation. • JNK, STAT3, and Akt contribute to EZH2 phosphorylation. • Oxidative stress is involved in As{sup 3+}-induced EZH2 phosphorylation. • As{sup 3+} induces direct interaction of Akt and EZH2. • Phosphorylated EZH2 localized in cytoplasm.

  12. Mthfr gene ablation enhances susceptibility to arsenic prenatal toxicity

    International Nuclear Information System (INIS)

    Wlodarczyk, Bogdan J.; Zhu, Huiping; Finnell, Richard H.

    2014-01-01

    Background: In utero exposure to arsenic is known to adversely affect reproductive outcomes. Evidence of arsenic teratogenicity varies widely and depends on individual genotypic differences in sensitivity to As. In this study, we investigated the potential interaction between 5,10-methylenetetrahydrofolate reductase (Mthfr) genotype and arsenic embryotoxicity using the Mthfr knockout mouse model. Methods: Pregnant dams were treated with sodium arsenate, and reproductive outcomes including: implantation, resorption, congenital malformation and fetal birth weight were recorded at E18.5. Results: When the dams in Mthfr +/− × Mthfr +/− matings were treated with 7.2 mg/kg As, the resorption rate increased to 43.4%, from a background frequency of 7.2%. The As treatment also induced external malformations (40.9%) and significantly lowered the average fetal birth weight among fetuses, without any obvious toxic effect on the dam. When comparing the pregnancy outcomes resulting from different mating scenarios (Mthfr +/+ × Mthfr +/− , Mthfr +/− × Mthfr +/− and Mthfr −/− × Mthfr+/− ) and arsenic exposure; the resorption rate showed a linear relationship with the number of null alleles (0, 1 or 2) in the Mthfr dams. Fetuses from nullizygous dams had the highest rate of external malformations (43%) and lowest average birth weight. When comparing the outcomes of reciprocal matings (nullizygote × wild-type versus wild-type × nullizygote) after As treatment, the null dams showed significantly higher rates of resorptions and malformations, along with lower fetal birth weights. Conclusions: Maternal genotype contributes to the sensitivity of As embryotoxicity in the Mthfr mouse model. The fetal genotype, however, does not appear to affect the reproductive outcome after in utero As exposure. - Highlights: • An interaction between Mthfr genotype and arsenic embryotoxicity is presented. • Maternal Mthfr genotype contributes to the sensitivity of As

  13. Induction of glutathione synthesis in human hepatocytes by acute and chronic arsenic exposure: Differential roles of mitogen-activated protein kinases

    International Nuclear Information System (INIS)

    Hou, Yongyong; Wang, Yi; Wang, Huihui; Xu, Yuanyuan

    2014-01-01

    Highlights: • Arsenic exposure increased intracellular levels of glutathione. • Mitogen-activated protein kinases were involved in glutathione homeostasis. • ERK contributed to glutathione synthesis during acute arsenic exposure. • Glutathione synthesis was regulated by p38 at least in part independent of NRF2 during chronic arsenic exposure. - Abstract: Glutathione (GSH) is a vital component of antioxidant defense which protects cells from toxic insults. Previously we found intracellular GSH was involved in cell resistance against arsenic-induced cytotoxicity. However, molecular mechanisms of GSH homeostasis during arsenic exposure are largely undefined. Here, we investigated roles of mitogen-activated protein kinases (MAPKs) in GSH synthesis pathway with two arsenic exposure strategies by using Chang human hepatocytes. In one strategy, acute arsenic exposure (20 μM, 24 h) was applied, as MAPK signaling is generally considered to be transient. In the other one, chronic arsenic exposure (500 nM, 20 weeks) was applied, which mimicked the general human exposure to arsenic. We found that acute arsenic exposure activated extracellular signal-regulated 1/2 kinases (ERK1/2) and c-Jun N-terminal kinase (JNK) in parallel with increased transcription and nuclear translocation of factor-erythroid 2-related factor 2 (NRF2) and enhanced expression of γ-glutamyl cysteine ligase catalytic subunit (GCLC), resulting in elevated intracellular GSH levels. Specific ERK inhibitor abolished arsenic-induced NRF2 nuclear translocation and GSH synthesis. During chronic arsenic exposure which induced a malignant cellular phenotype, continuous p38 activation and NRF2 nuclear translocation were observed with enhanced GSH synthesis. Specific p38 inhibitor attenuated arsenic-enhanced GSH synthesis without changing NRF2 nuclear translocation. Taken together, our results indicate MAPK pathways play an important role in cellular GSH homeostasis in response to arsenic. However, the

  14. Arsenic and 17-β-estradiol bind to each other and neutralize each other’s signaling effects

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Sukhdeep [Center for Protein Science, Design and Engineering (CPSDE), Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector-81, SAS Nagar, Punjab 140306 (India); Mukherjee, Tapan K. [Department of Biotechnology, Maharishi Markandeshwar University, Mullana, Ambala, Haryana 133207 (India); Guptasarma, Purnananda, E-mail: guptasarma@iisermohali.ac.in [Center for Protein Science, Design and Engineering (CPSDE), Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Mohali, Knowledge City, Sector-81, SAS Nagar, Punjab 140306 (India)

    2016-09-02

    We report that arsenic trioxide (ATO) and 17-beta-estradiol (E2) abolish each other’s independent cell signaling effects in respect of cell survival and proliferation/migration of breast cancer (MCF-7) cells. The possibility that this is due to binding of ATO to E2 was confirmed through difference absorption spectroscopy, chromatography-coupled voltammometry and 1-D {sup 1}H and {sup 13}C NMR spectroscopy. Binding leads to attenuation of E2’s hydroxyl {sup 1}H peaks at its C17 and C3 carbon positions. The results suggest that ATO and E2 can titrate each other’s levels, potentially explaining why sustained arsenic exposure tends to be associated with delays in age of menarche, advanced age of menopause, poorer sperm quality, higher overall morbidity in men, and lower incidences of breast cancer in women in some arsenic-contaminated areas. - Highlights: • Difference absorption spectroscopy suggests that arsenic binds to estradiol. • Interaction with arsenic alters {sup 1}H and {sup 13}C NMR spectra of estradiol at positions C3 and C17. • Estradiol traps arsenic on C{sub 18} reverse-phase columns. • Estradiol and arsenic neutralize each other’s ability to stimulate scratch wound healing. • Arsenic appears to form pnictogen bonds with hydroxyls on estradiol.

  15. Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-κB, p38 and JNK MAPK pathway

    International Nuclear Information System (INIS)

    Ghosh, Jyotirmoy; Das, Joydeep; Manna, Prasenjit; Sil, Parames C.

    2009-01-01

    Cardiac dysfunction is a major cause of morbidity and mortality worldwide due to its complex pathogenesis. However, little is known about the mechanism of arsenic-induced cardiac abnormalities and the use of antioxidants as the possible protective agents in this pathophysiology. Conditionally essential amino acid, taurine, accounts for 25% to 50% of the amino acid pool in myocardium and possesses antioxidant properties. The present study has, therefore, been carried out to investigate the underlying mechanism of the beneficial role of taurine in arsenic-induced cardiac oxidative damage and cell death. Arsenic reduced cardiomyocyte viability, increased reactive oxygen species (ROS) production and intracellular calcium overload, and induced apoptotic cell death by mitochondrial dependent caspase-3 activation and poly-ADP ribose polymerase (PARP) cleavage. These changes due to arsenic exposure were found to be associated with increased IKK and NF-κB (p65) phosphorylation. Pre-exposure of myocytes to an IKK inhibitor (PS-1145) prevented As-induced caspase-3 and PARP cleavage. Arsenic also markedly increased the activity of p38 and JNK MAPKs, but not ERK to that extent. Pre-treatment with SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated NF-κB and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-κB activation. Taurine treatment suppressed these apoptotic actions, suggesting that its protective role in arsenic-induced cardiomyocyte apoptosis is mediated by attenuation of p38 and JNK MAPK signaling pathways. Similarly, arsenic intoxication altered a number of biomarkers related to cardiac oxidative stress and other apoptotic indices in vivo and taurine supplementation could reduce it. Results suggest that taurine prevented arsenic-induced myocardial pathophysiology, attenuated NF-κB activation via IKK, p38 and JNK MAPK signaling pathways and could possibly provide a protection against As-induced

  16. Arsenic content in Portland cement: a literature review.

    Science.gov (United States)

    Tenório de Franca, Talita Ribeiro; da Silva, Raphaela Juvenal; Sedycias de Queiroz, Michellini; Aguiar, Carlos Menezes

    2010-01-01

    Portland cement (PC) is a hydraulic binding material widely used in the building industry. The main interest in its use in dentistry is focused on a possible alternative to mineral trioxide aggregate (MTA) because PC is less expensive and is widely available. In dentistry, PC has been used in dental procedures such as pulpotomy, pulp capping, repair of root perforation and root-end filling. The purpose of this article is review the dental literature about the PC, its composition with special attention to arsenic content, properties, and application in dentistry. A bibliographic research was performed in Bireme, PubMed, LILACS and Scopus data bases looking for national and international studies about the PC composition, properties and clinical use. It was observed that PC has favorable biological properties very similar to those of MTA. The PC has shown good cell proliferation induction with formation of a monolayer cell, satisfactory inflammatory response, inhibitory effect of prostaglandin and antimicrobial effect. Studies have shown that PC is not cytotoxic, stimulates the apposition of reparative dentin and permits cellular attachment and growth. Regarding arsenic presence, its levels and release are low. PC has physical, chemical and biological properties similar to MTA. Arsenic levels and release are low, therefore, unable to cause toxic effects.

  17. Arsenic content in Portland cement: A literature review

    Directory of Open Access Journals (Sweden)

    Tenorio de Franca Talita

    2010-01-01

    Full Text Available Portland cement (PC is a hydraulic binding material widely used in the building industry. The main interest in its use in dentistry is focused on a possible alternative to mineral trioxide aggregate (MTA because PC is less expensive and is widely available. In dentistry, PC has been used in dental procedures such as pulpotomy, pulp capping, repair of root perforation and root-end filling. The purpose of this article is review the dental literature about the PC, its composition with special attention to arsenic content, properties, and application in dentistry. A bibliographic research was performed in Bireme, PubMed, LILACS and Scopus data bases looking for national and international studies about the PC composition, properties and clinical use. It was observed that PC has favorable biological properties very similar to those of MTA. The PC has shown good cell proliferation induction with formation of a monolayer cell, satisfactory inflammatory response, inhibitory effect of prostaglandin and antimicrobial effect. Studies have shown that PC is not cytotoxic, stimulates the apposition of reparative dentin and permits cellular attachment and growth. Regarding arsenic presence, its levels and release are low. PC has physical, chemical and biological properties similar to MTA. Arsenic levels and release are low, therefore, unable to cause toxic effects.

  18. Proteomic profiling reveals candidate markers for arsenic-induced skin keratosis.

    Science.gov (United States)

    Guo, Zhiling; Hu, Qin; Tian, Jijing; Yan, Li; Jing, Chuanyong; Xie, Heidi Qunhui; Bao, Wenjun; Rice, Robert H; Zhao, Bin; Jiang, Guibin

    2016-11-01

    Proteomics technology is an attractive biomarker candidate discovery tool that can be applied to study large sets of biological molecules. To identify novel biomarkers and molecular targets in arsenic-induced skin lesions, we have determined the protein profile of arsenic-affected human epidermal stratum corneum by shotgun proteomics. Samples of palm and foot sole from healthy subjects were analyzed, demonstrating similar protein patterns in palm and sole. Samples were collected from the palms of subjects with arsenic keratosis (lesional and adjacent non-lesional samples) and arsenic-exposed subjects without lesions (normal). Samples from non-exposed healthy individuals served as controls. We found that three proteins in arsenic-exposed lesional epidermis were consistently distinguishably expressed from the unaffected epidermis. One of these proteins, the cadherin-like transmembrane glycoprotein, desmoglein 1 (DSG1) was suppressed. Down-regulation of DSG1 may lead to reduced cell-cell adhesion, resulting in abnormal epidermal differentiation. The expression of keratin 6c (KRT6C) and fatty acid binding protein 5 (FABP5) were significantly increased. FABP5 is an intracellular lipid chaperone that plays an essential role in fatty acid metabolism in human skin. This raises a possibility that overexpression of FABP5 may affect the proliferation or differentiation of keratinocytes by altering lipid metabolism. KRT6C is a constituent of the cytoskeleton that maintains epidermal integrity and cohesion. Abnormal expression of KRT6C may affect its structural role in the epidermis. Our findings suggest an important approach for future studies of arsenic-mediated toxicity and skin cancer, where certain proteins may represent useful biomarkers of early diagnoses in high-risk populations and hopefully new treatment targets. Further studies are required to understand the biological role of these markers in skin pathogenesis from arsenic exposure. Copyright © 2016 Elsevier Ltd

  19. Arsenic-induced alterations in the contact hypersensitivity response in Balb/c mice

    International Nuclear Information System (INIS)

    Patterson, Rachel; Vega, Libia; Trouba, Kevin; Bortner, Carl; Germolec, Dori

    2004-01-01

    Previous studies in our laboratory indicate that arsenic alters secretion of growth promoting and inflammatory cytokines in the skin that can regulate the migration and maturation of Langerhans cells (LC) during allergic contact dermatitis. Therefore, we hypothesized that arsenic may modulate hypersensitivity responses to cutaneous sensitizing agents by altering cytokine production, LC migration, and T-cell proliferation. To investigate this hypothesis, we examined the induction and elicitation phases of dermal sensitization. Mice exposed to 50 mg/l arsenic in the drinking water for 4 weeks demonstrated a reduction in lymph node cell (LNC) proliferation and ear swelling following sensitization with 2,4-dinitrofluorobenzene (DNFB), compared to control mice. LC and T-cell populations in the draining lymph nodes of DNFB-sensitized mice were evaluated by fluorescence-activated cell sorting; activated LC were reduced in cervical lymph nodes, suggesting that LC migration may be altered following arsenic exposure. Lymphocytes from arsenic-treated animals sensitized with fluorescein isothiocyanate (FITC) exhibited reduced proliferative responses following T-cell mitogen stimulation in vitro; however, lymphocyte proliferation from nonsensitized, arsenic-treated mice was comparable to controls. Arsenic exposure also reduced the number of thioglycollate-induced peritoneal macrophages and circulating neutrophils. These studies demonstrate that repeated, prolonged exposure to nontoxic concentrations of sodium arsenite alters immune cell populations and results in functional changes in immune responses, specifically attenuation of contact hypersensitivity

  20. Role and mechanism of arsenic in regulating angiogenesis.

    Directory of Open Access Journals (Sweden)

    Ling-Zhi Liu

    Full Text Available Arsenic is a wide spread carcinogen associated with several kinds of cancers including skin, lung, bladder, and liver cancers. Lung is one of the major targets of arsenic exposure. Angiogenesis is the pivotal process during carcinogenesis and chronic pulmonary diseases, but the role and mechanism of arsenic in regulating angiogenesis remain to be elucidated. In this study we show that short time exposure of arsenic induces angiogenesis in both human immortalized lung epithelial cells BEAS-2B and adenocarcinoma cells A549. To study the molecular mechanism of arsenic-inducing angiogenesis, we find that arsenic induces reactive oxygen species (ROS generation, which activates AKT and ERK1/2 signaling pathways and increases the expression of hypoxia-inducible factor 1 (HIF-1 and vascular endothelial growth factor (VEGF. Inhibition of ROS production suppresses angiogenesis by decreasing AKT and ERK activation and HIF-1 expression. Inhibition of ROS, AKT and ERK1/2 signaling pathways is sufficient to attenuate arsenic-inducing angiogenesis. HIF-1 and VEGF are downstream effectors of AKT and ERK1/2 that are required for arsenic-inducing angiogenesis. These results shed light on the mechanism of arsenic in regulating angiogenesis, and are helpful to develop mechanism-based intervention to prevent arsenic-induced carcinogenesis and angiogenesis in the future.

  1. Perturbations in immune responses induced by concurrent subchronic exposure to arsenic and endosulfan

    International Nuclear Information System (INIS)

    Aggarwal, Manoj; Naraharisetti, Suresh Babu; Dandapat, S.; Degen, G.H.; Malik, J.K.

    2008-01-01

    The metalloid arsenic and the chlorinated insecticide endosulfan are common environmental contaminants. Humans, animals, and birds are exposed to these chemicals through water and food. Although health effects due to either arsenic or endosulfan exposure are documented, the toxicological impact of co-exposure to these environmental pollutants is unpredictable and unknown. The present study was undertaken to assess whether concurrent exposure to arsenic and endosulfan induces significant alterations in immunological functions. Day-old chicks were exposed to 3.7 ppm of arsenic via drinking water and to 30 ppm of endosulfan-mixed feed either individually or concurrently for up to 60 days. All the chicks were vaccinated with Ranikhet disease virus (F-strain; RD-F) on days 1 and 30. During the course of study and at term, parameters of cellular and humoral immunity were determined. None of the treatments altered the absolute body weight or body weight gain, except arsenic significantly reduced weight gain on day 60. Absolute, but not the relative, weights of spleen, thymus and bursa of Fabricius were significantly reduced in all the treatment groups. The metalloid and insecticide combination significantly depressed the ability of peripheral blood and splenic lymphocytes to proliferate in response to antigen RD-F and mitogen Con A. The delayed type hypersensitivity response to 2,4-dinitro-1-chlorobenzene or to PHA-P was also significantly decreased. Nitric oxide production by RD-F or lipopolysaccharide-stimulated peripheral blood and splenic mononuclear cells was significantly suppressed following concurrent exposure to arsenic and endosulfan. Furthermore, the combined exposure also decreased the antibody response to RD-F. The suppression of cellular and humoral immune responses was also evident following administration of individual compounds, and it was not exacerbated following concurrent exposure. To our knowledge, this is the first report describing the suppression

  2. High fat diet aggravates arsenic induced oxidative stress in rat heart and liver.

    Science.gov (United States)

    Dutta, Mousumi; Ghosh, Debosree; Ghosh, Arnab Kumar; Bose, Gargi; Chattopadhyay, Aindrila; Rudra, Smita; Dey, Monalisa; Bandyopadhyay, Arkita; Pattari, Sanjib K; Mallick, Sanjaya; Bandyopadhyay, Debasish

    2014-04-01

    Arsenic is a well known global groundwater contaminant. Exposure of human body to arsenic causes various hazardous effects via oxidative stress. Nutrition is an important susceptible factor which can affect arsenic toxicity by several plausible mechanisms. Development of modern civilization led to alteration in the lifestyle as well as food habits of the people both in urban and rural areas which led to increased use of junk food containing high level of fat. The present study was aimed at investigating the effect of high fat diet on heart and liver tissues of rats when they were co-treated with arsenic. This study was established by elucidating heart weight to body weight ratio as well as analysis of the various functional markers, oxidative stress biomarkers and also the activity of the antioxidant enzymes. Histological analysis confirmed the biochemical investigations. From this study it can be concluded that high fat diet increased arsenic induced oxidative stress. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Genetic polymorphisms in glutathione S-transferase (GST superfamily and risk of arsenic-induced urothelial carcinoma in residents of southwestern Taiwan

    Directory of Open Access Journals (Sweden)

    Hsueh Yu-Mei

    2011-07-01

    Full Text Available Abstract Background Arsenic exposure is an important public health issue worldwide. Dose-response relationship between arsenic exposure and risk of urothelial carcinoma (UC is consistently observed. Inorganic arsenic is methylated to form the metabolites monomethylarsonic acid and dimethylarsinic acid while ingested. Variations in capacity of xenobiotic detoxification and arsenic methylation might explain individual variation in susceptibility to arsenic-induced cancers. Methods To estimate individual susceptibility to arsenic-induced UC, 764 DNA specimens from our long-term follow-up cohort in Southwestern Taiwan were used and the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and arsenic methylation enzymes including GSTO1 and GSTO2 were genotyped. Results The GSTT1 null was marginally associated with increased urothelial carcinoma (UC risk (HR, 1.91, 95% CI, 1.00-3.65, while the association was not observed for other GSTs. Among the subjects with cumulative arsenic exposure (CAE ≥ 20 mg/L*year, the GSTT1 null genotype conferred a significantly increased cancer risk (RR, 3.25, 95% CI, 1.20-8.80. The gene-environment interaction between the GSTT1 and high arsenic exposure with respect to cancer risk was statistically significant (multiplicative model, p = 0.0151 and etiologic fraction was as high as 0.86 (95% CI, 0.51-1.22. The genetic effects of GSTO1/GSTO2 were largely confined to high arsenic level (CAE ≥ 20. Diplotype analysis showed that among subjects exposed to high levels of arsenic, the AGG/AGG variant of GSTO1 Ala140Asp, GSTO2 5'UTR (-183A/G, and GSTO2 Asn142Asp was associated with an increased cancer risk (HRs, 4.91, 95% CI, 1.02-23.74 when compared to the all-wildtype reference, respectively. Conclusions The GSTs do not play a critical role in arsenic-induced urothelial carcinogenesis. The genetic effects of GSTT1 and GSTO1 on arsenic-induced urothelial carcinogenesis are largely confined to very high exposure level.

  4. Ameliorative potential of Psidium guajava in induced arsenic toxicity in Wistar rats

    Directory of Open Access Journals (Sweden)

    Manju Roy and Sushovan Roy

    2011-04-01

    Full Text Available The study was undertaken to determine the effect of Psidium.guajava leaf extract on arsenic induced biochemical alterations in Wistar rats. Significant (P<0.05 increased glucose serum urea nitrogen and serum creatinine was observed whereas non significant decrease in total protein, calcium and phosphorus was observed. It is concluded that kidney damage caused by arsenic can be repaired up to some extent by AEPG50. [Veterinary World 2011; 4(2.000: 82-83

  5. Mineral trioxide aggregate: part 2 - a review of the material aspects.

    Science.gov (United States)

    Malhotra, Neeraj; Agarwal, Antara; Mala, Kundabala

    2013-03-01

    The purpose of this two-part series is to review the composition, properties, and products of mineral trioxide aggregate (MTA) materials. PubMed and MedLine electronic databases were used to identify scientific papers from January 1991 to May 2010. Based on the selected inclusion criteria, citations were referenced from the scientific peer-reviewed dental literature. Mineral trioxide aggregate is a refined form of the parent compound, Portland cement (PC), and demonstrates a strong biocompatibility due to the high pH level and the material's ability to form hydroxyapatite. Mineral trioxide aggregate materials provide better microleakage protection than traditional endodontic materials as observed in findings from dye-leakage, fluid-filtration, protein-leakage, and bacterial penetration-leakage studies and has been recognized as a bioactive material. Various MTA commercial products are available, including gray mineral trioxide aggregate (GMTA), white mineral trioxide aggregate (WMTA), and mineral trioxide aggregate-Angelus (AMTA). Although these materials are indicated for various dental uses and applications, long-term in-vivo clinical studies are needed. Part 1 of this article highlighted and discussed the composition and characteristics of the material. Part 2 provides an overview of commercially available MTA materials.

  6. Arsenic silences hepatic PDK4 expression through activation of histone H3K9 methylatransferase G9a

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Xi; Wu, Jianguo; Choiniere, Jonathan [Department of Physiology and Neurobiology and The Institute for Systems Genomics, University of Connecticut, Storrs, CT 062696 (United States); Yang, Zhihong [Department of Physiology and Neurobiology and The Institute for Systems Genomics, University of Connecticut, Storrs, CT 062696 (United States); Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516 (United States); Huang, Yi [Department of Physiology and Neurobiology and The Institute for Systems Genomics, University of Connecticut, Storrs, CT 062696 (United States); School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Bennett, Jason [Department of Physiology and Neurobiology and The Institute for Systems Genomics, University of Connecticut, Storrs, CT 062696 (United States); Wang, Li, E-mail: li.wang@uconn.edu [Department of Physiology and Neurobiology and The Institute for Systems Genomics, University of Connecticut, Storrs, CT 062696 (United States); Veterans Affairs Connecticut Healthcare System, West Haven, CT 06516 (United States); School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035 (China); Department of Internal Medicine, Section of Digestive Diseases, Yale University, New Haven, CT 06520 (United States)

    2016-08-01

    It is well established that increased liver cancer incidence is strongly associated with epigenetic silencing of tumor suppressor genes; the latter is contributed by the environmental exposure to arsenic. Pyruvate dehydrogenase kinase 4 (PDK4) is a mitochondrial protein that regulates the TCA cycle. However, the epigenetic mechanisms mediated by arsenic to control PDK4 expression remain elusive. In the present study, we showed that histone methyltransferase G9a- and Suv39H-mediated histone H3 lysine 9 (H3K9) methylations contributed to PDK4 silencing in hepatic cells. The PDK4 expression was induced by G9a inhibitor BRD4770 (BRD) and Suv39H inhibitor Chaetocin (CHA). In contrast, arsenic exposure decreased PDK4 expression by inducing G9a and increasing H3K9 di- and tri-methylations levels (H3K9me2/3). In addition, arsenic exposure antagonizes the effect of BRD by enhancing the enrichment of H3K9me2/3 in the PKD4 promoter. Moreover, knockdown of G9a using siRNA induced PDK4 expression in HCC cells. Furthermore, arsenic decreased hepatic PDK4 expression as well as diminished the induction of PDK4 by BRD in mouse liver and hepatocytes. Overall, the results suggest that arsenic causes aberrant repressive histone modification to silence PDK4 in both HCC cells and in mouse liver. - Graphical abstract: Schematic showing arsenic-mediated epigenetic pathway that inhibits PDK4 expression. (A) BRD induces PDK4 expression by decreasing G9a protein and histone H3K9me2 and H3K9me3 levels as well as diminishing their recruitment to the PDK4 promoter. (B) Arsenic counteracts the effect of BRD by increasing histone H3K9me2 and H3K9me3 levels as well as enhancing their enrichment to the PDK4 promoter. Display Omitted - Highlights: • Histone methyltrasferase G9a inhibitor BRD induces PDK4 expression. • Arsenic decreases PDK4 expression and increases H3K9me2 and me3 levels. • Arsenic enhances H3K9me2/me3 enrichment in the PDK4 promoter. • Arsenic antagonizes the activation of

  7. Arsenic silences hepatic PDK4 expression through activation of histone H3K9 methylatransferase G9a

    International Nuclear Information System (INIS)

    Zhang, Xi; Wu, Jianguo; Choiniere, Jonathan; Yang, Zhihong; Huang, Yi; Bennett, Jason; Wang, Li

    2016-01-01

    It is well established that increased liver cancer incidence is strongly associated with epigenetic silencing of tumor suppressor genes; the latter is contributed by the environmental exposure to arsenic. Pyruvate dehydrogenase kinase 4 (PDK4) is a mitochondrial protein that regulates the TCA cycle. However, the epigenetic mechanisms mediated by arsenic to control PDK4 expression remain elusive. In the present study, we showed that histone methyltransferase G9a- and Suv39H-mediated histone H3 lysine 9 (H3K9) methylations contributed to PDK4 silencing in hepatic cells. The PDK4 expression was induced by G9a inhibitor BRD4770 (BRD) and Suv39H inhibitor Chaetocin (CHA). In contrast, arsenic exposure decreased PDK4 expression by inducing G9a and increasing H3K9 di- and tri-methylations levels (H3K9me2/3). In addition, arsenic exposure antagonizes the effect of BRD by enhancing the enrichment of H3K9me2/3 in the PKD4 promoter. Moreover, knockdown of G9a using siRNA induced PDK4 expression in HCC cells. Furthermore, arsenic decreased hepatic PDK4 expression as well as diminished the induction of PDK4 by BRD in mouse liver and hepatocytes. Overall, the results suggest that arsenic causes aberrant repressive histone modification to silence PDK4 in both HCC cells and in mouse liver. - Graphical abstract: Schematic showing arsenic-mediated epigenetic pathway that inhibits PDK4 expression. (A) BRD induces PDK4 expression by decreasing G9a protein and histone H3K9me2 and H3K9me3 levels as well as diminishing their recruitment to the PDK4 promoter. (B) Arsenic counteracts the effect of BRD by increasing histone H3K9me2 and H3K9me3 levels as well as enhancing their enrichment to the PDK4 promoter. Display Omitted - Highlights: • Histone methyltrasferase G9a inhibitor BRD induces PDK4 expression. • Arsenic decreases PDK4 expression and increases H3K9me2 and me3 levels. • Arsenic enhances H3K9me2/me3 enrichment in the PDK4 promoter. • Arsenic antagonizes the activation of

  8. HPLC-HG-AFS determination of arsenic species in acute promyelocytic leukemia (APL) plasma and blood cells.

    Science.gov (United States)

    Guo, Meihua; Wang, Wenjing; Hai, Xin; Zhou, Jin

    2017-10-25

    Arsenic trioxide (ATO) has been successfully used in the treatment of acute promyelocytic leukemia (APL). To clarify the arsenic species in APL patients, high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) and HG-AFS methods were developed and validated to quantify the plasma concentrations of inorganic arsenic (As(III) and As(V)) and methylated metabolites (MMA and DMA), and the total amounts of arsenic in blood cells and plasma. Blood cells and plasma were digested with mixtures of HNO 3 H 2 O 2 and analyzed by HG-AFS. For arsenic speciation, plasma samples were prepared with perchloric acid to precipitate protein. The supernatant was separated on an anion-exchange column within 6min with isocratic elution using 13mM CH 3 COONa, 3mM NaH 2 PO 4 , 4mM KNO 3 and 0.2mM EDTA-2Na. The methods provided linearity range of 0.2-20ng/mL for total arsenic and 2.0-50ng/mL for four arsenic species. The developed methods for total arsenic and arsenic species determination were precise and accurate. The spiked recoveries ranged from 81.2%-108.6% and the coefficients of variation for intra- and inter-batch precision were less than 9.3% and 12.5%, respectively. The developed methods were applied successfully for the assay of total arsenic and arsenic species in 5 APL patients. The HPLC-HG-AFS may be a good alternative for arsenic species determination in APL patients with its simplicity and low-cost in comparison with HPLC-ICP-MS. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. High soil and groundwater arsenic levels induce high body arsenic loads, health risk and potential anemia for inhabitants of northeastern Iran.

    Science.gov (United States)

    Taheri, Masumeh; Mehrzad, Jalil; Mahmudy Gharaie, Mohamad Hosein; Afshari, Reza; Dadsetan, Ahmad; Hami, Shakiba

    2016-04-01

    Arsenic bioavailability in rock, soil and water resources is notoriously hazardous. Geogenic arsenic enters the body and adversely affects many biochemical processes in animals and humans, posing risk to public health. Chelpu is located in NE Iran, where realgar, orpiment and pyrite mineralization is the source of arsenic in the macroenvironment. Using cluster random sampling strategy eight rocks, 23 soils, 12 drinking water resources, 36 human urine and hair samples and 15 adult sheep urine and wool samples in several large-scale herds in the area were randomly taken for quantification of arsenic in rock/soil/water, wool/hair/urine. Arsenic levels in rock/soil/water and wool/hair/urine were measured using inductively coupled plasma spectroscopy and atomic absorption spectrophotometry, respectively. While arsenic levels in rocks, soils and water resources hazardously ranged 9.40-25,873.3 mg kg(-1), 7.10-1448.80 mg kg(-1) and 12-606 μg L(-1), respectively, arsenic concentrations in humans' hair and urine and sheep's wool and urine varied from 0.37-1.37 μg g(-1) and 9-271.4 μg L(-1) and 0.3-3.11 μg g(-1) and 29.1-1015 μg L(-1), respectively. Local sheep and human were widely sick and slightly anemic. Hematological examination of the inhabitants revealed that geogenic arsenic could harm blood cells, potentially resulting in many other hematoimmunological disorders including cancer. The findings warn widespread exposure of animals and human in this agroecologically and geopolitically important region (i.e., its proximity with Afghanistan, Pakistan and Turkmenistan) and give a clue on how arsenic could induce infectious and non-infectious diseases in highly exposed human/animals.

  10. Association of oxidative stress with arsenic methylation in chronic arsenic-exposed children and adults

    International Nuclear Information System (INIS)

    Xu Yuanyuan; Wang Yi; Zheng Quanmei; Li Xin; Li Bing; Jin Yaping; Sun Xiance; Sun Guifan

    2008-01-01

    Though oxidative stress is recognized as an important pathogenic mechanism of arsenic, and arsenic methylation capacity is suggested to be highly involved in arsenic-related diseases, the association of arsenic methylation capacity with arsenic-induced oxidative stress remains unclear. To explore oxidative stress and its association with arsenic methylation, cross-sectional studies were conducted among 208 high and 59 low arsenic-exposed subjects. Levels of urinary arsenic species [inorganic arsenic (iAs), monomethylated arsenic (MMA) and dimethylated arsenic (DMA)] were determined by hydride generation atomic absorption spectrometry. Proportions of urinary arsenic species, the first methylation ratio (FMR) and the secondary methylation ratio (SMR) were used as indicators for arsenic methylation capacity. Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations were analyzed by enzyme-linked immunosorbent assay kits. Reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity in whole blood were determined to reflect anti-oxidative status. The high arsenic-exposed children and adults were significantly increased in urinary 8-OHdG concentrations but decreased in blood GSH levels compared with the low exposed children and adults. In multiple linear regression models, blood GSH levels and urinary 8-OHdG concentrations of arsenic-exposed children and adults showed strong associations with the levels of urinary arsenic species. Arsenic-exposed subjects in the lower and the upper quartiles of proportions of urinary arsenic species, FMR or SMR were significantly different in urinary 8-OHdG, blood GSH and SOD. The associations of arsenic methylation capacity with 8-OHdG, GSH and SOD were also observed in multivariate regression analyses. These results may provide linkage between arsenic methylation capacity and oxidative stress in humans and suggest that adverse health effects induced by arsenic are related to arsenic methylation through oxidative stress

  11. All-Trans Retinoic Acid plus Arsenic Trioxide versus All-Trans Retinoic Acid plus Chemotherapy for Newly Diagnosed Acute Promyelocytic Leukemia: A Meta-Analysis.

    Directory of Open Access Journals (Sweden)

    Yafang Ma

    Full Text Available Recently, the all-trans retinoic acid (ATRA plus arsenic trioxide (ATO protocol has become a promising first-line therapeutic approach in patients with newly diagnosed acute promyelocytic leukemia (APL, but its benefits compared with standard ATRA plus chemotherapy regimen needs to be proven. Herein, we conducted a meta-analysis comparing the efficacy of ATRA plus ATO with ATRA plus chemotherapy for adult patients with newly diagnosed APL.We systematically searched biomedical electronic databases and conference proceedings through February 2016. Two reviewers independently assessed all studies for relevance and validity.Overall, three studies were eligible for inclusion in this meta-analysis, which included a total of 585 patients, with 317 in ATRA plus ATO group and 268 in ATRA plus chemotherapy group. Compared with patients who received ATRA and chemotherapy, patients who received ATRA plus ATO had a significantly better event-free survival (hazard ratio [HR] = 0.38, 95% confidence interval [CI]: 0.22-0.67, p = 0.009, overall survival (HR = 0.44, 95% CI: 0.24-0.82, p = 0.009, complete remission rate (relative risk [RR] = 1.05; 95% CI: 1.01-1.10; p = 0.03. There were no significant differences in early mortality (RR = 0.48; 95% CI: 0.22-1.05; p = 0.07.Thus, this analysis indicated that ATRA plus ATO protocol may be preferred to standard ATRA plus chemotherapy protocol, particularly in low-to-intermediate risk APL patients. Further larger trials were needed to provide more evidence in high-risk APL patients.

  12. Mthfr gene ablation enhances susceptibility to arsenic prenatal toxicity

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    Wlodarczyk, Bogdan J., E-mail: bwlodarczyk@austin.utexas.edu; Zhu, Huiping; Finnell, Richard H.

    2014-02-15

    Background: In utero exposure to arsenic is known to adversely affect reproductive outcomes. Evidence of arsenic teratogenicity varies widely and depends on individual genotypic differences in sensitivity to As. In this study, we investigated the potential interaction between 5,10-methylenetetrahydrofolate reductase (Mthfr) genotype and arsenic embryotoxicity using the Mthfr knockout mouse model. Methods: Pregnant dams were treated with sodium arsenate, and reproductive outcomes including: implantation, resorption, congenital malformation and fetal birth weight were recorded at E18.5. Results: When the dams in Mthfr{sup +/−} × Mthfr{sup +/−} matings were treated with 7.2 mg/kg As, the resorption rate increased to 43.4%, from a background frequency of 7.2%. The As treatment also induced external malformations (40.9%) and significantly lowered the average fetal birth weight among fetuses, without any obvious toxic effect on the dam. When comparing the pregnancy outcomes resulting from different mating scenarios (Mthfr{sup +/+} × Mthfr{sup +/−}, Mthfr{sup +/−} × Mthfr{sup +/−} and Mthfr{sup −/−} × {sup Mthfr+/−}) and arsenic exposure; the resorption rate showed a linear relationship with the number of null alleles (0, 1 or 2) in the Mthfr dams. Fetuses from nullizygous dams had the highest rate of external malformations (43%) and lowest average birth weight. When comparing the outcomes of reciprocal matings (nullizygote × wild-type versus wild-type × nullizygote) after As treatment, the null dams showed significantly higher rates of resorptions and malformations, along with lower fetal birth weights. Conclusions: Maternal genotype contributes to the sensitivity of As embryotoxicity in the Mthfr mouse model. The fetal genotype, however, does not appear to affect the reproductive outcome after in utero As exposure. - Highlights: • An interaction between Mthfr genotype and arsenic embryotoxicity is presented. • Maternal Mthfr genotype

  13. Comparison of optical and power Doppler ultrasound imaging for non-invasive evaluation of arsenic trioxide as a vascular disrupting agent in tumors.

    Science.gov (United States)

    Alhasan, Mustafa K; Liu, Li; Lewis, Matthew A; Magnusson, Jennifer; Mason, Ralph P

    2012-01-01

    Small animal imaging provides diverse methods for evaluating tumor growth and acute response to therapy. This study compared the utility of non-invasive optical and ultrasound imaging to monitor growth of three diverse human tumor xenografts (brain U87-luc-mCherry, mammary MCF7-luc-mCherry, and prostate PC3-luc) growing in nude mice. Bioluminescence imaging (BLI), fluorescence imaging (FLI), and Power Doppler ultrasound (PD US) were then applied to examine acute vascular disruption following administration of arsenic trioxide (ATO).During initial tumor growth, strong correlations were found between manual caliper measured tumor volume and FLI intensity, BLI intensity following luciferin injection, and traditional B-mode US. Administration of ATO to established U87 tumors caused significant vascular shutdown within 2 hrs at all doses in the range 5 to 10 mg/kg in a dose dependant manner, as revealed by depressed bioluminescent light emission. At lower doses substantial recovery was seen within 4 hrs. At 8 mg/kg there was >85% reduction in tumor vascular perfusion, which remained depressed after 6 hrs, but showed some recovery after 24 hrs. Similar response was observed in MCF7 and PC3 tumors. Dynamic BLI and PD US each showed similar duration and percent reductions in tumor blood flow, but FLI showed no significant changes during the first 24 hrs.The results provide further evidence for comparable utility of optical and ultrasound imaging for monitoring tumor growth, More specifically, they confirm the utility of BLI and ultrasound imaging as facile assays of the vascular disruption in solid tumors based on ATO as a model agent.

  14. African Journal of Biotechnology - Vol 10, No 61 (2011)

    African Journals Online (AJOL)

    Studying arsenic trioxide-induced apoptosis of Colo-16 cells with two-photon and .... Genetic polymorphism of exon 9-11 of the leptin gene receptor in breeder hens of ... Determination of taste receptor type 1 member 1 (TAS1R1) gene ...

  15. Novel chitosan/PVA/zerovalent iron biopolymeric nanofibers with enhanced arsenic removal applications.

    Science.gov (United States)

    Chauhan, Divya; Dwivedi, Jaya; Sankararamakrishnan, Nalini

    2014-01-01

    Enhanced removal application of both forms of inorganic arsenic from arsenic-contaminated aquifers at near-neutral pH was studied using a novel electrospun chitosan/PVA/zerovalent iron (CPZ) nanofibrous mat. CPZ was carefully examined using scanning electron microscopy (SEM) equipped with energy-dispersive X-ray analysis (EDX), transmission electron microscopy (TEM), atomic fluorescence spectroscopy (AFM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA). Application of the adsorbent towards the removal of total inorganic arsenic in batch mode has also been studied. A suitable mechanism for the adsorption has also been discussed. CPZ nanofibers mat was found capable to remove 200.0±10.0 mg g(-1) of As(V) and 142.9±7.2 mg g(-1) of As(III) from aqueous solution of pH 7.0 at ambient condition. Addition of ethylenediaminetetraacetic acid (EDTA) enabled the stability of iron in zerovalent state (ZVI). Enhanced capacity of the fibrous mat could be attributed to the high surface area of the fibers, presence of ZVI, and presence of functional groups such as amino, carboxyl, and hydroxyl groups of the chitosan and EDTA. Both Langmuir and Freundlich adsorption isotherms were applicable to describe the removal process. The possible mechanism of adsorption has been explained in terms of electrostatic attraction between the protonated amino groups of chitosan/arsenate ions and oxidation of arsenite to arsenate by Fentons generated from ZVI and subsequent complexation of the arsenate with the oxidized iron. These CPZ nanofibrous mats has been prepared with environmentally benign naturally occurring biodegradable biopolymer chitosan, which offers unique advantage in the removal of arsenic from contaminated groundwater.

  16. IDENTIFICATION OF INTERSPECIES CONCORDANCE OF MECHANISMS OF ARSENIC-INDUCED BLADDER CANCER

    Science.gov (United States)

    Exposure to arsenic causes cancer by inducing a variety of responses that affect the expression of genes associated with numerous biological pathways leading to altered cell growth and proliferation, signaling, apoptosis and oxidative stress response. Affymetrix GeneChip® arrays ...

  17. Hijacking membrane transporters for arsenic phytoextraction

    Science.gov (United States)

    LeBlanc, Melissa S.; McKinney, Elizabeth C.; Meagher, Richard B.; Smith, Aaron P.

    2012-01-01

    Arsenic is a toxic metalloid and recognized carcinogen. Arsenate and arsenite are the most common arsenic species available for uptake by plants. As an inorganic phosphate (Pi) analog, arsenate is acquired by plant roots through endogenous Pi transport systems. Inside the cell, arsenate is reduced to the thiol-reactive form arsenite. Glutathione (GSH)-conjugates of arsenite may be extruded from the cell or sequestered in vacuoles by members of the ATP-binding cassette (ABC) family of transporters. In the present study we sought to enhance both plant arsenic uptake through Pi transporter overexpression, and plant arsenic tolerance through ABC transporter overexpression. We demonstrate that Arabidopsis thaliana plants overexpressing the high-affinity Pi transporter family members, AtPht1;1 or AtPht1;7, are hypersensitive to arsenate due to increased arsenate uptake. These plants do not exhibit increased sensitivity to arsenite. Co-overexpression of the yeast ABC transporter YCF1 in combination with AtPht1;1 or AtPht1;7 suppresses the arsenate-sensitive phenotype while further enhancing arsenic uptake. Taken together, our results support an arsenic transport mechanism in which arsenate uptake is increased through Pi transporter overexpression, and arsenic tolerance is enhanced through YCF1-mediated vacuolar sequestration. This work substantiates the viability of coupling enhanced uptake and vacuolar sequestration as a means for developing a prototypical engineered arsenic hyperaccumulator. PMID:23108027

  18. Presence of arsenic in different types of MTA and white and gray Portland cement.

    Science.gov (United States)

    Monteiro Bramante, Clóvis; Demarchi, Ana Claudia Cardoso Oliveira; de Moraes, Ivaldo Gomes; Bernadineli, Norberti; Garcia, Roberto Brandão; Spångberg, Lars S W; Duarte, Marco Antonio Hungaro

    2008-12-01

    The presence of arsenic in various types of mineral trioxide aggregate (MTA) and Portland cements were evaluated to verify if they comply with the ISO-recommended limit for water-based cements of 2 mg arsenic/kg material. An amount of 5 mL of hydrochloric acid was added to 2 g each of MTA and Portland cement to be analyzed. After 15 minutes, the material was filtered and the volume of supernatant was diluted with reagent-grade water up to 40 mL. Atomic absorption spectrophotometry readings were performed in triplicate. The following mean values were obtained: CPM (Egeo, Buenos Aires, Argentina) 11.06 mg/kg; CPM sealer (Egeo) 10.30 mg/kg; MTA-Obtura (Angelus, Londrina, PR, Brazil) 0.39 mg/kg; Experimental MTA: 10.30 mg/kg; White MTA-Angelus (Angelus) 1.03 mg/kg; Gray MTA-Angelus (Angelus) 5.91 mg/kg; ProRoot-MTA (Dentsply/Tulsa Dental Specialties, Tulsa, OK) 5.25 mg/kg; Gray Portland cement (Votorantim Cimentos, Cubatão, SP, Brazil): 34.27 mg/kg; and White Portland cement (Cimento Rio Branco, Rio de Janeiro, RJ, Brazil) 0.52 mg/kg. All tested materials presented arsenic in their composition. The form of arsenic was not analyzed nor the toxicity of the arsenic found. Only MTA-Obtura, White MTA-Angelus, and White Portland cement presented arsenic levels below the limit set in the ISO 9917-1 standard.

  19. Low level arsenic promotes progressive inflammatory angiogenesis and liver blood vessel remodeling in mice

    International Nuclear Information System (INIS)

    Straub, Adam C.; Stolz, Donna B.; Vin, Harina; Ross, Mark A.; Soucy, Nicole V.; Klei, Linda R.; Barchowsky, Aaron

    2007-01-01

    The vascular effects of arsenic in drinking water are global health concerns contributing to human disease worldwide. Arsenic targets the endothelial cells lining blood vessels, and endothelial cell activation or dysfunction may underlie the pathogenesis of both arsenic-induced vascular diseases and arsenic-enhanced tumorigenesis. The purpose of the current studies was to demonstrate that exposing mice to drinking water containing environmentally relevant levels of arsenic promoted endothelial cell dysfunction and pathologic vascular remodeling. Increased angiogenesis, neovascularization, and inflammatory cell infiltration were observed in Matrigel plugs implanted in C57BL/6 mice following 5-week exposures to 5-500 ppb arsenic [Soucy, N.V., Mayka, D., Klei, L.R., Nemec, A.A., Bauer, J.A., Barchowsky, A., 2005. Neovascularization and angiogenic gene expression following chronic arsenic exposure in mice. Cardiovasc.Toxicol 5, 29-42]. Therefore, functional in vivo effects of arsenic on endothelial cell function and vessel remodeling in an endogenous vascular bed were investigated in the liver. Liver sinusoidal endothelial cells (LSEC) became progressively defenestrated and underwent capillarization to decrease vessel porosity following exposure to 250 ppb arsenic for 2 weeks. Sinusoidal expression of PECAM-1 and laminin-1 proteins, a hallmark of capillarization, was also increased by 2 weeks of exposure. LSEC caveolin-1 protein and caveolae expression were induced after 2 weeks of exposure indicating a compensatory change. Likewise, CD45/CD68-positive inflammatory cells did not accumulate in the livers until after LSEC porosity was decreased, indicating that inflammation is a consequence and not a cause of the arsenic-induced LSEC phenotype. The data demonstrate that the liver vasculature is an early target of pathogenic arsenic effects and that the mouse liver vasculature is a sensitive model for investigating vascular health effects of arsenic

  20. Urinary Arsenic Metabolites of Subjects Exposed to Elevated Arsenic Present in Coal in Shaanxi Province, China

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    Linsheng Yang

    2011-06-01

    Full Text Available In contrast to arsenic (As poisoning caused by naturally occurring inorganic arsenic-contaminated water consumption, coal arsenic poisoning (CAP induced by elevated arsenic exposure from coal combustion has rarely been reported. In this study, the concentrations and distributions of urinary arsenic metabolites in 57 volunteers (36 subjects with skin lesions and 21 subjects without skin lesions, who had been exposed to elevated levels of arsenic present in coal in Changshapu village in the south of Shaanxi Province (China, were reported. The urinary arsenic species, including inorganic arsenic (iAs [arsenite (iAsIII and arsenate (iAsV], monomethylarsonic acid (MMAV and dimethylarsinic acid (DMAV, were determined by high-performance liquid chromatography (HPLC combined with inductively coupled plasma mass spectroscopy (ICP-MS. The relative distributions of arsenic species, the primary methylation index (PMI = MMAV/iAs and the secondary methylation index (SMI = DMAV/MMAV were calculated to assess the metabolism of arsenic. Subjects with skin lesions had a higher concentration of urinary arsenic and a lower arsenic methylation capability than subjects without skin lesions. Women had a significantly higher methylation capability of arsenic than men, as defined by a higher percent DMAV and SMI in urine among women, which was the one possible interpretation of women with a higher concentration of urinary arsenic but lower susceptibility to skin lesions. The findings suggested that not only the dose of arsenic exposure but also the arsenic methylation capability have an impact on the individual susceptibility to skin lesions induced by coal arsenic exposure.

  1. Effect of applying an arsenic-resistant and plant growth-promoting rhizobacterium to enhance soil arsenic phytoremediation by Populus deltoides LH05-17.

    Science.gov (United States)

    Wang, Q; Xiong, D; Zhao, P; Yu, X; Tu, B; Wang, G

    2011-11-01

    Bioremediation of highly arsenic (As)-contaminated soil is difficult because As is very toxic for plants and micro-organisms. The aim of this study was to investigate soil arsenic removal effects using poplar in combination with the inoculation of a plant growth-promoting rhizobacterium (PGPR). A rhizobacterium D14 was isolated and identified within Agrobacterium radiobacter. This strain was highly resistant to arsenic and produced indole acetic acid and siderophore. Greenhouse pot bioremediation experiments were performed for 5 months using poplar (Populus deltoides LH05-17) grown on As-amended soils, inoculated with strain D14. The results showed that P. deltoides was an efficient arsenic accumulator; however, high As concentrations (150 and 300 mg kg(-1)) inhibited its growth. With the bacterial inoculation, in the 300 mg kg(-1) As-amended soils, 54% As in the soil was removed, which was higher than the uninoculated treatments (43%), and As concentrations in roots, stems and leaves were significantly increased by 229, 113 and 291%, respectively. In addition, the As translocation ratio [(stems + leaves)/roots = 0·8] was significantly higher than the uninoculated treatments (0·5). About 45% As was translocated from roots to the above-ground tissues. The plant height and dry weight of roots, stems and leaves were all enhanced; the contents of chlorophyll and soluble sugar, and the activities of superoxide dismutase and catalase were all increased; and the content of a toxic compound malondialdehyde was decreased. The results indicated that the inoculation of strain D14 could contribute to the increase in the As tolerance of P. deltoides, promotion of the growth, increase in the uptake efficiency and enhancement of As translocation. The use of P. deltoides in combination with the inoculation of strain D14 provides a potential application for efficient soil arsenic bioremediation. © 2011 The Authors. Journal of Applied Microbiology ©2011 The Society for Applied

  2. All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague–Dawley rats

    International Nuclear Information System (INIS)

    Chatterjee, A.; Chatterji, U.

    2011-01-01

    Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin–eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ERα), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ERα, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: ► Arsenic disrupts the uterine histology and

  3. All-trans retinoic acid protects against arsenic-induced uterine toxicity in female Sprague-Dawley rats

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, A.; Chatterji, U., E-mail: urmichatterji@gmail.com

    2011-12-15

    Background and purpose: Arsenic exposure frequently leads to reproductive failures by disrupting the rat uterine histology, hormonal integrity and estrogen signaling components of the rat uterus, possibly by generating reactive oxygen species. All-trans retinoic acid (ATRA) was assessed as a prospective therapeutic agent for reversing reproductive disorders. Experimental approach: Rats exposed to arsenic for 28 days were allowed to either recover naturally or were treated simultaneously with ATRA for 28 days or treatment continued up to 56 days. Hematoxylin-eosin double staining was used to evaluate changes in the uterine histology. Serum gonadotropins and estradiol were assayed by ELISA. Expression of the estrogen receptor (ER{alpha}), an estrogen responsive gene vascular endothelial growth factor (VEGF), and cell cycle regulatory proteins, cyclin D1 and CDK4, was assessed by RT-PCR, immunohistochemistry and western blot analysis. Key results: ATRA ameliorated sodium arsenite-induced decrease in circulating estradiol and gonadotropin levels in a dose- and time-dependent manner, along with recovery of luminal epithelial cells and endometrial glands. Concomitant up regulation of ER{alpha}, VEGF, cyclin D1, CDK4 and Ki-67 was also observed to be more prominent for ATRA-treated rats as compared to the rats that were allowed to recover naturally for 56 days. Conclusions and implications: Collectively, the results reveal that ATRA reverses arsenic-induced disruption of the circulating levels of gonadotropins and estradiol, and degeneration of luminal epithelial cells and endometrial glands of the rat uterus, indicating resumption of their functional status. Since structural and functional maintenance of the pubertal uterus is under the influence of estradiol, ATRA consequently up regulated the estrogen receptor and resumed cellular proliferation, possibly by an antioxidant therapeutic approach against arsenic toxicity. Highlights: Black-Right-Pointing-Pointer Arsenic

  4. Transplacental arsenic carcinogenesis in mice

    International Nuclear Information System (INIS)

    Waalkes, Michael P.; Liu, Jie; Diwan, Bhalchandra A.

    2007-01-01

    Our work has focused on the carcinogenic effects of in utero arsenic exposure in mice. Our data show that a short period of maternal exposure to inorganic arsenic in the drinking water is an effective, multi-tissue carcinogen in the adult offspring. These studies have been reproduced in three temporally separate studies using two different mouse strains. In these studies pregnant mice were treated with drinking water containing sodium arsenite at up to 85 ppm arsenic from days 8 to 18 of gestation, and the offspring were observed for up to 2 years. The doses used in all these studies were well tolerated by both the dam and offspring. In C3H mice, two separate studies show male offspring exposed to arsenic in utero developed liver carcinoma and adrenal cortical adenoma in a dose-related fashion during adulthood. Prenatally exposed female C3H offspring show dose-related increases in ovarian tumors and lung carcinoma and in proliferative lesions (tumors plus preneoplastic hyperplasia) of the uterus and oviduct. In addition, prenatal arsenic plus postnatal exposure to the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA) in C3H mice produces excess lung tumors in both sexes and liver tumors in females. Male CD1 mice treated with arsenic in utero develop tumors of the liver and adrenal and renal hyperplasia while females develop tumors of urogenital system, ovary, uterus and adrenal and hyperplasia of the oviduct. Additional postnatal treatment with diethylstilbestrol or tamoxifen after prenatal arsenic in CD1 mice induces urinary bladder transitional cell proliferative lesions, including carcinoma and papilloma, and enhances the carcinogenic response in the liver of both sexes. Overall this model has provided convincing evidence that arsenic is a transplacental carcinogen in mice with the ability to target tissues of potential human relevance, such as the urinary bladder, lung and liver. Transplacental carcinogenesis clearly occurs with other agents in humans

  5. Oxidative DNA damage of peripheral blood polymorphonuclear leukocytes, selectively induced by chronic arsenic exposure, is associated with extent of arsenic-related skin lesions

    International Nuclear Information System (INIS)

    Pei, Qiuling; Ma, Ning; Zhang, Jing; Xu, Wenchao; Li, Yong; Ma, Zhifeng; Li, Yunyun; Tian, Fengjie; Zhang, Wenping; Mu, Jinjun; Li, Yuanfei; Wang, Dongxing; Liu, Haifang; Yang, Mimi; Ma, Caifeng; Yun, Fen

    2013-01-01

    There is increasing evidence that oxidative stress is an important risk factor for arsenic-related diseases. Peripheral blood leukocytes constitute an important defense against microorganisms or pathogens, while the research on the impact of chronic arsenic exposure on peripheral blood leukocytes is much more limited, especially at low level arsenic exposure. The purpose of the present study was to explore whether chronic arsenic exposure affects oxidative stress of peripheral blood leukocytes and possible linkages between oxidative stress and arsenic-induced skin lesions. 75 male inhabitants recruited from an As-endemic region of China were investigated in the present study. The classification of arsenicosis was based on the degree of skin lesions. Arsenic levels were measured in drinking water and urine by Atomic Fluorescence Spectroscopy. Urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) was tested by Enzyme-Linked Immunosorbent Assay. 8-OHdG of peripheral blood leukocytes was evaluated using immunocytochemical staining. 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs), but not in monocytes (MNs). The 8-OHdG staining of PMN cytoplasm was observed in all investigated populations, while the 8-OHdG staining of PMN nuclei was frequently found along with the elevated amounts of cell debris in individuals with skin lesion. Urinary arsenic levels were increased in the severe skin lesion group compared with the normal group. No relationship was observed between drinking water arsenic or urine 8-OHdG and the degree of skin lesions. These findings indicated that the target and persistent oxidative stress in peripheral blood PMNs may be employed as a sensitive biomarker directly to assess adverse health effects caused by chronic exposure to lower levels of arsenic. -- Highlights: ► Male inhabitants were investigated from an As-endemic region of China. ► 8-OHdG-positive reactions were only present in polymorphonuclear leukocytes (PMNs).

  6. The Role of Antioxidants in Biochemical Disorders Induced by Arsenic in Adult male Rats

    International Nuclear Information System (INIS)

    Hassanin, M.M.; Zaki, Z.T.; Emarah, E.A.M.; Hussein, A.M.M.

    2010-01-01

    The present investigation included biochemical, radiometric, molecular studies and histopathological examination to evaluate the protective role of Antox tablets toward Arsenic toxicity in adult male albino rats (Rattus rattus). Arsenic were given as sodium arsenate to different groups in drinking water at a dose of 100 mg/L, for 3 and 6 weeks led to severe tissue damage as revealed by an elevation of serum total protein and alteration of serum protein fractions. Using radioimmunoassay it was found that serum total testosterone level was significantly decreased. The decreased level of total testosterone paralleled the observed testicular damage. Treatment of male rats with antioxidant (Antox) along with arsenic led to an improvement in both the biochemical and histological alterations induced by arsenic. Thus the protective role of Antox is attributed to its antioxidant and free radicals scavenging properties of its components (selenium, vitamin A acetate, ascorbic acid and vitamin E).

  7. A cross sectional study of anemia and iron deficiency as risk factors for arsenic-induced skin lesions in Bangladeshi women

    Directory of Open Access Journals (Sweden)

    Molly L. Kile

    2016-02-01

    Full Text Available Abstract Background In the Ganges Delta, chronic arsenic poisoning is a health concern affecting millions of people who rely on groundwater as their potable water source. The prevalence of anemia is also high in this region, particularly among women. Moreover, arsenic is known to affect heme synthesis and erythrocytes and the risk of arsenic-induced skin lesions appears to differ by sex. Methods We conducted a case-control study in 147 arsenic-exposed Bangladeshi women to assess the association between anemia and arsenic-induced skin lesions. Results We observed that the odds of arsenic-related skin lesions were approximately three times higher among women who were anemic (hemoglobin < 120 g/L compared to women with normal hemoglobin levels [Odds Ratio (OR = 3.32, 95 % Confidence Intervals (CI: 1.29, 8.52] after adjusting for arsenic levels in drinking water and other covariates. Furthermore, 75 % of the women with anemia had adequate iron stores (serum ferritin ≥12 μg/L, suggesting that the majority of anemia detected in this population was unrelated to iron depletion. Conclusions Considering the magnitude of arsenic exposure and prevalence of anemia in Bangladeshi women, additional research is warranted that identifies the causes of anemia so that effective interventions can be implemented while arsenic remediation efforts continue.

  8. Radiation-induced physical ageing in network arsenic-sulfide/selenide glasses

    International Nuclear Information System (INIS)

    Shpotyuk, M; Golovchak, R; Kozdras, A; Shpotyuk, O

    2010-01-01

    Effect of radiation-induced physical ageing is investigated by differential scanning calorimetry method in As x Se 100-x (10 ≤ x ≤ 42) and As x S 100-x (30 ≤ x ≤ 42) glasses. Obtained results are compared with conventional physical ageing at normal conditions. Significant radiation-induced physical ageing is recorded for glassy As x S 100-x within 30 ≤ x x Se 100-x glasses from the same compositional interval do not show any measurable changes in DSC curves after γ-irradiation. Observed difference in radiation-induced physical ageing in arsenic-sulfide/selenide glasses is explained by a greater lifetime of γ-induced excitations within sulfur-based network in comparison with selenium-based one.

  9. Arsenic may be involved in fluoride-induced bone toxicity through PTH/PKA/AP1 signaling pathway.

    Science.gov (United States)

    Zeng, Qi-bing; Xu, Yu-yan; Yu, Xian; Yang, Jun; Hong, Feng; Zhang, Ai-hua

    2014-01-01

    Chronic exposure to combined fluoride and arsenic continues to be a major public health problem worldwide, affecting thousands of people. In recent years, more and more researchers began to focus on the interaction between the fluorine and the arsenic. In this study, the selected investigation site was located in China. The study group was selected from people living in fluoride-arsenic polluted areas due to burning coal. The total number of participants was 196; including the fluoride-arsenic anomaly group (130) and the fluoride-arsenic normal group (63). By observing the changes in gene and protein expression of PTH/PKA/AP1 signaling pathway, the results show that fluoride can increase the expression levels of PTH, PKA, and AP1, but arsenic can only affect the expression of AP1; fluoride and arsenic have an interaction on the expression of AP1. Further study found that fluoride and arsenic can affect the mRNA expression level of c-fos gene (AP1 family members), and have an interaction on the expression of c-fos, but not c-jun. The results indicate that PTH/PKA/AP1 signaling pathway may play an important role in bone toxicity of fluoride. Arsenic can affect the expression of c-fos, thereby affecting the expression of transcription factor AP1, indirectly involved in fluoride-induced bone toxicity. Copyright © 2013. Published by Elsevier B.V.

  10. INFLUENCE OF MORINGA OLEIFERA (DRUM-STICK FRUIT EXTRACT ON HAEMATOLOGICAL PROFILE FOLLOWING REPEATED EXPOSURE TO LOW LEVELS OF ARSENIC THROUGH FEED ON RATS

    Directory of Open Access Journals (Sweden)

    Vaibhav R. Pachade

    2012-01-01

    Full Text Available Effect of Moringa oleifera fruits hot methanolic extract (MFE, if any, in minimizing the adverse reactions of repeated exposure to arsenic trioxide (AT in feed was investigated in Wistar rats with reference to haematological profile. Three groups of rats each containing 10 (5male+5female were used. The group I served as negative control. Rats of group II were fed arsenic trioxide (AT alone @ 100 ppm in feed while those of group III simultaneously received AT (@100 ppm and MFE (50 mg/kg/day for 28 days. Blood samples were collected from retroorbital plexus for estimation of hematological parameters (haemoglobin, PCV, TEC, MCH, MCHC, MCV of different groups on 0 day, 15th day and 29th day respectively. Exposure to AT through feed in group II resulted in significant (P<0.05 decrease in haemoglobin, TEC and MCHC, accompanied by increased MCV, with no significant alteration of PCV or MCH of the rats. While rats of group III treated with AT (@100 ppm and MFE (50 mg/kg/day also resulted in same consequences as it was in group II but it was slightly less than that of group II suggesting of mild non significant protective effect.

  11. On the effect of interaction of molybdenum trioxide and magnesium oxide in water

    International Nuclear Information System (INIS)

    Bunin, V.M.; Karelin, A.I.; Solov'eva, L.N.

    1992-01-01

    Interaction of molybdenum trioxide and magnesium oxide in water was studied. It is shown that molybdenum trioxide forms consecutively magnesium molybdate, dimolybdate and magnesium polymolybdates with magnesium oxide

  12. (--Epigallocatechin-3-Gallate Inhibits Arsenic-Induced Inflammation and Apoptosis through Suppression of Oxidative Stress in Mice

    Directory of Open Access Journals (Sweden)

    Nan-Hui Yu

    2017-04-01

    Full Text Available Background/Aims: Exposure to arsenic in individuals has been found to be associated with various health-related problems including skin lesions, cancer, and cardiovascular and immunological disorders. (--Epigallocatechin-3-gallate (EGCG, the main and active polyphenolic catechin present in green tea, has shown potent antioxidant, anti-apoptotic and anti-inflammatory activity in vivo and in vitro. Thus, the present study was conducted to investigate the protective effects of EGCG against arsenic-induced inflammation and immunotoxicity in mice. Methods: Serum IL-1β, IL-6 and TNF-α were determined by ELISA, tissue catalase (CAT, malonyldialdehyde (MDA, superoxide dismutase (SOD, glutathione (GSH, nitric oxide and caspase 3 by commercial kits, mitochondrial membrane potential with Rh 123, mitochondrial ROS with 2’,7’-dichlorofluorescin diacetate (DCFH-DA, apoptotic and necrotic cells and T-cell phenotyping with Flow cytometry analysis. Results: The results showed that arsenic treatment significantly increased oxidative stress levels (as indicated by catalase, malonyldialdehyde, superoxide dismutase, glutathione and reactive oxygen species, increased levels of inflammatory cytokines and promoted apoptosis. Arsenic exposure increased the relative frequency of the CD8+(Tc cell subpopulation (from 2.8 to 18.9% and decreased the frequency of CD4+(Th cells (from 5.2 to 2.7%. Arsenic exposure also significantly decreased the frequency of T(CD3 (from 32.5% to 19.2% and B(CD19 cells (from 55.1 to 32.5%. All of these effects induced by NaAsO2 were attenuated by EGCG. Conclusions: The present in vitro findings indicate that EGCG attenuates not only NaAsO2-induced immunosuppression but also inflammation and apoptosis.

  13. Radiation-induced physical ageing in network arsenic-sulfide/selenide glasses

    Energy Technology Data Exchange (ETDEWEB)

    Shpotyuk, M; Golovchak, R; Kozdras, A; Shpotyuk, O, E-mail: shpotyuk@novas.lviv.ua

    2010-11-15

    Effect of radiation-induced physical ageing is investigated by differential scanning calorimetry method in As{sub x}Se{sub 100-x} (10 {<=} x {<=} 42) and As{sub x}S{sub 100-x} (30 {<=} x {<=} 42) glasses. Obtained results are compared with conventional physical ageing at normal conditions. Significant radiation-induced physical ageing is recorded for glassy As{sub x}S{sub 100-x} within 30 {<=} x < 40 range, while As{sub x}Se{sub 100-x} glasses from the same compositional interval do not show any measurable changes in DSC curves after {gamma}-irradiation. Observed difference in radiation-induced physical ageing in arsenic-sulfide/selenide glasses is explained by a greater lifetime of {gamma}-induced excitations within sulfur-based network in comparison with selenium-based one.

  14. Vascular Hyperpermeability Response in Animals Systemically Exposed to Arsenic.

    Science.gov (United States)

    Chen, Shih-Chieh; Chang, Chao-Yuah; Lin, Ming-Lu

    2018-01-01

    The mechanisms underlying cardiovascular diseases induced by chronic exposure to arsenic remain unclarified. The objectives of this study were to investigate whether increased vascular leakage is induced by inflammatory mustard oil in mice systemically exposed to various doses of arsenic and whether an increased vascular leakage response is still present in arsenic-fed mice after arsenic discontinuation for 2 or 6 months. ICR mice were fed water or various doses of sodium arsenite (10, 15, or 20 mg/kg/day; 5 days/week) for 8 weeks. In separate experiments, the mice were treated with sodium arsenite (20 mg/kg) for 2 or 8 weeks, followed by arsenic discontinuation for 2 or 6 months. Vascular permeability to inflammatory mustard oil was quantified using Evans blue (EB) techniques. Both arsenic-exposed and water-fed (control) mice displayed similar basal levels of EB leakage in the ears brushed with mineral oil, a vehicle of mustard oil. The levels of EB leakage induced by mustard oil in the arsenic groups fed with sodium arsenite (10 or 15 mg/kg) were similar to those of water-fed mice. However, increased levels of EB leakage in response to mustard oil stimulation were significantly higher in mice treated with sodium arsenite (20 mg/kg; high dose) than in arsenic-fed (10 or 15 mg/kg; low and middle doses) or control mice. After arsenic discontinuation for 2 or 6 months, mustard oil-induced vascular EB leakage in arsenic-fed (20 mg/kg) mice was similar to that in control mice. Dramatic increases in mustard oil-induced vascular leakage were only present in mice systemically exposed to the high arsenic dose, indicating the synergistic effects of the high arsenic dose and mustard oil.

  15. Programming voltage reduction in phase change memory cells with tungsten trioxide bottom heating layer/electrode

    International Nuclear Information System (INIS)

    Rao Feng; Song Zhitang; Gong Yuefeng; Wu Liangcai; Feng Songlin; Chen, Bomy

    2008-01-01

    A phase change memory cell with tungsten trioxide bottom heating layer/electrode is investigated. The crystalline tungsten trioxide heating layer promotes the temperature rise in the Ge 2 Sb 2 Te 5 layer which causes the reduction in the reset voltage compared to a conventional phase change memory cell. Theoretical thermal simulation and calculation for the reset process are applied to understand the thermal effect of the tungsten trioxide heating layer/electrode. The improvement in thermal efficiency of the PCM cell mainly originates from the low thermal conductivity of the crystalline tungsten trioxide material.

  16. The potential DNA toxic changes among workers exposed to antimony trioxide.

    Science.gov (United States)

    El Shanawany, Safaa; Foda, Nermine; Hashad, Doaa I; Salama, Naglaa; Sobh, Zahraa

    2017-05-01

    Occupational exposure to antimony has gained much interest when specific toxic effects were noticed among workers processing antimony. Thus, the aim of the present work was to investigate the potential DNA oxidative damage occurring among Egyptian workers occupationally exposed to antimony trioxide. The study was conducted on 25 subjects exposed to antimony trioxide while working in the polymerization process of polyester in Misrayon and Polyester Fiber Company, KafrEldawwar, Beheira, Egypt. Urinary antimony levels were assessed using inductive coupled plasma-optical emission spectrometry (ICP-OES) and considered as a biological exposure index. DNA damage and total oxidant capacity (TOC) were assessed using ELISA. DNA damage was detected in the form of increased apurinic/apyrimidinic (AP) sites among antimony trioxide-exposed workers compared to control subjects, but it could not be explained by oxidative mechanisms due to lack of significant correlation between DNA damage and measured TOC. Antimony trioxide might have a genotoxic impact on occupationally exposed workers which could not be attributed to oxidative stress in the studied cases.

  17. Molecular basis for arsenic-Induced alteration in nitric oxide production and oxidative stress: implication of endothelial dysfunction

    International Nuclear Information System (INIS)

    Kumagai, Yoshito; Pi Jingbo

    2004-01-01

    Accumulated epidemiological studies have suggested that prolonged exposure of humans to arsenic in drinking water is associated with vascular diseases. The exact mechanism of how this occurs currently unknown. Nitric oxide (NO), formed by endothelial NO synthase (eNOS), plays a crucial role in the vascular system. Decreased availability of biologically active NO in the endothelium is implicated in the pathophysiology of several vascular diseases and inhibition of eNOS by arsenic is one of the proposed mechanism s for arsenic-induced vascular diseases. In addition, during exposure to arsenic, overproduction of reactive oxygen species (ROS) can occur, resulting in oxidative stress, which is another major risk factor for vascular dysfunction. The molecular basis for decreased NO levels and increased oxidative stress during arsenic exposure is poorly understood. In this article, evidence for arsenic-mediated alteration in NO production and oxidative stress is reviewed. The results of a cross-sectional study in an endemic area of chronic arsenic poisoning and experimental animal studies to elucidate a potential mechanism for the impairment of NO formation and oxidative stress caused by prolonged exposure to arsenate in the drinking water are also reviewed

  18. Arsenic and human health effects: A review.

    Science.gov (United States)

    Abdul, Khaja Shameem Mohammed; Jayasinghe, Sudheera Sammanthi; Chandana, Ediriweera P S; Jayasumana, Channa; De Silva, P Mangala C S

    2015-11-01

    Arsenic (As) is ubiquitous in nature and humans being exposed to arsenic via atmospheric air, ground water and food sources are certain. Major sources of arsenic contamination could be either through geological or via anthropogenic activities. In physiological individuals, organ system is described as group of organs that transact collectively and associate with other systems for conventional body functions. Arsenic has been associated with persuading a variety of complications in body organ systems: integumentary, nervous, respiratory, cardiovascular, hematopoietic, immune, endocrine, hepatic, renal, reproductive system and development. In this review, we outline the effects of arsenic on the human body with a main focus on assorted organ systems with respective disease conditions. Additionally, underlying mechanisms of disease development in each organ system due to arsenic have also been explored. Strikingly, arsenic has been able to induce epigenetic changes (in utero) and genetic mutations (a leading cause of cancer) in the body. Occurrence of various arsenic induced health effects involving emerging areas such as epigenetics and cancer along with their respective mechanisms are also briefly discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Enhancing arsenic removal from groundwater at household level with naturally occurring iron

    Directory of Open Access Journals (Sweden)

    Anitha Kumari Sharma

    2016-06-01

    Full Text Available A supply of drinking water low in Arsenic (As prevents arsenic poisoning. The presence of high concentrations of iron (Fe in groundwater under the alluvial plains of the large rivers in Southeast Asia is a prerequisite for the simple removal of As. This study investigated the mechanisms and possibilities for enhancing As removal with naturally occurring Fe in a reliable, low cost and sustainable way. The results of the study show that As removal with Fe is greatly enhanced by the addition of an oxidizing agent (preferably KMnO4 immediately after the pumping of groundwater. Further enhancement of As removal in the presence of Fe can be achieved by adding a small volume of a concentrated basic solution of MnO4- and AlO2-, which has a combined oxidation, coagulation and buffering capacity. Best results were obtained when this solution was mixed with the groundwater immediately after its pumping until a pale pink color appeared. Maximum required reaction time was 10 minutes and subsequent filtration of the water was able to reduce the As concentration to near zero. Concentrations of MnO4- and AlO2- can be varied in the solution to achieve sufficient As removal to suit different Fe/As ratios and the presence of interfering co-occurring anions.

  20. Small System Use of a Solid Arsenic Oxidizing Media in Place of Chemical Oxidation to Enhance Arsenic Removals

    Science.gov (United States)

    As part of the USEPA Arsenic Demonstration Program, an arsenic removal adsorptive media treatment system (10 gpm) was installed at Head Start School in Buckeye Lake, Ohio on June 28, 2006. The source water (ground water) contained around 20 µg/L of arsenic, existing predominatel...

  1. Arsenic Hyperaccumulation Strategies: An Overview

    Directory of Open Access Journals (Sweden)

    Zahra Souri

    2017-07-01

    Full Text Available Arsenic (As pollution, which is on the increase around the world, poses a growing threat to the environment. Phytoremediation, an important green technology, uses different strategies, including As uptake, transport, translocation, and detoxification, to remediate this metalloid. Arsenic hyperaccumulator plants have developed various strategies to accumulate and tolerate high concentrations of As. In these plants, the formation of AsIII complexes with GSH and phytochelatins and their transport into root and shoot vacuoles constitute important mechanisms for coping with As stress. The oxidative stress induced by reactive oxygen species (ROS production is one of the principal toxic effects of As; moreover, the strong antioxidative defenses in hyperaccumulator plants could constitute an important As detoxification strategy. On the other hand, nitric oxide activates antioxidant enzyme and phytochelatins biosynthesis which enhances As stress tolerance in plants. Although several studies have focused on transcription, metabolomics, and proteomic changes in plants induced by As, the mechanisms involved in As transport, translocation, and detoxification in hyperaccumulator plants need to be studied in greater depth. This review updates recent progress made in the study of As uptake, translocation, chelation, and detoxification in As hyperaccumulator plants.

  2. Combined Administration of Taurine and Monoisoamyl Dmsa Protects Arsenic Induced Oxidative Injury in Rats

    Directory of Open Access Journals (Sweden)

    Swaran J. S. Flora

    2008-01-01

    Full Text Available Arsenic is a naturally occurring element that is ubiquitously present in the environment. High concentration of naturally occurring arsenic in drinking water is a major health problem in different parts of the world. Despite arsenic being a health hazard and a well documented carcinogen, no safe, effective and specific preventive or therapeutic measures are available. Among various recent strategies adopted, administration of an antioxidant has been reported to be the most effective. The present study was designed to evaluate the therapeutic efficacy of monoisoamyl dimercaptosuccinic acid (MiADMSA, administered either individually or in combination with taurine post chronic arsenic exposure in rats. Arsenic exposed male rats (25 ppm, sodium arsenite in drinking water for 24 weeks were treated with taurine (100 mg/kg, i.p., once daily, monoisoamyl dimercaptosuccinic acid (MiADMSA (50 mg/kg, oral, once daily either individually or in combination for 5 consecutive days. Biochemical variables indicative of oxidative stress along-with arsenic concentration in blood, liver and kidney were measured. Arsenic exposure significantly reduced blood δ-aminolevulinic acid dehydratase (ALAD activity, a key enzyme involved in the heme biosynthesis and enhanced zinc protoporphyrin (ZPP level. Clinical hematological variables like white blood cells (WBC, mean cell hemoglobin (MCH, and mean cell hemoglobin concentration (MCHC showed significant decrease with a significant elevation in platelet (PLT count. These changes were accompanied by significant decrease in superoxide dismutase (SOD activity and increased catalase activity. Arsenic exposure caused a significant decrease in hepatic and renal glutathione (GSH level and an increase in oxidized glutathione (GSSG. These biochemical changes were correlated with an increased uptake of arsenic in blood, liver and kidney. Administration of taurine significantly reduced hepatic oxidative stress however co

  3. A Potential Synergy between Incomplete Arsenic Methylation Capacity and Demographic Characteristics on the Risk of Hypertension: Findings from a Cross-Sectional Study in an Arsenic-Endemic Area of Inner Mongolia, China

    Directory of Open Access Journals (Sweden)

    Yongfang Li

    2015-03-01

    Full Text Available Inefficient arsenic methylation capacity has been associated with various health hazards induced by arsenic. In this study, we aimed to explore the interaction effect of lower arsenic methylation capacity with demographic characteristics on hypertension risk. A total of 512 adult participants (126 hypertension subjects and 386 non-hypertension subjects residing in an arsenic-endemic area in Inner Mongolia, China were included. Urinary levels of inorganic arsenic (iAs, monomethylarsonic acid (MMA, and dimethylarsinic acid (DMA were measured for all subjects. The percentage of urinary arsenic metabolites (iAs%, MMA%, and DMA%, primary methylation index (PMI and secondary methylation index (SMI were calculated to assess arsenic methylation capacity of individuals. Results showed that participants carrying a lower methylation capacity, which is characterized by lower DMA% and SMI, have a higher risk of hypertension compared to their corresponding references after adjusting for multiple confounders. A potential synergy between poor arsenic methylation capacity (higher MMA%, lower DMA% and SMI and older age or higher BMI were detected. The joint effects of higher MMA% and lower SMI with cigarette smoking also suggest some evidence of synergism. The findings of present study indicated that inefficient arsenic methylation capacity was associated with hypertension and the effect might be enhanced by certain demographic factors.

  4. Arsenic removal by using colloidal adsorption flotation utilizing Fe(OH)3 floc in a dissolved air flotation system; Eliminacion de arsenico mediante flotacion por adsorcion coloidal utilizando floculos de Fe(OH){sub 3} en un sistema de flotacion por aire disuelto

    Energy Technology Data Exchange (ETDEWEB)

    Pavez, O.; Palacios, J. M.; Aguilar, C.

    2009-07-01

    In the present work, the influence of Fe/As ratio on the As removal, from aqueous solutions, applying flotation by colloidal adsorption was studied. Ferric chloride was used as coagulant and dodec il sulfate as collector, and arsenic trioxide was utilized to preparing the solutions. The obtained results show that the highest arsenic removal was accomplished in the range of pH between 4 and 5,5, and the increasing of the initial concentration of Fe(III), increases the removal of arsenic from the solution. However, with the decreasing of the initial concentration of arsenic in the solution, it is required a larger Fe/As ratio for its removal. For solutions containing: 13,73, 1,71 and 0,105 mg/L of arsenic, it was shown that to remove around 95% of the dissolved arsenic, a Fe/As ratios of approximately 6/1, 18/1 and 800/1, respectively, are required. (Author) 31 refs.

  5. Mineral Trioxide Aggregate and Portland Cement for Direct Pulp Capping in Dog: A Histopathological Evaluation

    Directory of Open Access Journals (Sweden)

    Maryam Bidar

    2014-09-01

    Full Text Available Background and aims. Mineral trioxide aggregate and calcium hydroxide are considered the gold standard pulp-capping materials. Recently, Portland cement has been introduced with properties similar to those of mineral trioxide aggregate. His-topathological effects of direct pulp capping using mineral trioxide aggregate and Portland cements on dog dental pulp tis-sue were evaluated in the present study. Materials and methods. This histopatological study was carried out on 64 dog premolars. First, the pulp was exposedwith a sterile bur. Then, the exposed pulp was capped with white or gray mineral trioxide aggregates and white or gray Port-land cements in each quadrant and sealed with glass-ionomer. The specimens were evaluated under a light microscope after 6 months. Statistical analysis was carried out using Kruskal-Wallis test. Statistical significance was defined at α=5%. Results. There was no acute inflammation in any of the specimens. Chronic inflammation in white and gray mineral triox-ide aggregates and white and gray Portland cements was reported to be 45.5%, 27.3%, 57.1% and 34.1%, respectively. Al-though the differences were not statistically significant, severe inflammation was observed mostly adjacent to white mineral trioxide aggregate. The largest extent of increased vascularization (45% and the least increase in fibrous tissue were ob-served adjacent to white mineral trioxide aggregate, with no significant differences. In addition, the least calcified tissue formed adjacent to white mineral trioxide aggregate, although the difference was not significant. Conclusion. The materials used in this study were equally effective as pulp protection materials following direct pulp cap-ping in dog teeth.

  6. Arsenic-induced skin lesions among Atacameño people in Northern Chile despite good nutrition and centuries of exposure.

    Science.gov (United States)

    Smith, A H; Arroyo, A P; Mazumder, D N; Kosnett, M J; Hernandez, A L; Beeris, M; Smith, M M; Moore, L E

    2000-07-01

    It has been suggested that the indigenous Atacameño people in Northern Chile might be protected from the health effects of arsenic in drinking water because of many centuries of exposure. Here we report on the first intensive investigation of arsenic-induced skin lesions in this population. We selected 11 families (44 participants) from the village of Chiu Chiu, which is supplied with water containing between 750 and 800 microg/L inorganic arsenic. For comparison, 8 families (31 participants) were also selected from a village where the water contains approximately 10 microg/L inorganic arsenic. After being transported to the nearest city for blind assessment, participants were examined by four physicians with experience in studying arsenic-induced lesions. Four of the six men from the exposed village, who had been drinking the contaminated water for more than 20 years, were diagnosed with skin lesions due to arsenic, but none of the women had definite lesions. A 13-year-old girl had definite skin pigmentation changes due to arsenic, and a 19-year-old boy had both pigmentation changes and keratoses on the palms of his hands and the soles of his feet. Family interviews identified a wide range of fruits and vegetables consumed daily by the affected participants, as well as the weekly intake of red meat and chicken. However, the prevalence of skin lesions among men and children in the small population studied was similar to that reported with corresponding arsenic drinking water concentrations in both Taiwan and West Bengal, India--populations in which extensive malnutrition has been thought to increase susceptibility.

  7. Combined Efficacy of Gallic Acid and MiADMSA with Limited Beneficial Effects Over MiADMSA Against Arsenic-induced Oxidative Stress in Mouse.

    Science.gov (United States)

    Pachauri, Vidhu; Flora, Sjs

    2015-01-01

    Gallic acid is an organic acid known for its antioxidant and anticancer properties. The present study is focused on evaluating the role of gallic acid in providing better therapeutic outcomes against arsenic-induced toxicity. Animals pre-exposed to arsenic were treated with monoisoamyl meso-2,3-dimercaptosuccinic acid (MiADMSA), a new chelating drug, alone and in combination with gallic acid, consecutively for 10 days. The study suggests that (1) gallic acid in presence of MiADMSA is only moderately beneficial against arsenic, (2) monotherapy with gallic acid is more effective than in combination with MiADMSA after arsenic exposure in reducing oxidative injury, and (3) MiADMSA monotherapy as reported previously provides significant therapeutic efficacy against arsenic. Thus, based on the present results, we conclude that gallic acid is effective against arsenic-induced oxidative stress but provides limited additional beneficial effects when administered in combination with MiADMSA. We still recommend that lower doses of gallic acid be evaluated both individually and in combination with MiADMSA, as it might not exhibit the shortcomings we observed with higher doses in this study.

  8. Detoxification system for inorganic arsenic: transformation of As2O3 into TMAO by vitamin B12 derivatives and conversion of TMAO into arsenobetaine.

    Science.gov (United States)

    Nakamura, Koichiro; Hisaeda, Yoshio; Pan, Ling; Yamauchi, Hiroshi

    2008-11-07

    A new two-step synthetic pathway developed for the transformation of arsenic trioxide [iAs(III); As(2)O(3)] into arsenobetaine (AB; Me(3)As(+)CH(2)CO(2)(-)) involves treatment of iAs(III) with native B(12) or biomimetic B(12) in the presence of glutathione (GSH) to give TMAO with a high selectivity and a high conversion rate; subsequent treatment of TMAO with iodoacetic acid in the presence of GSH gives arsenobetaine.

  9. Arsenic in Ground Water of the United States

    Science.gov (United States)

    ... Team More Information Arsenic in groundwater of the United States Arsenic in groundwater is largely the result of ... Gronberg (2011) for updated arsenic map. Featured publications United States Effects of human-induced alteration of groundwater flow ...

  10. Direct separation of arsenic and antimony oxides by high-temperature filtration with porous FeAl intermetallic.

    Science.gov (United States)

    Zhang, Huibin; Liu, Xinli; Jiang, Yao; Gao, Lin; Yu, Linping; Lin, Nan; He, Yuehui; Liu, C T

    2017-09-15

    A temperature-controlled selective filtration technology for synchronous removal of arsenic and recovery of antimony from the fume produced from reduction smelting process of lead anode slimes was proposed. The chromium (Cr) alloyed FeAl intermetallic with an asymmetric pore structure was developed as the high-temperature filter material after evaluating its corrosive resistance, structural stability and mechanical properties. The results showed that porous FeAl alloyed with 20wt.% Cr had a long term stability in a high-temperature sulfide-bearing environment. The separation of arsenic and antimony trioxides was realized principally based on their disparate saturated vapor pressures at specific temperature ranges and the asymmetric membrane of FeAl filter elements with a mean pore size of 1.8μm. Pilot-scale filtration tests showed that the direct separation of arsenic and antimony can be achieved by a one-step or two-step filtration process. A higher removal percentage of arsenic can reach 92.24% at the expense of 6∼7% loss of antimony in the two-step filtration process at 500∼550°C and 300∼400°C. The FeAl filters had still good permeable and mechanical properties with 1041h of uninterrupted service, which indicates the feasibility of this high-temperature filtration technology. Copyright © 2017. Published by Elsevier B.V.

  11. Oxidative stress and hepatic stellate cell activation are key events in arsenic induced liver fibrosis in mice

    International Nuclear Information System (INIS)

    Ghatak, Subhadip; Biswas, Ayan; Dhali, Gopal Krishna; Chowdhury, Abhijit; Boyer, James L.; Santra, Amal

    2011-01-01

    Arsenic is an environmental toxicant and carcinogen. Exposure to arsenic is associated with development of liver fibrosis and portal hypertension through ill defined mechanisms. We evaluated hepatic fibrogenesis after long term arsenic exposure in a murine model. BALB/c mice were exposed to arsenic by daily gavages of 6 μg/gm body weight for 1 year and were evaluated for markers of hepatic oxidative stress and fibrosis, as well as pro-inflammatory, pro-apoptotic and pro-fibrogenic factors at 9 and 12 months. Hepatic NADPH oxidase activity progressively increased in arsenic exposure with concomitant development of hepatic oxidative stress. Hepatic steatosis with occasional collection of mononuclear inflammatory cells and mild portal fibrosis were the predominant liver lesion observed after 9 months of arsenic exposure, while at 12 months, the changes included mild hepatic steatosis, inflammation, necrosis and significant fibrosis in periportal areas. The pathologic changes in the liver were associated with markers of hepatic stellate cells (HSCs) activation, matrix reorganization and fibrosis including α-smooth muscle actin, transforming growth factor-β1, PDGF-Rβ, pro-inflammatory cytokines and enhanced expression of tissue inhibitor of metalloproteinase-1 and pro(α) collagen type I. Moreover, pro-apoptotic protein Bax was dominantly expressed and Bcl-2 was down-regulated along with increased number of TUNEL positive hepatocytes in liver of arsenic exposed mice. Furthermore, HSCs activation due to increased hepatic oxidative stress observed after in vivo arsenic exposure was recapitulated in co-culture model of isolated HSCs and hepatocytes exposed to arsenic. These findings have implications not only for the understanding of the pathology of arsenic related liver fibrosis but also for the design of preventive strategies in chronic arsenicosis.

  12. Exiguobacterium mediated arsenic removal and its protective effect against arsenic induced toxicity and oxidative damage in freshwater fish, Channa striata

    Directory of Open Access Journals (Sweden)

    Neha Pandey

    2015-01-01

    Full Text Available Arsenic is a toxic metalloid existing widely in the environment, and its removal from contaminated water has become a global challenge. The use of bacteria in this regard finds a promising solution. In the present study, Exiguobacterium sp. As-9, which is an arsenic resistant bacterium, was selected with respect to its arsenic removal efficiency. Quantification of arsenic in the water treated with bacterium showed that Exiguobacterium efficiently removed up to 99% of arsenic in less than 20 h. In order to reveal the possible effect of this bacterium in removal of arsenic from water and protecting fishes from the detrimental effects of arsenic, we initiated a range of studies on fresh water fish, Channa striata. It was observed that the fishes introduced into bacteria treated water displayed no symptoms of arsenic toxicity which was marked by a decreased oxidative damage, whereas the fishes exposed to arsenic revealed a significant (p < 0.05 increase in the oxidative stress together with the elevated levels of malondialdehyde. Determination of the bioaccumulation of arsenic in the liver tissues of C. striata using hydride generation atomic absorption spectrophotometry (HG-AAS revealed an increased As(III accumulation in the fishes exposed to arsenic whereas the arsenic level in the control and bacteria treated fishes were found below the detectable limit. In conclusion, this study presents the strategies of bacterial arsenic removal with possible directions for future research.

  13. A Phytoremediation Strategy for Arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Meagher, Richard B.

    2005-06-01

    A Phytoremediation Strategy for Arsenic Progress Report May, 2005 Richard B. Meagher Principal Investigator Arsenic pollution affects the health of several hundred millions of people world wide, and an estimated 10 million Americans have unsafe levels of arsenic in their drinking water. However, few environmentally sound remedies for cleaning up arsenic contaminated soil and water have been proposed. Phytoremediation, the use of plants to extract and sequester environmental pollutants, is one new technology that offers an ecologically sound solution to a devastating problem. We propose that it is less disruptive to the environment to harvest and dispose of several thousand pounds per acre of contaminated aboveground plant material, than to excavate and dispose of 1 to 5 million pounds of contaminated soil per acre (assumes contamination runs 3 ft deep). Our objective is to develop a genetics-based phytoremediation strategy for arsenic removal that can be used in any plant species. This strategy requires the enhanced expression of several transgenes from diverse sources. Our working hypothesis is that organ-specific expression of several genes controlling the transport, electrochemical state, and binding of arsenic will result in the efficient extraction and hyperaccumulation of arsenic into aboveground plant tissues. This hypothesis is supported by theoretical arguments and strong preliminary data. We proposed six Specific Aims focused on testing and developing this arsenic phytoremediation strategy. During the first 18 months of the grant we made significant progress on five Specific Aims and began work on the sixth as summarized below. Specific Aim 1: Enhance plant arsenic resistance and greatly expand sinks for arsenite by expressing elevated levels of thiol-rich, arsenic-binding peptides. Hyperaccumulation of arsenic depends upon making plants that are both highly tolerant to arsenic and that have the capacity to store large amounts of arsenic aboveground

  14. Effects of Nrf2 deficiency on arsenic metabolism in mice.

    Science.gov (United States)

    Wang, Huihui; Zhu, Jiayu; Li, Lu; Li, Yongfang; Lv, Hang; Xu, Yuanyuan; Sun, Guifan; Pi, Jingbo

    2017-12-15

    Inorganic arsenic (iAs) is a known toxicant and carcinogen. Worldwide arsenic exposure has become a threat to human health. The severity of arsenic toxicity is strongly correlated with the speed of arsenic metabolism (methylation) and clearance. Furthermore, oxidative stress is recognized as a major mechanism for arsenic-induced toxicity. Nuclear factor-E2-related factor 2 (Nrf2), a key regulator in cellular adaptive antioxidant response, is clearly involved in alleviation of arsenic-induced oxidative damage. Multiple studies demonstrate that Nrf2 deficiency mice are more vulnerable to arsenic-induced intoxication. However, what effect Nrf2 deficiency might have on arsenic metabolism in mice is still unknown. In the present study, we measured the key enzymes involved in arsenic metabolism in Nrf2-WT and Nrf2-KO mice. Our results showed that basal transcript levels of glutathione S-transferase omega 2 (Gsto2) were significantly higher and GST mu 1 (Gstm1) lower in Nrf2-KO mice compared to Nrf2-WT control. Arsenic speciation and methylation rate in liver and urine was then studied in mice treated with 5mg/kg sodium arsenite for 12h. Although there were some alterations in arsenic metabolism enzymes between Nrf2-WT and Nrf2-KO mice, the Nrf2 deficiency had no significant effect on arsenic methylation. These results suggest that the Nrf2-KO mice are more sensitive to arsenic than Nrf2-WT mainly because of differences in adaptive antioxidant detoxification capacity rather than arsenic methylation capacity. Copyright © 2017. Published by Elsevier Inc.

  15. Sources and circulation of water and arsenic in the Giant Mine, Yellowknife, NWT, Canada.

    Science.gov (United States)

    Clark, Ian D; Raven, Kenneth G

    2004-06-01

    Recovery of gold from arsenopyrite-hosted ore in the Giant Mine camp, Yellowknife, NWT, Canada, has left a legacy of arsenic contamination that poses challenges for mine closure planning. Seepage from underground chambers storing some 237,000 tonnes of arsenic trioxide dust, has As concentrations exceeding 4000 ppm. Other potential sources and sinks of As also exist. Sources and movement of water and arsenic are traced using the isotopes of water and sulphate. Mine waters (16 ppm As; AsV/AsIII approximately 150) are a mixture of two principal water sources--locally recharged, low As groundwaters (0.5 ppm As) and Great Slave Lake (GSL; 0.004 ppm As) water, formerly used in ore processing and discharged to the northwest tailings impoundment (NWTP). Mass balance with delta18O shows that recirculation of NWTP water to the underground through faults and unsealed drillholes contributes about 60% of the mine water. Sulphate serves to trace direct infiltration to the As2O3 chambers. Sulphate in local, low As groundwaters (0.3-0.6 ppm As; delta34SSO4 approximately 4% and delta18OSO4 approximately -10%) originates from low-temperature aqueous oxidation of sulphide-rich waste rock. The high As waters gain a component of 18O-enriched sulphate derived from roaster gases (delta18OSO4) = + 3.5%), consistent with their arsenic source from the As2O3 chambers. High arsenic in NWTP water (approximately 8 ppm As; delta18OSO4 = -2%) derived from mine water, is attenuated to close to 1 ppm during infiltration back to the underground, probably by oxidation and sorption by ferrihydrite. Copyright 2004 Taylor and Francis Ltd.

  16. Arsenic Removal from Groundwater by Solar Driven Inline-Electrolytic Induced Co-Precipitation and Filtration—A Long Term Field Test Conducted in West Bengal

    OpenAIRE

    Otter, Philipp; Malakar, Pradyut; Jana, Bana Bihari; Grischek, Thomas; Benz, Florian; Goldmaier, Alexander; Feistel, Ulrike; Jana, Joydev; Lahiri, Susmita; Alvarez, Juan Antonio

    2017-01-01

    Arsenic contamination in drinking water resources is of major concern in the Ganga delta plains of West Bengal in India and Bangladesh. Here, several laboratory and field studies on arsenic removal from drinking water resources were conducted in the past and the application of strong-oxidant-induced co-precipitation of arsenic on iron hydroxides is still considered as the most promising mechanism. This paper suggests an autonomous, solar driven arsenic removal setting and presents the finding...

  17. Thermodynamic and kinetic studies of As2O3 toxicological effects on human insulin in generation diabetes mellitus

    Science.gov (United States)

    Mohsennia, Mohsen; Motaharinejad, Atieh; Rafiee-Pour, Hossain-Ali; Torabbeigi, Marzieh

    2017-12-01

    The interaction of arsenic trioxide with human insulin was investigated by circular dichroism (CD), cyclic voltammetry and electrophoresis techniques. The interfacial behavior of insulin in presence of As2O3 onto the Ag electrode surface was studied at 310 K in phosphate buffer solution (PBS). According to Far-UV CD spectroscopy results, As2O3 caused to decrease in structural compactness and variety of alpha helix into beta structures. Near-UV CD indicated that As2O3 dissociates disulfide linkage in insulin structure. The kinetic parameters, including charge-transfer coefficient and apparent heterogeneous electron transfer rate constant were also determined. The thermodynamic parameters of insulin denaturation in presence of arsenic trioxide were calculated and reported. The obtained results indicated strong adsorption of insulin in presence of arsenic trioxide onto the Ag surface via chemisorptions.

  18. In situ chemical fixation of arsenic-contaminated soils: Anexperimental study

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Li; Donahoe, Rona J.; Redwine, James C.

    2007-03-27

    This paper reports the results of an experimentalstudytesting a low-cost in situ chemical fixation method designed to reclaimarsenic-contaminated subsurface soils. Subsurface soils from severalindustrial sites in southeastern U.S. were contaminated with arsenicthrough heavy application of herbicide containing arsenic trioxide. Themean concentrations of environmentally available arsenic in soilscollected from the two study sites, FW and BH, are 325 mg/kg and 900mg/kg, respectively. The soils are sandy loams with varying mineralogicaland organic contents. The previous study [Yang L, Donahoe RJ. The form,distribution and mobility of arsenic in soils contaminated by arsenictrioxide, at sites in Southeast USA. Appl Geochem 2007;22:320 341]indicated that a large portion of the arsenic in both soils is associatedwith amorphous aluminum and iron oxyhydroxides and shows very slowrelease against leaching by synthetic precipitation. The soil's amorphousaluminum and iron oxyhydroxides content was found to have the mostsignificant effect on its ability to retain arsenic.Based on thisobservation, contaminated soils were reacted with different treatmentsolutions in an effort to promote the formation of insolublearsenic-bearing phases and thereby decrease the leachability of arsenic.Ferrous sulfate, potassium permanganate and calcium carbonate were usedas the reagents for the chemical fixation solutions evaluated in threesets of batch experiments: (1) FeSO4; (2) FeSO4 and KMnO4; (3) FeSO4,KMnO4 and CaCO3. The optimum treatment solutions for each soil wereidentified based on the mobility of arsenic during sequential leaching oftreated and untreated soils using the fluids described in EPA Method 1311[USEPA. Method 1311: toxicity characteristic leaching procedure. Testmethods for evaluating solid waste, physical/chemical methods. 3rd ed.Washington, DC: U.S. Environmental Protection Agency, Office of SolidWaste. U.S. Government Printing Office; 1992]toxic characteristicsleaching

  19. MRP-1 expression levels determine strain-specific susceptibility to sodium arsenic-induced renal injury between C57BL/6 and BALB/c mice

    International Nuclear Information System (INIS)

    Kimura, Akihiko; Ishida, Yuko; Wada, Takashi; Yokoyama, Hitoshi; Mukaida, Naofumi; Kondo, Toshikazu

    2005-01-01

    To clarify the pathophysiological mechanism underlying acute renal injury caused by acute exposure to arsenic, we subcutaneously injected both BALB/c and C57BL/6 mice with sodium arsenite (NaAs; 13.5 mg/kg). BALB/c mice exhibited exaggerated elevation of serum blood urea nitrogen (BUN) and creatinine (CRE) levels, compared with C57BL/6 mice. Moreover, half of BALB/c mice died by 24 h, whereas all C57BL/6 mice survived. Histopathological examination on kidney revealed severe hemorrhages, acute tubular necrosis, neutrophil infiltration, cast formation, and disappearance of PAS-positive brush borders in BALB/c mice, later than 10 h. These pathological changes were remarkably attenuated in C57BL/6 mice, accompanied with lower intrarenal arsenic concentrations, compared with BALB/c mice. Among heavy metal inducible proteins including multidrug resistance-associated protein (MRP)-1, multidrug resistance gene (MDR)-1, metallothionein (MT)-1, and arsenite inducible, cysteine- and histidine-rich RNA-associated protein (AIRAP), intrarenal MDR-1, MT-1, and AIRAP gene expression was enhanced to a similar extent in both strains, whereas NaAs challenge augmented intrarenal MRP-1 mRNA and protein expression levels in C57BL/6 but not BALB/c mice. Moreover, the administration of a specific inhibitor of MRP-1, MK-571, significantly exaggerated acute renal injury in C57BL/6 mice. Thus, MRP-1 is crucially involved in arsenic efflux and eventually prevention of acute renal injury upon acute exposure to NaAs

  20. Beam-induced redox transformation of arsenic during As K-edge XAS measurements: availability of reducing or oxidizing agents and As speciation.

    Science.gov (United States)

    Han, Young Soo; Jeong, Hoon Young; Hyun, Sung Pil; Hayes, Kim F; Chon, Chul Min

    2018-05-01

    During X-ray absorption spectroscopy (XAS) measurements of arsenic (As), beam-induced redox transformation is often observed. In this study, the As species immobilized by poorly crystallized mackinawite (FeS) was assessed for the susceptibility to beam-induced redox reactions as a function of sample properties including the redox state of FeS and the solid-phase As speciation. The beam-induced oxidation of reduced As species was found to be mediated by the atmospheric O 2 and the oxidation products of FeS [e.g. Fe(III) (oxyhydr)oxides and intermediate sulfurs]. Regardless of the redox state of FeS, both arsenic sulfide and surface-complexed As(III) readily underwent the photo-oxidation upon exposure to the atmospheric O 2 during XAS measurements. With strict O 2 exclusion, however, both As(0) and arsenic sulfide were less prone to the photo-oxidation by Fe(III) (oxyhydr)oxides than NaAsO 2 and/or surface-complexed As(III). In case of unaerated As(V)-reacted FeS samples, surface-complexed As(V) was photocatalytically reduced during XAS measurements, but arsenic sulfide did not undergo the photo-reduction.

  1. Inorganic Arsenic Induces NRF2-Regulated Antioxidant Defenses in Both Cerebral Cortex and Hippocampus in Vivo.

    Science.gov (United States)

    Zhang, Yang; Duan, Xiaoxu; Li, Jinlong; Zhao, Shuo; Li, Wei; Zhao, Lu; Li, Wei; Nie, Huifang; Sun, Guifang; Li, Bing

    2016-08-01

    Inorganic arsenic is reported to induce the reactive oxygen species-mediated oxidative stress, which is supposed to be one of the main mechanisms of arsenic-related neurological diseases. Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of antioxidant defense systems, up-regulates the expression of target genes to fight against oxidative damages caused by harmful substances, including metals. In the present study, mice were used as a model to investigate the oxidative stress levels and the expressions of NRF2-regulated antioxidant substances in both cerebral cortex and hippocampus with 5, 10 and 20 mg/kg NaAsO2 exposure intra-gastrically. Our results showed that acute NaAsO2 treatment resulted in decreased total anti-oxidative capacity (T-AOC) and increased maleic dialdehyde production in the nervous system. We also detected rapidly elevation of NRF2 protein levels by enhancement of Nrf2 transcription, especially at 20 mg/kg NaAsO2 exposure group. In the meantime, mRNA and protein levels of Nrf2 encoding antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) were consistently elevated time- and dose-dependently both in the cerebral cortex and hippocampus. Taken together, the presence study demonstrated the activation of NRF2 pathway, an early antioxidant defensive response, in both cerebral cortex and hippocampus upon inorganic arsenic (iAs) exposure in vivo. A better knowledge on the roles of NRF2 pathway in maintaining cellular redox homeostasis would be helpful for the strategies on improvement of neurotoxicity related to this metalloid.

  2. An attempt to electrically enhance phytoremediation of arsenic contaminated water

    KAUST Repository

    Kubiak, Jan J.; Khankhane, Premraj J.; Kleingeld, Pieter J.; Lima, Ana T.

    2012-01-01

    Water polluted with arsenic presents a challenge for remediation. A combination of phyto- and electro-remediation was attempted in this study. Four tanks were setup in order to assess the arsenic removal ability of the two methods separately

  3. Enhanced carcinogenicity by coexposure to arsenic and iron and a novel remediation system for the elements in well drinking water.

    Science.gov (United States)

    Kumasaka, Mayuko Y; Yamanoshita, Osamu; Shimizu, Shingo; Ohnuma, Shoko; Furuta, Akio; Yajima, Ichiro; Nizam, Saika; Khalequzzaman, Md; Shekhar, Hossain U; Nakajima, Tamie; Kato, Masashi

    2013-03-01

    Various carcinomas including skin cancer are explosively increasing in arsenicosis patients who drink arsenic-polluted well water, especially in Bangladesh. Although well drinking water in the cancer-prone areas contains various elements, very little is known about the effects of elements except arsenic on carcinogenicity. In order to clarify the carcinogenic effects of coexposure to arsenic and iron, anchorage-independent growth and invasion in human untransformed HaCaT and transformed A431 keratinocytes were examined. Since the mean ratio of arsenic and iron in well water was 1:10 in cancer-prone areas of Bangladesh, effects of 1 μM arsenic and 10 μM iron were investigated. Iron synergistically promoted arsenic-mediated anchorage-independent growth in untransformed and transformed keratinocytes. Iron additionally increased invasion in both types of keratinocytes. Activities of c-SRC and ERK that regulate anchorage-independent growth and invasion were synergistically enhanced in both types of keratinocytes. Our results suggest that iron promotes arsenic-mediated transformation of untransformed keratinocytes and progression of transformed keratinocytes. We then developed a low-cost and high-performance adsorbent composed of a hydrotalcite-like compound for arsenic and iron. The adsorbent rapidly reduced concentrations of both elements from well drinking water in cancer-prone areas of Bangladesh to levels less than those in WHO health-based guidelines for drinking water. Thus, we not only demonstrated for the first time increased carcinogenicity by coexposure to arsenic and iron but also proposed a novel remediation system for well drinking water.

  4. Surface-enhanced raman spectroscopy substrate for arsenic sensing in groundwater

    Science.gov (United States)

    Yang, Peidong; Mulvihill, Martin; Tao, Andrea R.; Sinsermsuksakul, Prasert; Arnold, John

    2015-06-16

    A surface-enhanced Raman spectroscopy (SERS) substrate formed from a plurality of monolayers of polyhedral silver nanocrystals, wherein at least one of the monolayers has polyvinypyrrolidone (PVP) on its surface, and thereby configured for sensing arsenic is described. Highly active SERS substrates are formed by assembling high density monolayers of differently shaped silver nanocrystals onto a solid support. SERS detection is performed directly on this substrate by placing a droplet of the analyte solution onto the nanocrystal monolayer. Adsorbed polymer, polyvinypyrrolidone (PVP), on the surface of the nanoparticles facilitates the binding of both arsenate and arsenite near the silver surface, allowing for highly accurate and sensitive detection capabilities.

  5. Relationship between arsenic and selenium in workers occupationally exposed to inorganic arsenic.

    Science.gov (United States)

    Janasik, Beata; Zawisza, Anna; Malachowska, Beata; Fendler, Wojciech; Stanislawska, Magdalena; Kuras, Renata; Wasowicz, Wojciech

    2017-07-01

    The interaction between arsenic (As) and selenium (Se) has been one of the most extensively studied. The antagonism between As and Se suggests that low Se status plays an important role in aggravating arsenic toxicity in diseases development. The objective of this study was to assess the Se contents in biological samples of inorganic As exposed workers (n=61) and in non-exposed subjects (n=52). Median (Me) total arsenic concentration in urine of exposed workers was 21.83μg/g creat. (interquartile range (IQR) 15.49-39.77) and was significantly higher than in the control group - (Me 3.75μg/g creat. (IQR 2.52-9.26), piAs+MMA+DMA) was significantly associated with the high total selenium urine excretion (B=0.14 (95%CI (confidence interval) 0.05-0.23)). Combination of both arsenic and selenium status to assess the risk of arsenic-induced diseases requires more studies with regard to both the analysis of speciation, genetics and the influence of factors such as nutritional status. Copyright © 2017 Elsevier GmbH. All rights reserved.

  6. Polaron interaction energies in reduced tungsten trioxide

    International Nuclear Information System (INIS)

    Iguchi, E.; Salje, E.; Tilley, R.J.D.

    1981-01-01

    Consideration of the properties of reduced tungsten trioxide suggest that the mobile charge carriers are polarons. As it is uncertain how the presence of polarons will influence the microstructures of the crystallographic shear (CS) planes present in reduced tungsten trioxide we have calculated both the polaron-CS plane and polaron-polaron interaction energy for a variety of circumstances. Three CS plane geometries were considered, (102), (103), and (001) CS plane arrays, and the nominal compositions of the crystals ranged from WO 2 70 to WO 3 0 . The polarons were assumed to have radii from 0.6 to 1.0 nm and the polaron-CS plane electrostatic interaction was assumed to be screened. The results suggest that for the most part the total interaction energy is small and is unlikely to be of major importance in controlling the microstructures found in CS planes. However, at very high polaron densities the interaction energy could be appreciable and may have some influence on the existence range of CS phases

  7. Health Effects of Chronic Arsenic Exposure

    Directory of Open Access Journals (Sweden)

    Young-Seoub Hong

    2014-09-01

    Full Text Available Arsenic is a unique element with distinct physical characteristics and toxicity whose importance in public health is well recognized. The toxicity of arsenic varies across its different forms. While the carcinogenicity of arsenic has been confirmed, the mechanisms behind the diseases occurring after acute or chronic exposure to arsenic are not well understood. Inorganic arsenic has been confirmed as a human carcinogen that can induce skin, lung, and bladder cancer. There are also reports of its significant association to liver, prostate, and bladder cancer. Recent studies have also suggested a relationship with diabetes, neurological effects, cardiac disorders, and reproductive organs, but further studies are required to confirm these associations. The majority of research to date has examined cancer incidence after a high exposure to high concentrations of arsenic. However, numerous studies have reported various health effects caused by chronic exposure to low concentrations of arsenic. An assessment of the health effects to arsenic exposure has never been performed in the South Korean population; thus, objective estimates of exposure levels are needed. Data should be collected on the biological exposure level for the total arsenic concentration, and individual arsenic concentration by species. In South Korea, we believe that biological exposure assessment should be the first step, followed by regular health effect assessments.

  8. Sequestration of arsenic in ombrotrophic peatlands

    Science.gov (United States)

    Rothwell, James; Hudson-Edwards, Karen; Taylor, Kevin; Polya, David; Evans, Martin; Allott, Tim

    2014-05-01

    Peatlands can be important stores of arsenic but we are lacking spectroscopic evidence of the sequestration pathways of this toxic metalloid in peatland environments. This study reports on the solid-phase speciation of anthropogenically-derived arsenic in atmospherically contaminated peat from the Peak District National Park (UK). Surface and sub-surface peat samples were analysed by synchrotron X-ray absorption spectroscopy on B18 beamline at Diamond Light Source (UK). The results suggest that there are contrasting arsenic sequestration mechanisms in the peat. The bulk arsenic speciation results, in combination with strong arsenic-iron correlations at the surface, suggest that iron (hydr)oxides are key phases for the immobilisation of arsenic at the peat surface. In contrast, the deeper peat samples are dominated by arsenic sulphides (arsenopyrite, realgar and orpiment). Given that these peats receive inputs solely from the atmosphere, the presence of these sulphide phases suggests an in-situ authigenic formation. Redox oscillations in the peat due to a fluctuating water table and an abundant store of legacy sulphur from historic acid rain inputs may favour the precipitation of arsenic sequestering sulphides in sub-surface horizons. Oxidation-induced loss of these arsenic sequestering sulphur species by water table drawdown has important implications for the mobility of arsenic and the quality of waters draining peatlands.

  9. An attempt to electrically enhance phytoremediation of arsenic contaminated water

    NARCIS (Netherlands)

    Kubiak, J.J.; Khankhane, P.J.; Kleingeld, P.J.; Lima, A.T.

    2012-01-01

    Water polluted with arsenic presents a challenge for remediation. A combination of phyto- and electro-remediation was attempted in this study. Four tanks were setup in order to assess the arsenic removal ability of the two methods separately and in combination. Lemna minor was chosen for As

  10. 40 CFR 61.186 - Reporting requirements.

    Science.gov (United States)

    2010-07-01

    ...) NATIONAL EMISSION STANDARDS FOR HAZARDOUS AIR POLLUTANTS National Emission Standard for Inorganic Arsenic Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.186 Reporting requirements... at least 30 days prior notice of each reference opacity level determination required in § 61.183(a...

  11. Small Systems Use of a Solid Arsenic Oxidizing Media in Place of Chemical Oxidation to Enhance Arsenic Removal

    Science.gov (United States)

    Presentation provides information on the need to oxidize As III to As V to increase arsenic removal followed by information on the results of an arsenic demonstration project (Plainview CDS) using a solid oxidizing media (Filox) to oxidize As III. The presentation includes a sho...

  12. Phosphorus improves arsenic phytoremediation by Anadenanthera peregrina by alleviating induced oxidative stress.

    Science.gov (United States)

    Gomes, M P; Carvalho, M; Carvalho, G S; Marques, T C L L S M; Garcia, Q S; Guilherme, L R G; Soares, A M

    2013-01-01

    Due to similarities in their chemical behaviors, studies examining interactions between arsenic (As)--in special arsenate--and phosphorus (P) are important for better understanding arsenate uptake, toxicity, and accumulation in plants. We evaluated the effects of phosphate addition on plant biomass and on arsenate and phosphate uptake by Anadenanthera peregrina, an important Brazilian savanna legume. Plants were grown for 35 days in substrates that received combinations of 0, 10, 50, and 100 mg kg(-1) arsenate and 0, 200, and 400 mg kg(-1) phosphate. The addition of P increased the arsenic-phytoremediation capacity of A. peregrina by increasing As accumulation, while also alleviating As-induced oxidative stress. Arsenate phytotoxicity in A. peregrina is due to lipid peroxidation, but not hydrogen peroxide accumulation. Added P also increased the activity of important reactive oxygen species-scavenging enzymes (catalase and ascorbate peroxidase) that help prevent lipid peroxidation in leaves. Our findings suggest that applying P represents a feasible strategy for more efficient As phytoremediation using A. peregrina.

  13. Hydrogen-enriched water restoration of impaired calcium propagation by arsenic in primary keratinocytes

    Science.gov (United States)

    Yu, Wei-Tai; Chiu, Yi-Ching; Lee, Chih-Hung; Yoshioka, Tohru; Yu, Hsin-Su

    2013-11-01

    Endemic contamination of artesian water for drinking by arsenic is known to cause several human cancers, including cancers of the skin, bladder, and lungs. In skin, multiple arsenic-induced Bowen's disease (As-BD) can develop into invasive cancers after decades of arsenic exposure. The characteristic histological features of As-BD include full-layer epidermal dysplasia, apoptosis, and abnormal proliferation. Calcium propagation is an essential cellular event contributing to keratinocyte differentiation, proliferation, and apoptosis, all of which occur in As-BD. This study investigated how arsenic interferes calcium propagation of skin keratinocytes through ROS production and whether hydrogen-enriched water would restore arsenic-impaired calcium propagation. Arsenic was found to induce oxidative stress and inhibit ATP- and thapsigaragin-induced calcium propagation. Pretreatment of arsenic-treated keratinocytes by hydrogen-enriched water or beta-mercaptoethanol with potent anti-oxidative effects partially restored the propagation of calcium by ATP and by thapsigaragin. It was concluded that arsenic may impair calcium propagation, likely through oxidative stress and interactions with thiol groups in membrane proteins.

  14. Effects of arsenic on concentration and distribution of nutrients in the fronds of the arsenic hyperaccumulator Pteris vittata L

    International Nuclear Information System (INIS)

    Tu Cong; Ma, Lena Q.

    2005-01-01

    Pteris vittata was the first terrestrial plant known to hyperaccumulate arsenic (As). However, it is unclear how As hyperaccumulation influences nutrient uptake by this plant. P. vittata fern was grown in soil spiked with 0-500 mg As kg -1 in the greenhouse for 24 weeks. The concentrations of essential macro- (P, K, Ca, and Mg) and micro- (Fe, Mn, Cu, Zn, B and Mo) elements in the fronds of different age were examined. Both macro- and micronutrients in the fronds were found to be within the normal concentration ranges for non-hyperaccumulators. However, As hyperaccumulation did influence the elemental distribution among fronds of different age of P. vittata. Arsenic-induced P and K enhancements in the fronds contributed to the As-induced growth stimulation at low As levels. The frond P/As molar ratios of 1.0 can be used as the threshold value for normal growth of P. vittata. Potassium may function as a counter-cation for As in the fronds as shown by the As-induced K increases in the fronds. The present findings not only demonstrate that P. vittata has the ability to maintain adequate concentrations of essential nutrients while hyperaccumulating As from the soil, but also have implications for soil management (fertilization in particular) of P. vittata in As phytoextraction practice

  15. Arsenic augments the uptake of oxidized LDL by upregulating the expression of lectin-like oxidized LDL receptor in mouse aortic endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Hossain, Ekhtear [Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi (Japan); Ota, Akinobu, E-mail: aota@aichi-med-u.ac.jp [Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi (Japan); Karnan, Sivasundaram; Damdindorj, Lkhagvasuren [Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi (Japan); Takahashi, Miyuki [Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi (Japan); Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Aichi (Japan); Konishi, Yuko; Konishi, Hiroyuki; Hosokawa, Yoshitaka [Department of Biochemistry, Aichi Medical University School of Medicine, Nagakute, Aichi (Japan)

    2013-12-15

    Although chronic arsenic exposure is a well-known risk factor for cardiovascular diseases, including atherosclerosis, the molecular mechanism underlying arsenic-induced atherosclerosis remains obscure. Therefore, this study aimed to elucidate this molecular mechanism. We examined changes in the mRNA level of the lectin-like oxidized LDL (oxLDL) receptor (LOX-1) in a mouse aortic endothelial cell line, END-D, after sodium arsenite (SA) treatment. SA treatment significantly upregulated LOX-1 mRNA expression; this finding was also verified at the protein expression level. Flow cytometry and fluorescence microscopy analyses showed that the cellular uptake of fluorescence (Dil)-labeled oxLDL was significantly augmented with SA treatment. In addition, an anti-LOX-1 antibody completely abrogated the augmented uptake of Dil-oxLDL. We observed that SA increased the levels of the phosphorylated forms of nuclear factor of kappa light polypeptide gene enhancer in B cells (NF-κB)/p65. SA-induced upregulation of LOX-1 protein expression was clearly prevented by treatment with an antioxidant, N-acetylcysteine (NAC), or an NF-κB inhibitor, caffeic acid phenethylester (CAPE). Furthermore, SA-augmented uptake of Dil-oxLDL was also prevented by treatment with NAC or CAPE. Taken together, our results indicate that arsenic upregulates LOX-1 expression through the reactive oxygen species-mediated NF-κB signaling pathway, followed by augmented cellular oxLDL uptake, thus highlighting a critical role of the aberrant LOX-1 signaling pathway in the pathogenesis of arsenic-induced atherosclerosis. - Highlights: • Sodium arsenite (SA) increases LOX-1 expression in mouse aortic endothelial cells. • SA enhances cellular uptake of oxidized LDL in dose-dependent manner. • SA-induced ROS generation enhances phosphorylation of NF-κB. • SA upregulates LOX-1 expression through ROS-activated NF-κB signaling pathway.

  16. Optimization of chemical and instrumental parameters in hydride generation laser-induced breakdown spectrometry for the determination of arsenic, antimony, lead and germanium in aqueous samples.

    Science.gov (United States)

    Yeşiller, Semira Unal; Yalçın, Serife

    2013-04-03

    A laser induced breakdown spectrometry hyphenated with on-line continuous flow hydride generation sample introduction system, HG-LIBS, has been used for the determination of arsenic, antimony, lead and germanium in aqueous environments. Optimum chemical and instrumental parameters governing chemical hydride generation, laser plasma formation and detection were investigated for each element under argon and nitrogen atmosphere. Arsenic, antimony and germanium have presented strong enhancement in signal strength under argon atmosphere while lead has shown no sensitivity to ambient gas type. Detection limits of 1.1 mg L(-1), 1.0 mg L(-1), 1.3 mg L(-1) and 0.2 mg L(-1) were obtained for As, Sb, Pb and Ge, respectively. Up to 77 times enhancement in detection limit of Pb were obtained, compared to the result obtained from the direct analysis of liquids by LIBS. Applicability of the technique to real water samples was tested through spiking experiments and recoveries higher than 80% were obtained. Results demonstrate that, HG-LIBS approach is suitable for quantitative analysis of toxic elements and sufficiently fast for real time continuous monitoring in aqueous environments. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Arsenic-induced dose-dependent modulation of the NF-κB/IL-6 axis in thymocytes triggers differential immune responses

    International Nuclear Information System (INIS)

    Choudhury, Sreetama; Gupta, Payal; Ghosh, Sayan; Mukherjee, Sudeshna; Chakraborty, Priyanka; Chatterji, Urmi; Chattopadhyay, Sreya

    2016-01-01

    Highlights: • We for the first time explicitly show that arsenic exposure causes morphological damage to the thymus and results in heightened death of thymocytes. • Our data suggests that arsenic-induced apoptosis occurs due to increase in cellular oxidative and nitrosative stress. • We have for the first time established a non-classical role of NF-κB, correlating it with increase in FoxP3 expression. • The % of CD4+ CD25+ T cells were high and expression of FoxP3 has also increased at higher doses of arsenic indicating an nTreg bias. - Abstract: Arsenic contamination of drinking water is a matter of global concern. Arsenic intake impairs immune responses and leads to a variety of pathological conditions including cancer. In order to understand the intricate tuning of immune responses elicited by chronic exposure to arsenic, a mouse model was established by subjecting mice to different environmentally relevant concentrations of arsenic in drinking water for 30 days. Detailed study of the thymus, a primary immune organ, revealed arsenic-mediated tissue damage in both histological specimens and scanning electron micrographs. Analysis of molecular markers of apoptosis by Western blot revealed a dose-dependent activation of the apoptotic cascade. Enzymatic assays supported oxidative stress as an instigator of cell death. Interestingly, assessment of inflammatory responses revealed disparity in the NF-κB/IL-6/STAT3 axis, where it was found that in animals consuming higher amounts of arsenic NF-κB activation did not lead to the classical IL-6 upregulation response. This deviation from the canonical pathway was accompanied with a significant rise in numbers of CD4+ CD25+ FoxP3 expressing cells in the thymus. The cytokine profile of the animals exposed to higher doses of arsenic also indicated an immune-suppressed milieu, thus validating that arsenic shapes the immune environment in context to its dose of exposure and that at higher doses it leads to immune

  18. Folate deficiency enhances arsenic effects on expression of genes involved in epidermal differentiation in transgenic K6/ODC mouse skin

    International Nuclear Information System (INIS)

    Nelson, Gail M.; Ahlborn, Gene J.; Delker, Don A.; Kitchin, Kirk T.; O'Brien, Thomas G.; Chen Yan; Kohan, Michael J.; Roop, Barbara C.; Ward, William O.; Allen, James W.

    2007-01-01

    Chronic arsenic exposure in humans is associated with cancers of the skin, lung, bladder and other tissues. There is evidence that folate deficiency may increase susceptibility to arsenic effects, including skin lesions. K6/ODC mice develop skin tumors when exposed to 10 ppm sodium arsenite for 5 months. In the current study, K6/ODC mice maintained on either a folate deficient or folate sufficient diet were exposed to 0, 1, or 10 ppm sodium arsenite in the drinking water for 30 days. Total RNA was isolated from skin samples and gene expression analyzed using Affymetrix Mouse 430 2.0 GeneChips. Data from 24 samples, with 4 mice in each of the 6 treatment groups, were RMA normalized and analyzed by two-way ANOVA using GeneSpring TM . Top gene ontology (GO) categories for genes responding significantly to both arsenic treatment and folate deficiency include nucleotide metabolism and cell organization and biogenesis. For many of these genes, folate deficiency magnifies the response to arsenic treatment. In particular, expression of markers of epidermal differentiation, e.g., loricrin, small proline rich proteins and involucrin, was significantly reduced by arsenic in the folate sufficient animals, and reduced further or at a lower arsenic dose in the folate deficient animals. In addition, expression of a number of epidermal cell growth/proliferation genes and cellular movement genes was altered. These results indicate that arsenic disrupts the normal balance of cell proliferation and differentiation, and that folate deficiency exacerbates these effects, consistent with the view that folate deficiency is a nutritional susceptibility factor for arsenic-induced skin tumorigenesis

  19. Urinary arsenic speciation and its correlation with 8-OHdG in Chinese residents exposed to arsenic through coal burning

    Energy Technology Data Exchange (ETDEWEB)

    Li, X.; Pi, J.B.; Li, B.; Xu, Y.Y.; Jin, Y.P.; Sun, G.F. [China Medical University, Shenyang (China). Dept. for Occupational & Environmental Health

    2008-10-15

    In contrast to arsenicosis caused by consumption of water contaminated by naturally occurring inorganic arsenic, human exposure to this metalloid through coal burning has been rarely reported. In this study, arsenic speciation and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in urine were determined in the Chinese residents exposed to arsenic through coal burning in Guizhou, China, an epidemic area of chronic arsenic poisoning caused by coal burning. The urinary concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA) and total arsenic (tAs) of high-arsenic exposed subjects were significantly higher than those of low-arsenic exposed residents. A biomarker of oxidative DNA damage, urinary 8-OHdG level was significantly higher in high-arsenic exposed subjects than that of low exposed. Significant positive correlations were found between 8-OHdG levels and concentrations of iAs, MMA, DMA and tAs, respectively. In addition, a significant negative correlation was observed between 8-OHdG levels and the secondary methylation ratio (DMA/(MMA + DMA)). The results suggest that chronic arsenic exposure through burning coal rich in arsenic is associated with oxidative DNA damages, and that secondary methylation capacity is potentially related to the susceptibility of individuals to oxidative DNA damage induced by arsenic exposure through coal burning in domestic living.

  20. Ameliorating effect of microdoses of a potentized homeopathic drug, Arsenicum Album, on arsenic-induced toxicity in mice

    Directory of Open Access Journals (Sweden)

    Guha B

    2003-10-01

    Full Text Available Abstract Background Arsenic in groundwater and its accumulation in plants and animals have assumed a menacing proportion in a large part of West Bengal, India and adjoining areas of Bangladesh. Because of the tremendous magnitude of the problem, there seems to be no way to tackle the problem overnight. Efforts to provide arsenic free water to the millions of people living in these dreaded zones are being made, but are awfully inadequate. In our quest for finding out an easy, safe and affordable means to combat this problem, a homeopathic drug, Arsenicum Album-30, appears to yield promising results in mice. The relative efficacies of two micro doses of this drug, namely, Arsenicum Album-30 and Arsenicum Album-200, in combating arsenic toxicity have been determined in the present study on the basis of some accepted biochemical protocols. Methods Mice were divided into different sets of control (both positive and negative and treated series (As-intoxicated, As-intoxicated plus drug-fed. Alanine amino transferase (ALT and aspartate amino transferase (AST activities and reduced glutathione (GSH level in liver and blood were analyzed in the different series of mice at six different fixation intervals. Results Both Arsenicum Album-30 and Arsenicum Album-200 ameliorated arsenic-induced toxicity to a considerable extent as compared to various controls. Conclusions The results lend further support to our earlier views that microdoses of potentized Arsenicum Album are capable of combating arsenic intoxication in mice, and thus are strong candidates for possible use in human subjects in arsenic contaminated areas under medical supervision.

  1. Arsenic Remediation by Synthetic and Natural Adsorbents

    Directory of Open Access Journals (Sweden)

    Muhammad Saqaf Jagirani

    2017-06-01

    Full Text Available The contagion of toxic metals in water is a serious environmental and health concern and threatening problem worldwide. Particularly arsenic contamination in ground water has became great dilemma in the earlier decades. With advent in research for arsenic remediation, standard of drinking water is improving and now reduced to few parts per million (ppm level of arsenic in drinking water sources. However, due to continuous enhancement in environmental pollution, remediation techniques are still needed to achieve the drinking water quality standard. Development of novel and economically feasible removal techniques or materials for selective separation of this toxic specie has been the main focus of research. Several arsenic removal techniques, including membrane separation, coagulation, precipitation, anion exchange have been developed. The aim of this article is to review briefly arsenic chemistry and previous and current available technologies that have been reported various low-cost adsorbents for arsenic removal.

  2. The characterization, mobility, and persistence of roaster-derived arsenic in soils at Giant Mine, NWT

    Energy Technology Data Exchange (ETDEWEB)

    Bromstad, Mackenzie J.; Wrye, Lori A.; Jamieson, Heather E.

    2017-07-01

    Approximately 20,000 tonnes of arsenic (As)-bearing emissions from roasting gold (Au)-bearing arsenopyrite ore were aerially released from 1949 to 1999 at Giant Mine, near Yellowknife, Canada. Soil samples collected within 4 km of the former roaster from sites undisturbed by mining or other human activity contain up to 7700 mg/kg total As. Total As concentrations are highest within a few cm of the surface, and particularly enriched in soil pockets on rock outcrops. Scanning electron microscopy and synchrotron microanalysis show that roaster-derived arsenic trioxide (As2O3) has persisted in shallow soils in the area. Roaster-generated maghemite and hematite are also present. These anthropogenic forms of As are much more common in near-surface soils than natural As-bearing minerals. Comparison of the proportions of As, Sb, and Au concentrations in outcrop soil samples and historic As2O3-rich dust captured by emission controls suggest most of the roaster-derived As in soils at Giant was likely deposited before 1964. Topographic restriction by rock outcrops and a dry, cold climate likely contribute to the persistence of As2O3 in outcrop soils.

  3. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    International Nuclear Information System (INIS)

    Hsieh, Yi-Chen; Lien, Li-Ming; Chung, Wen-Ting; Hsieh, Fang-I; Hsieh, Pei-Fan; Wu, Meei-Maan; Tseng, Hung-Pin; Chiou, Hung-Yi; Chen, Chien-Jen

    2011-01-01

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 μg/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 μg/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 μg/l). - Highlights: →Arsenic metabolic genes might be associated with carotid atherosclerosis. → A case

  4. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

    2011-08-15

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

  5. Protective Effects of Combined Selenium and Punica granatum Treatment on Some Inflammatory and Oxidative Stress Markers in Arsenic-Induced Hepatotoxicity in Rats.

    Science.gov (United States)

    Shafik, Noha M; El Batsh, Maha M

    2016-01-01

    Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Punica granatum is known by its free radical scavenging properties. The aim of this study was to evaluate the protective role of combined selenium and P. granatum against arsenic-induced liver injury. Seventy-five female albino rats were divided into five groups (of 15 rats each). Toxicity was induced by oral sodium arsenite (5.5 mg/kg body weight (bw) daily) (group ІІ). Treatment of arsenic-intoxicated rats was induced by daily oral administration of sodium selenite (3 mg/kg bw) (group ІІІ), 100 mg of P. granatum ethanol extract per kilogram body weight dissolved in 300 mL distilled water in three divided doses (100 mL of this suspension every 8 h) (group IV), and combined daily oral treatment with both selenite and P. granatum ethanol extract (group V). After 3 weeks, serum and liver tissues were obtained from the decapitated rats for different estimations. Hepatotoxicity was demonstrated by significant elevation in liver weights and activities of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and decrease in serum total proteins and albumin (p granatum and selenium. It was concluded that combined P. granatum and selenium treatment had a synergistic hepatoprotective effect against arsenic toxicity through activation of Nrf2 anti-oxidant pathway.

  6. Clinical Assessment of Mineral Trioxide Aggregate in the Treatment ...

    African Journals Online (AJOL)

    2017-05-22

    May 22, 2017 ... (OH)2 (n = 49) or MTA (n = 51) and restored with composite resin in 73 patients. Periapical ... Clinical Assessment of Mineral Trioxide Aggregate in the Treatment of .... materials, light-cured glass ionomer cement base (Riva.

  7. Evidence against the nuclear in situ binding of arsenicals-oxidative stress theory of arsenic carcinogenesis

    International Nuclear Information System (INIS)

    Kitchin, Kirk T.; Wallace, Kathleen

    2008-01-01

    A large amount of evidence suggests that arsenicals act via oxidative stress in causing cancer in humans and experimental animals. It is possible that arsenicals could bind in situ close to nuclear DNA followed by Haber-Weiss type oxidative DNA damage. Therefore, we tested this hypothesis by using radioactive 73 As labeled arsenite and vacuum filtration methodology to determine the binding affinity and capacity of 73 As arsenite to calf thymus DNA and Type 2A unfractionated histones, histone H3, H4 and horse spleen ferritin. Arsenicals are known to release redox active Fe from ferritin. At concentrations up to about 1 mM, neither DNA nor any of the three proteins studied, Type II-A histones, histone H3, H4 or ferritin, bound radioactive arsenite in a specific manner. Therefore, it appears highly unlikely that initial in situ binding of trivalent arsenicals, followed by in situ oxidative DNA damage, can account for arsenic's carcinogenicity. This experimental evidence (lack of arsenite binding to DNA, histone Type II-A and histone H3, H4) does not rule out other possible oxidative stress modes of action for arsenic such as (a) diffusion of longer lived oxidative stress molecules, such as H 2 O 2 into the nucleus and ensuing oxidative damage, (b) redox chemistry by unbound arsenicals in the nucleus, or (c) arsenical-induced perturbations in Fe, Cu or other metals which are already known to oxidize DNA in vitro and in vivo

  8. Retreatability of Root Canals Obturated using Mineral Trioxide ...

    African Journals Online (AJOL)

    2018-04-04

    Apr 4, 2018 ... 2018 Nigerian Journal of Clinical Practice | Published by Wolters Kluwer ‑ Medknow. Background: ... remaining RCFM was evaluated using digital camera. The images ... trioxide aggregate-based and two resin-based sealers. Niger J Clin ... glass ionomer cement and the specimens were stored at. 37°C in ...

  9. [Comparison of Curative Effect between Fu Fang Huang Dai Pian and Arsenic Trioxide in Treatment of 45 Patients with Acute Promyelocytic Leukaemia].

    Science.gov (United States)

    Wang, Jian; Huang, Jun-Bin; Liu, Zu-Lin; Zhang, Bi-Hong; Xu, Hong-Gui; Xue, Hong-Man; Chen, Chun

    2017-12-01

    To investigate the clinical efficacy of Fu Fan Huang Dai Pian(RIF) and arsenic trioxide (ATO) regimens for treatment of children with acute promyelocytic leukemia (APL) and to explore the risk factors affecting the prognosis of patients. The clinical data of 45 newly diagnosed APL children admitted in our hospital from January 2004 to May 2017 were analyzed retrospectively. Among 45 APL children, 25 children were treated by chemotherapetic regimen including RIF (RIF group), another 20 children were treated by chemotherapeutic regimen including ATO (ATO group). The follow-up was performed in all APL children. The prognosis and incidence of side reactions from drugs in 2 groups were compared, and the high risk factors affecting the prognosis of patients were analyzed. The median follow-up time was 49.8% months. In RIF group, no early death occured in 25 APL children; 5 cases did not achieve complete remission (CR) after induction therapy, CR rate was 88%. Out of 25 cases 2 caes relapsed, 3 cases died, 20 cases maintained contined CR (CCR), 2 cases failed to be followed-up. In ATO group, 2 cases suffered from early death, 5 cases did not achieve CR after induction therapy, CR rate was 90%, 2 caese relapsed and died, 15 cases maintained CCR, the follow-up failed in 1 caes. The 5 year- OS and EFS rate in all the patients were predicted as (82.2±6.2)% and (76.4±6.6)% respectively. The OS and EFS rate in RIF group were (86.1±7.4)% and (78.4±8.6)% respectively, which were significantly different from OS and EFS rate (76.4%±10.6%) and (74.0%±10.1%) respectively in ATO group (all P>0.05). As for the side reaction from drug, except for the cardiac damage (P0.05). In addition, the 5 year-OS and EFS rates in APL children with CNSL were significantly lower than those in APL children without CNSL (all Phigh risk were significantly lower than those in APL children reached M1 after induction therapy and with low and standerd risk (Ptreatment of APL children. The CNSL, poor

  10. Arsenite-induced ROS/RNS generation causes zinc loss and inhibits the activity of poly (ADP-ribose) polymerase-1

    OpenAIRE

    Wang, Feng; Zhou, Xixi; Liu, Wenlan; Sun, Xi; Chen, Chen; Hudson, Laurie G.; Liu, Ke Jian

    2013-01-01

    Arsenic enhances genotoxicity of other carcinogenic agents such as ultraviolet radiation and benzo[a]pyrene. Recent reports suggest that inhibition of DNA repair is an important aspect of arsenic co-carcinogenesis, and DNA repair proteins such as poly (ADP ribose) polymerase (PARP)-1 are direct molecular targets of arsenic. Although arsenic has been shown to generate reactive oxygen/nitrogen species (ROS/RNS), little is known about the role of arsenic-induced ROS/RNS in the mechanism underlyi...

  11. Correlation of Breastmilk Arsenic With Maternal, Infant Urinary Arsenic and Drinking Water Arsenic in an Arsenic Affected Area of Bangladesh

    Science.gov (United States)

    Alauddin, M.; Islam, M. R.; Milton, A. H.; Alauddin, S. T.; Mouly, T.; Behri, E.; Ayesha, A.; Akter, S.; Islam, M. M.

    2016-12-01

    About 97% of population in Bangladesh depend on groundwater as the principle source of drinking water and this water is highly contaminated with inorganic arsenic. Consumption of arsenic contaminated drinking water by pregnant women raises the prospect of early life exposure to inorganic arsenic for newborn which may be lead to adverse health effect in later life. This work was carried out in parts of Gopalganj district in Bangladesh, a region affected by arsenic contamination in groundwater. The objective of the work was to assess potential early life exposure to arsenic for infants through breastfeeding by mothers who were drinking water with arsenic levels ranging from 100 to 300 µg/l. A cohort of 30 mother-baby pairs were selected for the current study. Breastmilk samples from mothers, urine samples from each pair of subjects at 1, 6 and 9 month age of infant were collected and total arsenic were determined in these samples. In addition speciation of urinary arsenic and metabolites were carried out in 12 mother-baby pairs. Median level for breastmilk arsenic were 0.50 µg/l. Urinary arsenic of infants did not correlate with breastmilk arsenic with progressing age of infants. Maternal and infant urinary total arsenic at 1 month age of infant showed some positive correlation (r = 0.39). In infant urine major metabolite were dimethyl arsenic acid (DMA) (approximately 70%) indicating good methylating capacity for infants at 1 and 6 months of age. In conclusion, infants were not exposed to arsenic through breastfeeding even though mothers were exposed to significant levels of arsenic through drinking water.

  12. Protective Effect of Psidium guajava in Arsenic-induced Oxidative Stress and Cytological Damage in Rats

    Science.gov (United States)

    Tandon, Neeraj; Roy, Manju; Roy, Sushovan; Gupta, Neelu

    2012-01-01

    This study was undertaken to evaluate the protective effect of aqueous extract of Psidium guajava leaves against sodium arsenite-induced toxicity in experimental rats. Animals were divided into four groups. Control group received arsenic free distilled water and three treatment groups (II, III, and IV) exposed to the arsenic (NaAsO2) (20 mg/kg b.wt) through drinking water. Group III and IV were administered a daily oral dose of P. guajava leaf extract 50 and 100 mg/kg b.wt. (AEPG50 and AEPG100) for the period of 6 weeks. Blood samples and organs were collected at the end of the experiment. Arsenic exposure resulted in significant rise in lipid peroxidation (LPO) levels in erythrocyte, liver, kidney, and brain. In addition toxin decreased (Pguajava) @100 mg/kg body weight) significantly restored activities of oxidative stress markers like LPO levels, GSH levels, SOD, and CAT activities but having the limited protective activity of the herbal extract was observed on tissues architecture. It is therefore concluded that prophylactic co-administration of AEPG could provide specific protection from oxidative injury and to some extent on tissue damage. PMID:23293461

  13. Arsenic trioxide synergistically enhances radiation response in human cervical cancer cells through ROS-dependent p38 MAPK and JNK signalling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Young-Hee; Park, Seung-Moo; Kim, Min-Jeong [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)] (and others)

    2006-07-01

    Many factors affect susceptibility of tumor cells to ionizing radiation. Among them intrinsic apoptosis sensitivity or resistancy seems to play an important role. The use of chemical modifiers as radiosensitizers in combination with low-dose irradiation may increase the therapeutic efficacy by overcoming a high apoptotic threshold. Several recent studies demonstrated additive effects of As{sub 2}O{sub 3} with conventional chemotherapeutic agents such as cisplatin, adriamycin, and etoposide, but no synergism. Previously, we have shown for the first time that As{sub 2}O{sub 3} sensitize human cervical cancer cells to ionizing radiation. Treatment of As{sub 2}O{sub 3} in combination of ionizing radiation has synergistic effects in decreasing clonogenic survival and in the regression of tumor growth in xenografts. We also have shown that the combination treatment enhanced apoptotic cell death through a reactive oxygen species-dependent pathway in human cervical cancer cells. In this study, we investigated the regulatory mechanism of ROS-mediated mitochondrial apoptotic cell death induced by combination treatment with As{sub 2}O{sub 3} and ionizing radiation in human cervical cancer cells.

  14. [Study of relationship between arsenic methylation and skin lesion in a population with long-term high arsenic exposure].

    Science.gov (United States)

    Su, Liqin; Cheng, Yibin; Lin, Shaobin; Wu, Chuanye

    2007-05-01

    To investigate the difference of arsenic metabolism in populations with long-term high arsenic exposure and explore the relationship between arsenic metabolism diversity and skin lesion. 327 residents in an arsenic polluted village were voluntarily enrolled in this study. Questionnaire survey and medical examination were carried out to learn basic information and detect skin lesions. Urinary inorganic and methylated arsenic were speciated by high performance liquid chromatography combined with hydride-generation atomic fluorescence spectrometry. Total arsenic concentration in hair was determined with DDC-Ag method. Hair arsenic content of studied polutions was generally high, but no significant difference were found among the studied four groups. MMA and DMA concentration in urine increased with studied polution age, and were positively related with skin lesion grade. The relative proportion of MMA in serious skin lesion group was significantly higher than in other 3 groups, while DMA/MMA ratio was significantly lower than control and mild group. The relative proportion of MMA was positively related with skin lesion grade, DMA/ MMA ratio was negatively related with skin lesion grade. Males could have higher arsenic cumulation and lower methylation capacity than those of females. The population of above 40 years old may have higher methylation capacity than those of adults below 40yeas old. Smokers and drinkers seemed lower methylation capacity than those of non-smokers and non-drinkers respectively. The methylation of arsenic could affect by several factors, including age gender, smoking and drinking. Arsenic methylation copacity mey be associated with skin lesion induced by arsenic exposure.

  15. Summary of the Preliminary Analysis of Savannah River Depleted Uranium Trioxide

    International Nuclear Information System (INIS)

    2010-01-01

    This report summarizes a preliminary special analysis of the Savannah River Depleted Uranium Trioxide waste stream (SVRSURANIUM03, Revision 2). The analysis is considered preliminary because a final waste profile has not been submitted for review. The special analysis is performed to determine the acceptability of the waste stream for shallow land burial at the Area 5 Radioactive Waste Management Site (RWMS) at the Nevada National Security Site (NNSS). The Savannah River Depleted Uranium Trioxide waste stream requires a special analysis because the waste stream's sum of fractions exceeds one. The 99Tc activity concentration is 98 percent of the NNSS Waste Acceptance Criteria and the largest single contributor to the sum of fractions.

  16. Catalase plays an important role in a genotoxic pathway of methylated arsenicals

    Science.gov (United States)

    Arsenic is a common contaminant of drinking water in many parts of the world. Consumption of arsenic-contaminated drinking water has been implicated in both cancerous and non-cancerous health conditions. However, the pathways that lead to arsenic-induced health conditions have no...

  17. Synthesis of vanadium trioxide

    International Nuclear Information System (INIS)

    Yankelevich, R.G.; Vinarov, I.V.; Sheka, I.A.; Pushek, N.G.

    1976-01-01

    There have been studied the conditions for production of vanadium trioxide in a single-stage process of V 2 O 5 reduction by gaseous ammonia. To determine the optimum conditions for V 2 O 5 reduction, there have been studied the temperature range of the reaction and the effect offered by the volumetric rate and time of ammonia injection. The following conditions have proved to be the optimum ones: temperature - 450 deg C, volumetric rate of NH 3 injection at a batch of 10 g - 4 l/h, time of recovery - 3 hours. In accordance with the adopted procedure there have been synthetized the samples containing 98 - 99% V 2 O 3 [ru

  18. Studying arsenic trioxide-induced apoptosis of Colo-16 cells with ...

    African Journals Online (AJOL)

    nj tonukari

    2011-10-10

    Oct 10, 2011 ... approved by Food and Drug Administration of U.S.A. for use in the treatment of ... changes in nuclear morphology, reactive oxygen species. (ROS) and ..... labeling and on immunological assays using antibodies directed to ...

  19. Effect of white mineral trioxide aggregate compared with biomimetic carbonated apatite on dentine bridge formation and inflammatory response in a dental pulp model.

    Science.gov (United States)

    Danesh, F; Vahid, A; Jahanbani, J; Mashhadiabbas, F; Arman, E

    2012-01-01

      To evaluate the effects of apatite precipitation on the biocompatibility and hard tissue induction properties of white mineral trioxide aggregate (WMTA) in a dental pulp model.   Pulp exposures were created on the axial walls of 32 sound canine teeth of eight dogs. Four additional sound teeth served as controls. The pulps were capped either with WMTA or apatite derivatives [biomimetic carbonated apatite (BCAp)] in the interaction of WMTA with a synthetic tissue fluid and restored with zinc oxide-eugenol cement. After 7 and 70 days, the animals were killed, and the histological specimens taken from the teeth were stained with haematoxylin and eosin for histomorphological evaluation. The Brown and Brenn technique was employed to stain bacteria. The data were subjected to nonparametric Kruskall-Wallis analysis and Mann-Whitney U_tests.   Biomimetic carbonated apatite did not induce hard tissue bridge formation. WMTA performed significantly better than BCAp in this respect at both periods (P 0.05).   White mineral trioxide aggregate induced hard tissue formation via a mechanism other than that postulated via apatite formation. © 2011 International Endodontic Journal.

  20. The Legacy of Arsenic Contamination from Giant Mine, Northern Canada: An Assessment of Impacts Based on Lake Water and Lake Sediment Core Analysis

    Science.gov (United States)

    Blais, J. M.; Korosi, J.

    2016-12-01

    The Giant Mine, which operated between 1948 and 2004 and located near the City of Yellowknife (Northwest Territories, Canada), has left a legacy of arsenic, antimony, and mercury contamination extending to the present day. Over 20,000 tonnes of arsenic trioxide dust was released from roaster stack emissions during its first 10 years of operations, leading to a significant contamination of the surrounding landscape. Here we present a summary of impacts by the recent contamination from Giant Mine on the surrounding region. A survey we conducted of 25 lakes of the region in 2010 revealed that most lake water within a 15 km radius of the roaster stack had arsenic concentrations in water > 10 mg/L, the standard for drinking water, with concentrations declining exponentially with increasing distance from the roaster stack. Sediment cores from lakes were collected near the Giant Mine roaster stack and radiometrically dated by 137Cs and excess 210Pb. Arsenic concentrations in these sediments increased by 1700% during the 1950s and 60s, consistent with the history of arsenic releases from roaster emissions. Correspondingly, pelagic diatoms and cladocerans were extirpated from one lake during this period, based on microfossil analysis of lake sediment deposits. Sediment core analysis further showed that this lake ecosystem has not recovered, even ten years after closure of the mine. Likely causes for the lack of recent recovery are explored with the use of sediment toxicity bioassays, using a novel paleo-ecotoxicological approach of using toxicity assessments of radiometrically dated lake sediment horizons.

  1. Arsenic geochemistry of groundwater in Southeast Asia.

    Science.gov (United States)

    Kim, Kyoung-Woong; Chanpiwat, Penradee; Hanh, Hoang Thi; Phan, Kongkea; Sthiannopkao, Suthipong

    2011-12-01

    The occurrence of high concentrations of arsenic in the groundwater of the Southeast Asia region has received much attention in the past decade. This study presents an overview of the arsenic contamination problems in Vietnam, Cambodia, Lao People's Democratic Republic and Thailand. Most groundwater used as a source of drinking water in rural areas has been found to be contaminated with arsenic exceeding the WHO drinking water guideline of 10 μg·L(-1). With the exception of Thailand, groundwater was found to be contaminated with naturally occurring arsenic in the region. Interestingly, high arsenic concentrations (> 10 μg·L(-1)) were generally found in the floodplain areas located along the Mekong River. The source of elevated arsenic concentrations in groundwater is thought to be the release of arsenic from river sediments under highly reducing conditions. In Thailand, arsenic has never been found naturally in groundwater, but originates from tin mining activities. More than 10 million residents in Southeast Asia are estimated to be at risk from consuming arsenic-contaminated groundwater. In Southeast Asia, groundwater has been found to be a significant source of daily inorganic arsenic intake in humans. A positive correlation between groundwater arsenic concentration and arsenic concentration in human hair has been observed in Cambodia and Vietnam. A substantial knowledge gap exists between the epidemiology of arsenicosis and its impact on human health. More collaborative studies particularly on the scope of public health and its epidemiology are needed to conduct to fulfill the knowledge gaps of As as well as to enhance the operational responses to As issue in Southeast Asian countries.

  2. Binational Arsenic Exposure Survey: Methodology and Estimated Arsenic Intake from Drinking Water and Urinary Arsenic Concentrations

    Directory of Open Access Journals (Sweden)

    Robin B. Harris

    2012-03-01

    Full Text Available The Binational Arsenic Exposure Survey (BAsES was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001, urinary inorganic arsenic concentration (p < 0.001, and urinary sum of species (p < 0.001. Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated.

  3. Chronic exposure to low concentration of arsenic is immunotoxic to fish: Role of head kidney macrophages as biomarkers of arsenic toxicity to Clarias batrachus

    International Nuclear Information System (INIS)

    Datta, Soma; Ghosh, Debabrata; Saha, Dhira Rani; Bhattacharaya, Shelley; Mazumder, Shibnath

    2009-01-01

    The present study was aimed at elucidating the effect of chronic low-level arsenic exposure on the head kidney (HK) of Clarias batrachus and at determining the changes in head kidney macrophage (HKM) activity in response to arsenic exposure. Chronic exposure (30 days) to arsenic (As 2 O 3 , 0.50 μM) led to significant increase in arsenic content in the HK accompanied by reduction in both HKM number and head kidney somatic index (HKSI). Arsenic induced HK hypertrophy, reduction in melano-macrophage population and increased hemosiderin accumulation. Transmission electron microscopy of 30 days exposed HKM revealed prominent endoplasmic reticulum, chromatin condensation and loss in structural integrity of nuclear membrane. Head kidney macrophages from exposed fish demonstrated significant levels of superoxide anions but on infection with Aeromonas hydrophila were unable to clear the intracellular bacteria and died. Exposure-challenge experiments with A. hydrophila revealed that chronic exposure to micromolar concentration of arsenic interfered with the phagocytic potential of HKM, helped in intracellular survival of the ingested bacteria inside the HKM inducing significant HKM cytotoxicity. The immunosuppressive effect of arsenic was further evident from the ability of A. hydrophila to colonize and disseminate efficiently in exposed fish. Enzyme linked immunosorbent assay indicated that chronic exposure to arsenic suppressed the production of pro-inflammatory 'IL-1β like' factors from HKM. It is concluded that arsenic even at very low concentration is immunotoxic to fish and the changes observed in HKM may provide a useful early biomarker of low-level xenobiotic exposure

  4. Chronic exposure to low concentration of arsenic is immunotoxic to fish: Role of head kidney macrophages as biomarkers of arsenic toxicity to Clarias batrachus

    Energy Technology Data Exchange (ETDEWEB)

    Datta, Soma; Ghosh, Debabrata [Immunobiology Laboratory, School of Life Sciences, Visva Bharati University, Santiniketan 731 235 (India); Saha, Dhira Rani [Microscopy Laboratory, National Institute of Cholera and Enteric Diseases, P-33, Scheme XM, C.I.T. Road, Beliaghata, Kolkata 700 010 (India); Bhattacharaya, Shelley [Environmental Toxicology Laboratory, School of Life Sciences, Visva Bharati University, Santiniketan 731 235 (India); Mazumder, Shibnath [Immunobiology Laboratory, School of Life Sciences, Visva Bharati University, Santiniketan 731 235 (India)], E-mail: shibnath1@yahoo.co.in

    2009-04-09

    The present study was aimed at elucidating the effect of chronic low-level arsenic exposure on the head kidney (HK) of Clarias batrachus and at determining the changes in head kidney macrophage (HKM) activity in response to arsenic exposure. Chronic exposure (30 days) to arsenic (As{sub 2}O{sub 3}, 0.50 {mu}M) led to significant increase in arsenic content in the HK accompanied by reduction in both HKM number and head kidney somatic index (HKSI). Arsenic induced HK hypertrophy, reduction in melano-macrophage population and increased hemosiderin accumulation. Transmission electron microscopy of 30 days exposed HKM revealed prominent endoplasmic reticulum, chromatin condensation and loss in structural integrity of nuclear membrane. Head kidney macrophages from exposed fish demonstrated significant levels of superoxide anions but on infection with Aeromonas hydrophila were unable to clear the intracellular bacteria and died. Exposure-challenge experiments with A. hydrophila revealed that chronic exposure to micromolar concentration of arsenic interfered with the phagocytic potential of HKM, helped in intracellular survival of the ingested bacteria inside the HKM inducing significant HKM cytotoxicity. The immunosuppressive effect of arsenic was further evident from the ability of A. hydrophila to colonize and disseminate efficiently in exposed fish. Enzyme linked immunosorbent assay indicated that chronic exposure to arsenic suppressed the production of pro-inflammatory 'IL-1{beta} like' factors from HKM. It is concluded that arsenic even at very low concentration is immunotoxic to fish and the changes observed in HKM may provide a useful early biomarker of low-level xenobiotic exposure.

  5. Atorvastatin acts synergistically with N-acetyl cysteine to provide therapeutic advantage against Fas-activated erythrocyte apoptosis during chronic arsenic exposure in rats

    Energy Technology Data Exchange (ETDEWEB)

    Biswas, Debabrata; Sen, Gargi; Sarkar, Avik; Biswas, Tuli

    2011-01-01

    Arsenic is an environmental toxicant that reduces the lifespan of circulating erythrocytes during chronic exposure. Our previous studies had indicated involvement of hypercholesterolemia and reactive oxygen species (ROS) in arsenic-induced apoptotic death of erythrocytes. In this study, we have shown an effective recovery from arsenic-induced death signaling in erythrocytes in response to treatment with atorvastatin (ATV) and N-acetyl cysteine (NAC) in rats. Our results emphasized on the importance of cholesterol in the promotion of ROS-mediated Fas signaling in red cells. Arsenic-induced activation of caspase 3 was associated with phosphatidylserine exposure on the cell surface and microvesiculation of erythrocyte membrane. Administration of NAC in combination with ATV, proved to be more effective than either of the drugs alone towards the rectification of arsenic-mediated disorganization of membrane structural integrity, and this could be linked with decreased ROS accumulation through reduced glutathione (GSH) repletion along with cholesterol depletion. Moreover, activation of caspase 3 was capable of promoting aggregation of band 3 with subsequent binding of autologous IgG and opsonization by C3b that led to phagocytosis of the exposed cells by the macrophages. NAC-ATV treatment successfully amended these events and restored lifespan of erythrocytes from the exposed animals almost to the control level. This work helped us to identify intracellular membrane cholesterol enrichment and GSH depletion as the key regulatory points in arsenic-mediated erythrocyte destruction and suggested a therapeutic strategy against Fas-activated cell death related to enhanced cholesterol and accumulation of ROS.

  6. Antioxidative responses to arsenic in the arsenic-hyperaccumulator Chinese brake fern (Pteris vittata L.)

    International Nuclear Information System (INIS)

    Cao Xinde; Ma, Lena Q.; Tu Cong

    2004-01-01

    This study measured antioxidative responses of Chinese brake fern (Pteris vittata L.) upon exposure to arsenic (As) of different concentrations. Chinese brake fern was grown in an artificially-contaminated soil containing 0 to 200 mg As kg -1 (Na 2 HAsO 4 ) for 12 weeks in a greenhouse. Soil As concentrations at ≤20 mg kg -1 enhanced plant growth, with 12-71% biomass increase compared to the control. Such beneficial effects were not observed at >20 mg As kg -1 . Plant As concentrations increased with soil As concentrations, with more As being accumulated in the fronds (aboveground biomass) than in the roots and with maximum frond As concentration being 4675 mg kg -1 . Arsenic uptake by Chinese brake enhanced uptake of nutrient elements K, P, Fe, Mn, and Zn except Ca and Mg, whose concentrations mostly decreased. The contents of non-enzymatic antioxidants (glutathione, acid-soluble thiol) followed similar trends as plant As concentrations, increasing with soil As concentrations, with greater contents in the fronds than in the roots especially when exposed to high As concentrations (>50 mg kg -1 ). The activities of enzymatic antioxidants (superoxide dismutase, catalase, ascorbate peroxidase, guaiacol peroxidase) in Chinese brake followed the same trends as plant biomass, increasing with soil As up to 20 mg kg -1 and then decreased. The results indicated though both enzymatic and non-enzymatic antioxidants played significant roles in As detoxification and hyperaccumulation in Chinese brake, the former is more important at low As exposure (≤20 mg kg -1 ), whereas the latter is more critical at high As exposure (50-200 mg kg -1 ). - At low levels of arsenic exposure, enzymatic antioxidants are important for arsenic detoxification and accumulation in Chinese brake fern, while non-enzymatic antioxidants were more important at high arsenic exposure

  7. Interactions of arsenic and phenanthrene on their uptake and antioxidative response in Pteris vittata L

    International Nuclear Information System (INIS)

    Sun Lu; Yan Xiulan; Liao Xiaoyong; Wen Yi; Chong Zhongyi; Liang Tao

    2011-01-01

    The interactions of arsenic and phenanthrene on plant uptake and antioxidative response of Pteris vitatta L. were studied hydroponically. The combination of arsenic and phenanthrene decreased arsenic contents in fronds by 30-51%, whereas increased arsenic concentrations 1.2-1.6 times in roots, demonstrating the suppression of arsenic translocation compared to the corresponding treatment without phenanthrene. Under the co-exposure, As(III) concentrations in fronds deceased by 12-73%, and at higher arsenic exposure level (≥10 mg/L), As(V) in fronds and As(III) in roots increased compared to the single arsenic treatment. Arsenic exposure elevated phenanthrene concentrations in root by 39-164%. The co-existence of arsenic and phenanthrene had little impact on plant arsenic accumulation, although synergistic effect on antioxidants was observed, suggesting the special physiological process of P. vitatta in the co-exposure and application potential of P. vitatta in phytoremediation of arsenic and PAHs co-contamination. - Highlights: → Pteris vitatta L. show tolerance to the arsenic and phenanthrene co-exposure. → P. vitatta efficiently accumulate arsenic and simultaneously enhance phenanthrene dissipation. → Phenanthrene suppresses arsenic translocation from roots to fronds. → Phenanthrene causes As(III) elevation in roots while reduction in fronds. → Synergistic effect potentiates the toxicity and antioxidants in plant. - Pteris vitatta L. not only efficiently accumulate arsenic but also enhance phenanthrene dissipation under the arsenic and phenanthrene co-exposure.

  8. Interactions of arsenic and phenanthrene on their uptake and antioxidative response in Pteris vittata L

    Energy Technology Data Exchange (ETDEWEB)

    Sun Lu [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China); Graduate University of the Chinese Academy of Sciences, Beijing 100049 (China); Yan Xiulan [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China); Liao Xiaoyong, E-mail: liaoxy@igsnrr.ac.cn [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China); Wen Yi; Chong Zhongyi; Liang Tao [Beijing Key Lab of Industrial Land Contamination and Remediation, Institute of Geographical Sciences and Natural Resources Research, Chinese Academy of Sciences (CAS), Beijing 100101 (China)

    2011-12-15

    The interactions of arsenic and phenanthrene on plant uptake and antioxidative response of Pteris vitatta L. were studied hydroponically. The combination of arsenic and phenanthrene decreased arsenic contents in fronds by 30-51%, whereas increased arsenic concentrations 1.2-1.6 times in roots, demonstrating the suppression of arsenic translocation compared to the corresponding treatment without phenanthrene. Under the co-exposure, As(III) concentrations in fronds deceased by 12-73%, and at higher arsenic exposure level ({>=}10 mg/L), As(V) in fronds and As(III) in roots increased compared to the single arsenic treatment. Arsenic exposure elevated phenanthrene concentrations in root by 39-164%. The co-existence of arsenic and phenanthrene had little impact on plant arsenic accumulation, although synergistic effect on antioxidants was observed, suggesting the special physiological process of P. vitatta in the co-exposure and application potential of P. vitatta in phytoremediation of arsenic and PAHs co-contamination. - Highlights: > Pteris vitatta L. show tolerance to the arsenic and phenanthrene co-exposure. > P. vitatta efficiently accumulate arsenic and simultaneously enhance phenanthrene dissipation. > Phenanthrene suppresses arsenic translocation from roots to fronds. > Phenanthrene causes As(III) elevation in roots while reduction in fronds. > Synergistic effect potentiates the toxicity and antioxidants in plant. - Pteris vitatta L. not only efficiently accumulate arsenic but also enhance phenanthrene dissipation under the arsenic and phenanthrene co-exposure.

  9. A study on the alkali leaching of complex compound for molybdenum trioxide and ferric oxide

    International Nuclear Information System (INIS)

    Kim, C.G.; Whang, Y.K.

    1981-01-01

    This study is to determine the alkali-leaching meachanism by which complex compound by the reaction made between molybdenite (MoS 2 ) and ferric oxide (Fe 2 O 3 ) in the roasted are when molybdenum trioxide (MoO 3 ) is formed by the roasting reaction of molybdenite concentrate. The results obtained from this experiment are summarized as follows: The heating reaction analysis shows that the complex compound of iron molybdates (Fe 2 O 3 .3-4 MoO 3 ) is formed by the reaction of molybdenum trioxide and ferric oxide at temperatures of above 500 0 C. It is shown that at various reaction temperature below 400 0 C molybdenum trioxide is almost completely leached by caustic soda irrespective of the mole ratio of two chemical samples used for the experiment, whereas at temperature above 400 0 C the leaching rate of molybdenum trioxide decreases except that it varies from 70.77% at a temperature of 900 0 C at which the mole ratio is 1 to 1 to 84.08% at a temperature of 1000 0 C. The x-ray diffraction analysis has shown that the complex compound reacted at a temperature of 1000 0 C produces a complex compound with the crystal structure of iron molybdates, and the alkali-leached residues even with 19.0% of molybdenum trioxide, however, contain only α-Fe 2 O 3 , without showing iron molybdates. The crystalline compound of iron molybdates obtained as a result of heating reaction was leached by using caustic soda, while MoO 3 and Fe 2 O 3 in the leaching residue was found to contain other compounds unable to be leached by caustic soda. (author)

  10. Sorption of Arsenic from Desalination Concentrate onto Drinking Water Treatment Solids: Operating Conditions and Kinetics

    Directory of Open Access Journals (Sweden)

    Xuesong Xu

    2018-01-01

    Full Text Available Selective removal of arsenic from aqueous solutions with high salinity is required for safe disposal of the concentrate and protection of the environment. The use of drinking water treatment solids (DWTS to remove arsenic from reverse osmosis (RO concentrate was studied by batch sorption experiments. The impacts of solution chemistry, contact time, sorbent dosage, and arsenic concentration on sorption were investigated, and arsenic sorption kinetics and isotherms were modeled. The results indicated that DWTS were effective in removing arsenic from RO concentrate. The arsenic sorption process followed a pseudo-second-order kinetic model. Multilayer adsorption was simulated by Freundlich equation. The maximum sorption capacities were calculated to be 170 mg arsenic per gram of DWTS. Arsenic sorption was enhanced by surface precipitation onto the DWTS due to the high amount of calcium in the RO concentrate and the formation of ternary complexes between arsenic and natural organic matter (NOM bound by the polyvalent cations in DWTS. The interactions between arsenic and NOM in the solid phase and aqueous phase exhibited two-sided effects on arsenic sorption onto DWTS. NOM in aqueous solution hindered the arsenic sorption onto DWTS, while the high organic matter content in solid DWTS phase enhanced arsenic sorption.

  11. Blockade and enhancement of glutamate receptor responses in Xenopus oocytes by methylated arsenicals

    Energy Technology Data Exchange (ETDEWEB)

    Krueger, Katharina; Gruner, Janina; Madeja, Michael; Musshoff, Ulrich [Universitaetsklinikum Muenster, Institut fuer Physiologie I, Muenster (Germany); Hartmann, Louise M.; Hirner, Alfred V. [Universitaet Duisburg-Essen, Institut fuer Umweltanalytik, Essen (Germany); Binding, Norbert [Universitaetsklinikum Muenster, Institut fuer Arbeitsmedizin, Muenster (Germany)

    2006-08-15

    Pentavalent and trivalent organoarsenic compounds belong to the major metabolites of inorganic arsenicals detected in humans. Recently, the question was raised whether the organic arsenicals represent metabolites of a detoxification process or methylated species with deleterious biological effects. In this study, the effects of trivalent arsenite (AsO{sub 3} {sup 3-}; iA{sup III}), the pentavalent organoarsenic compounds monomethylarsonic acid (CH{sub 3}AsO(OH){sub 2}; MMA{sup V}) and dimethylarsinic acid ((CH{sub 3}){sub 2}AsO(OH); DMA{sup V}) and the trivalent compounds monomethylarsonous acid (CH{sub 3}As(OH){sub 2}, MMA{sup III}) and dimethylarsinous acid ((CH{sub 3}){sub 2}As(OH); DMA{sup III}) were tested on glutamate receptors and on voltage-operated potassium and sodium channels heterologously expressed in Xenopus oocytes. Membrane currents of ion channels were measured by conventional two-electrode voltage-clamp techniques. The effects of arsenite were tested in concentrations of 1-1,000 {mu}mol/l and the organic arsenical compounds were tested in concentrations of 0.1-100 {mu}mol/l. We found no significant effects on voltage-operated ion channels; however, the arsenicals exert different effects on glutamate receptors. While MMA{sup V} and MMA{sup III} significantly enhanced ion currents through N-methyl-d-aspartate (NMDA) receptor ion channels with threshold concentrations <10 {mu}mol/l, DMA{sup V} and DMA{sup III} significantly reduced NMDA-receptor mediated responses with threshold concentrations <0.1 {mu}mol/l; iA{sup III} had no effects on glutamate receptors of the NMDA type. MMA{sup III} and DMA{sup V} significantly reduced ion currents through {alpha}-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-receptor ion channels with threshold concentrations <10 {mu}mol/l (MMA{sup III}) and <1 {mu}mol/l (DMA{sup V}). MMA{sup V} and iA{sup III} had no significant effects on glutamate receptors of the AMPA type. The effects of MMA{sup V}, MMA

  12. Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Herbert, Katharine J. [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia); Holloway, Adele [Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000 (Australia); Cook, Anthony L. [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia); Chin, Suyin P. [Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS 7000 (Australia); Snow, Elizabeth T., E-mail: elizabeth.snow@utas.edu.au [School of Health Sciences, University of Tasmania, Launceston, TAS 7250 (Australia)

    2014-11-15

    Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylation of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation

  13. Arsenic exposure disrupts epigenetic regulation of SIRT1 in human keratinocytes

    International Nuclear Information System (INIS)

    Herbert, Katharine J.; Holloway, Adele; Cook, Anthony L.; Chin, Suyin P.; Snow, Elizabeth T.

    2014-01-01

    Arsenic is an environmental toxin which increases skin cancer risk for exposed populations worldwide; however the underlying biomolecular mechanism for arsenic-induced carcinogenesis is complex and poorly defined. Recent investigations show that histone deacetylase and DNA methyltransferase activity is impaired, and epigenetic patterns of gene regulation are consistently altered in cancers associated with arsenic exposure. Expression of the histone deacetylase SIRT1 is altered in solid tumours and haematological malignancies; however its role in arsenic-induced pathology is unknown. In this study we investigated the effect of arsenic on epigenetic regulation of SIRT1 and its targeting microRNA, miR-34a in primary human keratinocytes. Acetylation of histone H4 at lysine 16 (H4K16) increased in keratinocytes exposed to 0.5 μM arsenite [As(III)]; and this was associated with chromatin remodelling at the miR-34a promoter. Moreover, although SIRT1 protein initially increased in these As(III)-exposed cells, after 24 days expression was not significantly different from untreated controls. Extended exposure to low-dose As(III) (0.5 μM; > 5 weeks) compromised the pattern of CpG methylation at SIRT1 and miR-34a gene promoters, and this was associated with altered expression for both genes. We have found that arsenic alters epigenetic regulation of SIRT1 expression via structural reorganisation of chromatin at the miR-34a gene promoter in the initial 24 h of exposure; and over time, through shifts in miR-34a and SIRT1 gene methylation. Taken together, this investigation demonstrates that arsenic produces cumulative disruptions to epigenetic regulation of miR-34a expression, and this is associated with impaired coordination of SIRT1 functional activity. - Highlights: • Submicromolar arsenic concentrations disrupt SIRT1 activity and expression in human keratinocytes. • Arsenic-induced chromatin remodelling at the miR-34a gene promoter is associated with hyperacetylation

  14. The Effect of Adding Antimony Trioxide (Sb2O3 ‎On A.C Electrical Properties of (PVA-PEG Films

    Directory of Open Access Journals (Sweden)

    Akeel Shakir Alkelaby

    2017-12-01

    Full Text Available In this work, many samples have been prepared by adding Antimony Trioxide (Sb2O3 to the polyvinyl alcohol-poly ethylene glycol (PVA-PEG. The effect of the Sb2O3 added as a filler with different weight percentages on the A.C electrical properties have been investigated. The samples were prepared as films by solution cast technique. The experimental results of the A.C electrical properties show that the dielectric constant increase with the increasing frequency of applied electrical field and concentration of the Antimony Trioxide. Dielectric loss decrease with the increasing the frequency, while it increases with the increase of the concentration of the Antimony Trioxide. The A.C electrical conductivity increase with increasing the Antimony Trioxide contain and frequency for the composition.

  15. Characterization of intracellular inclusions in the urothelium of mice exposed to inorganic arsenic.

    Science.gov (United States)

    Dodmane, Puttappa R; Arnold, Lora L; Muirhead, David E; Suzuki, Shugo; Yokohira, Masanao; Pennington, Karen L; Dave, Bhavana J; Lu, Xiufen; Le, X Chris; Cohen, Samuel M

    2014-01-01

    Inorganic arsenic (iAs) is a known human carcinogen at high exposures, increasing the incidences of urinary bladder, skin, and lung cancers. In most mammalian species, ingested iAs is excreted mainly through urine primarily as dimethylarsinic acid (DMA(V)). In wild-type (WT) mice, iAs, DMA(V), and dimethylarsinous acid (DMA(III)) exposures induce formation of intramitochondrial urothelial inclusions. Arsenite (iAs(III)) also induced intranuclear inclusions in arsenic (+3 oxidation state) methyltransferase knockout (As3mt KO) mice. The arsenic-induced formation of inclusions in the mouse urothelium was dose and time dependent. The inclusions do not occur in iAs-treated rats and do not appear to be related to arsenic-induced urothelial cytotoxicity. Similar inclusions in exfoliated urothelial cells from humans exposed to iAs have been incorrectly identified as micronuclei. We have characterized the urothelial inclusions using transmission electron microscopy (TEM), DNA-specific 4',6-diamidino-2-phenylindole (DAPI), and non-DNA-specific Giemsa staining and determined the arsenical content. The mouse inclusions stained with Giemsa but not with the DAPI stain. Analysis of urothelial mitochondrial- and nuclear-enriched fractions isolated from WT (C57BL/6) and As3mt KO mice exposed to arsenate (iAs(V)) for 4 weeks showed higher levels of iAs(V) in the treated groups. iAs(III) was the major arsenical present in the enriched nuclear fraction from iAs(V)-treated As3mt KO mice. In conclusion, the urothelial cell inclusions induced by arsenicals appear to serve as a detoxifying sequestration mechanism similar to other metals, and they do not represent micronuclei.

  16. Failure of antimony trioxide to induce micronuclei or chromosomal aberrations in rat bone-marrow after sub-chronic oral dosing.

    Science.gov (United States)

    Kirkland, David; Whitwell, James; Deyo, James; Serex, Tessa

    2007-03-05

    Antimony trioxide (Sb2O3, CAS 1309-64-4) is widely used as a flame retardant synergist in a number of household products, as a fining agent in glass manufacture, and as a catalyst in the manufacture of various types of polyester plastics. It does not induce point mutations in bacteria or mammalian cells, but is able to induce chromosomal aberrations (CA) in cultured cells in vitro. Although no CA or micronuclei (MN) have been induced after acute oral dosing of mice, repeated oral dosing for 14 or 21 days resulted in increased CA in one report, but did not result in increased MN in another. In order to further investigate its in vivo genotoxicity, Sb2O3 was dosed orally to groups of rats for 21 days at 250, 500 and 1000 mg/kg day. There were no clinical signs of toxicity in the Sb2O3-exposed animals except for some reductions in body-weight gain in the top dose group. Toxicokinetic measurements in a separate study confirmed bone-marrow exposure, and at higher levels than would have been achieved by single oral dosing. Large numbers of cells were scored for CA (600 metaphases/sex group) and MN (12,000 PCE/sex group) but frequencies of CA or MN in Sb2O3-treated rats were very similar to controls, and not biologically or statistically different, at all doses. These results provide further indication that Sb2O3 is not genotoxic to the bone marrow of rodents after 21 days of oral administration at high doses close to the maximum tolerated dose.

  17. The Arsenic Resistance-Associated Listeria Genomic Island LGI2 Exhibits Sequence and Integration Site Diversity and a Propensity for Three Listeria monocytogenes Clones with Enhanced Virulence.

    Science.gov (United States)

    Lee, Sangmi; Ward, Todd J; Jima, Dereje D; Parsons, Cameron; Kathariou, Sophia

    2017-11-01

    In the foodborne pathogen Listeria monocytogenes , arsenic resistance is encountered primarily in serotype 4b clones considered to have enhanced virulence and is associated with an arsenic resistance gene cluster within a 35-kb chromosomal region, Listeria genomic island 2 (LGI2). LGI2 was first identified in strain Scott A and includes genes putatively involved in arsenic and cadmium resistance, DNA integration, conjugation, and pathogenicity. However, the genomic localization and sequence content of LGI2 remain poorly characterized. Here we investigated 85 arsenic-resistant L. monocytogenes strains, mostly of serotype 4b. All but one of the 70 serotype 4b strains belonged to clonal complex 1 (CC1), CC2, and CC4, three major clones associated with enhanced virulence. PCR analysis suggested that 53 strains (62.4%) harbored an island highly similar to LGI2 of Scott A, frequently (42/53) in the same location as Scott A ( LMOf2365_2257 homolog). Random-primed PCR and whole-genome sequencing revealed seven novel insertion sites, mostly internal to chromosomal coding sequences, among strains harboring LGI2 outside the LMOf2365_2257 homolog. Interestingly, many CC1 strains harbored a noticeably diversified LGI2 (LGI2-1) in a unique location ( LMOf2365_0902 homolog) and with a novel additional gene. With few exceptions, the tested LGI2 genes were not detected in arsenic-resistant strains of serogroup 1/2, which instead often harbored a Tn 554 -associated arsenic resistance determinant not encountered in serotype 4b. These findings indicate that in L. monocytogenes , LGI2 has a propensity for certain serotype 4b clones, exhibits content diversity, and is highly promiscuous, suggesting an ability to mobilize various accessory genes into diverse chromosomal loci. IMPORTANCE Listeria monocytogenes is widely distributed in the environment and causes listeriosis, a foodborne disease with high mortality and morbidity. Arsenic and other heavy metals can powerfully shape the

  18. Magnetic mesoporous Fe/carbon aerogel structures with enhanced arsenic removal efficiency.

    Science.gov (United States)

    Lin, Yi-Feng; Chen, Jia-Ling

    2014-04-15

    Wastewater treatment has drawn significant research attention due to its associated environmental issues. Adsorption is a promising method for treating wastewater. The development of an adsorbent with a high surface area is important. Therefore, we successfully developed mesoporous Fe/carbon aerogel (CA) structures with high specific surface areas of 48 7m(2)/g via the carbonization of composite Fe3O4/phenol-formaldehyde resin structures, which were prepared using a hydrothermal process with the addition of phenol. The mesoporous Fe/CA structures were further used for the adsorption of arsenic ions with a maximum arsenic-ion uptake of calculated 216.9 mg/g, which is higher than that observed for other arsenic adsorbents. Ferromagnetic behavior was observed for the as-prepared mesoporous Fe/CA structures with an excellent response to applied external magnetic fields. As a result, the adsorbent Fe/CA structures can be easily separated from the solution using an external magnetic field. This study develops the mesoporous Fe/CA structures with high specific surface areas and an excellent response to an applied external magnetic field to provide a feasible approach for wastewater treatment including the removal of arsenic ions. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Acetylated H4K16 by MYST1 protects UROtsa cells from arsenic toxicity and is decreased following chronic arsenic exposure

    International Nuclear Information System (INIS)

    Jo, William Jaime; Ren, Xuefeng; Chu, Feixia; Aleshin, Maria; Wintz, Henri; Burlingame, Alma; Smith, Martyn Thomas; Vulpe, Chris Dillon; Zhang Luoping

    2009-01-01

    Arsenic, a human carcinogen that is associated with an increased risk of bladder cancer, is commonly found in drinking water. An important mechanism by which arsenic is thought to be carcinogenic is through the induction of epigenetic changes that lead to aberrant gene expression. Previously, we reported that the SAS2 gene is required for optimal growth of yeast in the presence of arsenite (As III ). Yeast Sas2p is orthologous to human MYST1, a histone 4 lysine 16 (H4K16) acetyltransferase. Here, we show that H4K16 acetylation is necessary for the resistance of yeast to As III through the modulation of chromatin state. We further explored the role of MYST1 and H4K16 acetylation in arsenic toxicity and carcinogenesis in human bladder epithelial cells. The expression of MYST1 was knocked down in UROtsa cells, a model of bladder epithelium that has been used to study arsenic-induced carcinogenesis. Silencing of MYST1 reduced acetylation of H4K16 and induced sensitivity to As III and to its more toxic metabolite monomethylarsonous acid (MMA III ) at doses relevant to high environmental human exposures. In addition, both As III and MMA III treatments decreased global H4K16 acetylation levels in a dose- and time-dependent manner. This indicates that acetylated H4K16 is required for resistance to arsenic and that a reduction in its levels as a consequence of arsenic exposure may contribute to toxicity in UROtsa cells. Based on these findings, we propose a novel role for the MYST1 gene in human sensitivity to arsenic.

  20. Color in 'tungsten trioxide' thin films

    International Nuclear Information System (INIS)

    Gerard, P.; Deneuville, A.; Hollinger, G.; Duc, Tran Minh

    1977-01-01

    We show that evaporated tungsten trioxide amorphous layers commonly used in electrochromic displays actually have the composition WO_2_._7H_y (0.2< y<0.5). We emphasize that coloration of virgin transparent films can be obtained without injection of any external ion into the layer, and further that around a critical substoichiometry by sputtering, namely, WO_2_._5, one can prepare blue virgin layers without any hydrogen. The effect of substoichiometry on the valence of tungsten atoms has been followed by XPS measurements of sputtered layers.

  1. Color in ''tungsten trioxide'' thin films

    International Nuclear Information System (INIS)

    Gerard, P.; Deneuville, A.; Hollinger, G.; Tran Minh Duc

    1977-01-01

    We show that evaporated tungsten trioxide amorphous layers commonly used in electrochromic displays actually have the composition WO/sub 2.7/H/sub y/ (0.2< y<0.5). We emphasize that coloration of virgin transparent films can be obtained without injection of any external ion into the layer, and further that around a critical substoichiometry by sputtering, namely, WO/sub 2.5/, one can prepare blue virgin layers without any hydrogen. The effect of substoichiometry on the valence of tungsten atoms has been followed by XPS measurements of sputtered layers

  2. MiADMSA reverses impaired mitochondrial energy metabolism and neuronal apoptotic cell death after arsenic exposure in rats

    Energy Technology Data Exchange (ETDEWEB)

    Dwivedi, Nidhi; Mehta, Ashish; Yadav, Abhishek [Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior-474 002 (India); Binukumar, B.K.; Gill, Kiran Dip [Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh-160 012 (India); Flora, Swaran J.S., E-mail: sjsflora@hotmail.com [Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior-474 002 (India)

    2011-11-15

    Arsenicosis, due to contaminated drinking water, is a serious health hazard in terms of morbidity and mortality. Arsenic induced free radicals generated are known to cause cellular apoptosis through mitochondrial driven pathway. In the present study, we investigated the effect of arsenic interactions with various complexes of the electron transport chain and attempted to evaluate if there was any complex preference of arsenic that could trigger apoptosis. We also evaluated if chelation with monoisoamyl dimercaptosuccinic acid (MiADMSA) could reverse these detrimental effects. Our results indicate that arsenic exposure induced free radical generation in rat neuronal cells, which diminished mitochondrial potential and enzyme activities of all the complexes of the electron transport chain. Moreover, these complexes showed differential responses towards arsenic. These early events along with diminished ATP levels could be co-related with the later events of cytosolic migration of cytochrome c, altered bax/bcl{sub 2} ratio, and increased caspase 3 activity. Although MiADMSA could reverse most of these arsenic-induced altered variables to various extents, DNA damage remained unaffected. Our study for the first time demonstrates the differential effect of arsenic on the complexes leading to deficits in bioenergetics leading to apoptosis in rat brain. However, more in depth studies are warranted for better understanding of arsenic interactions with the mitochondria. -- Research highlights: Black-Right-Pointing-Pointer Arsenic impairs mitochondrial energy metabolism leading to neuronal apoptosis. Black-Right-Pointing-Pointer Arsenic differentially affects mitochondrial complexes, I - III and IV being more sensitive than complex II. Black-Right-Pointing-Pointer Arsenic-induced apoptosis initiates through ROS generation or impaired [Ca{sup 2+}]i homeostasis. Black-Right-Pointing-Pointer MiADMSA reverses arsenic toxicity via intracellular arsenic- chelation, antioxidant

  3. Determination of antimony trioxide in fire-retardant conveyor belts

    Energy Technology Data Exchange (ETDEWEB)

    Rytych-Witwicka, B.; Szmyd, E.

    1976-12-01

    Two methods for the determination of antimony trioxide in rubber and pvc are described. One is a colorimetric method based on the reaction of antimony with rhodamine B; the other is a polarographic method. The results of the two methods show a satisfactory consistency and the methods themselves appear rapid and effective.

  4. Arsenic-induced alteration in the expression of genes related to type 2 diabetes mellitus

    International Nuclear Information System (INIS)

    Diaz-Villasenor, Andrea; Burns, Anna L.; Hiriart, Marcia; Cebrian, Mariano E.; Ostrosky-Wegman, Patricia

    2007-01-01

    Chronic exposure to high concentrations of arsenic in drinking water is associated with an increased risk for developing type 2 diabetes. The present revision focuses on the effect of arsenic on tissues that participate directly in glucose homeostasis, integrating the most important published information about the impairment of the expression of genes related to type 2 diabetes by arsenic as one of the possible mechanisms by which it leads to the disease. Many factors are involved in the manner in which arsenic contributes to the occurrence of diabetes. The reviewed studies suggest that arsenic might increase the risk for type 2 diabetes via multiple mechanisms, affecting a cluster of regulated events, which in conjunction trigger the disease. Arsenic affects insulin sensitivity in peripheral tissue by modifying the expression of genes involved in insulin resistance and shifting away cells from differentiation to the proliferation pathway. In the liver arsenic disturbs glucose production, whereas in pancreatic beta-cells arsenic decreases insulin synthesis and secretion and reduces the expression of antioxidant enzymes. The consequences of these changes in gene expression include the reduction of insulin secretion, induction of oxidative stress in the pancreas, alteration of gluconeogenesis, abnormal proliferation and differentiation pattern of muscle and adipocytes as well as peripheral insulin resistance

  5. A review on environmental factors regulating arsenic methylation in humans

    International Nuclear Information System (INIS)

    Tseng, C.-H.

    2009-01-01

    Subjects exposed to arsenic show significant inter-individual variation in urinary patterns of arsenic metabolites but insignificant day-to-day intra-individual variation. The inter-individual variation in arsenic methylation can be partly responsible for the variation in susceptibility to arsenic toxicity. Wide inter-ethnic variation and family correlation in urinary arsenic profile suggest a genetic effect on arsenic metabolism. In this paper the environmental factors affecting arsenic metabolism are reviewed. Methylation capacity might reduce with increasing dosage of arsenic exposure. Furthermore, women, especially at pregnancy, have better methylation capacity than their men counterparts, probably due to the effect of estrogen. Children might have better methylation capacity than adults and age shows inconsistent relevance in adults. Smoking and alcohol consumption might be associated with a poorer methylation capacity. Nutritional status is important in the methylation capacity and folate may facilitate the methylation and excretion of arsenic. Besides, general health conditions and medications might influence the arsenic methylation capacity; and technical problems can cause biased estimates. The consumption of seafood, seaweed, rice and other food with high arsenic contents and the extent of cooking and arsenic-containing water used in food preparation may also interfere with the presentation of the urinary arsenic profile. Future studies are necessary to clarify the effects of the various arsenic metabolites including the trivalent methylated forms on the development of arsenic-induced human diseases with the consideration of the effects of confounding factors and the interactions with other effect modifiers

  6. [Acetyl-11-keto-beta-boswellic acid and arsenic trioxide regulate the productions and activities of matrix metalloproteinases in human skin fibroblasts and human leukemia cell line THP-1].

    Science.gov (United States)

    Liang, Ya-hui; Li, Ping; Zhao, Jing-xia; Liu, Xin; Huang, Qi-fu

    2010-11-01

    In order to reveal the treatment mechanism of Chinese medicine with the effect of activating blood and resolving putridity, we selected acetyl-11-keto-beta-boswellic acid (AKBA) and arsenic trioxide (ATO), the main monomeric components of frankincense and arsenolite which are two most commonly used Chinese medicine with effect of activating blood and resolving putridity. We combined AKBA and ATO as a compound, and explored its regulatory role in productions and activities of matrix metalloproteinase (MMP)-1, MMP-2 and MMP-9 in human skin fibroblasts (HSFbs) and human acute monocytic leukemia cell line THP-1 in inflammatory state. In order to simulate the inflammatory micro-environment of chronic wounds, we established 3 cell models: HSFb model activated by tumor necrosis factor-alpha (TNF-α), THP-1 cell model activated by phorbol-12-myristate-13-acetate (PMA) and HSFb-THP-1 cell coculture system. AKBA and ATO were cocultured with these cell models. Enzyme-linked immunosorbent assay (ELISA), gelatin zymography assay and reverse transcription-polymerase chain reaction (RT-PCR) were used to test the secretions, activities and mRNA expressions of MMP-1, MMP-2 and MMP-9. In the study of the regulatory mechanism of AKBA and ATO on MMPs, AKBA and ATO were cocultured with the cell models. ELISA was used to test the secretions of TNF-α and interleukin-1beta (IL-β) and Western blot was used to test the phosphorylation levels of extracellular signal-regulated kinases 1 and 2 (ERK1/2) and p38 mitogen-activated proteinkinase (p38MAPK). Compound of AKBA and ATO inhibited MMP-1, MMP-2 and MMP-9 mRNA expressions, secretions and activities respectively in HSFbs and THP-1 cells in inflammatory state (PTHP-1 cells and cell coculture system (PTHP-1 cells (P<0.05, P<0.01). The combined use of AKBA and ATO which in line with the rule of activating blood and resolving putridity inhibits fibroblasts and inflammatory cells in producing MMPs in inflammatory state through inhibiting the

  7. Improved Outcomes With Retinoic Acid and Arsenic Trioxide Compared With Retinoic Acid and Chemotherapy in Non-High-Risk Acute Promyelocytic Leukemia: Final Results of the Randomized Italian-German APL0406 Trial.

    Science.gov (United States)

    Platzbecker, Uwe; Avvisati, Giuseppe; Cicconi, Laura; Thiede, Christian; Paoloni, Francesca; Vignetti, Marco; Ferrara, Felicetto; Divona, Mariadomenica; Albano, Francesco; Efficace, Fabio; Fazi, Paola; Sborgia, Marco; Di Bona, Eros; Breccia, Massimo; Borlenghi, Erika; Cairoli, Roberto; Rambaldi, Alessandro; Melillo, Lorella; La Nasa, Giorgio; Fiedler, Walter; Brossart, Peter; Hertenstein, Bernd; Salih, Helmut R; Wattad, Mohammed; Lübbert, Michael; Brandts, Christian H; Hänel, Mathias; Röllig, Christoph; Schmitz, Norbert; Link, Hartmut; Frairia, Chiara; Pogliani, Enrico Maria; Fozza, Claudio; D'Arco, Alfonso Maria; Di Renzo, Nicola; Cortelezzi, Agostino; Fabbiano, Francesco; Döhner, Konstanze; Ganser, Arnold; Döhner, Hartmut; Amadori, Sergio; Mandelli, Franco; Ehninger, Gerhard; Schlenk, Richard F; Lo-Coco, Francesco

    2017-02-20

    Purpose The initial results of the APL0406 trial showed that the combination of all- trans-retinoic acid (ATRA) and arsenic trioxide (ATO) is at least not inferior to standard ATRA and chemotherapy (CHT) in first-line therapy of low- or intermediate-risk acute promyelocytic leukemia (APL). We herein report the final analysis on the complete series of patients enrolled onto this trial. Patients and Methods The APL0406 study was a prospective, randomized, multicenter, open-label, phase III noninferiority trial. Eligible patients were adults between 18 and 71 years of age with newly diagnosed, low- or intermediate-risk APL (WBC at diagnosis ≤ 10 × 10 9 /L). Overall, 276 patients were randomly assigned to receive ATRA-ATO or ATRA-CHT between October 2007 and January 2013. Results Of 263 patients evaluable for response to induction, 127 (100%) of 127 patients and 132 (97%) of 136 patients achieved complete remission (CR) in the ATRA-ATO and ATRA-CHT arms, respectively ( P = .12). After a median follow-up of 40.6 months, the event-free survival, cumulative incidence of relapse, and overall survival at 50 months for patients in the ATRA-ATO versus ATRA-CHT arms were 97.3% v 80%, 1.9% v 13.9%, and 99.2% v 92.6%, respectively ( P < .001, P = .0013, and P = .0073, respectively). Postinduction events included two relapses and one death in CR in the ATRA-ATO arm and two instances of molecular resistance after third consolidation, 15 relapses, and five deaths in CR in the ATRA-CHT arm. Two patients in the ATRA-CHT arm developed a therapy-related myeloid neoplasm. Conclusion These results show that the advantages of ATRA-ATO over ATRA-CHT increase over time and that there is significantly greater and more sustained antileukemic efficacy of ATO-ATRA compared with ATRA-CHT in low- and intermediate-risk APL.

  8. Combined Efficacy of Gallic Acid and MiADMSA with Limited Beneficial Effects Over MiADMSA Against Arsenic-induced Oxidative Stress in Mouse

    OpenAIRE

    Pachauri, Vidhu; Flora, SJS

    2015-01-01

    Gallic acid is an organic acid known for its antioxidant and anticancer properties. The present study is focused on evaluating the role of gallic acid in providing better therapeutic outcomes against arsenic-induced toxicity. Animals pre-exposed to arsenic were treated with monoisoamyl meso -2,3-dimercaptosuccinic acid (MiADMSA), a new chelating drug, alone and in combination with gallic acid, consecutively for 10 days. The study suggests that (1) gallic acid in presence of MiADMSA is only mo...

  9. Phytoextraction by arsenic hyperaccumulator Pteris vittata L. from six arsenic-contaminated soils: Repeated harvests and arsenic redistribution

    Energy Technology Data Exchange (ETDEWEB)

    Gonzaga, Maria I.S.; Santos, Jorge A.G. [Department of Soil Chemistry, Universidade Federal da Bahia, Cruz das Almas, 44380000 (Brazil); Ma, Lena Q. [Soil and Water Science Department, University of Florida, 2169 McCarty Hall, Gainesville, FL 32611-0290 (United States)], E-mail: lqma@ifas.ufl.edu

    2008-07-15

    This greenhouse experiment evaluated arsenic removal by Pteris vittata and its effects on arsenic redistribution in soils. P. vittata grew in six arsenic-contaminated soils and its fronds were harvested and analyzed for arsenic in October, 2003, April, 2004, and October, 2004. The soil arsenic was separated into five fractions via sequential extraction. The ferns grew well and took up arsenic from all soils. Fern biomass ranged from 24.8 to 33.5 g plant{sup -1} after 4 months of growth but was reduced in the subsequent harvests. The frond arsenic concentrations ranged from 66 to 6,151 mg kg{sup -1}, 110 to 3,056 mg kg{sup -1}, and 162 to 2,139 mg kg{sup -1} from the first, second and third harvest, respectively. P. vittata reduced soil arsenic by 6.4-13% after three harvests. Arsenic in the soils was primarily associated with amorphous hydrous oxides (40-59%), which contributed the most to arsenic taken up by P. vittata (45-72%). It is possible to use P. vittata to remediate arsenic-contaminated soils by repeatedly harvesting its fronds. - Pteris vittata was effective in continuously removing arsenic from contaminated soils after three repeated harvests.

  10. Investigating Arsenic Mobilization Mechanisms as well as Complexation Between Arsenic and Polysulfides Associated With a Bangladeshi Rice Paddy

    Science.gov (United States)

    Lin, T.; Kampalath, R.; Jay, J.

    2009-12-01

    The presence of arsenic in the groundwater has led to the largest environmental poisoning in history. Although it is a worldwide issue that affects numerous countries, including Taiwan, Bangladesh, India, China, Mexico, Peru, Australia, and the United States, the issue is of greatest concern in the West Bengal region. In the Ganges Delta, as many as 2 million people are diagnosed with arsenicosis each year. The World Health Organization (WHO) estimates 200,000 to 270,000 arsenic-induced cancer-related deaths in Bangladesh alone. More than 100 million people in the country consume groundwater that exceeds the WHO limit as 50% of the 8 million wells contain groundwater with more than 10 μg/L. Despite the tragic public health implications of this problem, we do not yet have a complete answer to the question of why dissolved arsenic concentrations are so high in the groundwater of the Ganges Delta. Since 1999, we have been intensively studying a field site in Munshiganj, Bangladesh with extremely high levels of arsenic in groundwater (up to 1.2 mg/L). Sediment cores were collected from two locations at the field site: 1) the rice paddy and 2) edge of a nearby irrigation pond. Recharge from irrigation ponds have recently been hypothesized to be an important site of arsenic mobilization. Recent work has proposed mineral dissolution under phosphorus-limited conditions as an important mechanism for arsenic mobilization. Using microcosms with paddy and pond sediment, we are comparing arsenic release via this mechanism with that resulting from reduction of iron hydroxides at our site. Concurrently, we are looking at enhanced solubility of As in the presence of polysulfides as the effects of elemental sulfur on As solubility have not been well researched. We hypothesize that the presence of elemental sulfur, and consequent formation of polysulfides, will substantially increase the solubility of orpiment in sulfidic water and that sorption of these complexes will

  11. Environmental arsenic exposure, selenium and sputum alpha-1 antitrypsin

    DEFF Research Database (Denmark)

    Burgess, Jefferey L; Kurzius-Spencer, Margaret; Poplin, Gerald S

    2014-01-01

    Exposure to arsenic in drinking water is associated with increased respiratory disease. Alpha-1 antitrypsin (AAT) protects the lung against tissue destruction. The objective of this study was to determine whether arsenic exposure is associated with changes in airway AAT concentration and whether...... this relationship is modified by selenium. A total of 55 subjects were evaluated in Ajo and Tucson, Arizona. Tap water and first morning void urine were analyzed for arsenic species, induced sputum for AAT and toenails for selenium and arsenic. Household tap-water arsenic, toenail arsenic and urinary inorganic...... arsenic and metabolites were significantly higher in Ajo (20.6±3.5 μg/l, 0.54±0.77 μg/g and 27.7±21.2 μg/l, respectively) than in Tucson (3.9±2.5 μg/l, 0.16±0.20 μg/g and 13.0±13.8 μg/l, respectively). In multivariable models, urinary monomethylarsonic acid (MMA) was negatively, and toenail selenium...

  12. Curcumin and turmeric attenuate arsenic-induced angiogenesis in ovo.

    Science.gov (United States)

    Pantazis, Panayotis; Varman, Aarthi; Simpson-Durand, Cindy; Thorpe, Jessica; Ramalingam, Satish; Subramaniam, Dharmalingam; Houchen, Courtney; Ihnat, Michael; Anant, Shrikant; Ramanujam, Rama P

    2010-01-01

    Trivalent arsenic [As(III)] is currently approved by the FDA for the treatment of chronic and acute leukemias. However, As(III) has also demonstrated damaging effects on human health, including development of cardiovascular disease, diabetes, and cancer. Further, As(III) is a potent angiogenic agent. In this context, curcumin, an active ingredient in the dietary agent turmeric, has demonstrated potent antiproliferative, antiinflammatory, and antiangiogenic properties. In this report, we have shown that both curcumin and turmeric inhibit expression of vascular endothelial growth factor in HCT-116 human colon cancer cells exposed to As(III). Further, in the chicken chorioallantoic membrane assay model, treatment with low As(III) concentrations results in extensive increase in blood vessel density, which, however, is reduced in the presence of curcumin or turmeric. Collectively, the findings reported here strongly suggest that turmeric and curcumin can dramatically attenuate the process of angiogenesis induced by low As(III) concentrations.

  13. 40 CFR 61.183 - Emission monitoring.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 8 2010-07-01 2010-07-01 false Emission monitoring. 61.183 Section 61... Emissions From Arsenic Trioxide and Metallic Arsenic Production Facilities § 61.183 Emission monitoring. (a..., calibrate, maintain, and operate a continuous monitoring system for the measurement of the opacity of each...

  14. Arsenic biotransformation and volatilization in transgenic rice

    Science.gov (United States)

    Meng, Xiang-Yan; Qin, Jie; Wang, Li-Hong; Duan, Gui-Lan; Sun, Guo-Xin; Wu, Hui-Lan; Chu, Cheng-Cai; Ling, Hong-Qing; Rosen, Barry P.; Zhu, Yong-Guan

    2011-01-01

    Summary Biotransformation of arsenic includes oxidation, reduction, methylation and conversion to more complex organic arsenicals. Members of the class of arsenite [As(III)] S-adenosylmethyltransferase enzymes catalyze As(III) methylation to a variety of mono-, di- and trimethylated species, some of which are less toxic than As(III) itself. However, no methyltransferase gene has been identified in plants. Here, an arsM gene from the soil bacterium Rhodopseudomonas palustris was expressed in Japonica rice (Oryza sativa L.) cultivar Nipponbare, and the transgenic rice produced methylated arsenic species, which were measured by inductively coupled plasma mass spectrometry (ICP-MS) and high performance liquid chromatography-inductively coupled plasma-mass spectrometry (HPLC-ICP-MS). Both monomethylarsenate [MAs(V)] and dimethylarsenate [DMAs(V)] were detected in the root and shoot of transgenic rice. After 12-d exposure to As(III), the transgenic rice gave off 10-fold more volatile arsenicals. The present study demonstrates that expression of an arsM gene in rice induces arsenic methylation and volatilization, providing a potential stratagem for phytoremediation theoretically. PMID:21517874

  15. Arsenic pollution sources.

    Science.gov (United States)

    Garelick, Hemda; Jones, Huw; Dybowska, Agnieszka; Valsami-Jones, Eugenia

    2008-01-01

    Arsenic is a widely dispersed element in the Earth's crust and exists at an average concentration of approximately 5 mg/kg. There are many possible routes of human exposure to arsenic from both natural and anthropogenic sources. Arsenic occurs as a constituent in more than 200 minerals, although it primarily exists as arsenopyrite and as a constituent in several other sulfide minerals. The introduction of arsenic into drinking water can occur as a result of its natural geological presence in local bedrock. Arsenic-containing bedrock formations of this sort are known in Bangladesh, West Bengal (India), and regions of China, and many cases of endemic contamination by arsenic with serious consequences to human health are known from these areas. Significant natural contamination of surface waters and soil can arise when arsenic-rich geothermal fluids come into contact with surface waters. When humans are implicated in causing or exacerbating arsenic pollution, the cause can almost always be traced to mining or mining-related activities. Arsenic exists in many oxidation states, with arsenic (III) and (V) being the most common forms. Similar to many metalloids, the prevalence of particular species of arsenic depends greatly on the pH and redox conditions of the matrix in which it exists. Speciation is also important in determining the toxicity of arsenic. Arsenic minerals exist in the environment principally as sulfides, oxides, and phosphates. In igneous rocks, only those of volcanic origin are implicated in high aqueous arsenic concentrations. Sedimentary rocks tend not to bear high arsenic loads, and common matrices such as sands and sandstones contain lower concentrations owing to the dominance of quartz and feldspars. Groundwater contamination by arsenic arises from sources of arsenopyrite, base metal sulfides, realgar and orpiment, arsenic-rich pyrite, and iron oxyhydroxide. Mechanisms by which arsenic is released from minerals are varied and are accounted for by

  16. Influence of the mode of preparation of the UO3 trioxide on its specific surface

    International Nuclear Information System (INIS)

    Sauteron, J.

    1960-01-01

    As the specific surface of uranium trioxide UO 3 closely depends on the preparation mode and conditions, the authors report and discuss several results obtained on uranium trioxides produced either by precipitation of uranyl nitrate (with oxygenated water, liquid or gaseous ammoniac, and ammonium carbonate), then by calcination at 350 C, or by thermal decomposition of the uranyl nitrate. The authors also studied the influence of calcination temperature of ammonium uranate on the specific surface of the obtained oxide (between 200 and 900 deg.) [fr

  17. Cellular shear stiffness reflects progression of arsenic-induced transformation during G1

    DEFF Research Database (Denmark)

    Muñoz, Alexandra; Eldridge, Will J; Jakobsen, Nina Munkholt

    2017-01-01

    epithelial cells were exposed to sodium arsenite to initiate early stages of transformation. Exposed cells were cultured in soft agar to further transformation and select for clonal populations exhibiting anchorage independent growth. Shear stiffness of various cell populations in G1 was assessed using...... reduced stiffness relative to control clonal lines, which were cultured in soft agar but did not receive arsenic treatment. The relative standard deviation of the stiffness of Arsenic clones was reduced compared to control clones, as well as to the arsenic exposed cell population. Cell stiffness...

  18. [Mixture Leaching Remediation Technology of Arsenic Contaminated Soil].

    Science.gov (United States)

    Chen, Xun-feng; Li, Xiao-ming; Chen, Can; Yang, Qi; Deng, Lin-jing; Xie, Wei-qiang; Zhong, Yui; Huang, Bin; Yang, Wei-qiang; Zhang, Zhi-bei

    2016-03-15

    Soil contamination of arsenic pollution has become a severely environmental issue, while soil leaching is an efficient method for remediation of arsenic-contaminated soil. In this study, batch tests were primarily conducted to select optimal mixture leaching combination. Firstly, five conventional reagents were selected and combined with each other. Secondly, the fractions were analyzed before and after the tests. Finally, to explore the feasibility of mixed leaching, three soils with different arsenic pollution levels were used to compare the leaching effect. Comparing with one-step washing, the two-step sequential washing with different reagents increased the arsenic removal efficiency. These results showed that the mixture of 4 h 0.5 mol · L⁻¹ NaOH + 4 h 0.1 mol · L⁻¹ EDTA was found to be practicable, which could enhance the removal rate of arsenic from 66.67% to 91.83%, and the concentration of arsenic in soil was decreased from 186 mg · kg⁻¹ to 15.2 mg · kg⁻¹. Furthermore, the results indicated that the distribution of fractions of arsenic in soil changed apparently after mixture leaching. Leaching process could significantly reduce the available contents of arsenic in soil. Moreover, the mixture of 0.5 mol · L⁻¹ NaOH + 0.1 mol L⁻¹ EDTA could well decrease the arsenic concentration in aluminum-type soils, while the mixture of 0.5 mol · L⁻¹ OX + 0.5 mol · L⁻¹ NaOH could well decrease the arsenic concentration in iron-type soils.

  19. Urinary arsenic species, toenail arsenic, and arsenic intake estimates in a Michigan population with low levels of arsenic in drinking water.

    Science.gov (United States)

    Rivera-Núñez, Zorimar; Meliker, Jaymie R; Meeker, John D; Slotnick, Melissa J; Nriagu, Jerome O

    2012-01-01

    The large disparity between arsenic concentrations in drinking water and urine remains unexplained. This study aims to evaluate predictors of urinary arsenic in a population exposed to low concentrations (≤50 μg/l) of arsenic in drinking water. Urine and drinking water samples were collected from a subsample (n=343) of a population enrolled in a bladder cancer case-control study in southeastern Michigan. Total arsenic in water and arsenic species in urine were determined using ICP-MS: arsenobetaine (AsB), arsenite (As[III]), arsenate (As[V]), methylarsenic acid (MMA[V]), and dimethylarsenic acid (DMA[V]). The sum of As[III], As[V], MMA[V], and DMA[V] was denoted as SumAs. Dietary information was obtained through a self-reported food intake questionnaire. Log(10)-transformed drinking water arsenic concentration at home was a significant (Pwater were removed and further improved when analyses were applied to individuals who consumed amounts of home drinking water above the median volume (R(2)=0.40, Pwater was 0.42. Results show that arsenic exposure from drinking water consumption is an important determinant of urinary arsenic concentrations, even in a population exposed to relatively low levels of arsenic in drinking water, and suggest that seafood intake may influence urinary DMA[V] concentrations.

  20. ARSENIC-INDUCED SKIN CONDITIONS IDENTIFIED IN SOUTHWEST DERMATOLOGY PRACTICE: AN EPIDEMIOLOGIC TOOL?

    Science.gov (United States)

    Populations living in the Southwest United States are more likely to be exposed to elevated drinking water arsenic levels compared to other areas of the country. Skin changes, including hyperpigmentation and generalized hyperkeratosis, are the most common signs of chronic arsenic...

  1. Investigation of arsenic accumulation and biochemical response of in vitro developed Vetiveria zizanoides plants.

    Science.gov (United States)

    Singh, Shraddha; Sounderajan, Suvarna; Kumar, Kiran; Fulzele, D P

    2017-11-01

    Vetiver grass (Vetiveria zizanoides L. Nash) is found to be a suitable candidate for the phytoremediation of heavy metals. An investigation of arsenic (As) accumulation, translocation and tolerance was conducted in V. zizanoides plantlets upon exposure to different concentrations of arsenic (10, 50, 100 and 200µM) for 7 and 14 d. V. zizanoides plants were found effective in remediation of As, maximum being at 200µM after 14 d of exposure. The results of TBARS and photosynthetic pigments demonstrated that plants did not experience significant toxicity at all the concentrations of As after 7 days, however an increase in their level was found after 14 d. The up-regulation of antioxidant enzyme activities of superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), catalase (CAT) and glutathione s-transferase (GST) in a coordinated and complementary manner enhanced tolerance to plants against arsenic induced oxidative stress. Taken together, the results indicated that in vitro developed plants of V. zizanoides have the potential to remediate and tolerate varying levels of As. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: Some novel findings

    International Nuclear Information System (INIS)

    Samadder, Asmita; Das, Jayeeta; Das, Sreemanti; De, Arnab; Saha, Santu Kumar; Bhattacharyya, Soumya Sundar; Khuda-Bukhsh, Anisur Rahman

    2013-01-01

    Diabetes is a menacing problem, particularly to inhabitants of groundwater arsenic contaminated areas needing new medical approaches. This study examines if PLGA loaded nano-insulin (NIn), administered either intraperitoneally (i.p.) or through oral route, has a greater cost-effective anti-hyperglycemic potential than that of insulin in chronically arsenite-fed hyperglycemic mice. The particle size, morphology and zeta potential of nano-insulin were determined using dynamic light scattering method, scanning electronic and atomic force microscopies. The ability of the nano-insulin (NIn) to cross the blood–brain barrier (BBB) was also checked. Circular dichroic spectroscopic (CD) data of insulin and nano-insulin in presence or absence of arsenic were compared. Several diabetic markers in different groups of experimental and control mice were assessed. The mitochondrial functioning through indices like cytochrome c, pyruvate-kinase, glucokinase, ATP/ADP ratio, mitochondrial membrane potential, cell membrane potential and calcium-ion level was also evaluated. Expressions of the relevant marker proteins and mRNAs like insulin, GLUT2, GLUT4, IRS1, IRS2, UCP2, PI3, PPARγ, CYP1A1, Bcl2, caspase3 and p38 for tracking-down the signaling cascade were also analyzed. Results revealed that i.p.-injected nano-encapsulated-insulin showed better results; NIn, due to its smaller size, faster mobility, site-specific release, could cross BBB and showed positive modulation in mitochondrial signaling cascades and other downstream signaling molecules in reducing arsenic-induced-hyperglycemia. CD data indicated that nano-insulin had less distorted secondary structure as compared with that of insulin in presence of arsenic. Thus, overall analyses revealed that PLGA nano-insulin showed better efficacy in combating arsenite-induced-hyperglycemia than that of insulin and therefore, has greater potentials for use in nano-encapsulated form. - Highlights: ► PLGA encapsulated nano

  3. Poly(lactic-co-glycolic) acid loaded nano-insulin has greater potentials of combating arsenic induced hyperglycemia in mice: Some novel findings

    Energy Technology Data Exchange (ETDEWEB)

    Samadder, Asmita; Das, Jayeeta; Das, Sreemanti; De, Arnab; Saha, Santu Kumar; Bhattacharyya, Soumya Sundar; Khuda-Bukhsh, Anisur Rahman, E-mail: prof_arkb@yahoo.co.in

    2013-02-15

    Diabetes is a menacing problem, particularly to inhabitants of groundwater arsenic contaminated areas needing new medical approaches. This study examines if PLGA loaded nano-insulin (NIn), administered either intraperitoneally (i.p.) or through oral route, has a greater cost-effective anti-hyperglycemic potential than that of insulin in chronically arsenite-fed hyperglycemic mice. The particle size, morphology and zeta potential of nano-insulin were determined using dynamic light scattering method, scanning electronic and atomic force microscopies. The ability of the nano-insulin (NIn) to cross the blood–brain barrier (BBB) was also checked. Circular dichroic spectroscopic (CD) data of insulin and nano-insulin in presence or absence of arsenic were compared. Several diabetic markers in different groups of experimental and control mice were assessed. The mitochondrial functioning through indices like cytochrome c, pyruvate-kinase, glucokinase, ATP/ADP ratio, mitochondrial membrane potential, cell membrane potential and calcium-ion level was also evaluated. Expressions of the relevant marker proteins and mRNAs like insulin, GLUT2, GLUT4, IRS1, IRS2, UCP2, PI3, PPARγ, CYP1A1, Bcl2, caspase3 and p38 for tracking-down the signaling cascade were also analyzed. Results revealed that i.p.-injected nano-encapsulated-insulin showed better results; NIn, due to its smaller size, faster mobility, site-specific release, could cross BBB and showed positive modulation in mitochondrial signaling cascades and other downstream signaling molecules in reducing arsenic-induced-hyperglycemia. CD data indicated that nano-insulin had less distorted secondary structure as compared with that of insulin in presence of arsenic. Thus, overall analyses revealed that PLGA nano-insulin showed better efficacy in combating arsenite-induced-hyperglycemia than that of insulin and therefore, has greater potentials for use in nano-encapsulated form. - Highlights: ► PLGA encapsulated nano

  4. Organic transformations catalyzed by methylrhenium trioxide

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Zuolin [Iowa State Univ., Ames, IA (United States)

    1995-10-06

    Methylrhenium trioxide (MTO), CH3ReO3, was first prepared in 1979. MTO forms stable or unstable adducts with electron-rich ligands, such as amines (quinuclidine, 1,4-diazabicyclo-octane, pyridine, aniline, 2,2'-bipyridine), alkynes, olefins, 1,2-diols, catechols, hydrogen peroxide, water, thiophenols, 1,2-dithiols, triphenylphosphine, 2-aminophenols, 2-aminothiophenols, 8-hydroxyquinoline and halides (Cl-, Br-, I-). After coordination, different further reactions will occur for different reagents. Reactions described in this report include the dehydration of alcohols, direct amination of alcohols, activation of hydrogen peroxide, oxygen transfer, and decomposition of ethyl diazoacetate.

  5. Will mineral trioxide aggregate replace calcium hydroxide in treating pulpal and periodontal healing complications subsequent to dental trauma?

    DEFF Research Database (Denmark)

    Bakland, Leif K; Andreasen, Jens O

    2012-01-01

    Mineral trioxide aggregate (MTA) has over the last two decades begun to take the place of calcium hydroxide (CH) in the treatment of a variety of pulpal and periodontal healing complications following dental trauma. These conditions include teeth with: (i) exposed pulps, (ii) immature roots......, the quality of such induced hard tissues, and finally the dentin weakening effect of CH, which in some instances lead to cervical root fractures in immature teeth. MTA appears, from a relatively few clinical studies, to overcome these shortcomings of CH. The lack of long-term clinical studies, however, may...

  6. Ultramafic-derived arsenic in a fractured bedrock aquifer

    International Nuclear Information System (INIS)

    Ryan, Peter C.; Kim, Jonathan; Wall, Andrew J.; Moen, Jonathan C.; Corenthal, Lilly G.; Chow, Daniel R.; Sullivan, Colleen M.; Bright, Kevin S.

    2011-01-01

    Highlights: → Arsenic is elevated in groundwater from a fractured bedrock aquifer system in northern Vermont, USA. → The arsenic source is serpentinized ultramafic rock. → Antigorite, magnetite (MgCO 3 ) and magnetite (Fe 3 O 4 ) appear to be the main mineralogical hosts of arsenic in the ultramafic rock. → Arsenic appears to be introduced to the ultramafic rock when As-bearing fluids are driven out of sediments during subduction. → The occurrence of serpentinized ultramafic rocks in many orogenic belts suggests that similar arsenic anomalies may occur in geologically-similar terranes globally. - Abstract: In the fractured bedrock aquifer of northern Vermont, USA, As concentrations in groundwater range from 3 ) with lesser amounts in magnetite (Fe 3 O 4 ). Hydrochemistry of monitoring wells drilled into fractured ultramafic rock in a groundwater recharge area with no anthropogenic As source reveals above background As (2-9 μg/L) and an Mg-HCO 3 hydrochemical signature that reflects dissolution of antigorite and magnesite, confirming that As in groundwater can be derived from ultramafic rock dissolution. Arsenic mobility in groundwater affected by ultramafic rock dissolution may be enhanced by alkaline pH values and relatively high HCO 3 - concentrations.

  7. Success Rate of Formocresol Pulpotomy versus Mineral Trioxide Aggregate in Human Primary Molar Tooth

    Directory of Open Access Journals (Sweden)

    S E Jabbarifar

    2004-12-01

    Full Text Available Background: In spite of long time and broad use of formaldehyde derivates (Fixation agent in primary tooth pulp treatment, There is some concerns about these derivates such as variability, inconsistency success rate, mutagenicity, cytotoxicity, alergenicity, and some other potential health hazards of them. Therefore other alternative pulpotomy procedures like Bioactive glass (BAG, Glutaraldehyde (2%, Hydroxyappetite (HA, Bone dried freezed (BDF, ferric sulfate (15%, laser, Electrosurgery (ES, Bone Morphogenic proteins (BMP, recombinant protein-1 (RP1, and Mineral Trioxide Aggregate (MTA have been compared. The purpose of this clinical trial is to assess radiographic and clinical success rate of Formocresol (FC pulpotomy in compare with MTA in human primary molar teeth. Methods: 64 molars were pulpotomized equally and randomly with mineral trioxide Aggregate and Formocresol. Prior to trial, we defined a case as failure, when one or more of the events such as external root resorption, internal root resorption, periapical and furca lucency, pain, swelling, mobility, dental abscess, or early extraction appeared. Every treated tooth was defined as successful, if any noted evident was not shown. Results: Totally, 60 teeth treatment (92.2 percent were successful and 7.8 percent were failed. Failure and success rates for MTA group were 6.3 and 93.7 percent, respectively. Failure and success rates in FC group were 8.4 and 90.2 percent respectively. The difference between MTA and FC treatment methods was not significant (Fisher Exact test. Conclusion: Findings of this study show that mineral trioxide aggregate can be an alternative procedure for FC pulpotomy of primary tooth. Keywords: Mineral trioxide aggregate, formocresol, pulpotomy, success and failure rate.

  8. Complementary arsenic speciation methods: A review

    Energy Technology Data Exchange (ETDEWEB)

    Nearing, Michelle M., E-mail: michelle.nearing@rmc.ca; Koch, Iris, E-mail: koch-i@rmc.ca; Reimer, Kenneth J., E-mail: reimer-k@rmc.ca

    2014-09-01

    The toxicity of arsenic greatly depends on its chemical form and oxidation state (speciation) and therefore accurate determination of arsenic speciation is a crucial step in understanding its chemistry and potential risk. High performance liquid chromatography with inductively coupled mass spectrometry (HPLC–ICP-MS) is the most common analysis used for arsenic speciation but it has two major limitations: it relies on an extraction step (usually from a solid sample) that can be incomplete or alter the arsenic compounds; and it provides no structural information, relying on matching sample peaks to standard peaks. The use of additional analytical methods in a complementary manner introduces the ability to address these disadvantages. The use of X-ray absorption spectroscopy (XAS) with HPLC–ICP-MS can be used to identify compounds not extracted for HPLC–ICP-MS and provide minimal processing steps for solid state analysis that may help preserve labile compounds such as those containing arsenic-sulfur bonds, which can degrade under chromatographic conditions. On the other hand, HPLC–ICP-MS is essential in confirming organoarsenic compounds with similar white line energies seen by using XAS, and identifying trace arsenic compounds that are too low to be detected by XAS. The complementary use of electrospray mass spectrometry (ESI–MS) with HPLC–ICP-MS provides confirmation of arsenic compounds identified during the HPLC–ICP-MS analysis, identification of unknown compounds observed during the HPLC–ICP-MS analysis and further resolves HPLC–ICP-MS by identifying co-eluting compounds. In the complementary use of HPLC–ICP-MS and ESI–MS, HPLC–ICP-MS helps to focus the ESI–MS selection of ions. Numerous studies have shown that the information obtained from HPLC–ICP-MS analysis can be greatly enhanced by complementary approaches. - Highlights: • HPLC–ICP-MS is the most common method used for arsenic speciation. • HPLC limitations include

  9. Complementary arsenic speciation methods: A review

    International Nuclear Information System (INIS)

    Nearing, Michelle M.; Koch, Iris; Reimer, Kenneth J.

    2014-01-01

    The toxicity of arsenic greatly depends on its chemical form and oxidation state (speciation) and therefore accurate determination of arsenic speciation is a crucial step in understanding its chemistry and potential risk. High performance liquid chromatography with inductively coupled mass spectrometry (HPLC–ICP-MS) is the most common analysis used for arsenic speciation but it has two major limitations: it relies on an extraction step (usually from a solid sample) that can be incomplete or alter the arsenic compounds; and it provides no structural information, relying on matching sample peaks to standard peaks. The use of additional analytical methods in a complementary manner introduces the ability to address these disadvantages. The use of X-ray absorption spectroscopy (XAS) with HPLC–ICP-MS can be used to identify compounds not extracted for HPLC–ICP-MS and provide minimal processing steps for solid state analysis that may help preserve labile compounds such as those containing arsenic-sulfur bonds, which can degrade under chromatographic conditions. On the other hand, HPLC–ICP-MS is essential in confirming organoarsenic compounds with similar white line energies seen by using XAS, and identifying trace arsenic compounds that are too low to be detected by XAS. The complementary use of electrospray mass spectrometry (ESI–MS) with HPLC–ICP-MS provides confirmation of arsenic compounds identified during the HPLC–ICP-MS analysis, identification of unknown compounds observed during the HPLC–ICP-MS analysis and further resolves HPLC–ICP-MS by identifying co-eluting compounds. In the complementary use of HPLC–ICP-MS and ESI–MS, HPLC–ICP-MS helps to focus the ESI–MS selection of ions. Numerous studies have shown that the information obtained from HPLC–ICP-MS analysis can be greatly enhanced by complementary approaches. - Highlights: • HPLC–ICP-MS is the most common method used for arsenic speciation. • HPLC limitations include

  10. PKC δ Regulates Translation Initiation through PKR and eIF2 α in Response to Retinoic Acid in Acute Myeloid Leukemia Cells

    OpenAIRE

    Ozpolat, Bulent; Akar, Ugur; Tekedereli, Ibrahim; Alpay, S. Neslihan; Barria, Magaly; Gezgen, Baki; Zhang, Nianxiang; Coombes, Kevin; Kornblau, Steve; Lopez-Berestein, Gabriel

    2012-01-01

    Translation initiation and activity of eukaryotic initiation factor-alpha (eIF2 α ), the rate-limiting step of translation initiation, is often overactivated in malignant cells. Here, we investigated the regulation and role of eIF2 α in acute promyelocytic (APL) and acute myeloid leukemia (AML) cells in response to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), the front-line therapies in APL. ATRA and ATO induce Ser-51 phosphorylation (inactivation) of eIF2 α , through the induct...

  11. Arsenic implantation into polycrystalline silicon and diffusion to silicon substrate

    International Nuclear Information System (INIS)

    Tsukamoto, K.; Akasaka, Y.; Horie, K.

    1977-01-01

    Arsenic implantation into polycrystalline silicon and drive-in diffusion to silicon substrate have been investigated by MeV He + backscattering analysis and also by electrical measurements. The range distributions of arsenic implanted into polycrystalline silicon are well fitted to Gaussian distributions over the energy range 60--350 keV. The measured values of R/sub P/ and ΔR/sub P/ are about 10 and 20% larger than the theoretical predictions, respectively. The effective diffusion coefficient of arsenic implanted into polycrystalline silicon is expressed as D=0.63 exp[(-3.22 eV/kT)] and is independent of the arsenic concentration. The drive-in diffusion of arsenic from the implanted polycrystalline silicon layer into the silicon substrate is significantly affected by the diffusion atmosphere. In the N 2 atmosphere, a considerable amount of arsenic atoms diffuses outward to the ambient. The outdiffusion can be suppressed by encapsulation with Si 3 N 4 . In the oxidizing atmosphere, arsenic atoms are driven inward by growing SiO 2 due to the segregation between SiO 2 and polycrystalline silicon, and consequently the drive-in diffusion of arsenic is enhanced. At the interface between the polycrystalline silicon layer and the silicon substrate, arsenic atoms are likely to segregate at the polycrystalline silicon side

  12. Evaluation of the sustainability of deep groundwater as an arsenic-safe resource in the Bengal Basin

    OpenAIRE

    Michael, Holly A.; Voss, Clifford I.

    2008-01-01

    Tens of millions of people in the Bengal Basin region of Bangladesh and India drink groundwater containing unsafe concentrations of arsenic. This high-arsenic groundwater is produced from shallow (150 m where groundwater arsenic concentrations are nearly uniformly low, and many more wells are needed, however, the sustainability of deep, arsenic-safe groundwater has not been previously assessed. Deeper pumping could induce downward migration of dissolved arsenic, permanently destroying the dee...

  13. Seasonal Arsenic Accumulation in Stream Sediments at a Groundwater Discharge Zone

    DEFF Research Database (Denmark)

    MacKay, Allison A.; Gan, Ping; Yu, Ran

    2014-01-01

    Seasonal changes in arsenic and iron accumulation rates were examined in the sediments of a brook that receives groundwater discharges of arsenic and reduced iron. Clean glass bead columns were deployed in sediments for known periods over the annual hydrologic cycle to monitor changes in arsenic...... and iron concentrations in bead coatings. The highest accumulation rates occurred during the dry summer period (July-October) when groundwater discharges were likely greatest at the sample locations. The intermediate flow period (October-March), With higher surface water: levels, was associated with losses...... of arsenic and iron from bead column coatings at. depths below 2-6 cm. Batch incubations indicated iron releases from solids to be induced by biological reduction of iron (oxy)hydroxide solids. Congruent arsenic releases during incubation were limited by the high arsenic sorption capacity (0.536 mg...

  14. Exercise Prevents Memory Impairment Induced by Arsenic Exposure in Mice: Implication of Hippocampal BDNF and CREB

    OpenAIRE

    Sun, Bao-Fei; Wang, Qing-Qing; Yu, Zi-Jiang; Yu, Yan; Xiao, Chao-Lun; Kang, Chao-Sheng; Ge, Guo; Linghu, Yan; Zhu, Jun-De; Li, Yu-Mei; Li, Qiang-Ming; Luo, Shi-Peng; Yang, Dang; Li, Lin; Zhang, Wen-Yan

    2015-01-01

    High concentrations of arsenic, which can be occasionally found in drinking water, have been recognized as a global health problem. Exposure to arsenic can disrupt spatial memory; however, the underlying mechanism remains unclear. In the present study, we tested whether exercise could interfere with the effect of arsenic exposure on the long-term memory (LTM) of object recognition in mice. Arsenic (0, 1, 3, and 10 mg/ kg, i.g.) was administered daily for 12 weeks. We found that arsenic at dos...

  15. Arsenic exposure at low-to-moderate levels and skin lesions, arsenic metabolism, neurological functions, and biomarkers for respiratory and cardiovascular diseases: Review of recent findings from the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh

    International Nuclear Information System (INIS)

    Chen Yu; Parvez, Faruque; Gamble, Mary; Islam, Tariqul; Ahmed, Alauddin; Argos, Maria; Graziano, Joseph H.; Ahsan, Habibul

    2009-01-01

    The contamination of groundwater by arsenic in Bangladesh is a major public health concern affecting 35-75 million people. Although it is evident that high levels (> 300 μg/L) of arsenic exposure from drinking water are related to adverse health outcomes, health effects of arsenic exposure at low-to-moderate levels (10-300 μg/L) are not well understood. We established the Health Effects of Arsenic Longitudinal Study (HEALS) with more than 20,000 men and women in Araihazar, Bangladesh, to prospectively investigate the health effects of arsenic predominately at low-to-moderate levels (0.1 to 864 μg/L, mean 99 μg/L) of arsenic exposure. Findings to date suggest adverse effects of low-to-moderate levels of arsenic exposure on the risk of pre-malignant skin lesions, high blood pressure, neurological dysfunctions, and all-cause and chronic disease mortality. In addition, the data also indicate that the risk of skin lesion due to arsenic exposure is modifiable by nutritional factors, such as folate and selenium status, lifestyle factors, including cigarette smoking and body mass index, and genetic polymorphisms in genes related to arsenic metabolism. The analyses of biomarkers for respiratory and cardiovascular functions support that there may be adverse effects of arsenic on these outcomes and call for confirmation in large studies. A unique strength of the HEALS is the availability of outcome data collected prospectively and data on detailed individual-level arsenic exposure estimated using water, blood and repeated urine samples. Future prospective analyses of clinical endpoints and related host susceptibility will enhance our knowledge on the health effects of low-to-moderate levels of arsenic exposure, elucidate disease mechanisms, and give directions for prevention.

  16. Urinary total arsenic and 8-hydroxydeoxyguanosine are associated with renal cell carcinoma in an area without obvious arsenic exposure

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chao-Yuan [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Su, Chien-Tien [Department of Family Medicine, Taipei Medical University Hospital, Taipei, Taiwan (China); Chung, Chi-Jung [Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Pu, Yeong-Shiau [Department of Urology, National Taiwan University Hospital, College of Medicine National Taiwan University, Taipei, Taiwan (China); Chu, Jan-Show [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Yang, Hsiu-Yuan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Wu, Chia-Chang [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Department of Urology, Taipei Medical Universtiy-Shuang Ho Hospital, Taipei, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China)

    2012-08-01

    8-Hydroxydeoxyguanosine (8-OHdG) is one of the most reliable and abundant markers of DNA damage. The study was designed to explore the relationship between urinary 8-OHdG and renal cell carcinoma (RCC) and to investigate whether individuals with a high level of 8-OHdG would have a modified odds ratio (OR) of arsenic-related RCC. This case–control study was conducted with 132 RCC patients and 245 age- and sex-matched controls from a hospital-based pool between November 2006 and May 2009. Pathological verification of RCC was completed by image-guided biopsy or surgical resection of renal tumors. Urinary 8-OHdG levels were determined using liquid chromatography with tandem mass spectrometry (LC–MS/MS). Concentrations of urinary arsenic species, including inorganic arsenic, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Level of urinary 8-OHdG was significantly associated with the OR of RCC in a dose–response relationship after multivariate adjustment. Urinary 8-OHdG was significantly related to urinary total arsenic. The greatest OR (3.50) was seen in the individuals with high urinary 8-OHdG and high urinary total arsenic. A trend test indicated that the OR of RCC was increased with one of these factors and was further increased with both (p = 0.002). In conclusion, higher urinary 8-OHdG was a strong predictor of the RCC. High levels of 8-OHdG combined with urinary total arsenic might be indicative of arsenic-induced RCC. -- Highlights: ► Urinary 8-OHdG was significantly related to urinary total arsenic. ► Higher urinary 8-OHdG was a strong predictor of RCC risk. ► Urinary 8-OHdG may modify arsenic related RCC risk.

  17. Arsenic induced toxicity in broiler chicks and its alleviation with ascorbic acid: a toxico-patho-biochemical study

    Science.gov (United States)

    Khan, Ahrar; Sharaf, Rabia; Khan, Muhammad Zargham; Saleemi, Muhammad Kashif; Mahmood, Fazal

    2013-01-01

    To find out toxico-pathological effects of arsenic (As) and ameliorating effect of ascorbic acid (Vit C), broilers birds were administered 50 and 250 mg/kg arsenic and Vit C, respectively alone/in combination. As-treated birds exhibited severe signs of toxicity such as dullness, depression, increased thirst, open mouth breathing and watery diarrhea. All these signs were partially ameliorated with the treatment of Vit C. As-treated birds showed a significant decrease in serum total proteins while serum enzymes, urea and creatinine were significantly increased. Alkaline phosphatase and lactate dehydrogenase completely whereas proteins, aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine were partial ameliorated in birds treated with As+Vit C as compared to As-treated and control birds. Pale and hemorrhagic liver and swollen kidneys were observed in As-treated birds. Histopathologically, liver exhibited congestion and cytoplasmic vacuolation while in kidneys, condensation of tubular epithelium nuclei, epithelial necrosis, increased urinary spaces, sloughing of tubules from basement membrane and cast deposition were observed in As-treated birds. Pathological lesions were partially ameliorated with the treatment of Vit C. It can be concluded that arsenic induces biochemical and histopathological alterations in broiler birds; however, these toxic effects can be partially attenuated by Vit C.

  18. Attenuation of arsenic neurotoxicity by curcumin in rats

    International Nuclear Information System (INIS)

    Yadav, Rajesh S.; Sankhwar, Madhu Lata; Shukla, Rajendra K.; Chandra, Ramesh; Pant, Aditya B.; Islam, Fakhrul; Khanna, Vinay K.

    2009-01-01

    In view of continued exposure to arsenic and associated human health risk including neurotoxicity, neuroprotective efficacy of curcumin, a polyphenolic antioxidant, has been investigated in rats. A significant decrease in locomotor activity, grip strength (26%) and rota-rod performance (82%) was observed in rats treated with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) as compared to controls. The arsenic treated rats also exhibited a decrease in the binding of striatal dopamine receptors (32%) and tyrosine hydroxylase (TH) immunoreactivity (19%) in striatum. Increased arsenic levels in corpus striatum (6.5 fold), frontal cortex (6.3 fold) and hippocampus (7.0 fold) associated with enhanced oxidative stress in these brain regions, as evident by an increase in lipid perioxidation, protein carbonyl and a decrease in the levels of glutathione and activity of superoxide dismutase, catalase and glutathione peroxidase with differential effects were observed in arsenic treated rats compared to controls. Simultaneous treatment with arsenic (sodium arsenite, 20 mg/kg body weight, p.o., 28 days) and curcumin (100 mg/kg body weight, p.o., 28 days) caused an increase in locomotor activity and grip strength and improved the rota-rod performance in comparison to arsenic treated rats. Binding of striatal dopamine receptors and TH expression increased while arsenic levels and oxidative stress decreased in these brain regions in co-treated rats as compared to those treated with arsenic alone. No significant effect on any of these parameters was observed in rats treated with curcumin (100 mg/kg body weight, p.o., 28 days) alone compared to controls. A significant protection in behavioral, neurochemical and immunohistochemical parameters in rats simultaneously treated with arsenic and curcumin suggest the neuroprotective efficacy of curcumin.

  19. Quantification of the Intracellular Life Time of Water Molecules to Measure Transport Rates of Human Aquaglyceroporins.

    Science.gov (United States)

    Palmgren, Madelene; Hernebring, Malin; Eriksson, Stefanie; Elbing, Karin; Geijer, Cecilia; Lasič, Samo; Dahl, Peter; Hansen, Jesper S; Topgaard, Daniel; Lindkvist-Petersson, Karin

    2017-12-01

    Orthodox aquaporins are transmembrane channel proteins that facilitate rapid diffusion of water, while aquaglyceroporins facilitate the diffusion of small uncharged molecules such as glycerol and arsenic trioxide. Aquaglyceroporins play important roles in human physiology, in particular for glycerol metabolism and arsenic detoxification. We have developed a unique system applying the strain of the yeast Pichia pastoris, where the endogenous aquaporins/aquaglyceroporins have been removed and human aquaglyceroporins AQP3, AQP7, and AQP9 are recombinantly expressed enabling comparative permeability measurements between the expressed proteins. Using a newly established Nuclear Magnetic Resonance approach based on measurement of the intracellular life time of water, we propose that human aquaglyceroporins are poor facilitators of water and that the water transport efficiency is similar to that of passive diffusion across native cell membranes. This is distinctly different from glycerol and arsenic trioxide, where high glycerol transport efficiency was recorded.

  20. Suppression of NRF2–ARE activity sensitizes chemotherapeutic agent-induced cytotoxicity in human acute monocytic leukemia cells

    International Nuclear Information System (INIS)

    Peng, Hui; Wang, Huihui; Xue, Peng; Hou, Yongyong; Dong, Jian; Zhou, Tong; Qu, Weidong; Peng, Shuangqing; Li, Jin; Carmichael, Paul L.; Nelson, Bud; Clewell, Rebecca; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

    2016-01-01

    Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of the antioxidant response element (ARE)-dependent transcription, plays a pivotal role in chemical detoxification in normal and tumor cells. Consistent with previous findings that NRF2–ARE contributes to chemotherapeutic resistance of cancer cells, we found that stable knockdown of NRF2 by lentiviral shRNA in human acute monocytic leukemia (AML) THP-1 cells enhanced the cytotoxicity of several chemotherapeutic agents, including arsenic trioxide (As 2 O 3 ), etoposide and doxorubicin. Using an ARE-luciferase reporter expressed in several human and mouse cells, we identified a set of compounds, including isonicotinic acid amides, isoniazid and ethionamide, that inhibited NRF2–ARE activity. Treatment of THP-1 cells with ethionamide, for instance, significantly reduced mRNA expression of multiple ARE-driven genes under either basal or As 2 O 3 -challenged conditions. As determined by cell viability and cell cycle, suppression of NRF2–ARE by ethionamide also significantly enhanced susceptibility of THP-1 and U937 cells to As 2 O 3 -induced cytotoxicity. In THP-1 cells, the sensitizing effect of ethionamide on As 2 O 3 -induced cytotoxicity was highly dependent on NRF2. To our knowledge, the present study is the first to demonstrate that ethionamide suppresses NRF2–ARE signaling and disrupts the transcriptional network of the antioxidant response in AML cells, leading to sensitization to chemotherapeutic agents. - Highlights: • Identification of novel inhibitors of ARE-dependent transcription • Suppression of NRF2–ARE sensitizes THP-1 cells to chemotherapy. • Ethionamide suppresses ARE-dependent transcriptional activity. • Ethionamide and isoniazid increase the cytotoxicity of As 2 O 3 in AML cells. • Sensitization of THP-1 cells to As 2 O 3 toxicity by ethionamide is NRF2-dependent.

  1. Raman spectra of thiolated arsenicals with biological importance.

    Science.gov (United States)

    Yang, Mingwei; Sun, Yuzhen; Zhang, Xiaobin; McCord, Bruce; McGoron, Anthony J; Mebel, Alexander; Cai, Yong

    2018-03-01

    Surface enhanced Raman scattering (SERS) has great potential as an alternative tool for arsenic speciation in biological matrices. SERS measurements have advantages over other techniques due to its ability to maintain the integrity of arsenic species and its minimal requirements for sample preparation. Up to now, very few Raman spectra of arsenic compounds have been reported. This is particularly true for thiolated arsenicals, which have recently been found to be widely present in humans. The lack of data for Raman spectra in arsenic speciation hampers the development of new tools using SERS. Herein, we report the results of a study combining the analysis of experimental Raman spectra with that obtained from density functional calculations for some important arsenic metabolites. The results were obtained with a hybrid functional B3LYP approach using different basis sets to calculate Raman spectra of the selected arsenicals. By comparing experimental and calculated spectra of dimethylarsinic acid (DMA V ), the basis set 6-311++G** was found to provide computational efficiency and precision in vibrational frequency prediction. The Raman frequencies for the rest of organoarsenicals were studied using this basis set, including monomethylarsonous acid (MMA III ), dimethylarsinous acid (DMA III ), dimethylmonothioarinic acid (DMMTA V ), dimethyldithioarsinic acid (DMDTA V ), S-(Dimethylarsenic) cysteine (DMA III (Cys)) and dimethylarsinous glutathione (DMA III GS). The results were compared with fingerprint Raman frequencies from As─O, As─C, and As─S obtained under different chemical environments. These fingerprint vibrational frequencies should prove useful in future measurements of different species of arsenic using SERS. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Controls on the distribution of arsenic in lake sediments impacted by 65 years of gold ore processing in subarctic Canada: the role of organic matter

    Science.gov (United States)

    Galloway, Jennifer; Palmer, Michael; Swindles, Graeme T.; Sanei, Hamed; Jamieson, Heather E.; Parsons, Michael; Macumber, Andrew L.; Patterson, Tim; Falck, Hendrik

    2017-04-01

    Gold mines in the Yellowknife region of the Northwest Territories, Canada, operated from 1938 to 2003 and released approximately 20,000 tonnes of arsenic trioxide to the environment through stack emissions. This release resulted in highly elevated arsenic concentrations in lake surface waters and sediments relative to Canadian drinking water standards and guidelines for the protection of aquatic life. High northern latitudes are experiencing substantial impacts, including changes in bio-physico-chemical processes, due to climate change. Determining the affect of warming climate on contamination is complicated by the fact that little is known of climate change controls on As mobility and bioavailability. Further, while the role of dissolved organic matter in As cycling is relatively well characterized in soils and wetland sediments, few studies have investigated the role of solid organic matter in lacustrine systems. We use a meta-analytical approach to better understand controls on sedimentary arsenic distribution in lakes within a 50 km2 area of historic mineral processing activities. Arsenic concentrations in near surface sediments of the 100 lakes studied range from 5 mg/kg to over 10,000 mg/kg (median 81 mg/kg). Distance from the historical Giant Mine roaster stack and the amount of labile organic matter (S1 carbon as determined by Rock Eval pyrolysis) in lake sediments are the variables most strongly correlated with sedimentary As concentrations (Spearman's rank correlation As:distance from historic roaster rs=-0.57, pcoating of pre-existing solid-phase As-mineral complexes, direct As-organic matter interactions, and promotion of microbial-mediated reduction and precipitation of As-bearing minerals.

  3. Phytoremediation of arsenic contaminated soil by arsenic accumulators: a three year study.

    Science.gov (United States)

    Raj, Anshita; Singh, Nandita

    2015-03-01

    To investigate whether phytoremediation can remove arsenic from the contaminated area, a study was conducted for three consecutive years to determine the efficiency of Pteris vittata, Adiantum capillus veneris, Christella dentata and Phragmites karka, on arsenic removal from the arsenic contaminated soil. Arsenic concentrations in the soil samples were analysed after harvesting in 2009, 2010 and 2011 at an interval of 6 months. Frond arsenic concentrations were also estimated in all the successive harvests. Fronds resulted in the greatest amount of arsenic removal. Root arsenic concentrations were analysed in the last harvest. Approximately 70 % of arsenic was removed by P. vittata which was recorded as the highest among the four plant species. However, 60 % of arsenic was removed by A. capillus veneris, 55.1 % by C. dentata and 56.1 % by P. karka of arsenic was removed from the contaminated soil in 3 years.

  4. Antimony Trioxide (ATO) - Summary of External Peer Review and Public Comments and Disposition

    Science.gov (United States)

    This document summarizes the public and external peer review comments that the EPA’s Office of Pollution Prevention and Toxics (OPPT) received for the draft work plan risk assessment for Antimony Trioxide (ATO).

  5. Microbial effects on the release and attenuation of arsenic in the shallow subsurface of a natural geochemical anomaly

    International Nuclear Information System (INIS)

    Drahota, Petr; Falteisek, Lukáš; Redlich, Aleš; Rohovec, Jan; Matoušek, Tomáš; Čepička, Ivan

    2013-01-01

    Critical factors leading to arsenic release and attenuation from the shallow subsurface were studied with multidisciplinary approach in the natural gold–arsenic geochemical anomaly at Mokrsko (Czech Republic). The results show that microbial reduction promotes arsenic release from Fe(III) (hydr)oxides and Fe(III) arsenates, thereby enhancing dissolved arsenic in the shallow groundwater at average concentration of 7.76 mg/L. In the organic-rich aggregates and wood particles, however, microbial sulfate reduction triggers the formation of realgar deposits, leading to accumulation of As in the distinct organic-rich patches of the shallow subsurface. We conclude that precipitation of realgar in the shallow subsurface of soil/sediment depends on specific and non-trivial combination of water and rock chemistry, microbial community composition and spatial organisation of the subsurface zone, where speciation in saturated environments varied on a centimeter scale from reduced (decomposed wood, H 2 S and realgar present) to oxidized (goethite and arsenate minerals are present). Highlights: •Very high As(III) concentrations were detected in the shallow groundwater. •Arsenic is bound to Fe(III) (hydr)oxides, Fe(III) arsenates and newly-formed realgar. •Reductive dissolution of Fe(III) and As(V) minerals by bacteria leads to mobilization of arsenic. •Precipitation of realgar is constrained to anaerobic domains around and within organic particles. -- Microbial reduction of Fe(III) and As(V) minerals leads to mobilization of As and induces a mineralogical transition toward realgar formation

  6. Arsenic compound-induced increases in glutathione levels in cultured Chinese hamster V79 cells and mechanisms associated with changes in {gamma}-glutamylcysteine synthetase activity, cystine uptake and utilization of cysteine

    Energy Technology Data Exchange (ETDEWEB)

    Ochi, Takafumi [Department of Environmental Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-01 (Japan)

    1997-11-01

    Increases in the glutathione (GSH) level in cultured Chinese hamster V79 cells incubated with arsenic compounds were investigated in terms of changes in the activity of {gamma}-glutamylcysteine synthetase ({gamma}-GCS), rate of cystine uptake, and utilization of cysteine. Arsenite at subtoxic concentrations caused a marked increase of the GSH level at 8 h after addition and then declined. Increase in the GSH level caused by arsenite was associated with an increase in the rate of cystine uptake, but not in {gamma}-GCS activity. Increase in the rate of uptake of cystine was attributed mainly to an increase in the utilization of cysteine in the synthesis of GSH. Dimethylarsinic acid (DMAA) also caused an increase in the GSH level in a time- and concentration-dependent manner. Increase in the GSH level was accompanied by increases in {gamma}-GCS activity and in the uptake of cystine. DMAA caused a reduction in the rate of utilization of cysteine for protein synthesis while enhancing the rate of cysteine utilization for GSH synthesis. Cycloheximide inhibited increases in {gamma}-GCS activity caused by DMAA and in the rate of cystine uptake caused by arsenite and DMAA. The cystine transport system is suggested to be induced by arsenite and DMAA with {gamma}-GCS induced in cells incubated with DMAA. Among the arsenic compounds, methylarsonic acid (MAA) was not effective in causing an increase in the GSH level. Accordingly, increases in the GSH level caused by arsenite and DMAA may be specific phenomena in which the cells responded to the arsenicals by increasing the GSH level. (orig.) With 13 figs., 1 tab., 47 refs.

  7. Arsenic and diabetes and hypertension in human populations: A review

    International Nuclear Information System (INIS)

    Chen, C.-J.; Wang, S.-L.; Chiou, J.-M.; Tseng, C.-H.; Chiou, H.-Y.; Hsueh, Y.-M.; Chen, S.-Y.; Wu, M.-M.; Lai, M.-S.

    2007-01-01

    Long-term exposure to ingested arsenic from drinking water has been well documented to be associated with an increased risk of diabetes mellitus and hypertension in a dose-response relationship among residents of arseniasis-endemic areas in southwestern Taiwan and Bangladesh. An increased risk of self-reported hypertension but not diabetes was reported in a community-based study of residents who consumed drinking water with a low level of arsenic. Increased glycosylated hemoglobin level and systolic blood pressure were observed in workers occupationally exposed to arsenic. Inconsistent findings of arsenic and diabetes in occupational studies may result from the healthy worker effect and the variation in exposure measurement, age composition, number of patients, accuracy in diagnosis and classification of underlying causes of death, competing causes of death, and method to detect diabetes. The dose-response relationship and toxicological mechanisms of arsenic-induced diabetes and hypertension need further elucidation

  8. Electric heating of a unit for uranium trioxide production

    International Nuclear Information System (INIS)

    Faron, R.; Striff, A.

    1985-01-01

    Ammonium diuranate U 2 O 7 (NH 4 ) 2 containing about 50% of water is dried and transformed by calcination in uranium trioxide UO 3 . Drying and calcination was obtained by air heated by two burners using domestic fuel. In 1984 the plant was transformed for utilization of electric heating improving maintenance cost, decreasing heat losses and by energy saving the payback period on investment is of 2.6 years [fr

  9. Synthesis of magnetic wheat straw for arsenic adsorption

    International Nuclear Information System (INIS)

    Tian, Ye; Wu, Min; Lin, Xiaobo; Huang, Pei; Huang, Yong

    2011-01-01

    Highlights: → This work provides a way for fabricating low-cost arsenic adsorbents using agro- or plant-residues. → The introduction of wheat straw template highly enhances the arsenic adsorption of Fe 3 O 4 . → This magnetic adsorbent can be separated and collected by magnetic control easily and rapidly. → This adsorbent can be regenerated. → - Abstract: Magnetic wheat straw (MWS) with different Fe 3 O 4 content was synthesized by using in-situ co-precipitation method. It was characterized by powder X-ray diffraction (XRD) and vibrating sample magnetometer (VSM). This material can be used for arsenic adsorption from water, and can be easily separated by applied magnetic field. The introduction of wheat straw template highly enhanced the arsenic adsorption of Fe 3 O 4 . Among three adsorption isotherm models examined, the data fitted Langmuir model better. Fe 3 O 4 content and initial pH value influenced its adsorption behavior. Higher Fe 3 O 4 content corresponded to a higher adsorption capacity. In the pH range of 3-11, As(V) adsorption was decreased with increasing of pH; As(III) adsorption had the highest capacity at pH 7-9. Moreover, by using 0.1 mol L -1 NaOH aqueous solution, it could be regenerated. This work provided an efficient way for making use of agricultural waste.

  10. Arsenic removal by magnetic nanocrystalline barium hexaferrite

    Energy Technology Data Exchange (ETDEWEB)

    Patel, Hasmukh A.; Byun, Jeehye; Yavuz, Cafer T., E-mail: yavuz@kaist.ac.kr [Graduate School of EEWS, Korea Advanced Institute of Science and Technology (KAIST) (Korea, Republic of)

    2012-07-15

    Nanoscale magnetite (Fe{sub 3}O{sub 4}) (<15 nm) is known to remove arsenic efficiently but is very difficult to separate or require high magnetic fields to separate out from the waste water after treatment. Anisotropic hexagonal ferrite (BaFe{sub 12}O{sub 19}, BHF) is a well-known permanent magnet (i.e., fridge magnets) and attractive due to its low cost in making large quantities. BHF offers a viable alternative to magnetite nanocrystals for arsenic removal since it features surfaces similar to iron oxides but with much enhanced magnetism. Herein, we employ BHF nanocrystalline materials for the first time in arsenic removal from wastewater. Our results show better (75 %) arsenic removal than magnetite of the similar sizes. The BHF nanoparticles, 6.06 {+-} 0.52 nm synthesized by thermolysis method at 320 Degree-Sign C do not show hexagonal phase, however, subsequent annealing at 750 Degree-Sign C produced pure hexagonal BHF in >200 nm assemblies. By using BHF, we demonstrate that nanoparticle removal is more efficient and fixed bed type cartridge applications are more possible.

  11. Arsenic (+3 oxidation state) methyltransferase and the inorganic arsenic methylation phenotype

    International Nuclear Information System (INIS)

    Li Jiaxin; Waters, Stephen B.; Drobna, Zuzana; Devesa, Vicenta; Styblo, Miroslav; Thomas, David J.

    2005-01-01

    Inorganic arsenic is enzymatically methylated; hence, its ingestion results in exposure to the parent compound and various methylated arsenicals. Both experimental and epidemiological evidences suggest that some of the adverse health effects associated with chronic exposure to inorganic arsenic may be mediated by these methylated metabolites. If i As methylation is an activation process, then the phenotype for inorganic arsenic methylation may determine risk associated with exposure to this metalloid. We examined inorganic arsenic methylation phenotypes and arsenic (+3 oxidation state) methyltransferase genotypes in four species: three that methylate inorganic arsenic (human (Homo sapiens), rat (Rattus norwegicus), and mouse (Mus musculus)) and one that does not methylate inorganic arsenic (chimpanzee, Pan troglodytes). The predicted protein products from arsenic (+3 oxidation state) methyltransferase are similar in size for rat (369 amino acid residues), mouse (376 residues), and human (375 residues). By comparison, a 275-nucleotide deletion beginning at nucleotide 612 in the chimpanzee gene sequence causes a frameshift that leads to a nonsense mutation for a premature stop codon after amino acid 205. The null phenotype for inorganic arsenic methylation in the chimpanzee is likely due to the deletion in the gene for arsenic (+3 oxidation state) methyltransferase that yields an inactive truncated protein. This lineage-specific loss of function caused by the deletion event must have occurred in the Pan lineage after Homo-Pan divergence about 5 million years ago

  12. Formation of self-ordered porous anodized alumina template for growing tungsten trioxide nanowires

    Science.gov (United States)

    Hussain, Tajamal; Shah, Asma Tufail; Shehzad, Khurram; Mujahid, Adnan; Farooqi, Zahoor Hussain; Raza, Muhammad Hamid; Ahmed, Mirza Nadeem; Nisa, Zaib Un

    2015-12-01

    Uniform porous anodized aluminum oxide (AAO) membrane has been synthesized by two-step anodization for fabricating tungsten trioxide (WO3) nanowires. Under assayed conditions, uniform porous structure of alumina (Al2O3) membrane with long range ordered hexagonal arrangements of nanopores was achieved. The self-assembled template possesses pores of internal diameter of 50 nm and interpore distance ( d int) of 80 nm with a thickness of about 80 µm, i.e., used for fabrication of nanostructures. WO3 nanowires have been fabricated by simple electroless deposition method inside Al2O3 nanopores. SEM images show tungsten trioxide nanowire with internal diameter of about 50 nm, similar to porous diameter of AAO template. XRD results showed that nanowires exist in cubic crystalline state with minor proportion of monoclinic phase.

  13. Blood Pressure Associated with Arsenic Methylation and Arsenic Metabolism Caused by Chronic Exposure to Arsenic in Tube Well Water.

    Science.gov (United States)

    Wei, Bing Gan; Ye, Bi Xiong; Yu, Jiang Ping; Yang, Lin Sheng; Li, Hai Rong; Xia, Ya Juan; Wu, Ke Gong

    2017-05-01

    The effects of arsenic exposure from drinking water, arsenic metabolism, and arsenic methylation on blood pressure (BP) were observed in this study. The BP and arsenic species of 560 participants were determined. Logistic regression analysis was applied to estimate the odds ratios of BP associated with arsenic metabolites and arsenic methylation capability. BP was positively associated with cumulative arsenic exposure (CAE). Subjects with abnormal diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) usually had higher urinary iAs (inorganic arsenic), MMA (monomethylated arsenic), DMA (dimethylated arsenic), and TAs (total arsenic) than subjects with normal DBP, SBP, and PP. The iAs%, MMA%, and DMA% differed slightly between subjects with abnormal BP and those with normal BP. The PMI and SMI were slightly higher in subjects with abnormal PP than in those with normal PP. Our findings suggest that higher CAE may elevate BP. Males may have a higher risk of abnormal DBP, whereas females have a higher risk of abnormal SBP and PP. Higher urinary iAs may increase the risk of abnormal BP. Lower PMI may elevate the BP. However, higher SMI may increase the DBP and SBP, and lower SMI may elevate the PP. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  14. Arsenic induced clinico-hemato-pathological alterations in broilers and its attenuation by vitamin e and selenium

    International Nuclear Information System (INIS)

    Mashkoor, J.; Khan, A.; Khan, M.Z.; Saleemi, M.K.; Mahmood, F.

    2012-01-01

    Present study was carried out to know the arsenic (As) induced toxico-pathological alterations in broiler chicks and their attenuation with vitamin E (Vit E) and selenium (Se). A total of 90 day-old broiler chicks were equally distributed into 5 groups. Groups 1-4 were administered As at 50 mg/kg BW daily through feed for 30 days. In addition to A , groups 2 to 4 received Vitamin E at 150 mg/kg BW, selenium at 0.25 mg/kg BW and Vitamin E plus selenium, respectively. Group 5 (Control) received normal drinking water for 30 days. Dullness, depression, open mouth breathing, increased thirst; ruffled feathers, pale comb, skin irritation and watery diarrhea were the most striking clinical signs. The body weight and feed intake was significantly decreased in treated birds. The erythrocyte counts, hemoglobin concentration and packed cell volume decreased (P<0.05) in treated broilers with As or As with Se and Vit E. Grossly pale and hemorrhagic liver and swollen kidneys were observed in As treated birds. Arsenic treated groups showed significant decrease in serum. Histopathologically, liver exhibited congestion and cytoplasmic vacuolation. In kidneys, condensation of tubular epithelium nuclei, epithelial cell necrosis, increased urinary spaces, sloughing of tubules from basement membrane and cast deposition were observed. In conclusion As induced toxico-pathological alterations and vitamin E and selenium partially ameliorate the toxic effects in broilers chicks. (author)

  15. Removal of arsenic from potable water by adsorptive media treatment techniques

    International Nuclear Information System (INIS)

    Yousuf, S.; Khan, S.; Aslam, M.T.; Khan, A.R.

    2012-01-01

    Summary: This study was conducted to investigate the arsenic removal efficiency of different adsorptive media from water. Different naturally occurring materials such as bauxite, plastic clay, plaster of Paris, lime, alum, and alumina etc. were used for the development of media to remove arsenic As/sup +5/ present in the artificially contaminated water. Different ratios of the selected materials were combined and ignited at 9000 C to enhance its arsenic removing efficiency. It was found that the media bauxite, plastic clay, lime (1:1:1) has a maximum removal (99%) of As +5 species from aqueous media and can be used on- site to reduce the arsenic contamination of potable water. Furthermore, the materials used in this experiment were cheaply and abundantly available within the country. The method is very simple and economically viable, for removal of arsenic from potable water. (author)

  16. Chronic arsenic poisoning from burning high-arsenic-containing coal in Guizhou, China

    Energy Technology Data Exchange (ETDEWEB)

    Liu, J.; Zheng, B.S.; Aposhian, H.V.; Zhou, Y.S.; Chen, M.L.; Zhang, A.H.; Waalkes, M.P. [NIEHS, Research Triangle Park, NC (USA)

    2002-07-01

    Arsenic is an environmental hazard and the reduction of drinking water arsenic levels is under consideration. People are exposed to arsenic not only through drinking water but also through arsenic-contaminated air and food. Here the health effects of arsenic exposure from burning high arsenic-containing coal in Guizhou, China was investigated. Coal is burned inside the home in open pits for daily cooking and crop drying, producing a high concentration of arsenic in indoor air. Arsenic in the air coats and permeates food being dried producing high concentrations in food; however, arsenic concentrations in the drinking water are in the normal range. The estimated sources of total arsenic exposure in this area are from arsenic-contaminated food (50-80%), air (10-20%), water (1-5%), and direct contact in coal-mining workers (1%). At least 3,000 patients with arsenic poisoning were found in the Southwest Prefecture of Guizhou, and approximately 200,000 people are at risk for such over exposures. Skin lesions are common, including keratosis of the hands and feet, pigmentation on the trunk, skin ulceration, and skin cancers. Toxicities to internal organs, including lung dysfunction, neuropathy, and nephrotoxicity, are clinically evident. The prevalence of hepatomegaly was 20%, and cirrhosis, ascites, and liver cancer are the most serious outcomes of arsenic poisoning. The Chinese government and international organizations are attempting to improve the house conditions and the coal source, and thereby protect human health in this area.

  17. Absorption of foliar-applied arsenic by the arsenic hyperaccumulating fern (Pteris vittata L.)

    Energy Technology Data Exchange (ETDEWEB)

    Bondada, Bhaskar R.; Tu, Shuxin; Ma, Lena Q

    2004-10-01

    The fact that heavy metals can enter various domains of the plant system through foliar pathways spurred us to explore if the fronds of the Chinese brake fern (Pteris vittata L.), a hyperaccumulator of arsenic, a carcinogenic metalloid, was proficient in absorbing arsenic in the form of sprays. The specific objective of this study was to investigate the impact of frond age, form of arsenic, and time of application on the absorption of foliar-applied arsenic by the brake fern; also examined were the effects of foliar sprays on surface ultrastructure and arsenic speciation in the frond following absorption. Foliar sprays of different arsenic concentrations (0, 50, 100, 200, and 400 ppm) were applied to young and fertile fronds. A positive linear relationship existed between arsenic concentration and absorption; the arsenic concentration of fronds increased from 50 to 200 ppm. Time-course analysis with excised pinnae indicated an initial linear increase followed by a plateau at 48 h. The young fronds with immature sori absorbed more arsenic (3100 ppm) than the fertile mature fronds (890 ppm). In the frond, the arsenic absorption was greatest in the lamina of the pinnae followed by the sori and the rachis. Applying arsenic during night (20:00-22:00 h) or afternoon (12:00-14:00 h) resulted in greater absorption of arsenic than the application in the morning (08:00-10:00 h). The arsenic absorption was greater through abaxial surfaces than through adaxial surfaces. The brake fern absorbed more arsenic when it was applied in the form of arsenite. Regardless of the form of arsenic and the surface it was applied to, arsenic occurred as arsenite, the reduced and the most toxic form of arsenic, after having been absorbed by the fronds. Scanning electron microscopy revealed no surface morphological alterations following all arsenic sprays. The study unequivocally illustrated that the Chinese brake fern absorbed foliar-applied arsenic with great efficiency. Consequently, the

  18. Absorption of foliar-applied arsenic by the arsenic hyperaccumulating fern (Pteris vittata L.)

    International Nuclear Information System (INIS)

    Bondada, Bhaskar R.; Tu, Shuxin; Ma, Lena Q.

    2004-01-01

    The fact that heavy metals can enter various domains of the plant system through foliar pathways spurred us to explore if the fronds of the Chinese brake fern (Pteris vittata L.), a hyperaccumulator of arsenic, a carcinogenic metalloid, was proficient in absorbing arsenic in the form of sprays. The specific objective of this study was to investigate the impact of frond age, form of arsenic, and time of application on the absorption of foliar-applied arsenic by the brake fern; also examined were the effects of foliar sprays on surface ultrastructure and arsenic speciation in the frond following absorption. Foliar sprays of different arsenic concentrations (0, 50, 100, 200, and 400 ppm) were applied to young and fertile fronds. A positive linear relationship existed between arsenic concentration and absorption; the arsenic concentration of fronds increased from 50 to 200 ppm. Time-course analysis with excised pinnae indicated an initial linear increase followed by a plateau at 48 h. The young fronds with immature sori absorbed more arsenic (3100 ppm) than the fertile mature fronds (890 ppm). In the frond, the arsenic absorption was greatest in the lamina of the pinnae followed by the sori and the rachis. Applying arsenic during night (20:00-22:00 h) or afternoon (12:00-14:00 h) resulted in greater absorption of arsenic than the application in the morning (08:00-10:00 h). The arsenic absorption was greater through abaxial surfaces than through adaxial surfaces. The brake fern absorbed more arsenic when it was applied in the form of arsenite. Regardless of the form of arsenic and the surface it was applied to, arsenic occurred as arsenite, the reduced and the most toxic form of arsenic, after having been absorbed by the fronds. Scanning electron microscopy revealed no surface morphological alterations following all arsenic sprays. The study unequivocally illustrated that the Chinese brake fern absorbed foliar-applied arsenic with great efficiency. Consequently, the

  19. Arsenic removal by magnetic nanocrystalline barium hexaferrite

    International Nuclear Information System (INIS)

    Patel, Hasmukh A.; Byun, Jeehye; Yavuz, Cafer T.

    2012-01-01

    Nanoscale magnetite (Fe 3 O 4 ) ( 12 O 19 , BHF) is a well-known permanent magnet (i.e., fridge magnets) and attractive due to its low cost in making large quantities. BHF offers a viable alternative to magnetite nanocrystals for arsenic removal since it features surfaces similar to iron oxides but with much enhanced magnetism. Herein, we employ BHF nanocrystalline materials for the first time in arsenic removal from wastewater. Our results show better (75 %) arsenic removal than magnetite of the similar sizes. The BHF nanoparticles, 6.06 ± 0.52 nm synthesized by thermolysis method at 320 °C do not show hexagonal phase, however, subsequent annealing at 750 °C produced pure hexagonal BHF in >200 nm assemblies. By using BHF, we demonstrate that nanoparticle removal is more efficient and fixed bed type cartridge applications are more possible.

  20. Potential application of SERS for arsenic speciation in biological matrices.

    Science.gov (United States)

    Yang, Mingwei; Matulis, Shannon; Boise, Lawrence H; McGoron, Anthony J; Cai, Yong

    2017-08-01

    Speciation of arsenic is usually carried out using chromatography-based methods coupled with spectroscopic determination; however, the inevitable procedures involving sample preparation and separation could potentially alter the integrity of the arsenic metabolites present in biological samples. Surface-enhanced Raman spectroscopy (SERS) could be a promising alternative for providing a reliable arsenic analysis under the influence of a cellular matrix. A method for arsenic speciation using SERS in cellular matrix was developed in this study and four arsenicals were selected, including arsenite (As III ), arsenate (As V ), monomethylarsonic acid (MMA V ) and dimethylarsinic acid (DMA V ). Silver nanoparticles in the form of colliodal suspension with different surface charges, i.e., coated with citrate (AgNPs-Citrate) and spermine (AgNPs-Spermine) were employed as SERS substrates. Adsorption of arsenicals on nanoparticles in colloidal suspensions and the cellular matrix and the pH, size, and zeta potential of the colloidal suspensions were investigated for a better understanding of the SERS signal response of arsenicals in the colloidal suspensions or under the influence of cellular matrix. Arsenicals showed substantially different SERS responses in the two colloidal suspensions, mainly because of the distinct difference in the interaction between the arsenicals and the nanoparticles. Arsenic speciation in cell lysate could be successfully carried out in AgNPs-Spermine suspension, while AgNPs-Citrate could not yield significant SERS signals under the experimental conditions. This study proved that AgNPs-Spermine colloidal suspension could be a promising SERS substrate for studying arsenic metabolism in a biological matrix, reducing the bias caused by traditional techniques that involve sample extraction and pretreatment.

  1. Identification of arsenite-and arsenic diglutathione-binding proteins in human hepatocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Mizumura, Ayano; Watanabe, Takayuki [Graduate School of Pharmaceutical Sciences, Chiba University, Yayoi, Inage, Chiba 263-8522 (Japan); Kobayashi, Yayoi [Graduate School of Pharmaceutical Sciences, Chiba University, Yayoi, Inage, Chiba 263-8522 (Japan); Environmental Health Sciences Division, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506 (Japan); Hirano, Seishiro [Graduate School of Pharmaceutical Sciences, Chiba University, Yayoi, Inage, Chiba 263-8522 (Japan); Research Center for Environmental Risk, National Institute for Environmental Studies, 16-2 Onogawa, Tsukuba, Ibaraki 305-8506 (Japan)

    2010-01-15

    It is generally accepted that trivalent arsenicals are more toxic than the corresponding pentavalent arsenicals, since trivalent arsenicals bind the thiol groups of biomolecules, leading to a deterioration in cellular functions. In the present study, we prepared three different arsenic-bound sepharoses and investigated the binding of hepatic cytosolic proteins to pentavalent, trivalent, and glutathione-conjugated trivalent arsenicals. SDS-PAGE showed no proteins bound to pentavalent arsenic specifically. In contrast, we found a number of proteins that have specific and high affinity for trivalent arsenic. Two of those proteins were identified: protein disulfide isomerase-related protein 5 (PDSIRP5) and peroxiredoxin 1/enhancer protein (PRX1/EP). These proteins have vicinal cysteines, as previously reported. In contrast, one of the prominent proteins that did not bind to trivalent arsenic was identified as calreticulin precursor. Although there are 3 cysteines in calreticulin precursor, two of the cysteines are spaced more than 25 amino acids apart. Five synthetic peptides containing 2 vicinal cysteines were prepared to study whether they would inhibit the binding of PDSIRP5, PRX1/EP, and other arsenic-binding proteins to trivalent arsenicals. Only two of the five peptides effectively inhibited binding, suggesting that other amino acids besides the 2 vicinal cysteines may modulate the affinity of cysteine-rich proteins for trivalent arsenicals. We further investigated hepatic cytosolic proteins that bound specifically to glutathione-conjugated trivalent arsenic, which is the most abundant form of arsenical in bile fluid. Four proteins that bound specifically to glutathione-conjugated trivalent arsenic were identified; interestingly, these proteins were different from the trivalent arsenic-binding proteins. These results suggest that although glutathione-conjugation is an important process in the metabolism, excretion, and detoxification of arsenicals, glutathione

  2. Arsenic induces cell apoptosis in cultured osteoblasts through endoplasmic reticulum stress

    International Nuclear Information System (INIS)

    Tang, C.-H.; Chiu, Y.-C.; Huang, C.-F.; Chen, Y.-W.; Chen, P.-C.

    2009-01-01

    Osteoporosis is characterized by low bone mass resulting from an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts. Therefore, decreased bone formation by osteoblasts may lead to the development of osteoporosis, and rate of apoptosis is responsible for the regulation of bone formation. Arsenic (As) exists ubiquitously in our environment and increases the risk of neurotoxicity, liver injury, peripheral vascular disease and cancer. However, the effect of As on apoptosis of osteoblasts is mostly unknown. Here, we found that As induced cell apoptosis in osteoblastic cell lines (including hFOB, MC3T3-E1 and MG-63) and mouse bone marrow stromal cells (M2-10B4). As also induced upregulation of Bax and Bak, downregulation of Bcl-2 and dysfunction of mitochondria in osteoblasts. As also triggered endoplasmic reticulum (ER) stress, as indicated by changes in cytosolic-calcium levels. We found that As increased the expression and activities of glucose-regulated protein 78 (GRP78) and calpain. Transfection of cells with GRP78 or calpain siRNA reduced As-mediated cell apoptosis in osteoblasts. Therefore, our results suggest that As increased cell apoptosis in cultured osteoblasts and increased the risk of osteoporosis.

  3. Thorium coprecipitation method for spectrophotometric determination of arsenic (III) and arsenic (V) in groundwaters

    International Nuclear Information System (INIS)

    Tamari, Yuzo; Yamamoto, Nobuki; Tsuji, Haruo; Kusaka, Yuzuru

    1989-01-01

    A new coprecipitation method for the spectrophotometry of arsenic (III) and arsenic (V) in groundwater has been developed. Arsenic (III) and arsenic (V) were coprecipitated with thorium (IV) hydroxide from 1000ml of groundwater at pH9. The precipitate was centrifuged and then dissolved with hydrochloric acid. Arsenic (III) was spectrophotometrically determined by the usual silver diethylditiocarbamate (Ag-DDTC) method after generating the arsenic to arsine with sodium tetrahydroborate under masking the thorium with EDTA-NaF at pH6. From another portion of the same groundwater, both arsenic (III) and arsenic (V) were determined by the Ag-DDTC method after reducing all the arsenic to arsine with sodium tetrahydroborate at pH less than 1 in the presence of the EDTA-NaF. The concentration of arsenic (V) was obtained by subtracting that of arsenic (III) from the total for arsenic. (author)

  4. Developing robust arsenic awareness prediction models using machine learning algorithms.

    Science.gov (United States)

    Singh, Sushant K; Taylor, Robert W; Rahman, Mohammad Mahmudur; Pradhan, Biswajeet

    2018-04-01

    crucial role in arsenic awareness and outreach programs. Use of SVM or RF or a combination of the two, together with use of a larger sample size, could enhance the accuracy of arsenic awareness prediction. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Arsenic Removal from Groundwater by Solar Driven Inline-Electrolytic Induced Co-Precipitation and Filtration—A Long Term Field Test Conducted in West Bengal

    Science.gov (United States)

    Malakar, Pradyut; Jana, Bana Bihari; Benz, Florian; Goldmaier, Alexander; Feistel, Ulrike; Jana, Joydev; Lahiri, Susmita; Alvarez, Juan Antonio

    2017-01-01

    Arsenic contamination in drinking water resources is of major concern in the Ganga delta plains of West Bengal in India and Bangladesh. Here, several laboratory and field studies on arsenic removal from drinking water resources were conducted in the past and the application of strong-oxidant-induced co-precipitation of arsenic on iron hydroxides is still considered as the most promising mechanism. This paper suggests an autonomous, solar driven arsenic removal setting and presents the findings of a long term field test conducted in West Bengal. The system applies an inline-electrolytic cell for in situ chlorine production using the natural chloride content of the water and by that substituting the external dosing of strong oxidants. Co-precipitation of As(V) occurs on freshly formed iron hydroxide, which is removed by Manganese Greensand Plus® filtration. The test was conducted for ten months under changing source water conditions considering arsenic (187 ± 45 µg/L), iron (5.5 ± 0.8 mg/L), manganese (1.5 ± 0.4 mg/L), phosphate (2.4 ± 1.3 mg/L) and ammonium (1.4 ± 0.5 mg/L) concentrations. Depending on the system setting removal rates of 94% for arsenic (10 ± 4 µg/L), >99% for iron (0.03 ± 0.03 mg/L), 96% for manganese (0.06 ± 0.05 mg/L), 72% for phosphate (0.7 ± 0.3 mg/L) and 84% for ammonium (0.18 ± 0.12 mg/L) were achieved—without the addition of any chemicals/adsorbents. Loading densities of arsenic on iron hydroxides averaged to 31 µgAs/mgFe. As the test was performed under field conditions and the here proposed removal mechanisms work fully autonomously, it poses a technically feasible treatment alternative, especially for rural areas. PMID:28974053

  6. Arsenic Removal from Groundwater by Solar Driven Inline-Electrolytic Induced Co-Precipitation and Filtration-A Long Term Field Test Conducted in West Bengal.

    Science.gov (United States)

    Otter, Philipp; Malakar, Pradyut; Jana, Bana Bihari; Grischek, Thomas; Benz, Florian; Goldmaier, Alexander; Feistel, Ulrike; Jana, Joydev; Lahiri, Susmita; Alvarez, Juan Antonio

    2017-10-02

    Arsenic contamination in drinking water resources is of major concern in the Ganga delta plains of West Bengal in India and Bangladesh. Here, several laboratory and field studies on arsenic removal from drinking water resources were conducted in the past and the application of strong-oxidant-induced co-precipitation of arsenic on iron hydroxides is still considered as the most promising mechanism. This paper suggests an autonomous, solar driven arsenic removal setting and presents the findings of a long term field test conducted in West Bengal. The system applies an inline-electrolytic cell for in situ chlorine production using the natural chloride content of the water and by that substituting the external dosing of strong oxidants. Co-precipitation of As(V) occurs on freshly formed iron hydroxide, which is removed by Manganese Greensand Plus ® filtration. The test was conducted for ten months under changing source water conditions considering arsenic (187 ± 45 µg/L), iron (5.5 ± 0.8 mg/L), manganese (1.5 ± 0.4 mg/L), phosphate (2.4 ± 1.3 mg/L) and ammonium (1.4 ± 0.5 mg/L) concentrations. Depending on the system setting removal rates of 94% for arsenic (10 ± 4 µg/L), >99% for iron (0.03 ± 0.03 mg/L), 96% for manganese (0.06 ± 0.05 mg/L), 72% for phosphate (0.7 ± 0.3 mg/L) and 84% for ammonium (0.18 ± 0.12 mg/L) were achieved-without the addition of any chemicals/adsorbents. Loading densities of arsenic on iron hydroxides averaged to 31 µgAs/mgFe. As the test was performed under field conditions and the here proposed removal mechanisms work fully autonomously, it poses a technically feasible treatment alternative, especially for rural areas.

  7. Arsenic Removal from Groundwater by Solar Driven Inline-Electrolytic Induced Co-Precipitation and Filtration—A Long Term Field Test Conducted in West Bengal

    Directory of Open Access Journals (Sweden)

    Philipp Otter

    2017-10-01

    Full Text Available Arsenic contamination in drinking water resources is of major concern in the Ganga delta plains of West Bengal in India and Bangladesh. Here, several laboratory and field studies on arsenic removal from drinking water resources were conducted in the past and the application of strong-oxidant-induced co-precipitation of arsenic on iron hydroxides is still considered as the most promising mechanism. This paper suggests an autonomous, solar driven arsenic removal setting and presents the findings of a long term field test conducted in West Bengal. The system applies an inline-electrolytic cell for in situ chlorine production using the natural chloride content of the water and by that substituting the external dosing of strong oxidants. Co-precipitation of As(V occurs on freshly formed iron hydroxide, which is removed by Manganese Greensand Plus® filtration. The test was conducted for ten months under changing source water conditions considering arsenic (187 ± 45 µg/L, iron (5.5 ± 0.8 mg/L, manganese (1.5 ± 0.4 mg/L, phosphate (2.4 ± 1.3 mg/L and ammonium (1.4 ± 0.5 mg/L concentrations. Depending on the system setting removal rates of 94% for arsenic (10 ± 4 µg/L, >99% for iron (0.03 ± 0.03 mg/L, 96% for manganese (0.06 ± 0.05 mg/L, 72% for phosphate (0.7 ± 0.3 mg/L and 84% for ammonium (0.18 ± 0.12 mg/L were achieved—without the addition of any chemicals/adsorbents. Loading densities of arsenic on iron hydroxides averaged to 31 µgAs/mgFe. As the test was performed under field conditions and the here proposed removal mechanisms work fully autonomously, it poses a technically feasible treatment alternative, especially for rural areas.

  8. THE ROLE OF VALENCE AND METHYLATION STATE ON THE ACTIVITY OF ARSENIC DURING MITOSIS

    Science.gov (United States)

    Trivalent methylated arsenicals are much more potent DNA damaging agents, clastogens, and large deletion mutagens than are their inorganic and pentavalent counterparts. Previously we had noticed that many of the arsenicals induced "c-type" anaphases characteristic of spindle pois...

  9. In Vivo and In Vitro Arsenic Exposition Induces Oxidative Stress in Anterior Pituitary Gland.

    Science.gov (United States)

    Ronchetti, Sonia A; Bianchi, María S; Duvilanski, Beatriz H; Cabilla, Jimena P

    2016-07-01

    Inorganic arsenic (iAs) is at the top of toxic metalloids. Inorganic arsenic-contaminated water consumption is one of the greatest environmental health threats worldwide. Human iAs exposure has been associated with cancers of several organs, neurological disorders, and reproductive problems. Nevertheless, there are no reports describing how iAs affects the anterior pituitary gland. The aim of this study was to investigate the mechanisms involved in iAs-mediated anterior pituitary toxicity both in vivo and in vitro. We showed that iAs administration (from 5 to 100 ppm) to male rats through drinking water increased messenger RNA expression of several oxidative stress-responsive genes in the anterior pituitary gland. Serum prolactin levels diminished, whereas luteinizing hormone (LH) levels were only affected at the higher dose tested. In anterior pituitary cells in culture, 25 µmol/L iAs significantly decreased prolactin release in a time-dependent fashion, whereas LH levels remained unaltered. Cell viability was significantly reduced mainly by apoptosis evidenced by morphological and phosphatidylserine externalization studies. This process is characterized by early depolarization of mitochondrial membrane potential and increased levels of reactive oxygen species. Expression of some key oxidative stress-responsive genes, such as heme oxygenase-1 and metallothionein-1, was also stimulated by iAs exposure. The antioxidant N-acetyl cysteine prevented iAs-induced effects on the expression of oxidative stress markers, prolactin release, and apoptosis. In summary, the present work demonstrates for the first time that iAs reduces prolactin release both in vivo and in vitro and induces apoptosis in anterior pituitary cells, possibly resulting from imbalanced cellular redox status. © The Author(s) 2016.

  10. Deficiency in the nuclear factor E2-related factor 2 renders pancreatic β-cells vulnerable to arsenic-induced cell damage

    International Nuclear Information System (INIS)

    Yang, Bei; Fu, Jingqi; Zheng, Hongzhi; Xue, Peng; Yarborough, Kathy; Woods, Courtney G.; Hou, Yongyong; Zhang, Qiang; Andersen, Melvin E.; Pi, Jingbo

    2012-01-01

    Chronic human exposure to inorganic arsenic (iAs), a potent environmental oxidative stressor, is associated with increased prevalence of type 2 diabetes, where impairment of pancreatic β-cell function is a key pathogenic factor. Nuclear factor E2-related factor 2 (Nrf2) is a central transcription factor regulating cellular adaptive response to oxidative stress. However, persistent activation of Nrf2 in response to chronic oxidative stress, including inorganic arsenite (iAs 3+ ) exposure, blunts glucose-triggered reactive oxygen species (ROS) signaling and impairs glucose-stimulated insulin secretion (GSIS). In the current study, we found that MIN6 pancreatic β-cells with stable knockdown of Nrf2 (Nrf2-KD) by lentiviral shRNA and pancreatic islets isolated from Nrf2-knockout (Nrf2−/−) mice exhibited reduced expression of several antioxidant and detoxification enzymes in response to acute iAs 3+ exposure. As a result, Nrf2-KD MIN6 cells and Nrf2−/− islets were more susceptible to iAs 3+ and monomethylarsonous acid (MMA 3+ )-induced cell damage, as measured by decreased cell viability, augmented apoptosis and morphological change. Pretreatment of MIN6 cells with Nrf2 activator tert-butylhydroquinone protected the cells from iAs 3+ -induced cell damage in an Nrf2-dependent fashion. In contrast, antioxidant N‐acetyl cysteine protected Nrf2-KD MIN6 cells against acute cytotoxicity of iAs 3+ . The present study demonstrates that Nrf2-mediated antioxidant response is critical in the pancreatic β-cell defense mechanism against acute cytotoxicity by arsenic. The findings here, combined with our previous results on the inhibitory effect of antioxidants on ROS signaling and GSIS, suggest that Nrf2 plays paradoxical roles in pancreatic β-cell dysfunction induced by environmental arsenic exposure. -- Highlights: ► Lack of Nrf2 reduced expression of antioxidant genes induced by iAs 3+ in β-cells. ► Deficiency of Nrf2 in β-cells sensitized to iAs 3+ and MMA 3

  11. Deficiency in the nuclear factor E2-related factor 2 renders pancreatic β-cells vulnerable to arsenic-induced cell damage

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Bei [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Department of Histology and Embryology, College of Basic Medical Sciences, China Medical University, Shenyang 110001 (China); Fu, Jingqi; Zheng, Hongzhi; Xue, Peng; Yarborough, Kathy; Woods, Courtney G.; Hou, Yongyong; Zhang, Qiang; Andersen, Melvin E. [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States); Pi, Jingbo, E-mail: jpi@thehamner.org [Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC 27709 (United States)

    2012-11-01

    Chronic human exposure to inorganic arsenic (iAs), a potent environmental oxidative stressor, is associated with increased prevalence of type 2 diabetes, where impairment of pancreatic β-cell function is a key pathogenic factor. Nuclear factor E2-related factor 2 (Nrf2) is a central transcription factor regulating cellular adaptive response to oxidative stress. However, persistent activation of Nrf2 in response to chronic oxidative stress, including inorganic arsenite (iAs{sup 3+}) exposure, blunts glucose-triggered reactive oxygen species (ROS) signaling and impairs glucose-stimulated insulin secretion (GSIS). In the current study, we found that MIN6 pancreatic β-cells with stable knockdown of Nrf2 (Nrf2-KD) by lentiviral shRNA and pancreatic islets isolated from Nrf2-knockout (Nrf2−/−) mice exhibited reduced expression of several antioxidant and detoxification enzymes in response to acute iAs{sup 3+} exposure. As a result, Nrf2-KD MIN6 cells and Nrf2−/− islets were more susceptible to iAs{sup 3+} and monomethylarsonous acid (MMA{sup 3+})-induced cell damage, as measured by decreased cell viability, augmented apoptosis and morphological change. Pretreatment of MIN6 cells with Nrf2 activator tert-butylhydroquinone protected the cells from iAs{sup 3+}-induced cell damage in an Nrf2-dependent fashion. In contrast, antioxidant N‐acetyl cysteine protected Nrf2-KD MIN6 cells against acute cytotoxicity of iAs{sup 3+}. The present study demonstrates that Nrf2-mediated antioxidant response is critical in the pancreatic β-cell defense mechanism against acute cytotoxicity by arsenic. The findings here, combined with our previous results on the inhibitory effect of antioxidants on ROS signaling and GSIS, suggest that Nrf2 plays paradoxical roles in pancreatic β-cell dysfunction induced by environmental arsenic exposure. -- Highlights: ► Lack of Nrf2 reduced expression of antioxidant genes induced by iAs{sup 3+} in β-cells. ► Deficiency of Nrf2 in

  12. Biological monitoring of arsenic exposure of gallium arsenide- and inorganic arsenic-exposed workers by determination of inorganic arsenic and its metabolites in urine and hair

    Energy Technology Data Exchange (ETDEWEB)

    Yamauchi, H.; Takahashi, K.; Mashiko, M.; Yamamura, Y. (St. Marianna Univ. School of Medicine, Kawasaki (Japan))

    1989-11-01

    In an attempt to establish a method for biological monitoring of inorganic arsenic exposure, the chemical species of arsenic were measured in the urine and hair of gallium arsenide (GaAs) plant and copper smelter workers. Determination of urinary inorganic arsenic concentration proved sensitive enough to monitor the low-level inorganic arsenic exposure of the GaAs plant workers. The urinary inorganic arsenic concentration in the copper smelter workers was far higher than that of a control group and was associated with high urinary concentrations of the inorganic arsenic metabolites, methylarsonic acid (MAA) and dimethylarsinic acid (DMAA). The results established a method for exposure level-dependent biological monitoring of inorganic arsenic exposure. Low-level exposures could be monitored only by determining urinary inorganic arsenic concentration. High-level exposures clearly produced an increased urinary inorganic arsenic concentration, with an increased sum of urinary concentrations of inorganic arsenic and its metabolites (inorganic arsenic + MAA + DMAA). The determination of urinary arsenobetaine proved to determine specifically the seafood-derived arsenic, allowing this arsenic to be distinguished clearly from the arsenic from occupational exposure. Monitoring arsenic exposure by determining the arsenic in the hair appeared to be of value only when used for environmental monitoring of arsenic contamination rather than for biological monitoring.

  13. Enhanced arsenic removal from water by hierarchically porous CeO₂-ZrO₂ nanospheres: role of surface- and structure-dependent properties.

    Science.gov (United States)

    Xu, Weihong; Wang, Jing; Wang, Lei; Sheng, Guoping; Liu, Jinhuai; Yu, Hanqing; Huang, Xing-Jiu

    2013-09-15

    Arsenic contaminated natural water is commonly used as drinking water source in some districts of Asia. To meet the increasingly strict drinking water standards, exploration of efficient arsenic removal methods is highly desired. In this study, hierarchically porous CeO₂-ZrO₂ nanospheres were synthesized, and their suitability as arsenic sorbents was examined. The CeO₂-ZrO₂ hollow nanospheres showed an adsorption capacity of 27.1 and 9.2 mg g(-1) for As(V) and As(III), respectively, at an equilibrium arsenic concentration of 0.01 mg L(-1) (the standard for drinking water) under neutral conditions, indicating a high arsenic removal performance of the adsorbent at low arsenic concentrations. Such a great arsenic adsorption capacity was attributed to the high surface hydroxyl density and presence of hierarchically porous network in the hollow nanospheres. The analysis of Fourier transformed infrared spectra and X-ray photoelectron spectroscopy demonstrated that the adsorption of arsenic on the CeO₂-ZrO₂ nanospheres was completed through the formation of a surface complex by substituting hydroxyl with arsenic species. In addition, the CeO₂-ZrO₂ nanospheres were able to remove over 97% arsenic in real underground water with initial arsenic concentration of 0.376 mg L(-1) to meet the guideline limit of arsenic in drinking water regulated by the World Health Organization without any pre-treatment and/or pH adjustment. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Factors Affecting Elevated Arsenic and Methyl Mercury Concentrations in Small Shield Lakes Surrounding Gold Mines near the Yellowknife, NT, (Canada Region.

    Directory of Open Access Journals (Sweden)

    Adam James Houben

    Full Text Available Gold mines in the Yellowknife, NT, region--in particular, the Giant Mine--operated from 1949-99, releasing 237,000 tonnes of waste arsenic trioxide (As2O3 dust, among other compounds, from gold ore extraction and roasting processes. For the first time, we show the geospatial distribution of roaster-derived emissions of several chemical species beyond the mine property on otherwise undisturbed taiga shield lakes within a 25 km radius of the mine, 11 years after its closing. Additionally, we demonstrate that underlying bedrock is not a significant source for the elevated concentrations in overlying surface waters. Aquatic arsenic (As concentrations are well above guidelines for drinking water (10 μg/L and protection for aquatic life (5 μg/L, ranging up to 136 μg/L in lakes within 4 km from the mine, to 2.0 μg/L in lakes 24 km away. High conversion ratios of methyl mercury were shown in lakes near the roaster stack as well, with MeHg concentrations reaching 44% of total mercury. The risk of elevated exposures by these metals is significant, as many lakes used for recreation and fishing near the City of Yellowknife are within this radius of elevated As and methyl Hg concentrations.

  15. Arsenic in Food

    Science.gov (United States)

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Food Home Food Foodborne Illness & Contaminants Metals Arsenic Share ... of the Method used to Measure Arsenic in Foods Inductively Coupled Plasma-Mass Spectrometric Determination of Arsenic, ...

  16. Arsenic compromises conducting airway epithelial barrier properties in primary mouse and immortalized human cell cultures.

    Directory of Open Access Journals (Sweden)

    Cara L Sherwood

    Full Text Available Arsenic is a lung toxicant that can lead to respiratory illness through inhalation and ingestion, although the most common exposure is through contaminated drinking water. Lung effects reported from arsenic exposure include lung cancer and obstructive lung disease, as well as reductions in lung function and immune response. As part of their role in innate immune function, airway epithelial cells provide a barrier that protects underlying tissue from inhaled particulates, pathogens, and toxicants frequently found in inspired air. We evaluated the effects of a five-day exposure to environmentally relevant levels of arsenic {<4μM [~300 μg/L (ppb] as NaAsO2} on airway epithelial barrier function and structure. In a primary mouse tracheal epithelial (MTE cell model we found that both micromolar (3.9 μM and submicromolar (0.8 μM arsenic concentrations reduced transepithelial resistance, a measure of barrier function. Immunofluorescent staining of arsenic-treated MTE cells showed altered patterns of localization of the transmembrane tight junction proteins claudin (Cl Cl-1, Cl-4, Cl-7 and occludin at cell-cell contacts when compared with untreated controls. To better quantify arsenic-induced changes in tight junction transmembrane proteins we conducted arsenic exposure experiments with an immortalized human bronchial epithelial cell line (16HBE14o-. We found that arsenic exposure significantly increased the protein expression of Cl-4 and occludin as well as the mRNA levels of Cl-4 and Cl-7 in these cells. Additionally, arsenic exposure resulted in altered phosphorylation of occludin. In summary, exposure to environmentally relevant levels of arsenic can alter both the function and structure of airway epithelial barrier constituents. These changes likely contribute to the observed arsenic-induced loss in basic innate immune defense and increased infection in the airway.

  17. Arsenic Speciation and Extraction and the Significance of Biodegradable Acid on Arsenic Removal—An Approach for Remediation of Arsenic-Contaminated Soil

    Science.gov (United States)

    Nguyen Van, Thinh; Osanai, Yasuhito; Do Nguyen, Hai; Kurosawa, Kiyoshi

    2017-01-01

    A series of arsenic remediation tests were conducted using a washing method with biodegradable organic acids, including oxalic, citric and ascorbic acids. Approximately 80% of the arsenic in one sample was removed under the effect of the ascorbic and oxalic acid combination, which was roughly twice higher than the effectiveness of the ascorbic and citric acid combination under the same conditions. The soils treated using biodegradable acids had low remaining concentrations of arsenic that are primarily contained in the crystalline iron oxides and organic matter fractions. The close correlation between extracted arsenic and extracted iron/aluminum suggested that arsenic was removed via the dissolution of Fe/Al oxides in soils. The fractionation of arsenic in four contaminated soils was investigated using a modified sequential extraction method. Regarding fractionation, we found that most of the soil contained high proportions of arsenic (As) in exchangeable fractions with phosphorus, amorphous oxides, and crystalline iron oxides, while a small amount of the arsenic fraction was organic matter-bound. This study indicated that biodegradable organic acids can be considered as a means for arsenic-contaminated soil remediation.

  18. A Simple Metallothionein-Based Biosensor for Enhanced Detection of Arsenic and Mercury

    Directory of Open Access Journals (Sweden)

    Gordon W. Irvine

    2017-03-01

    Full Text Available Metallothioneins (MTs are a family of cysteine-rich proteins whose biological roles include the regulation of essential metal ions and protection against the harmful effects of toxic metals. Due to its high affinity for many toxic, soft metals, recombinant human MT isoform 1a was incorporated into an electrochemical-based biosensor for the detection of As3+ and Hg2+. A simple design was chosen to maximize its potential in environmental monitoring and MT was physically adsorbed onto paper discs placed on screen-printed carbon electrodes (SPCEs. This system was tested with concentrations of arsenic and mercury typical of contaminated water sources ranging from 5 to 1000 ppb. The analytical performance of the MT-adsorbed paper discs on SPCEs demonstrated a greater than three-fold signal enhancement and a lower detection limit compared to blank SPCEs, 13 ppb for As3+ and 45 ppb for Hg2+. While not being as low as some of the recommended drinking water limits, the sensitivity of the simple MT-biosensor would be potentially useful in monitoring of areas of concern with a known contamination problem. This paper describes the ability of the metal binding protein metallothionein to enhance the effectiveness of a simple, low-cost electrochemical sensor.

  19. The effect of arsenic contamination on amino acids metabolism in Spinacia oleracea L.

    Science.gov (United States)

    Pavlík, Milan; Pavlíková, Daniela; Staszková, Ludmila; Neuberg, Marek; Kaliszová, Regina; Száková, Jirina; Tlustos, Pavel

    2010-09-01

    Changes of amino acid concentrations (proline, glutamate, asparagine, aspartate, alanine) and glutamate kinase activity (GKA) in plants under arsenic chronic stress reported here reveal their role in plant arsenic stress adaptation. Results of the pot experiment confirmed the toxic effect of arsenic at tested levels (As1=25 mg As kg(-1) soil, As2=50 mg As kg(-1) soil, As3=75 mg As kg(-1) soil) for spinach. Growing available arsenic contents in soil were associated with the strong inhibition of above-ground biomass and with the enhancement of As plant content. The changes of glutamate, asparagine, aspartate and proline levels in the plants showed strong linear dependences on arsenic concentration in plants (R2=0.60-0.90). Compared to the untreated control, concentrations of free proline and aspartate of As3 treatment were enhanced up to 381% and 162%, respectively. The significant changes of glutamate were observed on As2 and As3 treatments (increased level up to 188, i.e. 617%). Arsenic in plants was shown to be an inhibitor of glutamase kinase activity (R2=0.91). Inhibition of GKA resulted in an increase in the content of glutamate that is used in synthesis of phytochelatins in plant cells. Concentration of alanine did not have a confirmed linear dependence on arsenic concentration in plant (R2=0.05). The changes of its concentrations could be affected by changes of pH in plant cell or induction of alanine aminotransferase by hypoxia. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  20. Monoblock Obturation Technique for Non-Vital Immature Permanent Maxillary Incisors Using Mineral Trioxide Aggregate: Results from Case Series

    International Nuclear Information System (INIS)

    Iqbal, Z.; Qureshi, A. H.

    2014-01-01

    Ten patients presented with non-vital immature teeth for root canal treatment. In all these cases the pre-operative clinical examination revealed apical periodontitis with a buccal sinus tract of endodontic origin. These cases were treated by a mineral trioxide aggregate (MTA) monoblock obturation technique. Follow-up evaluations were performed at 1 - 2 years after treatment. Eight out of 10 cases were associated with periradicular healing at follow-up evaluation. Mineral trioxide aggregate Monoblock obturation technique appears to be a valid material to obtain periradicular healing in teeth with open apices and necrotic pulps. (author)

  1. Understanding arsenic metabolism through spectroscopic determination of arsenic in human urine

    OpenAIRE

    Brima, Eid I.; Jenkins, Richard O.; Haris, Parvez I.

    2006-01-01

    In this review we discuss a range of spectroscopic techniques that are currently used for analysis of arsenic in human urine for understanding arsenic metabolism and toxicity, especially in relation to genetics/ethnicity, ingestion studies and exposure to arsenic through drinking water and diet. Spectroscopic techniques used for analysis of arsenic in human urine include inductively coupled plasma mass spectrometry (ICP-MS), hydride generation atomic absorption spectrometry (HG-AAS), hydride ...

  2. Chronic Arsenic Toxicity: Statistical Study of the Relationships Between Urinary Arsenic, Selenium and Antimony

    OpenAIRE

    Analía Boemo, BS; Irene María Lomniczi, PhD; Elsa Mónica Farfán Torres, PhD

    2012-01-01

    Background. The groundwater of Argentina’s Chaco plain presents arsenic levels above those suitable for human consumption. Studies suggest skin disorders among local populations caused by arsenic intake. The relationship between urinary arsenic and arsenic in drinking water is well known, but urinary arsenic alone is not enough for risk assessment due to modulating factors such as the intake of selenium and antimony. Objectives. Determining the relationship between urinary arsenic, seleniu...

  3. Seasonal arsenic accumulation in stream sediments at a groundwater discharge zone.

    Science.gov (United States)

    MacKay, Allison A; Gan, Ping; Yu, Ran; Smets, Barth F

    2014-01-21

    Seasonal changes in arsenic and iron accumulation rates were examined in the sediments of a brook that receives groundwater discharges of arsenic and reduced iron. Clean glass bead columns were deployed in sediments for known periods over the annual hydrologic cycle to monitor changes in arsenic and iron concentrations in bead coatings. The highest accumulation rates occurred during the dry summer period (July-October) when groundwater discharges were likely greatest at the sample locations. The intermediate flow period (October-March), with higher surface water levels, was associated with losses of arsenic and iron from bead column coatings at depths below 2-6 cm. Batch incubations indicated iron releases from solids to be induced by biological reduction of iron (oxy)hydroxide solids. Congruent arsenic releases during incubation were limited by the high arsenic sorption capacity (0.536 mg(As)/mg(Fe)) of unreacted iron oxide solids. The flooded spring (March-June) with high surface water flows showed the lowest arsenic and iron accumulation rates in the sediments. Comparisons of accumulation rates across a shoreline transect were consistent with greater rates at regions exposed above surface water levels for longer times and greater losses at locations submerged below surface water. Iron (oxy)hydroxide solids in the shallowest sediments likely serve as a passive barrier to sorb arsenic released to pore water at depth by biological iron reduction.

  4. Plants as useful vectors to reduce environmental toxic arsenic content.

    Science.gov (United States)

    Mirza, Nosheen; Mahmood, Qaisar; Maroof Shah, Mohammad; Pervez, Arshid; Sultan, Sikander

    2014-01-01

    Arsenic (As) toxicity in soil and water is an increasing menace around the globe. Its concentration both in soil and environment is due to natural and anthropogenic activities. Rising arsenic concentrations in groundwater is alarming due to the health risks to plants, animals, and human beings. Anthropogenic As contamination of soil may result from mining, milling, and smelting of copper, lead, zinc sulfide ores, hide tanning waste, dyes, chemical weapons, electroplating, gas exhaust, application of municipal sludge on land, combustion of fossil fuels, As additives to livestock feed, coal fly ash, and use of arsenical pesticides in agricultural sector. Phytoremediation can be viewed as biological, solar-driven, pump-and-treat system with an extensive, self-extending uptake network (the root system) that enhances the natural ecosystems for subsequent productive use. The present review presents recent scientific developments regarding phytoremediation of arsenic contaminated environments and its possible detoxification mechanisms in plants.

  5. Fracture resistance and histological findings of immature teeth treated with mineral trioxide aggregate

    DEFF Research Database (Denmark)

    Hatibovic-Kofman, S.; Raimundo, L.; Zheng, L.

    2008-01-01

    The objective of the present study was to test the hypothesis that the fracture strength of calcium hydroxide and mineral trioxide aggregate (MTA)-filled immature teeth decreased over time. Immature mandibular incisors from sheep were extracted and the pulps were extirpated using an apical approach...

  6. Elevated levels of plasma uric acid and its relation to hypertension in arsenic-endemic human individuals in Bangladesh

    Energy Technology Data Exchange (ETDEWEB)

    Huda, Nazmul [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh); Department of Medicine, Rajshahi Medical College, Rajshahi 6000 (Bangladesh); Hossain, Shakhawoat; Rahman, Mashiur [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh); Karim, Md. Rezaul [Department of Applied Nutrition and Food Technology, Islamic University, Kushtia 7003 (Bangladesh); Islam, Khairul [Department of Biochemistry and Molecular Biology, Mawlana Bhashani Science and Technology University, Santosh, Tangail 1902 (Bangladesh); Mamun, Abdullah Al; Hossain, Md. Imam; Mohanto, Nayan Chandra; Alam, Shahnur; Aktar, Sharmin; Arefin, Afroza; Ali, Nurshad; Salam, Kazi Abdus; Aziz, Abdul; Saud, Zahangir Alam [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh); Miyataka, Hideki; Himeno, Seiichiro [Laboratory of Molecular Nutrition and Toxicology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima 770-8514 (Japan); Hossain, Khaled, E-mail: khossainbio@gmail.com [Department of Biochemistry and Molecular Biology, Rajshahi University, Rajshahi 6205 (Bangladesh)

    2014-11-15

    Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, the association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. This study for the first time demonstrated the associations of arsenic exposure with PUA levels and its relationship with hypertension. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measured by inductively coupled plasma mass spectroscopy. PUA levels were measured using a colorimetric method. We found that PUA levels were significantly (p < 0.001) higher in males and females living in arsenic-endemic areas than those in non-endemic area. Arsenic exposure (water, hair and nail arsenic) levels showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen, and smoking. There were dose–response relationships between arsenic exposure and PUA levels. Furthermore, diastolic and systolic blood pressure showed significant positive correlations with PUA levels. Finally, the average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. These results suggest that arsenic exposure-related elevation of PUA levels may be implicated in arsenic-induced CVDs. - Highlights: • PUA levels were higher in arsenic-endemic subjects than in non-endemic subjects. • Drinking water, hair and nail arsenic showed significant associations with PUA levels. • Drinking water, hair and nail arsenic showed dose–response relationships with

  7. Elevated levels of plasma uric acid and its relation to hypertension in arsenic-endemic human individuals in Bangladesh

    International Nuclear Information System (INIS)

    Huda, Nazmul; Hossain, Shakhawoat; Rahman, Mashiur; Karim, Md. Rezaul; Islam, Khairul; Mamun, Abdullah Al; Hossain, Md. Imam; Mohanto, Nayan Chandra; Alam, Shahnur; Aktar, Sharmin; Arefin, Afroza; Ali, Nurshad; Salam, Kazi Abdus; Aziz, Abdul; Saud, Zahangir Alam; Miyataka, Hideki; Himeno, Seiichiro; Hossain, Khaled

    2014-01-01

    Blood uric acid has been recognized as a putative marker for cardiovascular diseases (CVDs). CVDs are the major causes of arsenic-related morbidity and mortality. However, the association of arsenic exposure with plasma uric acid (PUA) levels in relation to CVDs has not yet been explored. This study for the first time demonstrated the associations of arsenic exposure with PUA levels and its relationship with hypertension. A total of 483 subjects, 322 from arsenic-endemic and 161 from non-endemic areas in Bangladesh were recruited as study subjects. Arsenic concentrations in the drinking water, hair and nails of the study subjects were measured by inductively coupled plasma mass spectroscopy. PUA levels were measured using a colorimetric method. We found that PUA levels were significantly (p < 0.001) higher in males and females living in arsenic-endemic areas than those in non-endemic area. Arsenic exposure (water, hair and nail arsenic) levels showed significant positive correlations with PUA levels. In multiple regression analyses, arsenic exposure levels were found to be the most significant contributors on PUA levels among the other variables that included age, body mass index, blood urea nitrogen, and smoking. There were dose–response relationships between arsenic exposure and PUA levels. Furthermore, diastolic and systolic blood pressure showed significant positive correlations with PUA levels. Finally, the average PUA levels were significantly higher in the hypertensive group than those in the normotensive group in both males and females living in arsenic-endemic areas. These results suggest that arsenic exposure-related elevation of PUA levels may be implicated in arsenic-induced CVDs. - Highlights: • PUA levels were higher in arsenic-endemic subjects than in non-endemic subjects. • Drinking water, hair and nail arsenic showed significant associations with PUA levels. • Drinking water, hair and nail arsenic showed dose–response relationships with

  8. Matrix modification with silver for the electrothermal atomization of arsenic and selenium

    Science.gov (United States)

    Sanzolone, R.F.; Chao, T.T.

    1981-01-01

    Silver as a matrix modifier is shown to improve the carbon-rod atomization of both arsenic and selenium for atomic absorption spectrometry. Compared to nickel, the efficiency of silver is greater for arsenic and about the same for selenium. Silver fulfils two functions in its reaction, namely stabilization during the ashing stage and enhancement of absorbance in the final atomization. ?? 1981.

  9. Approaches to increase arsenic awareness in Bangladesh: an evaluation of an arsenic education program.

    Science.gov (United States)

    George, Christine Marie; Factor-Litvak, Pam; Khan, Khalid; Islam, Tariqul; Singha, Ashit; Moon-Howard, Joyce; van Geen, Alexander; Graziano, Joseph H

    2013-06-01

    The objective of this study was to design and evaluate a household-level arsenic education and well water arsenic testing intervention to increase arsenic awareness in Bangladesh. The authors randomly selected 1,000 study respondents located in 20 villages in Singair, Bangladesh. The main outcome was the change in knowledge of arsenic from baseline to follow-up 4 to 6 months after the household received the intervention. This was assessed through a pre- and postintervention quiz concerning knowledge of arsenic. Respondents were between 18 and 102 years of age, with an average age of 37 years; 99.9% were female. The knowledge of arsenic quiz scores for study participants were significantly higher at follow-up compared with baseline. The intervention was effective in increasing awareness of the safe uses of arsenic-contaminated water and dispelling the misconception that boiling water removes arsenic. At follow-up, nearly all respondents were able to correctly identify the meaning of a red (contaminated) and green (arsenic safe) well relative to arsenic (99%). The educational program also significantly increased the proportion of respondents who were able to correctly identify the health implications of arsenic exposure. However, the intervention was not effective in dispelling the misconceptions in the population that arsenicosis is contagious and that illnesses such as cholera, diarrhea, and vomiting could be caused by arsenic. Further research is needed to develop effective communication strategies to dispel these misconceptions. This study demonstrates that a household-level arsenic educational program can be used to significantly increase arsenic awareness in Bangladesh.

  10. Groundwater Arsenic Contamination in the Ganga River Basin: A Future Health Danger.

    Science.gov (United States)

    Chakraborti, Dipankar; Singh, Sushant K; Rahman, Mohammad Mahmudur; Dutta, Rathindra Nath; Mukherjee, Subhas Chandra; Pati, Shyamapada; Kar, Probir Bijoy

    2018-01-23

    This study highlights the severity of arsenic contamination in the Ganga River basin (GRB), which encompasses significant geographic portions of India, Bangladesh, Nepal, and Tibet. The entire GRB experiences elevated levels of arsenic in the groundwater (up to 4730 µg/L), irrigation water (~1000 µg/L), and in food materials (up to 3947 µg/kg), all exceeding the World Health Organization's standards for drinking water, the United Nations Food and Agricultural Organization's standard for irrigation water (100 µg/L), and the Chinese Ministry of Health's standard for food in South Asia (0.15 mg/kg), respectively. Several individuals demonstrated dermal, neurological, reproductive, cognitive, and cancerous effects; many children have been diagnosed with a range of arsenicosis symptoms, and numerous arsenic-induced deaths of youthful victims are reported in the GRB. Victims of arsenic exposure face critical social challenges in the form of social isolation and hatred by their respective communities. Reluctance to establish arsenic standards and unsustainable arsenic mitigation programs have aggravated the arsenic calamity in the GRB and put millions of lives in danger. This alarming situation resembles a ticking time bomb. We feel that after 29 years of arsenic research in the GRB, we have seen the tip of the iceberg with respect to the actual magnitude of the catastrophe; thus, a reduced arsenic standard for drinking water, testing all available drinking water sources, and sustainable and cost-effective arsenic mitigation programs that include the participation of the people are urgently needed.

  11. Arsenic tolerance in Arabidopsis is mediated by two ABCC-type phytochelatin transporters

    Science.gov (United States)

    Song, Won-Yong; Park, Jiyoung; Mendoza-Cózatl, David G.; Suter-Grotemeyer, Marianne; Shim, Donghwan; Hörtensteiner, Stefan; Geisler, Markus; Weder, Barbara; Rea, Philip A.; Rentsch, Doris; Schroeder, Julian I.; Lee, Youngsook; Martinoia, Enrico

    2010-01-01

    Arsenic is an extremely toxic metalloid causing serious health problems. In Southeast Asia, aquifers providing drinking and agricultural water for tens of millions of people are contaminated with arsenic. To reduce nutritional arsenic intake through the consumption of contaminated plants, identification of the mechanisms for arsenic accumulation and detoxification in plants is a prerequisite. Phytochelatins (PCs) are glutathione-derived peptides that chelate heavy metals and metalloids such as arsenic, thereby functioning as the first step in their detoxification. Plant vacuoles act as final detoxification stores for heavy metals and arsenic. The essential PC–metal(loid) transporters that sequester toxic metal(loid)s in plant vacuoles have long been sought but remain unidentified in plants. Here we show that in the absence of two ABCC-type transporters, AtABCC1 and AtABCC2, Arabidopsis thaliana is extremely sensitive to arsenic and arsenic-based herbicides. Heterologous expression of these ABCC transporters in phytochelatin-producing Saccharomyces cerevisiae enhanced arsenic tolerance and accumulation. Furthermore, membrane vesicles isolated from these yeasts exhibited a pronounced arsenite [As(III)]–PC2 transport activity. Vacuoles isolated from atabcc1 atabcc2 double knockout plants exhibited a very low residual As(III)–PC2 transport activity, and interestingly, less PC was produced in mutant plants when exposed to arsenic. Overexpression of AtPCS1 and AtABCC1 resulted in plants exhibiting increased arsenic tolerance. Our findings demonstrate that AtABCC1 and AtABCC2 are the long-sought and major vacuolar PC transporters. Modulation of vacuolar PC transporters in other plants may allow engineering of plants suited either for phytoremediation or reduced accumulation of arsenic in edible organs. PMID:21078981

  12. Enhanced removal of arsenic from a highly laden industrial effluent using a combined coprecipitation/nano-adsorption process.

    Science.gov (United States)

    Jiang, Yingnan; Hua, Ming; Wu, Bian; Ma, Hongrui; Pan, Bingcai; Zhang, Quanxing

    2014-05-01

    Effective arsenic removal from highly laden industrial wastewater is an important but challenging task. Here, a combined coprecipitation/nano-adsorption process, with ferric chloride and calcium chloride as coprecipitation agents and polymer-based nanocomposite as selective adsorbent, has been validated for arsenic removal from tungsten-smelting wastewater. On the basis of operating optimization, a binary FeCl3 (520 mg/L)-CaCl2 (300 mg/L) coprecipitation agent could remove more than 93% arsenic from the wastewater. The resulting precipitate has proved environmental safety based on leaching toxicity test. Fixed-bed column packed with zirconium or ferric-oxide-loaded nanocomposite was employed for further elimination of arsenic in coprecipitated effluent, resulting in a significant decrease of arsenic (from 0.96 to less than 0.5 mg/L). The working capacity of zirconium-loaded nanocomposite was 220 bed volumes per run, much higher than that of ferric-loaded nanocomposite (40 bed volumes per run). The exhausted zirconium-loaded nanocomposite could be efficiently in situ regenerated with a binary NaOH-NaCl solution for reuse without any significant capacity loss. The results validated the combinational coprecipitation/nano-adsorption process to be a potential alternative for effective arsenic removal from highly laden industrial effluent.

  13. Developmental and genetic modulation of arsenic biotransformation: A gene by environment interaction?

    International Nuclear Information System (INIS)

    Meza, Mercedes; Gandolfi, A. Jay; Klimecki, Walter T.

    2007-01-01

    The complexity of arsenic toxicology has confounded the identification of specific pathways of disease causation. One focal point of arsenic research is aimed at fully characterizing arsenic biotransformation in humans, a process that appears to be quite variable, producing a mixture of several arsenic species with greatly differing toxic potencies. In an effort to characterize genetic determinants of variability in arsenic biotransformation, a genetic association study of 135 subjects in western Sonora, Mexico was performed by testing 23 polymorphic sites in three arsenic biotransformation candidate genes. One gene, arsenic 3 methyltransferase (AS3MT), was strongly associated with the ratio of urinary dimethylarsinic acid to monomethylarsonic acid (D/M) in children (7-11 years) but not in adults (18-79 years). Subsequent analyses revealed that the high D/M values associated with variant AS3MT alleles were primarily due to lower levels of monomethylarsonic acid as percent of total urinary arsenic (%MMA5). In light of several reports of arsenic-induced disease being associated with relatively high %MMA5 levels, these findings raise the possibility that variant AS3MT individuals may suffer less risk from arsenic exposure than non-variant individuals. These analyses also provide evidence that, in this population, regardless of AS3MT variant status, children tend to have lower %MMA5 values than adults, suggesting that the global developmental regulation of arsenic biotransformation may interact with genetic variants in metabolic genes to result in novel genetic effects such as those in this report

  14. Effect of organic matter amendment, arsenic amendment and water management regime on rice grain arsenic species

    International Nuclear Information System (INIS)

    Norton, Gareth J.; Adomako, Eureka E.; Deacon, Claire M.; Carey, Anne-Marie; Price, Adam H.; Meharg, Andrew A.

    2013-01-01

    Arsenic accumulation in rice grain has been identified as a major problem in some regions of Asia. A study was conducted to investigate the effect of increased organic matter in the soil on the release of arsenic into soil pore water and accumulation of arsenic species within rice grain. It was observed that high concentrations of soil arsenic and organic matter caused a reduction in plant growth and delayed flowering time. Total grain arsenic accumulation was higher in the plants grown in high soil arsenic in combination with high organic matter, with an increase in the percentage of organic arsenic species observed. The results indicate that the application of organic matter should be done with caution in paddy soils which have high soil arsenic, as this may lead to an increase in accumulation of arsenic within rice grains. Results also confirm that flooding conditions substantially increase grain arsenic. -- Highlights: ► High soil arsenic and organic matter caused a reduction in plant growth. ► A delayed flowering time was observed in high arsenic and organic matter soil. ► Total grain arsenic increased in high arsenic and organic matter soil. ► Percentage organic arsenic in the grain altered in arsenic and organic matter soil. -- The addition of high amounts of organic matter to soils led to an increase in total rice grain arsenic, as well as alteration in the percentage arsenic species in the rice grains

  15. Effect of chronic intake of arsenic-contaminated water on liver

    International Nuclear Information System (INIS)

    Guha Mazumder, D.N.

    2005-01-01

    The hepatotoxic effect of arsenic when used in therapeutic dose has long been recognized. We described the nature and degree of liver involvement and its pathogenesis due to prolonged drinking of arsenic-contaminated water in West Bengal, India. From hospital-based studies on 248 cases of arsenicosis, hepatomegaly was found in 190 patients (76.6%). Non cirrhotic portal fibrosis was the predominant lesions in 63 out of 69 cases who underwent liver biopsy. The portal fibrosis was characterized by expansion of portal zones with streaky fibrosis, a few of which contained leash of vessels. However, portal hypertension was found in smaller number of cases. A cross-sectional epidemiological study was carried out on 7683 people residing in arsenic-affected districts of West Bengal. Out of these, 3467 and 4216 people consumed water-containing arsenic below and above 0.05 mg/l, respectively. Prevalence of hepatomegaly was significantly higher in arsenic-exposed people (10.2%) compared to controls (2.99%, P < 0.001). The incidence of hepatomegaly was found to have a linear relationship proportionate to increasing exposure of arsenic in drinking water in both sexes (P < 0.001). In an experimental study, BALB/C mice were given water contaminated with arsenic (3.2 mg/l) ad libitum for 15 months, the animals being sacrificed at 3-month intervals. We observed progressive reduction of hepatic glutathione and enzymes of anti-oxidative defense system associated with lipid peroxidation. Liver histology showed fatty infiltration at 12 months and hepatic fibrosis at 15 months. Our studies show that prolong drinking of arsenic-contaminated water is associated with hepatomegaly. Predominant lesion of hepatic fibrosis appears to be caused by arsenic induced oxystress

  16. Barium inhibits arsenic-mediated apoptotic cell death in human squamous cell carcinoma cells.

    Science.gov (United States)

    Yajima, Ichiro; Uemura, Noriyuki; Nizam, Saika; Khalequzzaman, Md; Thang, Nguyen D; Kumasaka, Mayuko Y; Akhand, Anwarul A; Shekhar, Hossain U; Nakajima, Tamie; Kato, Masashi

    2012-06-01

    Our fieldwork showed more than 1 μM (145.1 μg/L) barium in about 3 μM (210.7 μg/L) arsenic-polluted drinking well water (n = 72) in cancer-prone areas in Bangladesh, while the mean concentrations of nine other elements in the water were less than 3 μg/L. The types of cancer include squamous cell carcinomas (SCC). We hypothesized that barium modulates arsenic-mediated biological effects, and we examined the effect of barium (1 μM) on arsenic (3 μM)-mediated apoptotic cell death of human HSC-5 and A431 SCC cells in vitro. Arsenic promoted SCC apoptosis with increased reactive oxygen species (ROS) production and JNK1/2 and caspase-3 activation (apoptotic pathway). In contrast, arsenic also inhibited SCC apoptosis with increased NF-κB activity and X-linked inhibitor of apoptosis protein (XIAP) expression level and decreased JNK activity (antiapoptotic pathway). These results suggest that arsenic bidirectionally promotes apoptotic and antiapoptotic pathways in SCC cells. Interestingly, barium in the presence of arsenic increased NF-κB activity and XIAP expression and decreased JNK activity without affecting ROS production, resulting in the inhibition of the arsenic-mediated apoptotic pathway. Since the anticancer effect of arsenic is mainly dependent on cancer apoptosis, barium-mediated inhibition of arsenic-induced apoptosis may promote progression of SCC in patients in Bangladesh who keep drinking barium and arsenic-polluted water after the development of cancer. Thus, we newly showed that barium in the presence of arsenic might inhibit arsenic-mediated cancer apoptosis with the modulation of the balance between arsenic-mediated promotive and suppressive apoptotic pathways.

  17. Quantification of arsenic in activated carbon using particle induced X-ray emission

    International Nuclear Information System (INIS)

    Yadav, Nirbhay N.; Maheswaran, Saravanamuthu; Shutthanandan, Vaithiyalingam; Thevuthasan, Suntharampillai; Ngo, Huu H.; Vigneswaran, Saravanamuth

    2006-01-01

    To date, the trace elemental analysis of solids with inhomogeneous internal structure has been limited, particularly in the case of adsorbents. High-energy ion beam based particle induced X-ray emission (PIXE) is an ideal analytical tool suitable for simultaneous quantification of trace elements with high accuracy. In this study, PIXE was used to quantify arsenic in the adsorbents, granular activated carbon (GAC) and powder activated carbon (PAC). Pelletized and unmodified GAC and PAC samples were analyzed along with powder samples deposited on thin teflon filters. These sample preparation methods resulted in samples of various thicknesses and densities. PIXE measurements taken from these samples were compared to results from neutron activation analysis (NAA) and atomic absorption spectroscopy (AAS). There is a good agreement between the values from the NAA and pelletized PIXE measurements and some AAS measurements

  18. Drug-induced Inhibition and Trafficking Disruption of ion Channels: Pathogenesis of QT Abnormalities and Drug-induced Fatal Arrhythmias

    Science.gov (United States)

    Cubeddu, Luigi X.

    2016-01-01

    Risk of severe and fatal ventricular arrhythmias, presenting as Torsade de Pointes (TdP), is increased in congenital and acquired forms of long QT syndromes (LQTS). Drug-induced inhibition of K+ currents, IKs, IKr, IK1, and/or Ito, delay repolarization, prolong QT, and increase the risk of TdP. Drug-induced interference with IKr is the most common cause of acquired LQTS/TdP. Multiple drugs bind to KNCH2-hERG-K+ channels affecting IKr, including antiarrythmics, antibiotics, antivirals, azole-antifungals, antimalarials, anticancer, antiemetics, prokinetics, antipsychotics, and antidepressants. Azithromycin has been recently added to this list. In addition to direct channel inhibition, some drugs interfere with the traffic of channels from the endoplasmic reticulum to the cell membrane, decreasing mature channel membrane density; e.g., pentamidine, geldalamicin, arsenic trioxide, digoxin, and probucol. Other drugs, such as ketoconazole, fluoxetine, norfluoxetine, citalopram, escitalopram, donepezil, tamoxifen, endoxifen, atazanavir, and roxitromycin, induce both direct channel inhibition and impaired channel trafficking. Although many drugs prolong the QT interval, TdP is a rare event. The following conditions increase the risk of drug-induced TdP: a) Disease states/electrolyte levels (heart failure, structural cardiac disease, bradycardia, hypokalemia); b) Pharmacogenomic variables (presence of congenital LQTS, subclinical ion-channel mutations, history of or having a relative with history of drug-induced long QT/TdP); c) Pharmacodynamic and kinetic factors (high doses, women, elderly, metabolism inhibitors, combining two or more QT prolonging drugs, drugs that prolong the QT and increase QT dispersion, and drugs with multiple actions on ion channels). Because most of these conditions are preventable, careful evaluation of risk factors and increased knowledge of drug use associated with repolarization abnormalities are strongly recommended. PMID:26926294

  19. Understanding arsenic carcinogenicity by the use of animal models

    International Nuclear Information System (INIS)

    Wanibuchi, Hideki; Salim, Elsayed I.; Kinoshita, Anna; Shen Jun; Wei Min; Morimura, Keiichirou; Yoshida, Kaoru; Kuroda, Koichi; Endo, Ginji; Fukushima, Shoji

    2004-01-01

    Although numerous epidemiological studies have indicated that human arsenic exposure is associated with increased incidences of bladder, liver, skin, and lung cancers, limited attempts have been made to understand mechanisms of carcinogenicity using animal models. Dimethylarsinic acid (DMA), an organic arsenic compound, is a major metabolite of ingested inorganic arsenics in mammals. Recent in vitro studies have proven DMA to be a potent clastogenic agent, capable of inducing DNA damage including double strand breaks and cross-link formation. In our attempts to clarify DMA carcinogenicity, we have recently shown carcinogenic effects of DMA and its related metabolites using various experimental protocols in rats and mice: (1) a multi-organ promotion bioassay in rats; (2) a two-stage promotion bioassay by DMA of rat urinary bladder and liver carcinogenesis; (3) a 2-year carcinogenicity test of DMA in rats; (4) studies on the effects of DMA on lung carcinogenesis in rats; (5) promotion of skin carcinogenesis by DMA in keratin (K6)/ornithine decarboxylase (ODC) transgenic mice; (6) carcinogenicity of DMA in p53(+/-) knockout and Mmh/8-OXOG-DNA glycolase (OGG1) mutant mice; (7) promoting effects of DMA and related organic arsenicals in rat liver; (8) promoting effects of DMA and related organic arsenicals in a rat multi-organ carcinogenesis test; and (9) 2-year carcinogenicity tests of monomethylarsonic acid (MMA) and trimethylarsine oxide (TMAO) in rats. The results revealed that the adverse effects of arsenic occurred either by promoting and initiating carcinogenesis. These data, as covered in the present review, suggest that several mechanisms may be involved in arsenic carcinogenesis

  20. Evaluating Leaf and Canopy Reflectance of Stressed Rice Plants to Monitor Arsenic Contamination

    Directory of Open Access Journals (Sweden)

    Varaprasad Bandaru

    2016-06-01

    Full Text Available Arsenic contamination is a serious problem in rice cultivated soils of many developing countries. Hence, it is critical to monitor and control arsenic uptake in rice plants to avoid adverse effects on human health. This study evaluated the feasibility of using reflectance spectroscopy to monitor arsenic in rice plants. Four arsenic levels were induced in hydroponically grown rice plants with application of 0, 5, 10 and 20 µmol·L−1 sodium arsenate. Reflectance spectra of upper fully expanded leaves were acquired over visible and infrared (NIR wavelengths. Additionally, canopy reflectance for the four arsenic levels was simulated using SAIL (Scattering by Arbitrarily Inclined Leaves model for various soil moisture conditions and leaf area indices (LAI. Further, sensitivity of various vegetative indices (VIs to arsenic levels was assessed. Results suggest that plants accumulate high arsenic amounts causing plant stress and changes in reflectance characteristics. All leaf spectra based VIs related strongly with arsenic with coefficient of determination (r2 greater than 0.6 while at canopy scale, background reflectance and LAI confounded with spectral signals of arsenic affecting the VIs’ performance. Among studied VIs, combined index, transformed chlorophyll absorption reflectance index (TCARI/optimized soil adjusted vegetation index (OSAVI exhibited higher sensitivity to arsenic levels and better resistance to soil backgrounds and LAI followed by red edge based VIs (modified chlorophyll absorption reflectance index (MCARI and TCARI suggesting that these VIs could prove to be valuable aids for monitoring arsenic in rice fields.

  1. Factors Affecting Arsenic Methylation in Arsenic-Exposed Humans: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Shen, Hui; Niu, Qiang; Xu, Mengchuan; Rui, Dongsheng; Xu, Shangzhi; Feng, Gangling; Ding, Yusong; Li, Shugang; Jing, Mingxia

    2016-02-06

    Chronic arsenic exposure is a critical public health issue in many countries. The metabolism of arsenic in vivo is complicated because it can be influenced by many factors. In the present meta-analysis, two researchers independently searched electronic databases, including the Cochrane Library, PubMed, Springer, Embase, and China National Knowledge Infrastructure, to analyze factors influencing arsenic methylation. The concentrations of the following arsenic metabolites increase (piAs), monomethyl arsenic (MMA), dimethyl arsenic (DMA), and total arsenic. Additionally, the percentages of iAs (standard mean difference (SMD): 1.00; 95% confidence interval (CI): 0.60-1.40; p< 0.00001) and MMA (SMD: 0.49; 95% CI: 0.21-0.77; p = 0.0006) also increase, while the percentage of DMA (SMD: -0.57; 95% CI: -0.80--0.31; p< 0.0001), primary methylation index (SMD: -0.57; 95% CI: -0.94--0.20; p = 0.002), and secondary methylation index (SMD: -0.27; 95% CI: -0.46--0.90; p = 0.004) decrease. Smoking, drinking, and older age can reduce arsenic methylation, and arsenic methylation is more efficient in women than in men. The results of this analysis may provide information regarding the role of arsenic oxidative methylation in the arsenic poisoning process.

  2. Association of Environmental Arsenic Exposure, Genetic Polymorphisms of Susceptible Genes, and Skin Cancers in Taiwan

    Directory of Open Access Journals (Sweden)

    Ling-I Hsu

    2015-01-01

    Full Text Available Deficiency in the capability of xenobiotic detoxification and arsenic methylation may be correlated with individual susceptibility to arsenic-related skin cancers. We hypothesized that glutathione S-transferase (GST M1, T1, and P1, reactive oxygen species (ROS related metabolic genes (NQO1, EPHX1, and HO-1, and DNA repair genes (XRCC1, XPD, hOGG1, and ATM together may play a role in arsenic-induced skin carcinogenesis. We conducted a case-control study consisting of 70 pathologically confirmed skin cancer patients and 210 age and gender matched participants with genotyping of 12 selected polymorphisms. The skin cancer risks were estimated by odds ratio (OR and 95% confidence interval (CI using logistic regression. EPHX1 Tyr113His, XPD C156A, and GSTT1 null genotypes were associated with skin cancer risk (OR = 2.99, 95% CI = 1.01–8.83; OR = 2.04, 95% CI = 0.99–4.27; OR = 1.74, 95% CI = 1.00–3.02, resp.. However, none of these polymorphisms showed significant association after considering arsenic exposure status. Individuals carrying three risk polymorphisms of EPHX1 Tyr113His, XPD C156A, and GSTs presented a 400% increased skin cancer risk when compared to those with less than or equal to one polymorphism. In conclusion, GSTs, EPHX1, and XPD are potential genetic factors for arsenic-induced skin cancers. The roles of these genes for arsenic-induced skin carcinogenesis need to be further evaluated.

  3. Environmental Source of Arsenic Exposure

    OpenAIRE

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-01-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a ...

  4. Arsenic activates the expression of 3β-HSD in mouse Leydig cells through repression of histone H3K9 methylation

    International Nuclear Information System (INIS)

    Alamdar, Ambreen; Xi, Guochen; Huang, Qingyu; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2017-01-01

    Arsenic exposure has been associated with male reproductive dysfunction by disrupting steroidogenesis; however, the roles of epigenetic drivers, especially histone methylation in arsenic-induced steroidogenic toxicity remain not well documented. In this study, we investigated the role of histone H3 lysine 9 (H3K9) methylation in steroidogenesis disturbance in mouse Leydig cells (MLTC-1) due to arsenic exposure. Our results indicated that mRNA and protein expression levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) were both significantly up-regulated while the rest of key genes involved in steroidogenesis were down-regulated. Moreover, arsenic exposure significantly decreased the histone H3K9 di- and tri-methylation (H3K9me2/3) levels in MLTC-1 cells. Since H3K9 demethylation leads to gene activation, we further investigated whether the induction of 3β-HSD expression was ascribed to reduced H3K9 methylation. The results showed that H3K9me2/3 demethylase (JMJD2A) inhibitor, quercetin (Que) significantly attenuated the decrease of H3K9me2/3 and increase of 3β-HSD expression induced by arsenic. To further elucidate the mechanism for the activation of 3β-HSD, we determined the histone H3K9 methylation levels in Hsd3b gene promoter, which also showed significant decrease of H3K9me2/3 in the investigated region after arsenic exposure. Considering these results, we conclude that arsenic exposure induced 3β-HSD up-regulation by suppressing H3K9me2/3 status, which is suggested as a compensatory mechanism for steroidogenic disturbance in MLTC-1 cells. - Highlights: • Epigenetic mechanisms of arsenic-induced male reproductive toxicity remain unclear. • Arsenic disturbs the expression of key steroidogenic genes in MLTC-1 cells. • Histone H3K9 di- and tri-methylation was suppressed in arsenic-exposed cells. • Arsenic activates 3β-HSD expression through repression of histone H3K9 methylation.

  5. Arsenic activates the expression of 3β-HSD in mouse Leydig cells through repression of histone H3K9 methylation

    Energy Technology Data Exchange (ETDEWEB)

    Alamdar, Ambreen; Xi, Guochen [Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Huang, Qingyu, E-mail: qyhuang@iue.ac.cn [Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Centre for Epigenetics, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M (Denmark); Tian, Meiping [Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Eqani, Syed Ali Musstjab Akber Shah [Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China); Public Health and Environment Division, Department of Biosciences, COMSAT Institute of Information & Technology, Islamabad (Pakistan); Shen, Heqing, E-mail: hqshen@iue.ac.cn [Key Laboratory of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021 (China)

    2017-07-01

    Arsenic exposure has been associated with male reproductive dysfunction by disrupting steroidogenesis; however, the roles of epigenetic drivers, especially histone methylation in arsenic-induced steroidogenic toxicity remain not well documented. In this study, we investigated the role of histone H3 lysine 9 (H3K9) methylation in steroidogenesis disturbance in mouse Leydig cells (MLTC-1) due to arsenic exposure. Our results indicated that mRNA and protein expression levels of 3β-hydroxysteroid dehydrogenase (3β-HSD) were both significantly up-regulated while the rest of key genes involved in steroidogenesis were down-regulated. Moreover, arsenic exposure significantly decreased the histone H3K9 di- and tri-methylation (H3K9me2/3) levels in MLTC-1 cells. Since H3K9 demethylation leads to gene activation, we further investigated whether the induction of 3β-HSD expression was ascribed to reduced H3K9 methylation. The results showed that H3K9me2/3 demethylase (JMJD2A) inhibitor, quercetin (Que) significantly attenuated the decrease of H3K9me2/3 and increase of 3β-HSD expression induced by arsenic. To further elucidate the mechanism for the activation of 3β-HSD, we determined the histone H3K9 methylation levels in Hsd3b gene promoter, which also showed significant decrease of H3K9me2/3 in the investigated region after arsenic exposure. Considering these results, we conclude that arsenic exposure induced 3β-HSD up-regulation by suppressing H3K9me2/3 status, which is suggested as a compensatory mechanism for steroidogenic disturbance in MLTC-1 cells. - Highlights: • Epigenetic mechanisms of arsenic-induced male reproductive toxicity remain unclear. • Arsenic disturbs the expression of key steroidogenic genes in MLTC-1 cells. • Histone H3K9 di- and tri-methylation was suppressed in arsenic-exposed cells. • Arsenic activates 3β-HSD expression through repression of histone H3K9 methylation.

  6. Arsenic, Cadmium and Lead Exposure and Immunologic Function in Workers in Taiwan.

    Science.gov (United States)

    Wu, Chin-Ching; Sung, Fung-Chang; Chen, Yi-Chun

    2018-04-05

    There has been growing concern over the impact of environmental exposure to heavy metals and other trace elements on immunologic functions. This study investigated men's arsenic (As), cadmium (Cd) and lead (Pb) contents in hair samples and their associations with immunological indicators, including white blood cell (WBC), lymphocyte and monocyte counts, and the immunoglobulin (Ig) levels including IgA, IgG and IgE. We recruited 133 men from one antimony trioxide manufacturing plant, two glass manufacturing plants and two plastics manufacturing plants. The mean concentration of Cd [0.16 (SD = 0.03) ug/g] was lower than means of As [0.86 (SD = 0.16) ug/g] and Pb [0.91 (SD = 0.22) ug/g] in hair samples, exerting no relationship with immunologic functions for Cd. The Spearman's correlation analysis showed a positive relationship between monocyte counts and hair Pb levels, but negative relations between As and IgG and between As and IgE. In conclusion, findings from these industry workers suggest that As levels in hair may have a stronger relation with immunologic function than Cd and PB have. Further research is needed to confirm the negative relationship.

  7. Arsenic, Cadmium and Lead Exposure and Immunologic Function in Workers in Taiwan

    Directory of Open Access Journals (Sweden)

    Chin-Ching Wu

    2018-04-01

    Full Text Available There has been growing concern over the impact of environmental exposure to heavy metals and other trace elements on immunologic functions. This study investigated men’s arsenic (As, cadmium (Cd and lead (Pb contents in hair samples and their associations with immunological indicators, including white blood cell (WBC, lymphocyte and monocyte counts, and the immunoglobulin (Ig levels including IgA, IgG and IgE. We recruited 133 men from one antimony trioxide manufacturing plant, two glass manufacturing plants and two plastics manufacturing plants. The mean concentration of Cd [0.16 (SD = 0.03 ug/g] was lower than means of As [0.86 (SD = 0.16 ug/g] and Pb [0.91 (SD = 0.22 ug/g] in hair samples, exerting no relationship with immunologic functions for Cd. The Spearman’s correlation analysis showed a positive relationship between monocyte counts and hair Pb levels, but negative relations between As and IgG and between As and IgE. In conclusion, findings from these industry workers suggest that As levels in hair may have a stronger relation with immunologic function than Cd and PB have. Further research is needed to confirm the negative relationship.

  8. Plants as Useful Vectors to Reduce Environmental Toxic Arsenic Content

    Directory of Open Access Journals (Sweden)

    Nosheen Mirza

    2014-01-01

    Full Text Available Arsenic (As toxicity in soil and water is an increasing menace around the globe. Its concentration both in soil and environment is due to natural and anthropogenic activities. Rising arsenic concentrations in groundwater is alarming due to the health risks to plants, animals, and human beings. Anthropogenic As contamination of soil may result from mining, milling, and smelting of copper, lead, zinc sulfide ores, hide tanning waste, dyes, chemical weapons, electroplating, gas exhaust, application of municipal sludge on land, combustion of fossil fuels, As additives to livestock feed, coal fly ash, and use of arsenical pesticides in agricultural sector. Phytoremediation can be viewed as biological, solar-driven, pump-and-treat system with an extensive, self-extending uptake network (the root system that enhances the natural ecosystems for subsequent productive use. The present review presents recent scientific developments regarding phytoremediation of arsenic contaminated environments and its possible detoxification mechanisms in plants.

  9. Plants as Useful Vectors to Reduce Environmental Toxic Arsenic Content

    Science.gov (United States)

    Mirza, Nosheen; Mahmood, Qaisar; Maroof Shah, Mohammad; Pervez, Arshid; Sultan, Sikander

    2014-01-01

    Arsenic (As) toxicity in soil and water is an increasing menace around the globe. Its concentration both in soil and environment is due to natural and anthropogenic activities. Rising arsenic concentrations in groundwater is alarming due to the health risks to plants, animals, and human beings. Anthropogenic As contamination of soil may result from mining, milling, and smelting of copper, lead, zinc sulfide ores, hide tanning waste, dyes, chemical weapons, electroplating, gas exhaust, application of municipal sludge on land, combustion of fossil fuels, As additives to livestock feed, coal fly ash, and use of arsenical pesticides in agricultural sector. Phytoremediation can be viewed as biological, solar-driven, pump-and-treat system with an extensive, self-extending uptake network (the root system) that enhances the natural ecosystems for subsequent productive use. The present review presents recent scientific developments regarding phytoremediation of arsenic contaminated environments and its possible detoxification mechanisms in plants. PMID:24526924

  10. Correlation of arsenic exposure through drinking groundwater and urinary arsenic excretion among adults in Pakistan.

    Science.gov (United States)

    Ahmed, Mubashir; Fatmi, Zafar; Ali, Arif

    2014-01-01

    Long-term exposure to arsenic has been associated with manifestation of skin lesions (melanosis/keratosis) and increased risk of internal cancers (lung/bladder). The objective of the study described here was to determine the relationship between exposure of arsenic through drinking groundwater and urinary arsenic excretion among adults > or =15 years of age living in Khairpur district, Pakistan. Total arsenic was determined in drinking groundwater and in spot urine samples of 465 randomly selected individuals through hydride generation-atomic absorption spectrometry. Spearman's rank correlation coefficient was calculated between arsenic in drinking groundwater and arsenic excreted in urine. The median arsenic concentration in drinking water was 2.1 microg/L (range: 0.1-350), and in urine was 28.5 microg/L (range: 0.1-848). Positive correlation was found between total arsenic in drinking water and in urine (r = .52, p arsenic may be used as a biomarker of arsenic exposure through drinking water.

  11. Distribution of arsenic in groundwater in the area of Chalkidiki, Northern Greece

    International Nuclear Information System (INIS)

    Kouras, A.; Katsoyiannis, I.; Voutsa, D.

    2007-01-01

    An integrate study aiming at the occurrence and distribution of arsenic in groundwater in the area of Chalkidiki, Northern Greece has been carried out. Groundwater samples from public water supply wells and private wells were analysed for arsenic and other quality parameters (T, pH, EC, Ca, Mg, Na, K, Cl, HCO 3 , NO 3 , SO 4 , B, Fe, Mn). Arsenic showed high spatial variation; ranged from 0.001 to 1.840 mg/L. Almost 65% of the examined groundwaters exhibit arsenic concentrations higher than the maximum concentration limit of 0.010 mg/L, proposed for water intended for human consumption. Correlation analysis and principal component analysis were employed to find out possible relationships among the examined parameters and groundwater samples. Arsenic is highly correlated with potassium, boron, bicarbonate, sodium, manganese and iron suggesting common geogenic origin of these elements and conditions that enhance their mobility. Three groups of groundwater with different physicochemical characteristics were found in the study area: (a) groundwater with extremely high arsenic concentrations (1.6-1.9 mg/L) and high temperature (33-42 deg. C) from geothermal wells, (b) groundwater with relatively high arsenic concentrations (>0.050 mg/L), lower temperatures and relatively high concentrations of major ions, iron and manganese and, (c) groundwater with low arsenic concentrations that fulfil the proposed limits for dinking water

  12. Groundwater Arsenic Contamination in the Ganga River Basin: A Future Health Danger

    Science.gov (United States)

    Chakraborti, Dipankar; Rahman, Mohammad Mahmudur; Dutta, Rathindra Nath; Mukherjee, Subhas Chandra; Pati, Shyamapada; Kar, Probir Bijoy

    2018-01-01

    This study highlights the severity of arsenic contamination in the Ganga River basin (GRB), which encompasses significant geographic portions of India, Bangladesh, Nepal, and Tibet. The entire GRB experiences elevated levels of arsenic in the groundwater (up to 4730 µg/L), irrigation water (~1000 µg/L), and in food materials (up to 3947 µg/kg), all exceeding the World Health Organization’s standards for drinking water, the United Nations Food and Agricultural Organization’s standard for irrigation water (100 µg/L), and the Chinese Ministry of Health’s standard for food in South Asia (0.15 mg/kg), respectively. Several individuals demonstrated dermal, neurological, reproductive, cognitive, and cancerous effects; many children have been diagnosed with a range of arsenicosis symptoms, and numerous arsenic-induced deaths of youthful victims are reported in the GRB. Victims of arsenic exposure face critical social challenges in the form of social isolation and hatred by their respective communities. Reluctance to establish arsenic standards and unsustainable arsenic mitigation programs have aggravated the arsenic calamity in the GRB and put millions of lives in danger. This alarming situation resembles a ticking time bomb. We feel that after 29 years of arsenic research in the GRB, we have seen the tip of the iceberg with respect to the actual magnitude of the catastrophe; thus, a reduced arsenic standard for drinking water, testing all available drinking water sources, and sustainable and cost-effective arsenic mitigation programs that include the participation of the people are urgently needed. PMID:29360747

  13. Groundwater Arsenic Contamination in the Ganga River Basin: A Future Health Danger

    Directory of Open Access Journals (Sweden)

    Dipankar Chakraborti

    2018-01-01

    Full Text Available This study highlights the severity of arsenic contamination in the Ganga River basin (GRB, which encompasses significant geographic portions of India, Bangladesh, Nepal, and Tibet. The entire GRB experiences elevated levels of arsenic in the groundwater (up to 4730 µg/L, irrigation water (~1000 µg/L, and in food materials (up to 3947 µg/kg, all exceeding the World Health Organization’s standards for drinking water, the United Nations Food and Agricultural Organization’s standard for irrigation water (100 µg/L, and the Chinese Ministry of Health’s standard for food in South Asia (0.15 mg/kg, respectively. Several individuals demonstrated dermal, neurological, reproductive, cognitive, and cancerous effects; many children have been diagnosed with a range of arsenicosis symptoms, and numerous arsenic-induced deaths of youthful victims are reported in the GRB. Victims of arsenic exposure face critical social challenges in the form of social isolation and hatred by their respective communities. Reluctance to establish arsenic standards and unsustainable arsenic mitigation programs have aggravated the arsenic calamity in the GRB and put millions of lives in danger. This alarming situation resembles a ticking time bomb. We feel that after 29 years of arsenic research in the GRB, we have seen the tip of the iceberg with respect to the actual magnitude of the catastrophe; thus, a reduced arsenic standard for drinking water, testing all available drinking water sources, and sustainable and cost-effective arsenic mitigation programs that include the participation of the people are urgently needed.

  14. Arsenic activation analysis of freshwater fish through the precipitation of elemental arsenic

    International Nuclear Information System (INIS)

    Comparetto, G.M.; Jester, W.A.; Skinner, W.F.

    1982-01-01

    The activation analysis of trace elements of arsenic in biological samples is complicated by the interference of a 82 Br photo peak (554KeV) and the compton continuum with the major 76 As photo peak of 559 KeV. In addition, the half-lives of 24 Na, 82 Br, and 76 As are too similar to be resolved by varying irradiation and/or decay times. Thus post irradiation chemical separation of arsenic is often required. A study of existing radiochemistry techniques reported in the literature found that existing methods were complex x and/or lengthy. In this work, a more rapid and less extensive method was required to analyze a large number of fish samples exposed to fly ash sluice water from coalburning power plant. A method has been developed which involves the dissolution of irradiated homogenized fish samples, the addition of an arsenic carrier, and the reduction of arsenic to the +3 state. Arsenic is then precipitated as elemental arsenic. An important factor in this work was the discovery that this procedure produced arsenic yields of 81+-3% for both the fish samples and the NBC Orchard leaves standard employed in this analysis. Thus the determination of absolute arsenic yields is not required. This method has been used to analyze 32 of the fish samples the average arsenic content of which was found to vary between 0.08 and 4.8 ppm. (author)

  15. Role of microRNAs in senescence and its contribution to peripheral neuropathy in the arsenic exposed population of West Bengal, India.

    Science.gov (United States)

    Chatterjee, Debmita; Bandyopadhyay, Apurba; Sarma, Nilendu; Basu, Santanu; Roychowdhury, Tarit; Roy, Sib Sankar; Giri, Ashok K

    2018-02-01

    Arsenic induced senescence (AIS) has been identified in the population of West Bengal, India very recently. Also there is a high incidence of arsenic induced peripheral neuropathy (PN) throughout India. However, the epigenetic regulation of AIS and its contribution in arsenic induced PN remains unexplored. We recruited seventy two arsenic exposed and forty unexposed individuals from West Bengal to evaluate the role of senescence associated miRNAs (SA-miRs) in AIS and their involvement if any, in PN. The downstream molecules of the miRNA associated with the disease outcome, was also checked by immuoblotting. In vitro studies were conducted with HEK 293 cells and sodium arsenite exposure. Our results show that all the SA-miRs were upregulated in comparison to unexposed controls. miR-29a was the most significantly altered, highest expression being in the arsenic exposed group with PN, suggesting its association with the occurrence of PN. We looked for the expression of peripheral myelin protein 22 (PMP22), a specific target of miR-29a associated with myelination and found that both in vitro and in vivo results showed over-expression of the protein. Since this was quite contrary to miRNA regulation, we checked for intermediate players β-catenin and GSK-3β upon arsenic exposure which affects PMP22 expression. We found that β-catenin was upregulated in vitro and was also highest in the arsenic exposed group with PN while GSK-3β followed the reverse pattern. Our findings suggest that arsenic exposure alters the expression of SA-miRs and the mir-29a/beta catenin/PMP22 axis might be responsible for arsenic induced PN. Copyright © 2017. Published by Elsevier Ltd.

  16. Arsenic waste management: a critical review of testing and disposal of arsenic-bearing solid wastes generated during arsenic removal from drinking water.

    Science.gov (United States)

    Clancy, Tara M; Hayes, Kim F; Raskin, Lutgarde

    2013-10-01

    Water treatment technologies for arsenic removal from groundwater have been extensively studied due to widespread arsenic contamination of drinking water sources. Central to the successful application of arsenic water treatment systems is the consideration of appropriate disposal methods for arsenic-bearing wastes generated during treatment. However, specific recommendations for arsenic waste disposal are often lacking or mentioned as an area for future research and the proper disposal and stabilization of arsenic-bearing waste remains a barrier to the successful implementation of arsenic removal technologies. This review summarizes current disposal options for arsenic-bearing wastes, including landfilling, stabilization, cow dung mixing, passive aeration, pond disposal, and soil disposal. The findings from studies that simulate these disposal conditions are included and compared to results from shorter, regulatory tests. In many instances, short-term leaching tests do not adequately address the range of conditions encountered in disposal environments. Future research directions are highlighted and include establishing regulatory test conditions that align with actual disposal conditions and evaluating nonlandfill disposal options for developing countries.

  17. Arsenic and skin cancer – Case report with chemoprevention

    Directory of Open Access Journals (Sweden)

    Uwe Wollina

    2016-04-01

    Full Text Available ABSTRACT Introduction: Arsenic is a potentially hazardous metalloid that can cause skin cancer. We want to demonstrate a case of chronic arsenicosis and the potential of chemoprevention with retinoids. Case Report: This is a case report of a 72-year-old male patient who was exposed to arsenics by dust and direct skin contact over 3 years in a chemical plant in the late fourties. He developed multiple arsenic keratosis clincialll resembling actinic keratoses, Bowen’s disease and palmar minute keratoses. To prevent a transformation into invasive cancer and to lower the burden of precancerous and in situ cancer lesions, he was treated orally with acitretin 20 mg/day. During 9 months of chemopreventive retinoid therapy a partial response of pre-existent skin lesions was noted. Treatment was well tolerated. During follow-up of 5 years no invasive malignancy developed. Conclusions: Intense exposure to arsenics during a relatively short period of 3 years bears a life-long health hazard with the delayed development of multiple in situ carcinomas and precancerous lesions. Chemoprevention with retinoids can induce a partial response.

  18. Arsenic accumulation by two brake ferns growing on an arsenic mine and their potential in phytoremediation.

    Science.gov (United States)

    Wei, Chao-Yang; Chen, Tong-Bin

    2006-05-01

    In an area near an arsenic mine in Hunan Province of south China, soils were often found with elevated arsenic levels. A field survey was conducted to determine arsenic accumulation in 8 Cretan brake ferns (Pteris cretica) and 16 Chinese brake ferns (Pteris vittata) growing on these soils. Three factors were evaluated: arsenic concentration in above ground parts (fronds), arsenic bioaccumulation factor (BF; ratio of arsenic in fronds to soil) and arsenic translocation factor (TF; ratio of arsenic in fronds to roots). Arsenic concentrations in the fronds of Chinese brake fern were 3-704 mg kg-1, the BFs were 0.06-7.43 and the TFs were 0.17-3.98, while those in Cretan brake fern were 149-694 mg kg-1, 1.34-6.62 and 1.00-2.61, respectively. Our survey showed that both ferns were capable of arsenic accumulation under field conditions. With most of the arsenic being accumulated in the fronds, these ferns have potential for use in phytoremediation of arsenic contaminated soils.

  19. An evaluation of arsenic release from monolithic solids using a modified semi-dynamic leaching test

    International Nuclear Information System (INIS)

    Dermatas, Dimitris; Moon, Deok Hyun; Menounou, Nektaria; Meng, Xiaoguang; Hires, Richard

    2004-01-01

    Quicklime and quicklime-fly ash-based stabilization/solidification (S/S) effectiveness was evaluated by performing semi-dynamic leaching tests (American Nuclear Society 16.1). Artificial soil samples, contaminated with arsenic trioxide (As 2 O 3 ) as well as field soil samples contaminated with arsenic (As) were tested. The artificial soils were prepared by mixing amounts of kaolinite or montmorillonite with fine quartz sand. The S/S effectiveness was evaluated by measuring effective diffusion coefficients (D e ) and leachability indices (LX). Treatment was most effective in kaolinite-based artificial soils treated with quicklime and in quicklime-fly ash treated field soils. The experimental results indicate that D e values were lowered as a result of S/S treatment. Upon treatment LX values were higher than 9, suggesting that S/S treated soils are acceptable for 'controlled utilization'. Based on a model developed by de Groot and van der Sloot [G.J. de Groot, H.A. van der Sloot, in: T.M. Gilliam, C.C. Wiles (Eds.), Stabilization and Solidification of Hazardous, Radioactive, and Mixed Wastes, vol. 2, ASTM STP 1123, ASTM, PA, 1992, p. 149], the leaching mechanism for all of the treated soils was found to be controlled by diffusion. The effect of soluble silica (Si) on As leachability was also evaluated. When soluble Si concentration was less than 1 ppm, As leachability was the lowest. The controlling mechanism of As immobilization whether sorption, precipitation, or inclusion was also evaluated. It was determined that precipitation was the dominant mechanism

  20. Arsenic Methyltransferase

    Science.gov (United States)

    The metalloid arsenic enters the environment by natural processes (volcanic activity, weathering of rocks) and by human activity (mining, smelting, herbicides and pesticides). Although arsenic has been exploited for homicidal and suicidal purposes since antiquity, its significan...

  1. Importance of ERK activation in As2O3-induced differentiation and promyelocytic leukemia nuclear bodies formation in neuroblastoma cells.

    Science.gov (United States)

    Petit, A; Delaune, A; Falluel-Morel, A; Goullé, J-P; Vannier, J-P; Dubus, I; Vasse, M

    2013-11-01

    Neuroblastoma malignant cell growth is dependent on their undifferentiated status. Arsenic trioxide (As2O3) induces neuroblastoma cell differentiation in vitro, but its mechanisms still remains unknown. We used three human neuroblastoma cell lines (SH-SY5Y, IGR-N-91, LAN-1) that differ from their MYCN and p53 status to explore the intracellular events activated by As2O3 and involved in neurite outgrowth, a morphological marker of differentiation. As2O3 (2μM) induced neurite outgrowth in all cell lines, which was dependent on ERK activation but independent on MYCN status. This process was induced either by a sustained (3 days) or a transient (2h) incubation with As2O3, indicating that very early events trigger the induction of differentiation. In parallel, As2O3 induced a rapid assembly of promyelocytic leukemia nuclear bodies (PML-NB) in an ERK-dependent manner. In conclusion, mechanisms leading to neuroblastoma cell differentiation in response to As2O3 appear to involve the ERK pathway activation and PML-NB formation, which are observed in response to other differentiating molecules such as retinoic acid derivates. This open new perspectives based on the use of treatment combinations to potentiate the differentiating effects of each drug alone and reduce their adverse side effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Large-Batch Reduction of Molybdenum Trioxide

    Energy Technology Data Exchange (ETDEWEB)

    Kiggans, Jr, James O. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Lowden, Richard Andrew [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Menchhofer, Paul A. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Nunn, Stephen D. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Bryan, Chris [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

    2015-12-01

    Unconverted, isotopically-enriched molybdenum metal must be recovered from the spent radiopharmaceutical solution used in NorthStar’s Technetium-99m generator and reused. The recycle process begins by recovering the metal from the aqueous potassium molybdate (K2MoO4) solutions as molybdenum trioxide (MoO3) employing a process developed at Argonne National Laboratory. The MoO3 powder is subsequently reduced to molybdenum metal powder which can be blended with new powder and further processed into a flowable form to be used to produce target disks for irradiation. The molybdenum oxide reduction process has been examined and scaled to produce kilogram quantities of metal powder suitable for processing into a useable form employing spray drying or similar technique and ultimately used for target fabrication.

  3. Reaction Mechanism and Distribution Behavior of Arsenic in the Bottom Blown Copper Smelting Process

    Directory of Open Access Journals (Sweden)

    Qinmeng Wang

    2017-08-01

    Full Text Available The control of arsenic, a toxic and carcinogenic element, is an important issue for all copper smelters. In this work, the reaction mechanism and distribution behavior of arsenic in the bottom blown copper smelting process (SKS process were investigated and compared to the flash smelting process. There are obvious differences of arsenic distribution in the SKS process and flash process, resulting from the differences of oxygen potentials, volatilizations, smelting temperatures, reaction intensities, and mass transfer processes. Under stable production conditions, the distributions of arsenic among matte, slag, and gas phases are 6%, 12%, and 82%, respectively. Less arsenic is reported in the gas phase with the flash process than with the SKS process. The main arsenic species in gas phase are AsS (g, AsO (g, and As2 (g. Arsenic exists in the slag predominantly as As2O3 (l, and in matte as As (l. High matte grade is harmful to the elimination of arsenic to gas. The changing of Fe/SiO2 has slight effects on the distributions of arsenic. In order to enhance the removal of arsenic from the SKS smelting system to the gas phase, low oxygen concentration, low ratios of oxygen/ore, and low matte grade should be chosen. In the SKS smelting process, no dust is recycled, and almost all dust is collected and further treated to eliminate arsenic and recover valuable metals by other process streams.

  4. Disruption of canonical TGFβ-signaling in murine coronary progenitor cells by low level arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Allison, Patrick; Huang, Tianfang; Broka, Derrick; Parker, Patti [Department of Pharmacology and Toxicology College of Pharmacy, Southwest Environmental Health Sciences Center, Steele Children' s Research Center and Bio5 Institute, University of Arizona, Tucson, AZ 85721 (United States); Barnett, Joey V. [Department of Pharmacology, Vanderbilt Medical University, Nashville, TN (United States); Camenisch, Todd D., E-mail: camenisch@pharmacy.arizona.edu [Department of Pharmacology and Toxicology College of Pharmacy, Southwest Environmental Health Sciences Center, Steele Children' s Research Center and Bio5 Institute, University of Arizona, Tucson, AZ 85721 (United States)

    2013-10-01

    Exposure to arsenic results in several types of cancers as well as heart disease. A major contributor to ischemic heart pathologies is coronary artery disease, however the influences by environmental arsenic in this disease process are not known. Similarly, the impact of toxicants on blood vessel formation and function during development has not been studied. During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types including smooth muscle cells which contribute to the coronary vessels. The TGFβ family of ligands and receptors is essential for developmental cardiac epithelial to mesenchymal transition (EMT) and differentiation into coronary smooth muscle cells. In this in vitro study, 18 hour exposure to 1.34 μM arsenite disrupted developmental EMT programming in murine epicardial cells causing a deficit in cardiac mesenchyme. The expression of EMT genes including TGFβ2, TGFβ receptor-3, Snail, and Has-2 are decreased in a dose-dependent manner following exposure to arsenite. TGFβ2 cell signaling is abrogated as detected by decreases in phosphorylated Smad2/3 when cells are exposed to 1.34 μM arsenite. There is also loss of nuclear accumulation pSmad due to arsenite exposure. These observations coincide with a decrease in vimentin positive mesenchymal cells invading three-dimensional collagen gels. However, arsenite does not block TGFβ2 mediated smooth muscle cell differentiation by epicardial cells. Overall these results show that arsenic exposure blocks developmental EMT gene programming in murine coronary progenitor cells by disrupting TGFβ2 signals and Smad activation, and that smooth muscle cell differentiation is refractory to this arsenic toxicity. - Highlights: • Arsenic blocks TGFβ2 induced expression of EMT genes. • Arsenic blocks TGFβ2 triggered Smad2/3 phosphorylation and nuclear translocation. • Arsenic blocks epicardial cell differentiation into cardiac mesenchyme.

  5. A review of the epidemiologic literature on the role of environmental arsenic exposure and cardiovascular diseases

    International Nuclear Information System (INIS)

    Wang, C.-H.; Hsiao, C.K.; Chen, C.-L.; Hsu, L.-I; Chiou, H.-Y.; Chen, S.-Y.; Hsueh, Y.-M.; Wu, M.-M.; Chen, C.-J.

    2007-01-01

    Cardiovascular disease is the leading cause of mortality worldwide. Arsenic is a ubiquitous metalloid in the crust of the earth. Chronic arsenic poisoning is becoming an emerging epidemic in Asia. Epidemiological studies have shown that chronic arsenic poisoning through ingestion of arsenic-contaminated water is associated with various cardiovascular diseases in dose-response relationships. These cardiovascular disorders include carotid atherosclerosis detected by ultrasonography, impaired microcirculation, prolonged QT interval and increased QT dispersion in electrocardiography, and clinical outcomes such as hypertension, blackfoot disease (a unique peripheral vascular disease endemic in southwestern Taiwan), coronary artery disease and cerebral infarction. Chronic arsenic poisoning is an independent risk factor for cardiovascular disease. The adverse cardiovascular effects of long-term arsenic exposure may be persistent and/or irreversible. Arsenic-induced cardiovascular diseases in human population may result from the interaction among genetic, environment and nutritional factors. The major adverse cardiovascular effect of chronic arsenic poisoning has been established qualitatively and quantitatively in the high arsenic exposure areas, but the low-dose effect of arsenic on cardiovascular diseases remains to be explored. Cardiovascular death is the major cause of mortality worldwide, and a small increased risk may imply a large quantity of excess mortality

  6. The Arsenic crisis in Bangladesh (Invited)

    Science.gov (United States)

    Harvey, C.; Ashfaque, K.; Neumann, R. B.; Badruzzaman, B.; Ali, A.

    2010-12-01

    The Ganges Delta suffers from water-borne disease. Arsenic in the groundwater pumped from drinking water wells is causing severe and widespread disease, and these wells were installed, in part, to avoid pathogens in the surface water supply. I will discuss the hydrogeologic controls of arsenic concentrations in groundwater, specifically the role of enhanced groundwater circulation driven by irrigation pumping and the effects of the solute loads transported into aquifers with recharge through different surface features, such as rice fields, rivers, and ponds. I will contrast the approaches taken in Southeast Asia for studying groundwater contamination with methods used in the U.S. I will compare findings from several sites in the region and consider how improved models of the coupled hydrologic and biogeochemical system can be used to provide safer water.

  7. Arsenic contamination of groundwater and its induced health effects in Shahpur block, Bhojpur district, Bihar state, India: risk evaluation.

    Science.gov (United States)

    Chakraborti, Dipankar; Rahman, Mohammad Mahmudur; Ahamed, Sad; Dutta, Rathindra Nath; Pati, Shyamapada; Mukherjee, Subhash Chandra

    2016-05-01

    The objective of this study was to determine the magnitude of groundwater arsenic contamination in Shahpur block of Bhojpur district, Bihar state, India and its health effects such as dermal, neurological, obstetric effects, and cancer risk. The School of Environmental Studies (SOES) collected 4704 tube-well water samples from all 88 villages of Shahpur, which were analyzed for arsenic. We found 40.3 and 21.1 % of the tube-wells had arsenic above 10 and 50 μg/l, respectively, with maximum concentration of 1805 μg/l. The study shows that 75,000, 39,000, and 10,000 people could be exposed to arsenic-contaminated water greater than 10, 50, and 300 μg/l, respectively. Our medical team examined 1422 villagers from Shahpur and registered 161 (prevalence rate, 11.3 %) with arsenical skin lesions. Arsenical skin lesions were also observed in 29 children of 525 screened. We analyzed 579 biological samples (hair, nail, and urine) from Shahpur and found that 82, 89, and 91 % of hair, nail, and urine, respectively, had arsenic above the normal levels, indicating many people in the study area are sub-clinically affected. Arsenical neuropathy was observed in 48 % of 102 arsenicosis patients. The study also found that arsenic exposed women with severe skin lesions had adversely affected their pregnancies. The carcinogenic and non-carcinogenic risks were also estimated based on the generated data. Safe drinking water supply is urgently required to combat arsenic situation in affected villages of Shahpur.

  8. Alterations in apoptotic caspases and antioxidant enzymes in arsenic exposed rat brain regions: reversal effect of essential metals and a chelating agent.

    Science.gov (United States)

    Kadeyala, Praveen Kumar; Sannadi, Saritha; Gottipolu, Rajarami Reddy

    2013-11-01

    Arsenic (As) widely studied for its effects as a neurotoxicant. The present study was designed to evaluate the protective effect of calcium, zinc or monoisoamyl dimercaptosuccinic acid (MiADMSA), either individually or in combination on As induced oxidative stress and apoptosis in brain regions (cerebral cortex, hippocampus and cerebellum) of postnatal day (PND) 21, 28 and 3 months old rats. Arsenic exposure significantly decreased the activities of superoxide dismutase (SOD) isoforms, catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) with increase in glutathione s transferase (GST) while lipid peroxidation (LPx), arsenic levels, mRNA expression of caspase 3 and 9 were significantly increased in different brain regions. Arsenic induced alterations in these parameters were greater in PND 28 and more pronounced in cerebral cortex. From the results it is evident that combined supplementation of calcium and zinc along with MiADMSA would be most effective compared to individual administration in reducing arsenic induced neurotoxicity. Copyright © 2013. Published by Elsevier B.V.

  9. Environmental source of arsenic exposure.

    Science.gov (United States)

    Chung, Jin-Yong; Yu, Seung-Do; Hong, Young-Seoub

    2014-09-01

    Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made.

  10. Environmental Source of Arsenic Exposure

    Directory of Open Access Journals (Sweden)

    Jin-Yong Chung

    2014-09-01

    Full Text Available Arsenic is a ubiquitous, naturally occurring metalloid that may be a significant risk factor for cancer after exposure to contaminated drinking water, cigarettes, foods, industry, occupational environment, and air. Among the various routes of arsenic exposure, drinking water is the largest source of arsenic poisoning worldwide. Arsenic exposure from ingested foods usually comes from food crops grown in arsenic-contaminated soil and/or irrigated with arsenic-contaminated water. According to a recent World Health Organization report, arsenic from contaminated water can be quickly and easily absorbed and depending on its metabolic form, may adversely affect human health. Recently, the US Food and Drug Administration regulations for metals found in cosmetics to protect consumers against contaminations deemed deleterious to health; some cosmetics were found to contain a variety of chemicals including heavy metals, which are sometimes used as preservatives. Moreover, developing countries tend to have a growing number of industrial factories that unfortunately, harm the environment, especially in cities where industrial and vehicle emissions, as well as household activities, cause serious air pollution. Air is also an important source of arsenic exposure in areas with industrial activity. The presence of arsenic in airborne particulate matter is considered a risk for certain diseases. Taken together, various potential pathways of arsenic exposure seem to affect humans adversely, and future efforts to reduce arsenic exposure caused by environmental factors should be made.

  11. Inactivation of p15INK4b in chronic arsenic poisoning cases

    Directory of Open Access Journals (Sweden)

    Aihua Zhang

    2014-01-01

    Full Text Available Arsenic exposure from burning high arsenic-containing coal has been associated with human skin lesion and cancer. However, the mechanisms of arsenic-related carcinogenesis are not fully understood. Inactivation of critical tumor suppression genes by epigenetic regulation or genetic modification might contribute to arsenic-induced carcinogenicity. This study aims to clarify the correlation between arsenic pollution and functional defect of p15INK4b gene in arsenic exposure residents from a region of Guizhou Province, China. To this end, 103 arsenic exposure residents and 105 control subjects were recruited in this study. The results showed that the exposure group exhibited higher levels of urinary and hair arsenic compared with the control group (55.28 vs 28.87 μg/L, 5.16 vs 1.36 μg/g. Subjects with higher arsenic concentrations are more likely to have p15INK4b methylation and gene deletion (χ2 = 4.28, P = 0.04 and χ2 = 4.31, P = 0.04. We also found that the degree of p15INK4b hypermethylation and gene deletion occurred at higher incidence in the poisoning cases with skin cancer (3.7% and 14.81% in non-skin cancer group, 41.18% and 47.06 in skin cancer group, and were significantly associated with the stage of skin lesions (χ2 = 12.82, P < 0.01 and χ2 = 7.835, P = 0.005. These observations indicate that inactivation of p15INK4b through genetic alteration or epigenetic modification is a common event that is associated with arsenic exposure and the development of arsenicosis.

  12. Urinary arsenic profile affects the risk of urothelial carcinoma even at low arsenic exposure

    International Nuclear Information System (INIS)

    Pu, Y.-S.; Yang, S.-M.; Huang, Y.-K.; Chung, C.-J.; Huang, Steven K.; Chiu, Allen Wen-Hsiang; Yang, M.-H.; Chen, C.-J.; Hsueh, Y.-M.

    2007-01-01

    Arsenic exposure is associated with an increased risk of urothelial carcinoma (UC). To explore the association between individual risk and urinary arsenic profile in subjects without evident exposure, 177 UC cases and 313 age-matched controls were recruited between September 2002 and May 2004 for a case-control study. Urinary arsenic species including the following three categories, inorganic arsenic (As III + As V ), monomethylarsonic acid (MMA V ) and dimethylarsinic acid (DMA V ), were determined with high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Arsenic methylation profile was assessed by percentages of various arsenic species in the sum of the three categories measured. The primary methylation index (PMI) was defined as the ratio between MMA V and inorganic arsenic. Secondary methylation index (SMI) was determined as the ratio between DMA V and MMA V . Smoking is associated with a significant risk of UC in a dose-dependent manner. After multivariate adjustment, UC cases had a significantly higher sum of all the urinary species measured, higher percent MMA V , lower percent DMA V , higher PMI and lower SMI values compared with controls. Smoking interacts with the urinary arsenic profile in modifying the UC risk. Differential carcinogenic effects of the urinary arsenic profile, however, were seen more prominently in non-smokers than in smokers, suggesting that smoking is not the only major environmental source of arsenic contamination since the UC risk differs in non-smokers. Subjects who have an unfavorable urinary arsenic profile have an increased UC risk even at low exposure levels

  13. Epigenetic mediated transcriptional activation of WNT5A participates in arsenical-associated malignant transformation

    International Nuclear Information System (INIS)

    Jensen, Taylor J.; Wozniak, Ryan J.; Eblin, Kylee E.; Wnek, Sean M.; Gandolfi, A. Jay; Futscher, Bernard W.

    2009-01-01

    Arsenic is a human carcinogen with exposure associated with cancer of the lung, skin, and bladder. Many potential mechanisms have been implicated as playing a role in the process of arsenical-induced malignancy including the perturbation of signaling pathways and aberrant epigenetic regulation. We initiated studies to examine the role of a member of the non-canonical WNT signaling pathway, WNT5A, in UROtsa cells and arsenite [URO-ASSC] and monomethylarsonous acid [URO-MSC] malignantly transformed variants. We present data herein that suggest that WNT5A is transcriptionally activated during arsenical-induced malignant transformation. This WNT5A transcriptional activation is correlated with the enrichment of permissive histone modifications and the reduction of repressive modifications in the WNT5A promoter region. The epigenetic activation of WNT5A expression and acetylation of its promoter remain after the removal of the arsenical, consistent with the maintenance of an anchorage independent growth phenotype in these cells. Additionally, treatment with epigenetic modifying drugs supports a functional role for these epigenetic marks in controlling gene expression. Reduction of WNT5A using lentiviral shRNA greatly attenuated the ability of these cells to grow in an anchorage independent fashion. Extension of our model into human bladder cancer cell lines indicates that each of the cell lines examined also express WNT5A. Taken together, these data suggest that the epigenetic remodeling of the WNT5A promoter is correlated with its transcriptional activation and this upregulation likely participates in arsenical-induced malignant transformation

  14. Combination of Mineral Trioxide Aggregate and Platelet-rich Fibrin Promotes the Odontoblastic Differentiation and Mineralization of Human Dental Pulp Cells via BMP/Smad Signaling Pathway.

    Science.gov (United States)

    Woo, Su-Mi; Kim, Won-Jae; Lim, Hae-Soon; Choi, Nam-Ki; Kim, Sun-Hun; Kim, Seon-Mi; Jung, Ji-Yeon

    2016-01-01

    Recent reports have shown that the combined use of platelet-rich fibrin (PRF), an autologous fibrin matrix, and mineral trioxide aggregate (MTA) as root filling material is beneficial for the endodontic management of an open apex. However, the potential of the combination of MTA and PRF as an odontogenic inducer in human dental pulp cells (HDPCs) in vitro has not yet been studied. The purpose of this study was to evaluate the effect of the combination of MTA and PRF on odontoblastic maturation in HDPCs. HDPCs extracted from third molars were directly cultured with MTA and PRF extract (PRFe). Odontoblastic differentiation of HDPCs was evaluated by measuring the alkaline phosphatase (ALP) activity, and the expression of odontogenesis-related genes was detected using reverse-transcription polymerase chain reaction or Western blot. Mineralization formation was assessed by alizarin red staining. HDPCs treated with MTA and PRFe significantly up-regulated the expression of dentin sialoprotein and dentin matrix protein-1 and enhanced ALP activity and mineralization compared with those with MTA or PRFe treatment alone. In addition, the combination of MTA and PRFe induced the activation of bone morphogenic proteins (BMP)/Smad, whereas LDN193189, the bone morphogenic protein inhibitor, attenuated dentin sialophosphoprotein and dentin matrix protein-1 expression, ALP activity, and mineralization enhanced by MTA and PRFe treatment. This study shows that the combination of MTA and PRF has a synergistic effect on the stimulation of odontoblastic differentiation of HDPCs via the modulation of the BMP/Smad signaling pathway. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  15. Arsenic in the human food chain, biotransformation and toxicology--Review focusing on seafood arsenic.

    Science.gov (United States)

    Molin, Marianne; Ulven, Stine Marie; Meltzer, Helle Margrete; Alexander, Jan

    2015-01-01

    Fish and seafood are main contributors of arsenic (As) in the diet. The dominating arsenical is the organoarsenical arsenobetaine (AB), found particularly in finfish. Algae, blue mussels and other filter feeders contain less AB, but more arsenosugars and relatively more inorganic arsenic (iAs), whereas fatty fish contain more arsenolipids. Other compounds present in smaller amounts in seafood include trimethylarsine oxide (TMAO), trimethylarsoniopropionate (TMAP), dimethylarsenate (DMA), methylarsenate (MA) and sulfur-containing arsenicals. The toxic and carcinogenic arsenical iAs is biotransformed in humans and excreted in urine as the carcinogens dimethylarsinate (DMA) and methylarsonate (MA), producing reactive intermediates in the process. Less is known about the biotransformation of organoarsenicals, but new insight indicates that bioconversion of arsenosugars and arsenolipids in seafood results in urinary excretion of DMA, possibly also producing reactive trivalent arsenic intermediates. Recent findings also indicate that the pre-systematic metabolism by colon microbiota play an important role for human metabolism of arsenicals. Processing of seafood may also result in transformation of arsenicals. Copyright © 2015 Elsevier GmbH. All rights reserved.

  16. ARSENIC SPECIATION ANALYSIS IN HUMAN SALIVA

    Science.gov (United States)

    Background: Determination of arsenic species in human saliva is potentially useful for biomonitoring of human exposure to arsenic and for studying arsenic metabolism. However, there is no report on the speciation analysis of arsenic in saliva. Methods: Arsenic species in saliva ...

  17. The effect of nanocrystalline magnetite size on arsenic removal

    Directory of Open Access Journals (Sweden)

    J.T. Mayo et al

    2007-01-01

    Full Text Available Higher environmental standards have made the removal of arsenic from water an important problem for environmental engineering. Iron oxide is a particularly interesting sorbent to consider for this application. Its magnetic properties allow relatively routine dispersal and recovery of the adsorbent into and from groundwater or industrial processing facilities; in addition, iron oxide has strong and specific interactions with both As(III and As(V. Finally, this material can be produced with nanoscale dimensions, which enhance both its capacity and removal. The objective of this study is to evaluate the potential arsenic adsorption by nanoscale iron oxides, specifically magnetite (Fe3O4 nanoparticles. We focus on the effect of Fe3O4 particle size on the adsorption and desorption behavior of As(III and As(V. The results show that the nanoparticle size has a dramatic effect on the adsorption and desorption of arsenic. As particle size is decreased from 300 to 12 nm the adsorption capacities for both As(III and As(V increase nearly 200 times. Interestingly, such an increase is more than expected from simple considerations of surface area and suggests that nanoscale iron oxide materials sorb arsenic through different means than bulk systems. The desorption process, however, exhibits some hysteresis with the effect becoming more pronounced with small nanoparticles. This hysteresis most likely results from a higher arsenic affinity for Fe3O4 nanoparticles. This work suggests that Fe3O4 nanocrystals and magnetic separations offer a promising method for arsenic removal.

  18. Arsenic speciation in Chinese Herbal Medicines and human health implication for inorganic arsenic

    International Nuclear Information System (INIS)

    Liu Xiaojuan; Zhao Quanli; Sun Guoxin; Williams, Paul; Lu Xiujun; Cai Jingzhu; Liu Wenju

    2013-01-01

    Rice and drinking water are recognized as the dominant sources of arsenic (As) for human intake, while little is known about As accumulation and speciation in Chinese Herbal Medicines (CHMs), which have been available for many hundreds of years for the treatment of diseases in both eastern and western cultures. Inorganic arsenic was the predominant species in all of CHMs samples. The levels of inorganic arsenic in CHMs from fields and markets or pharmacies ranged from 63 to 550 ng/g with a mean of 208 ng/g and 94 to 8683 ng/g with a mean of 1092 ng/g, respectively. The highest concentration was found in the Chrysanthemum from pharmacies. It indicates that the risk of inorganic As in CHMs to human health is higher in medicines from markets or pharmacies than that collected directly from fields. Some CHMs may make a considerable contribution to the human intake of inorganic arsenic. - Highlights: ► Arsenic speciation was extracted using 1% HNO 3 in microwave. ► Inorganic arsenic was the predominant species in all of CHMs samples. ► The highest concentration of inorganic arsenic was found in the Chrysanthemum. - Inorganic arsenic was the predominant species in all of CHMs samples.

  19. Quantitative damage depth profiles in arsenic implanted HgCdTe

    Energy Technology Data Exchange (ETDEWEB)

    Lobre, C., E-mail: clement.lobre@cea.fr [CEA-Leti, MINATEC, 17 rue des Martyrs, 38054 Grenoble cedex 9 (France); Jalabert, D. [CEA-INAC/UJF-Grenoble 1 UMR-E, MINATEC, 17 rue des Martyrs, 38054 Grenoble cedex 9 (France); Vickridge, I.; Briand, E.; Benzeggouta, D. [Institut des NanoSciences de Paris, UMR 7588 du CNRS, Universite de Pierre et Marie Curie, Paris (France); Mollard, L. [CEA-Leti, MINATEC, 17 rue des Martyrs, 38054 Grenoble cedex 9 (France); Jouneau, P.H. [CEA-INAC/UJF-Grenoble 1 UMR-E, MINATEC, 17 rue des Martyrs, 38054 Grenoble cedex 9 (France); Ballet, P. [CEA-Leti, MINATEC, 17 rue des Martyrs, 38054 Grenoble cedex 9 (France)

    2013-10-15

    Rutherford backscattering experiments under channeling conditions (RBS-c) have been carried out on Hg{sub 0.77}Cd{sub 0.23}Te (MCT) layers implanted with arsenic. Accurate damage profiles have been extracted through a simple formalism for implanted and annealed layers. Quantitative damage profiles are correlated with structural defects observed by bright-field scanning transmission electron microscopy (BF-STEM) and chemical composition measured by secondary ion mass spectrometry (SIMS). Evolution of damage for increasing ion implantation fluence has been investigated by these three complementary techniques. Evidence is found of irradiation induced annealing during implantation. A fast damage recovery has been observed for post-implantation thermal anneals. In the case of an implanted layer annealed during 1 h, the damage profile, associated with arsenic concentration measurements, indicates the presence of complexes involving arsenic.

  20. Quantitative damage depth profiles in arsenic implanted HgCdTe

    International Nuclear Information System (INIS)

    Lobre, C.; Jalabert, D.; Vickridge, I.; Briand, E.; Benzeggouta, D.; Mollard, L.; Jouneau, P.H.; Ballet, P.

    2013-01-01

    Rutherford backscattering experiments under channeling conditions (RBS-c) have been carried out on Hg 0.77 Cd 0.23 Te (MCT) layers implanted with arsenic. Accurate damage profiles have been extracted through a simple formalism for implanted and annealed layers. Quantitative damage profiles are correlated with structural defects observed by bright-field scanning transmission electron microscopy (BF-STEM) and chemical composition measured by secondary ion mass spectrometry (SIMS). Evolution of damage for increasing ion implantation fluence has been investigated by these three complementary techniques. Evidence is found of irradiation induced annealing during implantation. A fast damage recovery has been observed for post-implantation thermal anneals. In the case of an implanted layer annealed during 1 h, the damage profile, associated with arsenic concentration measurements, indicates the presence of complexes involving arsenic

  1. Arsenic adsorption of lateritic soil, limestone powder, lime and fly ash on arsenic-contaminated soil

    Directory of Open Access Journals (Sweden)

    Wuthiphun, L.

    2007-05-01

    Full Text Available Arsenic adsorption efficiency of soil covering materials (lateritic soil, limestone powder, lime and fly ash on arsenic-contaminated soil obtained from Ronpiboon District, Nakhon Sri Thammarat Province tosolve arsenic air pollution problem was investigated using batch experiments. The four types of the aforementioned soil covering materials were examined to determine their arsenic adsorption efficiency, equilibriumtime as well as adsorption isotherms.The results revealed that among soil covering materials mixed with arsenic-contaminated soil at 10% w/w, the efficiency of arsenic adsorption of fly ash, lateritic soil, lime and limestone powder were 84, 60,38 and 1% respectively. The equilibrium time for lateritic soil at pH 4 was achieved within 4 hrs, whereas pH 7 and 12, the equilibrium time was 6 hrs. For fly ash, 2 hrs were required to reach the equilibrium at pH 12, while the equilibrium time was attained within 6 hrs at pH 4 and 7. Furthermore, lateritic soil possessedhigh arsenic adsorption efficiency at pH 7 and 4 and best fit with the Langmuir isotherm. The fly ash showing high arsenic adsorption efficiency at pH 12 and 7 fit the Freundlich isotherm at pH 12 and Langmuirisotherm at pH 7.This indicated that lateritic soil was suitable for arsenic adsorption at low pH, whilst at high pH,arsenic was well adsorbed by fly ash. The Freundlich and Langmuir isotherm could be used to determine quantities of soil covering materials for arsenic adsorption to prevent arsenic air pollution from arseniccontaminated soils.

  2. Arsenic and Fluoride Mobilization Mechanism in Groundwater of Indus Delta and Thar Desert, Sindh, Pakistan

    Directory of Open Access Journals (Sweden)

    VIQAR HUSAIN

    2012-06-01

    Full Text Available Indus deltaic plain consists of medium to fine grained sediments, rich in organic matter deposited during the Holocene period. Thar desert is covered with sand dunes and loess originated from transported sediments from Rann of Kutch or the Indus plain by monsoon winds or by the reworking of local alluvial deposits. Groundwater salinity and microbial pollution are common in both types of lanforms, but arsenic (AS and fluoride (F toxicity dominate in the groundwater of Indus delta and Thar desert, respectively. Arsenic concentration in Tando Mohammad Khan and Tando Allayar varies from 10-500 ppb and exhibits near neutral slightly alkaline pH ranging from 6.8 to 8.0. Arsenic distribution is patchy and seems to be related to the prsence of small scale redox zonation in the aquifer. High arsenic affected areas are densely populated and intensively cultivated and its hot spots are those from where the Indus river passed during the Holocene period including Tando Allayar and Tando Mohammad Khan. Extensive ground water irrigation has accelerated flow of groundwater that brought dissolved degraded organic matter in contact with arsenic bearing sediments, enhancing reduction processes and triggering release of arsenic from detrital bioitite and muscovite in the groundwater. Furthermore, unlined sanitation and microbial contamination contribute to degradation of organic matter that enhances the reduction of iron oxy-hydroxide leading to release of arsenic to groundwater. Fluoride is found in all the groundwater samples of Tharparkar district, in the range of 0.96-2.74mg/l. The pH of groundwater is alkaline (7.38-8.59, which is accelerating maximum (1.24%F dissolution in the groundwater. The favourable pH of groundwater and soil composition of Holocene sediments of Indus delta and slightly older alluvium of Thar desert, respectively are responsible for mobilization of arsenic and fluoride in groundwater of Sindh province of Pakistan.

  3. [Study on the variation of arsenic concentration in groundwater and chemical characteristics of arsenic in sediment cores at the areas with endemic arsenic poison disease in Jianghan Plain].

    Science.gov (United States)

    Zhou, Suhua; Ye, Hengpeng; Li, Mingjian; Xiong, Peisheng; Du, Dongyun; Wang, Jingwen

    2015-06-01

    To understand the variation of arsenic concentration in underground water at the endemic arsenic poison disease area of Jianghan Plain so as to better understand the spatial distribution of high arsenic groundwater, hydro-chemical evolution and source of arsenic in this region. Thirty underground water samples were collected respectively around 3 km radius of the two houses where arsenic poisoning patients lived, in Xiantao and Honghu. Sediment cores of three drillings were collected as well. Both paired t-test or paired Wilcoxon Signed Ranking Test were used to compare the arsenic concentration of water. The arsenic concentration in 2011-2012 appeared lower than that in 2006-2007 at the Nanhong village of Xiantao (t = 4.645 3, P arsenic concentration and Cl, HCO3(-), Fe, Mn. However, negative correlations were found between As and SO4(2-), NO3(-). The range of arsenic content in the sediment was 1.500 mg/kg to 17.289 mg/kg. The maximum arsenic content existed in the soil layer, while the minimum arsenic content existed in the sand layer. The concentration of arsenic varied widely with time and space at endemic arsenic poison disease area of Jianghan Plain. Characteristics of these water chemicals showed significant differences, when compared to the groundwater from Datong Basin, Shanxi Shanyin and Hetao Plain of Inner Mongolia, which presented a typical environment with high arsenic contents in the groundwater. The arsenic content in the sediment samples seemed related to the lithologic structure.

  4. Environmental biochemistry of arsenic

    Energy Technology Data Exchange (ETDEWEB)

    Tamaki, S.; Frankenberger, W.T. Jr. (Department of Soil and Environmental Sciences, University of California, Riverside (United States))

    1992-01-01

    Microorganisms are involved in the redistribution and global cycling of arsenic. Arsenic can accumulate and can be subject to various biotransformations including reduction, oxidation, and methylation. Bacterial methylation of inorganic arsenic is coupled to the methane biosynthetic pathway in methanogenic bacteria under anaerobic conditions and may be a mechanism for arsenic detoxification. The pathway proceeds by reduction of arsenate to arsenite followed by methylation to dimethylarsine. Fungi are also able to transform inorganic and organic arsenic compounds into volatile methylarsines. The pathway proceeds aerobically by arsenate reduction to arsenite followed by several methylation steps producing trimethylarsine. Volatile arsine gases are very toxic to mammals because they destroy red blood cells (LD50 in rats; 3.0 mg kg-1). Further studies are needed on dimethylarsine and trimethylarsine toxicity tests through inhalation of target animals. Marine algae transform arsenate into non-volatile methylated arsenic compounds (methanearsonic and dimethylarsinic acids) in seawater. This is considered to be a beneficial step not only to the primary producers, but also to the higher trophic levels, since non-volatile methylated arsenic is much less toxic to marine invertebrates. Freshwater algae like marine algae synthesize lipid-soluble arsenic compounds and do not produce volatile methylarsines. Aquatic plants also synthesize similar lipid-soluble arsenic compounds. In terrestrial plants, arsenate is preferentially taken up 3 to 4 times the rate of arsenite. In the presence of phosphate, arsenate uptake is inhibited while in the presence of arsenate, phosphate uptake is only slightly inhibited. There is a competitive interaction between arsenate and phosphate for the same uptake system in terrestrial plants.

  5. Electroadsorption-assisted direct determination of trace arsenic without interference using transmission X-ray fluorescence spectroscopy.

    Science.gov (United States)

    Jiang, Tian-Jia; Guo, Zheng; Liu, Jin-Huai; Huang, Xing-Jiu

    2015-08-18

    An analytical technique based on electroadsorption and transmission X-ray fluorescence (XRF) for the quantitative determination of arsenic in aqueous solution with ppb-level limits of detection (LOD) is proposed. The approach uses electroadsorption to enhance the sensitivity and LOD of the arsenic XRF response. Amine-functionalized carbonaceous microspheres (NH2-CMSs) are found to be the ideal materials for both the quantitative adsorption of arsenic and XRF analysis due to the basic amine sites on the surface and their noninterference in the XRF spectrum. In electroadsorptive X-ray fluorescence (EA-XRF), arsenic is preconcentrated by a conventional three-electrode system with a positive electricity field around the adsorbents. Then, the quantification of arsenic on the adsorbents is achieved using XRF. The electroadsorption preconcentration can realize the fast transfer of arsenic from the solution to the adsorbents and improve the LOD of conventional XRF compared with directly determining arsenic solution by XRF alone. The sensitivity of 0.09 cnt ppb(-1) is obtained without the interferences from coexisted metal ions in the determination of arsenic, and the LOD is found to be 7 ppb, which is lower than the arsenic guideline value of 10 ppb given by the World Health Organization (WHO). These results demonstrated that XRF coupled with electroadsorption was able to determine trace arsenic in real water sample.

  6. Background species effect on aqueous arsenic removal by nano zero-valent iron using fractional factorial design.

    Science.gov (United States)

    Tanboonchuy, Visanu; Grisdanurak, Nurak; Liao, Chih-Hsiang

    2012-02-29

    This study describes the removal of arsenic species in groundwater by nano zero-valent iron process, including As(III) and As(V). Since the background species may inhibit or promote arsenic removal. The influence of several common ions such as phosphate (PO4(3-)), bicarbonate (HCO3-)), sulfate (SO4(2-)), calcium (Ca2+), chloride (Cl-), and humic acid (HA) were selected to evaluate their effects on arsenic removal. In particular, a 2(6-2) fractional factorial design (FFD) was employed to identify major or interacting factors, which affect arsenic removal in a significant way. As a result of FFD evaluation, PO4(3-) and HA play the role of inhibiting arsenic removal, while Ca2+ was observed to play the promoting one. As for HCO3- and Cl-, the former one inhibits As(III) removal, whereas the later one enhances its removal; on the other hand, As(V) removal was affected only slightly in the presence of HCO3- or Cl-. Hence, it was suggested that the arsenic removal by the nanoiron process can be improved through pretreatment of PO4(3-) and HA. In addition, for the groundwater with high hardness, the nanoiron process can be an advantageous option because of enhancing characteristics of Ca2+. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Electrical properties of tungsten trioxide films

    International Nuclear Information System (INIS)

    Xu, Z.; Vetelino, J.F.; Lec, R.; Parker, D.C.

    1990-01-01

    Selectively doped semiconducting metal oxide (SMO) films have been shown to have applications as the sensing element in gas microsensors. Critical to the design and operation of these sensors is the SMO film. In the present work, the electrical properties of both intrinsic and extrinsic (doped with gold) tungsten trioxide (WO 3 ) films, which selectively sorb hydrogen sulfide (H 2 S), are investigated. Hall effect measurements are performed as a function of film thickness, temperature, gold-doping concentration, and H 2 S gas concentration. The conductivity was found to be n type and strongly dependent on temperature, gold doping concentration, and H 2 S gas concentration and less dependent on film thickness. The mobility was relatively high while the intrinsic carrier concentration was low when compared to typical semiconductor materials. The conductivity was shown to exhibit anomalous behavior at certain temperatures and H 2 S gas concentrations

  8. Expression of arsenic resistance genes in the obligate anaerobe Bacteroides vulgatus ATCC 8482, a gut microbiome bacterium.

    Science.gov (United States)

    Li, Jiaojiao; Mandal, Goutam; Rosen, Barry P

    2016-06-01

    The response of the obligate anaerobe Bacteroides vulgatus ATCC 8482, a common human gut microbiota, to arsenic was determined. B. vulgatus ATCC 8482 is highly resistant to pentavalent As(V) and methylarsenate (MAs(V)). It is somewhat more sensitive to trivalent inorganic As(III) but 100-fold more sensitive to methylarsenite (MAs(III)) than to As(III). B. vulgatus ATCC 8482 has eight continuous genes in its genome that we demonstrate form an arsenical-inducible transcriptional unit. The first gene of this ars operon, arsR, encodes a putative ArsR As(III)-responsive transcriptional repressor. The next three genes encode proteins of unknown function. The remaining genes, arsDABC, have well-characterized roles in detoxification of inorganic arsenic, but there are no known genes for MAs(III) resistance. Expression of each gene after exposure to trivalent and pentavalent inorganic and methylarsenicals was analyzed. MAs(III) was the most effective inducer. The arsD gene was the most highly expressed of the ars operon genes. These results demonstrate that this anaerobic microbiome bacterium has arsenic-responsive genes that confer resistance to inorganic arsenic and may be responsible for the organism's ability to maintain its prevalence in the gut following dietary exposure to inorganic arsenic. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. [Studies on markers of exposure and early effect in areas with arsenic pollution: methods and results of the project SEpiAs. Epidemiological studies on population exposed to low-to-moderate arsenic concentration in drinking water].

    Science.gov (United States)

    Bustaffa, Elisa; Bianchi, Fabrizio

    2014-01-01

    Arsenic and its inorganic compounds are classified as human carcinogens. Several epidemiological studies conducted in areas of the world characterized by high arsenic concentration in drinking water, even up to 3,000 μg/l, report associations between arsenic exposure and skin, bladder, lung, liver and kidney cancer as well as cardiovascular diseases, diabetes and reproductive and developmental effects. Since general population is not exposed to these high arsenic concentrations in the last years attention focused on adverse health effects that low-to-moderate arsenic concentrations (0-150 μg/l) in drinking water could induce. The World Health Organization recommends a maximum limit of 10 μg/l for arsenic in drinking water. Almost all epidemiological studies conducted on populations exposed to low-to-moderate arsenic concentrations in drinking water are limited due to problems arising from both individual exposure assessment and low subjects number. The aim of the present review is to collect literature-based evidences regarding adverse health effects associated with exposure to low-to-moderate arsenic concentrations in drinking water (10-150 μg/l) in order to obtain a comprehensive picture of the health outcomes that such exposure can have on general population.

  10. Remedial Investigation/Baseline Risk Assessment for the Ravines and Beach Area Study areas of the Surplus Operable Unit, Fort Sheridan, Illinois, Volume 3 - BRA Text and BRA Appendices A-L

    Science.gov (United States)

    1998-04-13

    in quadriplegia (Ledet et al, 1973). For chickens , the lowest oral lethal dose of trivalent arsenic as arsenic trioxide and sodium arsenite reported...Benchmarks for Wildlife: 1996 Revision (ES/ER/TM-86/R3). The Original Value (mg/kg/day) for the Test Organism (rat, mouse, dove, chicken , duck) was... roasted coffee and in charcoal broiled, barbecued or smoked meats. It is also found in creosote, coal tar, petroleum asphalt, and a variety of

  11. Suppression of NRF2–ARE activity sensitizes chemotherapeutic agent-induced cytotoxicity in human acute monocytic leukemia cells

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Hui [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing (China); Wang, Huihui [School of Public Health, China Medical University, 77 Puhe Road, Shenyang North New Area, Shenyang (China); Xue, Peng [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Key Laboratory of the Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai (China); Hou, Yongyong [School of Public Health, China Medical University, 77 Puhe Road, Shenyang North New Area, Shenyang (China); Dong, Jian [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan (China); Zhou, Tong [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Qu, Weidong [Key Laboratory of the Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai (China); Peng, Shuangqing [Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing (China); Li, Jin; Carmichael, Paul L. [Unilever, Safety & Environmental Assurance Centre, Colworth Science Park, Sharnbrook, Bedfordshire MK44 1LQ (United Kingdom); Nelson, Bud; Clewell, Rebecca; Zhang, Qiang; Andersen, Melvin E. [The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States); Pi, Jingbo, E-mail: jpi@mail.cmu.edu.cn [School of Public Health, China Medical University, 77 Puhe Road, Shenyang North New Area, Shenyang (China); The Hamner Institutes for Health Sciences, 6 Davis Drive, Research Triangle Park, NC (United States)

    2016-02-01

    Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of the antioxidant response element (ARE)-dependent transcription, plays a pivotal role in chemical detoxification in normal and tumor cells. Consistent with previous findings that NRF2–ARE contributes to chemotherapeutic resistance of cancer cells, we found that stable knockdown of NRF2 by lentiviral shRNA in human acute monocytic leukemia (AML) THP-1 cells enhanced the cytotoxicity of several chemotherapeutic agents, including arsenic trioxide (As{sub 2}O{sub 3}), etoposide and doxorubicin. Using an ARE-luciferase reporter expressed in several human and mouse cells, we identified a set of compounds, including isonicotinic acid amides, isoniazid and ethionamide, that inhibited NRF2–ARE activity. Treatment of THP-1 cells with ethionamide, for instance, significantly reduced mRNA expression of multiple ARE-driven genes under either basal or As{sub 2}O{sub 3}-challenged conditions. As determined by cell viability and cell cycle, suppression of NRF2–ARE by ethionamide also significantly enhanced susceptibility of THP-1 and U937 cells to As{sub 2}O{sub 3}-induced cytotoxicity. In THP-1 cells, the sensitizing effect of ethionamide on As{sub 2}O{sub 3}-induced cytotoxicity was highly dependent on NRF2. To our knowledge, the present study is the first to demonstrate that ethionamide suppresses NRF2–ARE signaling and disrupts the transcriptional network of the antioxidant response in AML cells, leading to sensitization to chemotherapeutic agents. - Highlights: • Identification of novel inhibitors of ARE-dependent transcription • Suppression of NRF2–ARE sensitizes THP-1 cells to chemotherapy. • Ethionamide suppresses ARE-dependent transcriptional activity. • Ethionamide and isoniazid increase the cytotoxicity of As{sub 2}O{sub 3} in AML cells. • Sensitization of THP-1 cells to As{sub 2}O{sub 3} toxicity by ethionamide is NRF2-dependent.

  12. Arsenic-induced stress activates sulfur metabolism in different organs of garlic (Allium sativum L.) plants accompanied by a general decline of the NADPH-generating systems in roots.

    Science.gov (United States)

    Ruíz-Torres, Carmelo; Feriche-Linares, Rafael; Rodríguez-Ruíz, Marta; Palma, José M; Corpas, Francisco J

    2017-04-01

    Arsenic (As) contamination is a major environmental problem which affects most living organisms from plants to animals. This metalloid poses a health risk for humans through its accumulation in crops and water. Using garlic (Allium sativum L.) plants as model crop exposed to 200μM arsenate, a comparative study among their main organs (roots and shoots) was made. The analysis of arsenic, glutathione (GSH), phytochelatins (PCs) and lipid peroxidation contents with the activities of antioxidant enzymes (catalase, superoxide dismutase, ascorbate-glutathione cycle), and the main components of the NADPH-generating system, including glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), NADP-malic enzyme (NADP-ME) and NADP-isocitrate dehydrogenase (NADP-ICDH) was carried out. Data showed a correlation among arsenic accumulation in the different organs, PCs content and the antioxidative response, with a general decline of the NADPH-generating systems in roots. Overall, our results demonstrate that there are clear connections between arsenic uptake, increase of their As-chelating capacity in roots and a decline of antioxidative enzyme activities (catalase and the ascorbate peroxidase) whose alteration provoked As-induced oxidative stress. Thus, the data suggest that roots act as barrier of arsenic mediated by a prominent sulfur metabolism which is characterized by the biosynthesis of high amount of PCs. Copyright © 2017 Elsevier GmbH. All rights reserved.

  13. Root perforations treatment using mineral trioxide aggregate and Portland cements.

    Science.gov (United States)

    Silva Neto, José Dias da; Brito, Rafael Horácio de; Schnaider, Taylor Brandão; Gragnani, Alfredo; Engelman, Mírian; Ferreira, Lydia Masako

    2010-12-01

    Clinical, radiological and histological evaluation of root perforations treated with mineral trioxide aggregate (MTA) or Portland cements, and calcium sulfate barrier. One molar and 11 premolar teeth of a male mongrel dog received endodontic treatment and furcations were perforated with a high-speed round bur and treated with a calcium sulfate barrier. MTA, Portland cement type II (PCII) and type V (PCV), and white Portland cement (WPC) were used as obturation materials. The teeth were restored with composite resin and periapical radiographs were taken. The animal was euthanized 120 days post-surgery for treatment evaluation. Right lower first premolar (MTA), right lower third premolar (PCV), left lower second premolar (MTA), and right lower second premolar (WPC): clinically normal, slightly radio-transparent area on the furcation, little inflammatory infiltrate, and new-bone formation. Left lower third premolar (PCII), right upper first premolar (WPC), right upper third premolar (PCII), and left upper first molar (PCV): clinically normal, radiopaque area on the furcation, and new-bone formation. Right upper second premolar (MTA), left upper second premolar (WPC), left upper third premolar (PCII): presence of furcation lesion, large radiolucent area, and intense inflammatory infiltrate. All obturation materials used in this study induced new-bone formation.

  14. Evaluation of Redox Conditions and Enhanced Arsenic Mobility from Waste Disposal in a Complex Fractured Crystalline-Rock Aquifer, Raymond, New Hampshire, USA (Note: article rewritten under new title)

    Science.gov (United States)

    (Note: This entry is no longer valid; the paper was rewritten and submitted to a different journal.) This paper highlights some methods that can be used at a local scale to assess whether waste disposal activities are responsible for enhanced arsenic mobility through redox-contro...

  15. Height and blood chemistry in adults with a history of developmental arsenic poisoning from contaminated milk powder

    DEFF Research Database (Denmark)

    Yorifuji, Takashi; Matsuoka, Kenichi; Grandjean, Philippe

    2017-01-01

    BACKGROUND: Arsenic poisoning interferes with bone metabolism in laboratory animal studies, and human studies suggest lowered bone mass density at elevated exposures. As the long-term consequences of developmental arsenic toxicity are poorly known, we carried out a clinical pilot study of survivors...... the unexposed participants (191 (44) U/L) (p=0.01). No other statistically significant difference was observed, and liver enzymes were within normal ranges. CONCLUSIONS: Adults who had suffered arsenic poisoning during infancy showed decreased height and elevated ALP that suggests abnormalities in bone...... metabolism possibly induced by arsenic incorporated in the bone matrix....

  16. Curcumin attenuates harmful effects of arsenic on neural stem/progenitor cells

    Directory of Open Access Journals (Sweden)

    Ali Jahanbazi Jahan-Abad

    2017-06-01

    Full Text Available Objective: Arsenic, an environmental pollutant, decreases neuronal migration as well as cellular maturation and inhibits the proliferation of neural progenitor cells. Curcumin has been described as an antioxidant and neuroprotective agent with strong therapeutic potential in some neurological disorders. Human adipose-derived stem cells (hADSCs, a source of multipotent stem cells, can self-renew and differentiate into neural cells. The aim of the present study was to investigate the preventive effect of curcumin against arsenic toxic effects on the viability, telomerase activity, and apoptosis of neural stem/progenitor cells (NSPCs derived from hADSCs. Materials and Methods: The characteristics of human adipose tissue were identified by immunocytochemistry for surface markers namely, CD105, CD73, and CD90. Using neurosphere assay, hADSCs were differentiated into neuronal cells. To characterize neural cells, expression of nestin, SOX2, MAP2, and GFAP were assessed by immunocytochemistry. Cytotoxicity and viability of NSPCs were evaluated by MTT assay. Reactive oxygen species (ROS generated by arsenic exposure, were measured and caspase 3/7 activity and caspase-3 processing as well as the telomerase activity were determined. Results: The isolated hADSCs positively expressed CD105, CD73, and CD90. Nestin, Sox2, GFAP, and MAP2 were expressed in the neurospheres derived from hADSCs. Curcumin/arsenic co-treatment significantly increased telomerase activity of NSPCs compared to arsenic group. Furthermore, curcumin significantly reduced arsenic-induced apoptosis (via inactivation of caspases as well as arsenic-associated ROS generation. Conclusion: Our findings revealed that curcumin has the potential to prevent harmful effects of arsenic on neurogenesis.

  17. Arsenic removal from water using a novel amorphous adsorbent developed from coal fly ash.

    Science.gov (United States)

    Zhang, Kaihua; Zhang, Dongxue; Zhang, Kai

    2016-01-01

    A novel effective adsorbent of alumina/silica oxide hydrate (ASOH) for arsenic removal was developed through simple chemical reactions using coal fly ash. The iron-modified ASOH with enhancing adsorption activity was further developed from raw fly ash based on the in situ technique. The adsorbents were characterized by X-ray diffraction, Fourier transform infrared spectrometry, scanning electron micrograph, laser particle size and Brunauer-Emmet-Teller surface area. The results show that the adsorbents are in amorphous and porous structure, the surface areas of which are 8-12 times that of the raw ash. The acidic hydrothermal treatment acts an important role in the formation of the amorphous structure of ASOH rather than zeolite crystal. A series of adsorption experiments for arsenic on them were studied. ASOH can achieve a high removal efficiency for arsenic of 96.4% from water, which is more than 2.5 times that of the raw ash. Iron-modified ASOH can enhance the removal efficiency to reach 99.8% due to the in situ loading of iron (Fe). The condition of synthesis pH = 2-4 is better for iron-modified ASOH to adsorb arsenic from water.

  18. Colour centres in amorphous tungsten trioxide thin films

    International Nuclear Information System (INIS)

    Kleperis, J.J.; Cikmach, P.D.; Lusis, A.R.

    1984-01-01

    Magnetic, optical, and electrical properties of thin tungsten trioxide (a-WO 3 ) films obtained on substrates with different temperatures and annealed in air and vacuum are investigated. On the basis of these results and recent structural investigations a structure model of the a-WO 3 film is given: a spatial network of tightly bounded clusters which are built from hydrated WO 6 octahedra. These octahedra contain terminal oxygens and being axially distorted they are the sites for localization of injected electrons. The colour centres formed are paramagnetic (ESR signal from W 5+ ) and their optical absorption is satisfactorily described by the intervalence charge transfer between the localized states of W 5+ and W 6+ ions. (author)

  19. Contribution to the study of sulfur trioxide formation and determination of the sulfuric acid dew point in boiler plants

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, H.

    1983-11-01

    This paper analyzes chemical reaction kinetics of the formation of sulfur trioxide and sulfuric acid in combustion air and flue gas of steam generators. Formulae for sulfuric acid equilibrium reactions according to Wahnschaffe (W. Grimm, 1972) and R. Hasse, H.W. Borgmann (1962) are presented. Theoretical acid dew point, combustion parameters with influence on the dew point temperature and formation of sulfates are further discussed. Sulfur trioxide formation at temperatures above 1,000 C as a non-equilibrium reaction is outlined as another variant of chemical reactions. A graphic evaluation is made of dew point conditions in brown coal dust fired, and heating oil fired steam generators. (11 refs.)

  20. Arsenic concentrations in Chinese coals

    International Nuclear Information System (INIS)

    Wang Mingshi; Zheng Baoshan; Wang Binbin; Li Shehong; Wu Daishe; Hu Jun

    2006-01-01

    The arsenic concentrations in 297 coal samples were collected from the main coal-mines of 26 provinces in China were determined by molybdenum blue coloration method. These samples were collected from coals that vary widely in coal rank and coal-forming periods from the five main coal-bearing regions in China. Arsenic content in Chinese coals range between 0.24 to 71 mg/kg. The mean of the concentration of Arsenic is 6.4 ± 0.5 mg/kg and the geometric mean is 4.0 ± 8.5 mg/kg. The level of arsenic in China is higher in northeastern and southern provinces, but lower in northwestern provinces. The relationship between arsenic content and coal-forming period, coal rank is studied. It was observed that the arsenic contents decreases with coal rank in the order: Tertiary > Early Jurassic > Late Triassic > Late Jurassic > Middle Jurassic > Late Permian > Early Carboniferous > Middle Carboniferous > Late Carboniferous > Early Permian; It was also noted that the arsenic contents decrease in the order: Subbituminous > Anthracite > Bituminous. However, compared with the geological characteristics of coal forming region, coal rank and coal-forming period have little effect on the concentration of arsenic in Chinese coal. The average arsenic concentration of Chinese coal is lower than that of the whole world. The health problems in China derived from in coal (arsenism) are due largely to poor local life-style practices in cooking and home heating with coal rather than to high arsenic contents in the coal

  1. Lake Mixing Regime Influences Arsenic Transfer from Sediments into the Water Column and Uptake in Plankton

    Science.gov (United States)

    Gawel, J.; Barrett, P. M.; Hull, E.; Burkart, K.; McLean, J.; Hargrave, O.; Neumann, R.

    2017-12-01

    The former ASARCO copper smelter in Ruston, WA, now a Superfund site, contaminated a large area of the south-central Puget Sound region with arsenic over its almost 100-year history. Arsenic, a priority Superfund contaminant and carcinogen, is a legacy pollutant impacting aquatic ecosystems in urban lakes downwind of the ASARCO emissions stack. We investigated the impact of lake mixing regime on arsenic transfer from sediments into lake water and aquatic biota. We regularly collected water column and plankton samples from four study lakes for two years, and deployed sediment porewater peepers and sediment traps to estimate arsenic flux rates to and from the sediments. In lakes with strong seasonal stratification, high aqueous arsenic concentrations were limited to anoxic hypolimnetic waters while low arsenic concentrations were observed in oxic surface waters. However, in polymictic, shallow lakes, we observed elevated arsenic concentrations throughout the entire oxic water column. Sediment flux estimates support higher rates of arsenic release from sediments and vertical transport. Because high arsenic in oxic waters results in spatial overlap between arsenate, a phosphate analog, and lake biota, we observed enhanced trophic transfer of arsenic in polymictic, shallow study lakes, with higher arsenic accumulation (up to an order of magnitude) in both phytoplankton and zooplankton compared to stratified lakes. Chemical and physical mechanisms for higher steady-state arsenic concentrations will be explored. Our work demonstrates that physical mixing processes coupled with sediment/water redox status exert significant control over bioaccumulation, making shallow, periodically-mixed urban lakes uniquely vulnerable to environmental and human health risks from legacy arsenic contamination.

  2. Arsenic and dichlorvos: Possible interaction between two environmental contaminants.

    Science.gov (United States)

    Flora, Swaran J S

    2016-05-01

    Metals are ubiquitously present in the environment and pesticides are widely used throughout the world. Environmental and occupational exposure to metal along with pesticide is an area of great concern to both the public and regulatory authorities. Our major concern is that combination of these toxicant present in environment may elicit toxicity either due to additive or synergistic interactions or 'joint toxic actions' among these toxicants. It poses a rising threat to human health. Water contamination particularly ground water contamination with arsenic is a serious problem in today's scenario since arsenic is associated with several kinds of health problems, such arsenic associated health anomalies are commonly called as 'Arsenism'. Uncontrolled use and spillage of pesticides into the environment has resulted in alarming situation. Moreover serious concerns are being addressed due to their persistence in the environmental matrices such as air, soil and surface water runoff resulting in continuous exposure of these harmful chemicals to human beings and animals. Bio-availability of these environmental toxicants has been enhanced much due to anthropological activities. Dreadfully very few studies are available on combined exposures to these toxicants on the animal or human system. Studies on the acute and chronic exposure to arsenic and DDVP are well reported and well defined. Arsenic is a common global ground water contaminant while dichlorvos is one of the most commonly and widely employed organophosphate based insecticide used in agriculture, horticulture etc. There is thus a real situation where a human may get exposed to these toxicants while working in a field. This review highlights the individual and combined exposure to arsenic and dichlorvos on health. Copyright © 2016 Elsevier GmbH. All rights reserved.

  3. Arsenic is associated with reduced effect of folic acid in myelomeningocele prevention: a case control study in Bangladesh

    Science.gov (United States)

    Background: Arsenic induces neural tube defects in several animal models, but its potential to cause neural tube defects in humans is unknown. Our objective was to investigate the associations between maternal arsenic exposure, periconceptional folic acid supplementation, and risk of posterior neura...

  4. Phytoremediation of arsenic contaminated soil by Pteris vittata L. I. Influence of phosphatic fertilizers and repeated harvests.

    Science.gov (United States)

    Mandal, Asit; Purakayastha, T J; Patra, A K; Sanyal, S K

    2012-12-01

    A greenhouse experiment was conducted to evaluate the effectiveness of diammonium phosphate (DAP), single superphosphate (SSP) and two growing cycles on arsenic removal by Chinese Brake Fern (Pteris vittata L.) from an arsenic contaminated Typic Haplustept of the Indian state of West Bengal. After harvest of Pteris vittata the total, Olsen's extractable and other five soil arsenic fractions were determined. The total biomass yield of P. vittata ranged from 10.7 to 16.2 g pot(-1) in first growing cycle and from 7.53 to 11.57 g pot(-1) in second growing cycle. The frond arsenic concentrations ranged from 990 to 1374 mg kg(-1) in first growing cycle and from 875 to 1371 mg kg(-1) in second growing cycle. DAP was most efficient in enhancing biomass yield, frond and root arsenic concentrations and total arsenic removal from soil. After first growing cycle, P. vittata reduced soil arsenic by 10 to 20%, while after two growing cycles Pteris reduced it by 18 to 34%. Among the different arsenic fractions, Fe-bound arsenic dominated over other fractions. Two successive harvests with DAP as the phosphate fertilizer emerged as the promising management strategy for amelioration of arsenic contaminated soil of West Bengal through phyotoextraction by P. vittata.

  5. Determination of total arsenic in soil and arsenic-resistant bacteria from selected ground water in Kandal Province, Cambodia

    International Nuclear Information System (INIS)

    Hamzah, A.; Wong, K.K.; Hasan, F.N.; Mustafa, S.; Khoo, K.S.; Sarmani, S.B.

    2013-01-01

    Cambodia has geological environments conducive to generation of high-arsenic groundwater and people are at high risk of chronic arsenic exposure. The aims of this study are to investigate the concentration of total arsenic and to isolate and identify arsenic-resistant bacteria from selected locations in Kandal Province, Cambodia. The INAA technique was used to measure the concentration of total arsenic in soils. The arsenic concentrations in soils were above permissible 5 mg/kg, ranging from 5.34 to 27.81 mg/kg. Bacteria resistant to arsenic from two arsenic-contaminated wells in Preak Russey were isolated by enrichment method in nutrient broth (NB). Colonies isolated from NB was then grown on minimal salt media (MSM) added with arsenic at increasing concentrations of 10, 20, 30, 50, 100 and 250 ppm. Two isolates that can tolerate 750 ppm of arsenic were identified as Enterobacter agglomerans and Acinetobacter lwoffii based on a series of biochemical, physiological and morphological analysis. Optimum growth of both isolates ranged from pH 6.6 to 7.0 and 30-35 deg C. E. agglomerans and A. lwoffii were able to remove 66.4 and 64.1 % of arsenic, respectively at the initial concentration of 750 ppm, within 72 h of incubation. Using energy dispersive X-ray technique, the percentage of arsenic absorbed by E. agglomerans and A. lwoffii was 0.09 and 0.15 %, respectively. This study suggested that arsenic-resistant E. agglomerans and A. lwoffii removed arsenic from media due to their ability to absorb arsenic. (author)

  6. Mineral sources and transport pathways for arsenic release in a coastal watershed, USA

    Science.gov (United States)

    Foley, Nora K.; Ayuso, Robert A.

    2008-01-01

    Metasedimentary bedrock of coastal Maine contains a diverse suite of As-bearing minerals that act as significant sources of elements found in ground and surface waters in the region. Arsenic sources in the Penobscot Formation include, in order of decreasing As content by weight: löllingite and realgar (c.70%), arsenopyrite, cobaltite, glaucodot, and gersdorffite (in the range of 34–45%), arsenian pyrite (Formation, the relative stability of primary As-bearing minerals follows a pattern where the most commonly observed highly altered minerals are pyrrhotite, realgar, niccolite, löllingite > glaucodot, arsenopyrite-cobaltian > arsenopyrite, cobaltite, gersdorffite, fine-grained pyrite, Ni-pyrite > coarse-grained pyrite. Reactions illustrate that oxidation of Fe-As disulphide group and As-sulphide minerals is the primary release process for As. Liberation of As by carbonation of realgar and orpiment in contact with high-pH groundwaters may contribute locally to elevated contents of As in groundwater, especially where As is decoupled from Fe. Released metals are sequestered in secondary minerals by sorption or by incorporation in crystal structures. Secondary minerals acting as intermediate As reservoirs include claudetite (c.75%), orpiment (61%), scorodite (c. 45%), secondary arsenopyrite (c. 46%), goethite (minerals. Reductive dissolution of Fe-oxide minerals may govern the ultimate release of iron and arsenic – especially As(V) – to groundwater; however, dissolution of claudetite (arsenic trioxide) may directly contribute As(III). Processes thought to explain the release of As from minerals in bedrock include oxidation of arsenian pyrite or arsenopyrite, or carbonation of As-sulphides, and most models based on these generally rely on discrete minerals or on a fairly limited series of minerals. In contrast, in the Penobscot Formation and other metasedimentary rocks of coastal Maine, oxidation of As-bearing Fe-cobalt-nickel-sulphide minerals, dissolution (by

  7. [Arsenical keratosis treated by dermatome shaving].

    Science.gov (United States)

    Kjerkegaard, Ulrik Knap; Heje, Jens Martin; Vestergaard, Christian; Stausbøl-Grøn, Birgitte; Stolle, Lars Bjørn

    2014-05-05

    Cutaneous malignancy in association with arsenic exposure is a rare but well-documented phenomenon. Signs of chronic arsenic exposure are very rare in Denmark today. However, arsenic was used in the medical treatment of psoriasis vulgaris up till the 1980's and several patients suffer from this arsenic treatment today. This case report shows that arsenical keratosis can be treated by dermatome shaving, a superficial destructive therapy.

  8. In situ treatment of arsenic contaminated groundwater by aquifer iron coating: Experimental study.

    Science.gov (United States)

    Xie, Xianjun; Wang, Yanxin; Pi, Kunfu; Liu, Chongxuan; Li, Junxia; Liu, Yaqing; Wang, Zhiqiang; Duan, Mengyu

    2015-09-15

    In situ arsenic removal from groundwater by an aquifer iron coating method has great potential to be a cost effective and simple groundwater remediation technology, especially in rural and remote areas where groundwater is used as the main water source for drinking. The in situ arsenic removal technology was first optimized by simulating arsenic removal in various quartz sand columns under anoxic conditions. The effectiveness was then evaluated in an actual high-arsenic groundwater environment. The arsenic removal mechanism by the coated iron oxide/hydroxide was investigated under different conditions using scanning electron microscopy (SEM)/X-ray absorption spectroscopy, electron probe microanalysis, and Fourier transformation infrared spectroscopy. Aquifer iron coating method was developed via a 4-step alternating injection of oxidant, iron salt and oxygen-free water. A continuous injection of 5.0 mmol/L FeSO4 and 2.5 mmol/L NaClO for 96 h can form a uniform goethite coating on the surface of quartz sand without causing clogging. At a flow rate of 7.2 mL/min of the injection reagents, arsenic (as Na2HAsO4) and tracer fluorescein sodium to pass through the iron-coated quartz sand column were approximately at 126 and 7 column pore volumes, respectively. The retardation factor of arsenic was 23.0, and the adsorption capacity was 0.11 mol As per mol Fe. In situ arsenic removal from groundwater in an aquifer was achieved by simultaneous injections of As(V) and Fe(II) reagents. Arsenic fixation resulted from a process of adsorption/co-precipitation with fine goethite particles by way of bidentate binuclear complexes. Therefore, the study results indicate that the high arsenic removal efficiency of the in situ aquifer iron coating technology likely resulted from the expanded specific surface area of the small goethite particles, which enhanced arsenic sorption capability and/or from co-precipitation of arsenic on the surface of goethite particles. Copyright © 2015

  9. Effects of arsenic on nitrate metabolism in arsenic hyperaccumulating and non-hyperaccumulating ferns

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Nandita [Soil and Water Science Department, University of Florida, Gainesville, Fl 32611-0290 (United States); Eco-Auditing group, National Botanical Research Institute, Rana Pratap Marg, Lucknow 226 001 (India); Ma, Lena Q., E-mail: lqma@ufl.ed [Soil and Water Science Department, University of Florida, Gainesville, Fl 32611-0290 (United States); Vu, Joseph C. [Chemistry Research Unit, CMAVE, USDA-ARS, Gainesville, FL 32608-1069 and Agronomy Department, University of Florida, Gainesville, FL 32611-0500 (United States); Raj, Anshita [Eco-Auditing group, National Botanical Research Institute, Rana Pratap Marg, Lucknow 226 001 (India)

    2009-08-15

    This study investigated the effects of arsenic on the in vitro activities of the enzymes (nitrate reductase and nitrite reductase) involved in nitrate metabolism in the roots, rhizomes, and fronds of four-month old Pteris vittata (arsenic - hyperaccumulator) and Pteris ensiformis (non-arsenic--hyperaccumulator) plants. The arsenic treatments (0, 150, and 300 muM as sodium arsenate) in hydroponics had adverse effects on the root and frond dry weights, and this effect was more evident in P. ensiformis than in P. vittata. Nitrate reductase and nitrite reductase activities of arsenate-treated plants were reduced more in P. ensiformis than in P. vittata. This effect was accompanied by similar decreases in tissue NO{sub 3}{sup -} concentrations. Therefore, this decrease is interpreted as being indirect, i.e., the consequence of the reduced NO{sub 3}{sup -} uptake and translocation in the plants. The study shows the difference in the tolerance level of the two Pteris species with varying sensitivity to arsenic. - Arsenic reduced the activity of nitrate and nitrite reductase more in Pteris ensiformis than Pteris vittata.

  10. In vitro assessment on the impact of soil arsenic in the eight rice varieties of West Bengal, India.

    Science.gov (United States)

    Bhattacharya, Piyal; Samal, Alok C; Majumdar, Jayjit; Banerjee, Satabdi; Santra, Subhas C

    2013-11-15

    Rice is an efficient accumulator of arsenic and thus irrigation with arsenic-contaminated groundwater and soil may induce human health hazard via water-soil-plant-human pathway. A greenhouse pot experiment was conducted on three high yielding, one hybrid and four local rice varieties to investigate the uptake, distribution and phytotoxicity of arsenic in rice plant. 5, 10, 20, 30 and 40 mg kg(-1) dry weights arsenic dosing was applied in pot soil and the results were compared with the control samples. All the studied high yielding and hybrid varieties (Ratna, IET 4094, IR 50 and Gangakaveri) were found to be higher accumulator of arsenic as compared to all but one local rice variety, Kerala Sundari. In these five rice varieties accumulation of arsenic in grain exceeded the WHO permissible limit (1.0 mg kg(-1)) at 20 mg kg(-1) arsenic dosing. Irrespective of variety, arsenic accumulation in different parts of rice plant was found to increase with increasing arsenic doses, but not at the same rate. A consistent negative correlation was established between soil arsenic and chlorophyll contents while carbohydrate accumulation depicted consistent positive correlation with increasing arsenic toxicity in rice plant. Copyright © 2012 Elsevier B.V. All rights reserved.

  11. Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart Study

    Science.gov (United States)

    Howard, Barbara V.; Umans, Jason G.; Gribble, Matthew O.; Best, Lyle G.; Francesconi, Kevin A.; Goessler, Walter; Lee, Elisa; Guallar, Eliseo; Navas-Acien, Ana

    2015-01-01

    OBJECTIVE Little is known about arsenic metabolism in diabetes development. We investigated the prospective associations of low-moderate arsenic exposure and arsenic metabolism with diabetes incidence in the Strong Heart Study. RESEARCH DESIGN AND METHODS A total of 1,694 diabetes-free participants aged 45–75 years were recruited in 1989–1991 and followed through 1998–1999. We used the proportions of urine inorganic arsenic (iAs), monomethylarsonate (MMA), and dimethylarsinate (DMA) over their sum (expressed as iAs%, MMA%, and DMA%) as the biomarkers of arsenic metabolism. Diabetes was defined as fasting glucose ≥126 mg/dL, 2-h glucose ≥200 mg/dL, self-reported diabetes history, or self-reported use of antidiabetic medications. RESULTS Over 11,263.2 person-years of follow-up, 396 participants developed diabetes. Using the leave-one-out approach to model the dynamics of arsenic metabolism, we found that lower MMA% was associated with higher diabetes incidence. The hazard ratios (95% CI) of diabetes incidence for a 5% increase in MMA% were 0.77 (0.63–0.93) and 0.82 (0.73–0.92) when iAs% and DMA%, respectively, were left out of the model. DMA% was associated with higher diabetes incidence only when MMA% decreased (left out of the model) but not when iAs% decreased. iAs% was also associated with higher diabetes incidence when MMA% decreased. The association between MMA% and diabetes incidence was similar by age, sex, study site, obesity, and urine iAs concentrations. CONCLUSIONS Arsenic metabolism, particularly lower MMA%, was prospectively associated with increased incidence of diabetes. Research is needed to evaluate whether arsenic metabolism is related to diabetes incidence per se or through its close connections with one-carbon metabolism. PMID:25583752

  12. Arsenic induced progesterone production in a caspase-3-dependent manner and changed redox status in preovulatory granulosa cells.

    Science.gov (United States)

    Yuan, Xiao-Hua; Lu, Cai-Ling; Yao, Nan; An, Li-Sha; Yang, Bai-Qing; Zhang, Chuan-Ling; Ma, Xu

    2012-01-01

    Arsenic contamination is a principal environmental health threat throughout the world. However, little is known about the effect of arsenic on steroidogenesis in granulosa cells (GCs). We found that the treatment of preovulatory GCs with arsenite stimulated progesterone production. A significant increase in serum level of progesterone was observed in female Sprague-Dawley rats following arsenite treatment at a dose of 10 mg/L/rat/day for 7 days. Further experiments demonstrated that arsenite treatment did not change the level of intracellular cyclic AMP (cAMP) or phosphorylated ERK1/2 in preovulatory GCs; however, progesterone production was significantly decreased when cAMP-dependent protein kinase (PKA) or ERK1/2 pathway was inhibited. This implied that the effect of arsenite on progesterone production may require cAMP/PKA and ERK1/2 signaling but not depend on them. Furthermore, we found that arsenite decreased intracellular reactive oxygen species (ROS) but increased the antioxidant glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm) in parallel to the changes in progesterone production. Progesterone antagonist blocked the arsenic-stimulated increase of GSH levels. Arsenite treatment induced caspase-3 activation, although no apoptosis was observed. Inhibition of caspase-3 activity significantly decreased progesterone production stimulated by arsenite or follicle-stimulating hormone (FSH). GSH depletion with buthionine sulfoximine led to cell apoptosis in response to arsenite treatment. Collectively, this study demonstrated for the first time that arsenite stimulates progesterone production through cleaved/active caspase-3-dependent pathway, and the increase of GSH level promoted by progesterone production may protect GCs against apoptosis and maintain the steroidogenesis of GCs in response to arsenite treatment. Copyright © 2011 Wiley Periodicals, Inc.

  13. Solar oxidation and removal of arsenic--Key parameters for continuous flow applications.

    Science.gov (United States)

    Gill, L W; O'Farrell, C

    2015-12-01

    Solar oxidation to remove arsenic from water has previously been investigated as a batch process. This research has investigated the kinetic parameters for the design of a continuous flow solar reactor to remove arsenic from contaminated groundwater supplies. Continuous flow recirculated batch experiments were carried out under artificial UV light to investigate the effect of different parameters on arsenic removal efficiency. Inlet water arsenic concentrations of up to 1000 μg/L were reduced to below 10 μg/L requiring 12 mg/L iron after receiving 12 kJUV/L radiation. Citrate however was somewhat surprisingly found to promote a detrimental effect on the removal process in the continuous flow reactor studies which is contrary to results found in batch scale tests. The impact of other typical water groundwater quality parameters (phosphate and silica) on the process due to their competition with arsenic for photooxidation products revealed a much higher sensitivity to phosphate ions compared to silicate. Other results showed no benefit from the addition of TiO2 photocatalyst but enhanced arsenic removal at higher temperatures up to 40 °C. Overall, these results have indicated the kinetic envelope from which a continuous flow SORAS single pass system could be more confidently designed for a full-scale community groundwater application at a village level. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Arsenic metabolism efficiency has a causal role in arsenic toxicity: Mendelian randomization and gene-environment interaction.

    Science.gov (United States)

    Pierce, Brandon L; Tong, Lin; Argos, Maria; Gao, Jianjun; Farzana, Jasmine; Roy, Shantanu; Paul-Brutus, Rachelle; Rahaman, Ronald; Rakibuz-Zaman, Muhammad; Parvez, Faruque; Ahmed, Alauddin; Quasem, Iftekhar; Hore, Samar K; Alam, Shafiul; Islam, Tariqul; Harjes, Judith; Sarwar, Golam; Slavkovich, Vesna; Gamble, Mary V; Chen, Yu; Yunus, Mohammad; Rahman, Mahfuzar; Baron, John A; Graziano, Joseph H; Ahsan, Habibul

    2013-12-01

    Arsenic exposure through drinking water is a serious global health issue. Observational studies suggest that individuals who metabolize arsenic efficiently are at lower risk for toxicities such as arsenical skin lesions. Using two single nucleotide polymorphisms(SNPs) in the 10q24.32 region (near AS3MT) that show independent associations with metabolism efficiency, Mendelian randomization can be used to assess whether the association between metabolism efficiency and skin lesions is likely to be causal. Using data on 2060 arsenic-exposed Bangladeshi individuals, we estimated associations for two 10q24.32 SNPs with relative concentrations of three urinary arsenic species (representing metabolism efficiency): inorganic arsenic (iAs), monomethylarsonic acid(MMA) and dimethylarsinic acid (DMA). SNP-based predictions of iAs%, MMA% and DMA% were tested for association with skin lesion status among 2483 cases and 2857 controls. Causal odds ratios for skin lesions were 0.90 (95% confidence interval[CI]: 0.87, 0.95), 1.19 (CI: 1.10, 1.28) and 1.23 (CI: 1.12, 1.36)for a one standard deviation increase in DMA%, MMA% and iAs%,respectively. We demonstrated genotype-arsenic interaction, with metabolism-related variants showing stronger associations with skin lesion risk among individuals with high arsenic exposure (synergy index: 1.37; CI: 1.11, 1.62). We provide strong evidence for a causal relationship between arsenic metabolism efficiency and skin lesion risk. Mendelian randomization can be used to assess the causal role of arsenic exposure and metabolism in a wide array of health conditions.exposure and metabolism in a wide array of health conditions.Developing interventions that increase arsenic metabolism efficiency are likely to reduce the impact of arsenic exposure on health.

  15. Use of Endophytic and Rhizosphere Bacteria To Improve Phytoremediation of Arsenic-Contaminated Industrial Soils by Autochthonous Betula celtiberica.

    Science.gov (United States)

    Mesa, Victoria; Navazas, Alejandro; González-Gil, Ricardo; González, Aida; Weyens, Nele; Lauga, Béatrice; Gallego, Jose Luis R; Sánchez, Jesús; Peláez, Ana Isabel

    2017-04-15

    The aim of this study was to investigate the potential of indigenous arsenic-tolerant bacteria to enhance arsenic phytoremediation by the autochthonous pseudometallophyte Betula celtiberica The first goal was to perform an initial analysis of the entire rhizosphere and endophytic bacterial communities of the above-named accumulator plant, including the cultivable bacterial species. B. celtiberica 's microbiome was dominated by taxa related to Flavobacteriales , Burkholderiales , and Pseudomonadales , especially the Pseudomonas and Flavobacterium genera. A total of 54 cultivable rhizobacteria and 41 root endophytes, mainly affiliated with the phyla Proteobacteria , Bacteroidetes , Firmicutes , and Actinobacteria , were isolated and characterized with respect to several potentially useful features for metal plant accumulation, such as the ability to promote plant growth, metal chelation, and/or mitigation of heavy-metal stress. Seven bacterial isolates were further selected and tested for in vitro accumulation of arsenic in plants; four of them were finally assayed in field-scale bioaugmentation experiments. The exposure to arsenic in vitro caused an increase in the total nonprotein thiol compound content in roots, suggesting a detoxification mechanism through phytochelatin complexation. In the contaminated field, the siderophore and indole-3-acetic acid producers of the endophytic bacterial consortium enhanced arsenic accumulation in the leaves and roots of Betula celtiberica , whereas the rhizosphere isolate Ensifer adhaerens strain 91R mainly promoted plant growth. Field experimentation showed that additional factors, such as soil arsenic content and pH, influenced arsenic uptake in the plant, attesting to the relevance of field conditions in the success of phytoextraction strategies. IMPORTANCE Microorganisms and plants have developed several ways of dealing with arsenic, allowing them to resist and metabolize this metalloid. These properties form the basis of

  16. Mouse arsenic (+3 oxidation state) methyltransferase genotype affects metabolism and tissue dosimetry of arsenicals after arsenite administration in drinking water.

    Science.gov (United States)

    Chen, Baowei; Arnold, Lora L; Cohen, Samuel M; Thomas, David J; Le, X Chris

    2011-12-01

    Arsenic (+3 oxidation state) methyltransferase (As3mt) catalyzes methylation of inorganic arsenic (iAs) producing a number of methylated arsenic metabolites. Although methylation has been commonly considered a pathway for detoxification of arsenic, some highly reactive methylated arsenicals may contribute to toxicity associated with exposure to inorganic arsenic. Here, adult female wild-type (WT) C57BL/6 mice and female As3mt knockout (KO) mice received drinking water that contained 1, 10, or 25 ppm (mg/l) of arsenite for 33 days and blood, liver, kidney, and lung were taken for arsenic speciation. Genotype markedly affected concentrations of arsenicals in tissues. Summed concentrations of arsenicals in plasma were higher in WT than in KO mice; in red blood cells, summed concentrations of arsenicals were higher in KO than in WT mice. In liver, kidney, and lung, summed concentrations of arsenicals were greater in KO than in WT mice. Although capacity for arsenic methylation is much reduced in KO mice, some mono-, di-, and tri-methylated arsenicals were found in tissues of KO mice, likely reflecting the activity of other tissue methyltransferases or preabsorptive metabolism by the microbiota of the gastrointestinal tract. These results show that the genotype for arsenic methylation determines the phenotypes of arsenic retention and distribution and affects the dose- and organ-dependent toxicity associated with exposure to inorganic arsenic.

  17. Neutron activation analysis of arsenic in Greece

    International Nuclear Information System (INIS)

    Grimanis, A.P.

    1989-01-01

    Arsenic is considered a toxic trace element for plant, animal, and human organisms. Arsenic and certain arsenic compounds have been listed as carcinogens by the U.S. Environmental Protection Agency. Arsenic is emitted in appreciable quantities into the atmosphere by coal combustion and the production of cement. Arsenic enters the aquatic environment through industrial activities such as smelting of metallic ores, metallurgical glassware, and ceramics as well as insecticide production and use. Neutron activation analysis (NAA) is a very sensitive, precise, and accurate method for determining arsenic. This paper is a review of research studies of arsenic in the Greek environment by NAA performed at our radioanalytical laboratory. The objectives of these studies were (a) to determine levels of arsenic concentrations in environmental materials, (b) to pinpoint arsenic pollution sources and estimate the extent of arsenic pollution, and (c) to find out whether edible marine organisms from the gulfs of Greece receiving domestic, industrial, and agricultural wastes have elevated concentrations of arsenic in their tissues that could render them dangerous for human consumption

  18. Paclitaxel and the dietary flavonoid fisetin: a synergistic combination that induces mitotic catastrophe and autophagic cell death in A549 non-small cell lung cancer cells.

    Science.gov (United States)

    Klimaszewska-Wisniewska, Anna; Halas-Wisniewska, Marta; Tadrowski, Tadeusz; Gagat, Maciej; Grzanka, Dariusz; Grzanka, Alina

    2016-01-01

    The use of the dietary polyphenols as chemosensitizing agents to enhance the efficacy of conventional cytostatic drugs has recently gained the attention of scientists and clinicians as a plausible approach for overcoming the limitations of chemotherapy (e.g. drug resistance and cytotoxicity). The aim of this study was to investigate whether a naturally occurring diet-based flavonoid, fisetin, at physiologically attainable concentrations, could act synergistically with clinically achievable doses of paclitaxel to produce growth inhibitory and/or pro-death effects on A549 non-small cell lung cancer cells, and if it does, what mechanisms might be involved. The drug-drug interactions were analyzed based on the combination index method of Chou and Talalay and the data from MTT assays. To provide some insights into the mechanism underlying the synergistic action of fisetin and paclitaxel, selected morphological, biochemical and molecular parameters were examined, including the morphology of cell nuclei and mitotic spindles, the pattern of LC3-II immunostaining, the formation of autophagic vacuoles at the electron and fluorescence microscopic level, the disruption of cell membrane asymmetry/integrity, cell cycle progression and the expression level of LC3-II, Bax, Bcl-2 and caspase-3 mRNA. Here, we reported the first experimental evidence for the existence of synergism between fisetin and paclitaxel in the in vitro model of non-small cell lung cancer. This synergism was, at least partially, ascribed to the induction of mitotic catastrophe. The switch from the cytoprotective autophagy to the autophagic cell death was also implicated in the mechanism of the synergistic action of fisetin and paclitaxel in the A549 cells. In addition, we revealed that the synergism between fisetin and paclitaxel was cell line-specific as well as that fisetin synergizes with arsenic trioxide, but not with mitoxantrone and methotrexate in the A549 cells. Our results provide rationale for

  19. Determinants and Consequences of Arsenic Metabolism Efficiency among 4,794 Individuals: Demographics, Lifestyle, Genetics, and Toxicity.

    Science.gov (United States)

    Jansen, Rick J; Argos, Maria; Tong, Lin; Li, Jiabei; Rakibuz-Zaman, Muhammad; Islam, Md Tariqul; Slavkovich, Vesna; Ahmed, Alauddin; Navas-Acien, Ana; Parvez, Faruque; Chen, Yu; Gamble, Mary V; Graziano, Joseph H; Pierce, Brandon L; Ahsan, Habibul

    2016-02-01

    Exposure to inorganic arsenic (iAs), a class I carcinogen, affects several hundred million people worldwide. Once absorbed, iAs is converted to monomethylated (MMA) and then dimethylated forms (DMA), with methylation facilitating urinary excretion. The abundance of each species in urine relative to their sum (iAs%, MMA%, and DMA%) varies across individuals, reflecting differences in arsenic metabolism capacity. The association of arsenic metabolism phenotypes with participant characteristics and arsenical skin lesions was characterized among 4,794 participants in the Health Effects of Arsenic Longitudinal Study (Araihazar, Bangladesh). Metabolism phenotypes include those obtained from principal component (PC) analysis of arsenic species. Two independent PCs were identified: PC1 appears to represent capacity to produce DMA (second methylation step), and PC2 appears to represent capacity to convert iAs to MMA (first methylation step). PC1 was positively associated (P 4.32/AS3MT region polymorphisms were strongly associated with PC1, but not PC2. Patterns of association for most variables were similar for PC1 and DMA%, and for PC2 and MMA% with the exception of arsenic exposure and SNP associations. Two distinct arsenic metabolism phenotypes show unique associations with age, sex, BMI, 10q24.32 polymorphisms, and skin lesions. This work enhances our understanding of arsenic metabolism kinetics and toxicity risk profiles. ©2015 American Association for Cancer Research.

  20. Endodontic treatment failure caused by arsen utilization as the devitalization material

    Directory of Open Access Journals (Sweden)

    Endang Sukartini

    2008-07-01

    Full Text Available Root canal treatment diagnoses as pulpitis irreversible can be treated in a non-vital condition with devitalization material. Arsenic is one of devitalization material that used in inflammatory pulp tissue before it is going to endodontic treatment. The long-term use of it or the leak of using this arsenic can cause the toxic effect of the pulp tissue. The case is going to report is about the damage of gingival tissue and alveolar that caused by the uncarefullness using of arsenic. Inappropriate arsenic applications cause the leak that able to spread to gingival tissue and will become necrosis. Now a day, the using of arsenic begin to leave because of the toxicity sad effect. This report is going to report how much the damage using arsenic trioxide (As2O3 and the effort from the leakness.