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Sample records for cadmium induced inhibition

  1. Melatonin alleviates cadmium-induced liver injury by inhibiting the TXNIP-NLRP3 inflammasome.

    Science.gov (United States)

    Cao, Zhengwang; Fang, Yiliang; Lu, Yonghui; Tan, Dunxian; Du, Changhong; Li, Yuming; Ma, Qinlong; Yu, Junmei; Chen, Mengyan; Zhou, Chao; Pei, Liping; Zhang, Lei; Ran, Haiying; He, Mindi; Yu, Zhengping; Zhou, Zhou

    2017-04-01

    Cadmium (Cd) is a persistent environmental and occupational contaminant that accumulates in the liver and induces oxidative stress and inflammation. Melatonin possesses potent hepatoprotective properties against the development and progression of acute and chronic liver injury. Nevertheless, the molecular mechanism underlying the protective effects of melatonin against Cd-induced hepatotoxicity remains obscure. In this study, we aimed to investigate the effects of melatonin on Cd-induced liver inflammation and hepatocyte death. Male C57BL/6 mice were intraperitoneally injected with melatonin (10 mg/kg) once a day for 3 days before exposure to CdCl2 (2.0 mg/kg). We found that Cd induced hepatocellular damage and inflammatory infiltration as well as increased serum ALT/AST enzymes. In addition, we showed that Cd triggered an inflammatory cell death, which is mediated by the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Moreover, melatonin treatment significantly alleviated Cd-induced liver injury by decreasing serum ALT/AST levels, suppressing pro-inflammatory cytokine production, inhibiting NLRP3 inflammasome activation, ameliorating oxidative stress, and attenuating hepatocyte death. Most importantly, melatonin markedly abrogated Cd-induced TXNIP overexpression and decreased the interaction between TXNIP and NLRP3 in vivo and in vitro. However, treatment with siRNA targeting TXNIP blocked the protective effects of melatonin in Cd-treated primary hepatocytes. Collectively, our results suggest that melatonin confers protection against Cd-induced liver inflammation and hepatocyte death via inhibition of the TXNIP-NLRP3 inflammasome pathway. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Cadmium inhibits mouse sperm motility through inducing tyrosine phosphorylation in a specific subset of proteins.

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    Wang, Lirui; Li, Yuhua; Fu, Jieli; Zhen, Linqing; Zhao, Na; Yang, Qiangzhen; Li, Sisi; Li, Xinhong

    2016-08-01

    Cadmium (Cd) has been reported to impair male fertility, primarily by disrupting sperm motility, but the underlying molecular mechanism remains unclear. Here we investigated the effects of Cd on sperm motility, tyrosine phosphorylation, AMP-activated protein kinase (AMPK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, and ATP levels in vitro. Our results demonstrated that Cd inhibited sperm motility, GAPDH activity, AMPK activity and ATP production, and induced tyrosine phosphorylation of 55-57KDa proteins. Importantly, all the parameters affected by Cd were restored to normal levels when incubated with 10μM Cd in the presence of 30μM ethylene diamine tetraacetic acid (EDTA). Interestingly, changes of tyrosine phosphorylation levels of 55-57KDa proteins are completely contrary to that of other parameters. These results suggest that Cd-induced tyrosine phosphorylation of 55-57KDa proteins might act as an engine to block intracellular energy metabolism and thus decrease sperm motility. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Curcumin inhibits adenosine deaminase and arginase activities in cadmium-induced renal toxicity in rat kidney

    Directory of Open Access Journals (Sweden)

    Ayodele Jacob Akinyemi

    2017-04-01

    Full Text Available In this study, the effect of enzymes involved in degradation of renal adenosine and l-arginine was investigated in rats exposed to cadmium (Cd and treated with curcumin, the principal active phytochemical in turmeric rhizome. Animals were divided into six groups (n = 6: saline/vehicle, saline/curcumin 12.5 mg/kg, saline/curcumin 25 mg/kg, Cd/vehicle, Cd/curcumin 12.5 mg/kg, and Cd/curcumin 25 mg/kg. The results of this study revealed that the activities of renal adenosine deaminase and arginase were significantly increased in Cd-treated rats when compared with the control (p < 0.05. However, co-treatment with curcumin inhibits the activities of these enzymes compared with Cd-treated rats. Furthermore, Cd intoxication increased the levels of some renal biomarkers (serum urea, creatinine, and electrolytes and malondialdehyde level with a concomitant decrease in functional sulfhydryl group and nitric oxide (NO. However, co-treatment with curcumin at 12.5 mg/kg and 25 mg/kg, respectively, increases the nonenzymatic antioxidant status and NO in the kidney, with a concomitant decrease in the levels of malondialdehyde and renal biomarkers. Therefore, our results reinforce the importance of adenosine deaminase and arginase activities in Cd poisoning conditions and suggest some possible mechanisms of action by which curcumin prevent Cd-induced renal toxicity in rats.

  4. Autophagy and gap junctional intercellular communication inhibition are involved in cadmium-induced apoptosis in rat liver cells

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    Zou, Hui [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China); Zhuo, Liling [College of Life Science, Zaozhuang University, Zaozhuang, Shandong, 277160 (China); Han, Tao; Hu, Di; Yang, Xiaokang; Wang, Yi; Yuan, Yan; Gu, Jianhong; Bian, Jianchun; Liu, Xuezhong [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China); Liu, Zongping, E-mail: liuzongping@yzu.edu.cn [College of Veterinary Medicine, Yangzhou University, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu, 225009 (China)

    2015-04-17

    Cadmium (Cd) is known to induce hepatotoxicity, yet the underlying mechanism of how this occurs is not fully understood. In this study, Cd-induced apoptosis was demonstrated in rat liver cells (BRL 3A) with apoptotic nuclear morphological changes and a decrease in cell index (CI) in a time- and concentration-dependent manner. The role of gap junctional intercellular communication (GJIC) and autophagy in Cd-induced apoptosis was investigated. Cd significantly induced GJIC inhibition as well as downregulation of connexin 43 (Cx43). The prototypical gap junction blocker carbenoxolone disodium (CBX) exacerbated the Cd-induced decrease in CI. Cd treatment was also found to cause autophagy, with an increase in mRNA expression of autophagy-related genes Atg-5, Atg-7, Beclin-1, and microtubule-associated protein light chain 3 (LC3) conversion from cytosolic LC3-I to membrane-bound LC3-II. The autophagic inducer rapamycin (RAP) prevented the Cd-induced CI decrease, while the autophagic inhibitor chloroquine (CQ) caused a further reduction in CI. In addition, CBX promoted Cd-induced autophagy, as well as changes in expression of Atg-5, Atg-7, Beclin-1 and LC3. CQ was found to block the Cd-induced decrease in Cx43 and GJIC inhibition, whereas RAP had opposite effect. These results demonstrate that autophagy plays a protective role during Cd-induced apoptosis in BRL 3A cells during 6 h of experiment, while autophagy exacerbates Cd-induced GJIC inhibition which has a negative effect on cellular fate. - Highlights: • GJIC and autophagy is crucial for biological processes. • Cd exposure causes GJIC inhibition and autophagy increase in BRL 3A cells. • Autophagy protects Cd induced BRL 3A cells apoptosis at an early stage. • Autophagy exacerbates Cd-induced GJIC inhibition. • GJIC plays an important role in autophagy induced cell death or survival.

  5. Bone marrow mesenchymal stem cells repair cadmium-induced rat testis injury by inhibiting mitochondrial apoptosis.

    Science.gov (United States)

    Wang, Yong-Jie; Yan, Jun; Zou, Xiao-Li; Guo, Ke-Jun; Zhao, Yue; Meng, Chun-Yang; Yin, Fei; Guo, Li

    2017-06-01

    Cadmium is a highly toxic metal with widespread exposure to people that can cause tissue injuries that lack effective treatment. The aim of this project was to uncover whether bone marrow mesenchymal stem cells (BMSCs) can repair cadmium-induced rat testis injury and to explore the role of mitochondrial apoptosis in this process. To this end, 21 adult male Wistar rats were randomly divided into control, model and therapy groups, 7 each, and were administered 0, 0.4 and 0.4 mg/kg body weight CdCl2 saline solution, respectively, by intraperitoneal injection 5 times per week for 5 weeks. Then, rats in the therapy group were treated with 10(7) BMSCs by retro-orbital injections, while the others were given equal volumes of phosphate buffered saline. Following 2-week BMSCs-treatment, the therapy rats were heavier than the model rats, despite there being no difference in testicular cadmium contents between these groups, which were both significantly higher than the control group. BMSCs were observed in the testis of the therapy rats, in which pathological changes improved significantly compared with the model group. Expression of the apoptosis-associated proteins Bim, Bax, Cytochrome C, Caspase-3, active-Caspase-3 and AIF increased, while Bcl-2 was reduced significantly in rat testes of model group compared with the other groups. Based on these findings, we conclude that cadmium can accumulate in rat testes where it caused severe tissue injury, BMSCs can be localized to the injured testicular tissue of rats and repair the tissue injury, these reparative effects may be highly related with mitochondrial apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Nano-composites chitosan-curcumin synergistically inhibits the oxidative stress induced by toxic metal cadmium.

    Science.gov (United States)

    Ahmad, Mohammad; Taweel, Gasem M Abu; Hidayathulla, Syed

    2017-12-08

    The present study intends to compare the influence of pre-treatment with nanoparticles of curcumin (Cr-NPS), chitosan (Ch-NPS) and nanocomposites chitosan-curcumin (CC-NPS) on cadmium (Cd)-induced oxidative damage in the liver, kidneys, and blood indices in Swiss strain adult male mice. The pretreated mice with Cr-NPS, Ch-NPS, and CC-NPS were exposed to Cd (10mg/kg) for three weeks. The non-enzymatic Oxidative Stress (OS) indices like lipid peroxides (TBARS), reduced total glutathione (GSH), enzymatic OS indices like catalase (CAT), glutathione S-transferase (GST) and superoxide dismutase (SOD) were estimated together with some blood indices. Cadmium was able to induce a significant increase in TBARS and a significant decrease in GSH, GST, CAT and SOD levels in all the tissues, which were pretreated with nanocomposite. Furthermore, the blood indices like counts of red and white blood cells, platelets, hemoglobin and packed cell volume were also depleted due to Cd exposure but remained unaffected and kept under normal levels in pretreated mice group. The results indicate that Cr-NPS, Ch-NPS, and CC-NPS may act as natural antioxidants and when compared among the three, CC-NPS appears to be the best antioxidant. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Mechanisms of cadmium induced genomic instability

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    Filipic, Metka, E-mail: metka.filipic@nib.si [National Institute of Biology, Department for Genetic Toxicology and Cancer Biology, Ljubljana (Slovenia)

    2012-05-01

    Cadmium is an ubiquitous environmental contaminant that represents hazard to humans and wildlife. It is found in the air, soil and water and, due to its extremely long half-life, accumulates in plants and animals. The main source of cadmium exposure for non-smoking human population is food. Cadmium is primarily toxic to the kidney, but has been also classified as carcinogenic to humans by several regulatory agencies. Current evidence suggests that exposure to cadmium induces genomic instability through complex and multifactorial mechanisms. Cadmium dose not induce direct DNA damage, however it induces increase in reactive oxygen species (ROS) formation, which in turn induce DNA damage and can also interfere with cell signalling. More important seems to be cadmium interaction with DNA repair mechanisms, cell cycle checkpoints and apoptosis as well as with epigenetic mechanisms of gene expression control. Cadmium mediated inhibition of DNA repair mechanisms and apoptosis leads to accumulation of cells with unrepaired DNA damage, which in turn increases the mutation rate and thus genomic instability. This increases the probability of developing not only cancer but also other diseases associated with genomic instability. In the in vitro experiments cadmium induced effects leading to genomic instability have been observed at low concentrations that were comparable to those observed in target organs and tissues of humans that were non-occupationally exposed to cadmium. Therefore, further studies aiming to clarify the relevance of these observations for human health risks due to cadmium exposure are needed.

  8. Ameliorative Effect of Grape Seed Proanthocyanidin Extract on Cadmium-Induced Meiosis Inhibition During Oogenesis in Chicken Embryos.

    Science.gov (United States)

    Hou, Fuyin; Xiao, Min; Li, Jian; Cook, Devin W; Zeng, Weidong; Zhang, Caiqiao; Mi, Yuling

    2016-04-01

    Cadmium (Cd) is an environmental endocrine disruptor that has toxic effects on the female reproductive system. Here the ameliorative effect of grape seed proanthocyanidin extract (GSPE) on Cd-induced meiosis inhibition during oogenesis was explored. As compared with controls, chicken embryos exposed to Cd (3 µg/egg) displayed a changed oocyte morphology, decreased number of meiotic germ cells, and decreased expression of the meiotic marker protein γH2AX. Real time RT-PCR also revealed a significant down-regulation in the mRNA expressions of various meiosis-specific markers (Stra8, Spo11, Scp3, and Dmc1) together with those of Raldh2, a retinoic acid (RA) synthetase, and of the receptors (RARα and RARβ). In addition, exposure to Cd increased the production of H2 O2 and malondialdehyde in the ovaries and caused a corresponding reduction in glutathione and superoxide dismutase. Simultaneous supplementation of GSPE (150 µg/egg) markedly alleviated the aforementioned Cd-induced embryotoxic effects by upregulating meiosis-related proteins and gene expressions and restoring the antioxidative level. Collectively, the findings provided novel insights into the underlying mechanism of Cd-induced meiosis inhibition and indicated that GSPE might potentially ameliorate related reproductive disorders. © 2016 Wiley Periodicals, Inc.

  9. Spirulina platensis feeding inhibited the anemia- and leucopenia-induced lead and cadmium in rats

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    Simsek, Nejdet [University of Atatuerk, Faculty of Veterinary Medicine, Department of Histology and Embryology, 25700 Erzurum (Turkey); Karadeniz, Ali, E-mail: karadenizali@gmail.com [University of Atatuerk, Faculty of Veterinary Medicine, Department of Physiology, 25700 Erzurum (Turkey); Kalkan, Yildiray; Keles, Osman N.; Unal, Buenyami [University of Atatuerk, Faculty of Medicine, Department of Histology and Embryology, 25240 Erzurum (Turkey)

    2009-05-30

    In the present investigation, the effect of Spirulina platensis (Sp) was undertaken on rats fed with lead and cadmium including diet by using physiological, enzymehistochemical and stereological methods. For this aim, 50 rats were equally divided into five groups as control (C), lead (Pb), Spirulina + lead (Sp + Pb), cadmium (Cd), and Spirulina + cadmium (Sp + Cd). Red blood cell (RBC) and white blood cell (WBC) counts, packed cell volume (PCV), and haemoglobine (Hb) concentrations were determined by haemocytometric methods in blood samples collected on 30th day. Population of T lymphocyte was counted by the {alpha}-naphthyl acetate esterase (ANAE) staining method, and reticulocytes were counted by stereological method. The counts of RBC, WBC, and ANAE positive T lymphocyte, and the values of Hb, PCV, and MCHC were decreased in the Pb and Cd groups compared to control group. Also, the number of reticulocytes (polychromatofilic erythrocyte) increased in the Pb groups, whereas it decreased in the Cd group. On the other hand, these values were ceased by S. platensis in the treated groups. These results suggest that S. platensis supplementation may be useful in adjuvant treatment of leukemia and anemia caused by lead and cadmium toxication.

  10. Incorporation of iron into chloroplasts triggers the restoration of cadmium induced inhibition of photosynthesis.

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    Solti, Ádám; Sárvári, Éva; Tóth, Brigitta; Mészáros, Ilona; Fodor, Ferenc

    2016-09-01

    Photosynthetic symptoms of acute Cd stress can be remedied by elevated Fe supply. To shed more light on the most important aspects of this recovery, the detailed Fe trafficking and accumulation processes as well as the changes in the status of the photosynthetic apparatus were investigated in recovering poplar plants. The Cd-free, Fe-enriched nutrient solution induced an immediate intensive Fe uptake. The increased Fe/Cd ratio in the roots initiated the translocation of Fe to the leaf with a short delay that ultimately led to the accumulation of Fe in the chloroplasts. The chloroplast Fe uptake was directly proportional to the Fe translocation to leaves. The accumulation of PSI reaction centers and the recovery of PSII function studied by Blue-Native PAGE and chlorophyll a fluorescence induction measurements, respectively, began in parallel to the increase in the Fe content of chloroplasts. The initial reorganization of PSII was accompanied by a peak in the antennae-based non-photochemical quenching. In conclusion, Fe accumulation of the chloroplasts is a process of prime importance in the recovery of photosynthesis from acute Cd stress. Copyright © 2016 Elsevier GmbH. All rights reserved.

  11. Zinc-induced protection against cadmium

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    Early, J.L.; Schnell, R.C.

    1978-02-01

    Pretreatment of male rats with cadmium acetate potentiates the duration of hexobarbital hypnosis and inhibits the rate of hepatic microsomal drug metabolism. Pretreatment of rats with zinc acetate protects against these alterations in drug action elicited by cadmium.

  12. Possible mechanism for cadmium-induced hypertension in rats

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    Revis, N.

    1978-01-01

    The mechanism of cadmium-induced hypertension was explored by measuring noradrenaline metabolism. Cadmium in vitro was shown to inhibit both monoamine oxidase and catechol-O-methyltransferase, the two enzymes which inactivate the neurotransmitters noradrenaline and adrenaline. However, rats which were injected or fed (via the drinking water) with cadmium showed that, among the tissues surveyed, these two enzymes were inhibited significantly only in the aorta. In vitro, cadmium was found to inhibit noradrenaline binding to membranes from the heart, lung, and kidney, while stimulating binding to aortic membranes, which suggests that the effects may be specific. These results suggest that, in the aorta, cadmium may inhibit the two catabolic enzymes of noradrenaline, while at the same time stimulating noradrenaline-binding. Thus the effects of noradrenaline on vascular smooth muscle would be increased as well as prolonged.

  13. Possible mechanism for cadmium-induced hypertension in rats

    Energy Technology Data Exchange (ETDEWEB)

    Revis, N.

    1978-02-13

    The mechanism of cadmium-induced hypertension was explored by measuring noradrenaline metabolism. Cadmium in vitro was shown to inhibit both monoamine oxidase and catechol-O-methyltransferase, the two enzymes which inactivate the neurotransmitters noradrenaline and adrenaline. However, rats which were injected or fed (via the drinking water) with cadmium showed that, among the tissues surveyed, these two enzymes were inhibited significantly only in the aorta. In vitro, cadmium was found to inhibit noradrenaline binding to membranes from the heart, lung, and kidney, while stimulating binding to aortic membranes, which suggests that the effects may be specific. These results suggest that, in the aorta, cadmium may inhibit the two catabolic enzymes of noradrenaline, while at the same time stimulating noradrenaline-binding. Thus the effects of noradrenaline on vascular smooth muscle would be increased as well as prolonged.

  14. Cadmium-induced testicular injury.

    Science.gov (United States)

    Siu, Erica R; Mruk, Dolores D; Porto, Catarina S; Cheng, C Yan

    2009-08-01

    Cadmium (Cd) is an environmental toxicant and an endocrine disruptor in humans and rodents. Several organs (e.g., kidney, liver) are affected by Cd and recent studies have illustrated that the testis is exceedingly sensitive to Cd toxicity. More important, Cd and other toxicants, such as heavy metals (e.g., lead, mercury) and estrogenic-based compounds (e.g., bisphenols) may account for the recent declining fertility in men among developed countries by reducing sperm count and testis function. In this review, we critically discuss recent data in the field that have demonstrated the Cd-induced toxicity to the testis is probably the result of interactions of a complex network of causes. This is likely to involve the disruption of the blood-testis barrier (BTB) via specific signal transduction pathways and signaling molecules, such as p38 mitogen-activated protein kinase (MAPK). We also summarize current studies on factors that confer and/or regulate the testis sensitivity to Cd, such as Cd transporters and metallothioneins, the impact of Cd on the testis as an endocrine disruptor and oxidative stress inducer, and how it may disrupt the Zn(2+) and/or Ca(2+) mediated cellular events. While much work is needed before a unified mechanistic pathway of Cd-induced testicular toxicity emerges, recent studies have helped to identify some of the likely mechanisms and/or events that take place during Cd-induced testis injury. Furthermore, some of the recent studies have shed lights on potential therapeutic or preventive approaches that can be developed in future studies by blocking or minimizing the destructive effects of Cd to testicular function in men.

  15. Salicylic acid alleviates cadmium-induced stress responses through the inhibition of Cd-induced auxin-mediated reactive oxygen species production in barley root tips.

    Science.gov (United States)

    Tamás, Ladislav; Mistrík, Igor; Alemayehu, Aster; Zelinová, Veronika; Bočová, Beáta; Huttová, Jana

    2015-01-15

    Auxin is a master regulator of root growth by modulating its development under the constantly changing environment. Recently, an antagonistic interaction was suggested between SA and IAA signaling. Therefore, the purpose of this work was to analyze and compare the effect of the indole-3-acetic acid (IAA) signaling inhibitor p-chlorophenoxyisobutyric acid (PCIB) and salicylic acid (SA) as a potential IAA signaling inhibitor on the root growth, enzyme activity and reactive oxygen species (ROS) production in Cd- and IAA-treated barley root tips. Exposure of plants to Cd resulted in a more than threefold increase of IAA content in the root apex even 3h after the treatment. In addition, exogenously applied IAA evoked root responses such as root growth inhibition and swelling, ROS generation and activation of lipoxygenase or glutathione peroxidase identical to those induced by Cd. Furthermore, both Cd- and IAA-induced stress responses were markedly reversed by PCIB or SA post-treatment. Similarly to PCIB, SA did not affect the IAA content of root tips, suggesting the action of SA on the IAA signaling pathway in barley roots. SA probably does not alleviate the Cd toxicity in roots, but rather prevents or partially inhibits the root defense response to the presence of Cd through the inhibition of Cd-induced IAA-mediated ROS generation in roots. Copyright © 2014 Elsevier GmbH. All rights reserved.

  16. antioxidants, cadmium-induced toxicity, serum biochemical

    African Journals Online (AJOL)

    Daniel Owu

    (1.51/gm) and selenium (0.25mg) which on their own had little or no effects on the serum basal phosphatases, hormonal and histological stability caused a reversal of the cadmium-induced biochemical, hormonal and histological toxicities of the ..... accessory sex tissues atrophy such as the prostate. (Waalkes et al 1997a).

  17. Feedback inhibition by thiols outranks glutathione depletion: a luciferase-based screen reveals glutathione-deficient γ-ECS and glutathione synthetase mutants impaired in cadmium-induced sulfate assimilation.

    Science.gov (United States)

    Jobe, Timothy O; Sung, Dong-Yul; Akmakjian, Garo; Pham, Allis; Komives, Elizabeth A; Mendoza-Cózatl, David G; Schroeder, Julian I

    2012-06-01

    Plants exposed to heavy metals rapidly induce changes in gene expression that activate and enhance detoxification mechanisms, including toxic-metal chelation and the scavenging of reactive oxygen species. However, the mechanisms mediating toxic heavy metal-induced gene expression remain largely unknown. To genetically elucidate cadmium-specific transcriptional responses in Arabidopsis, we designed a genetic screen based on the activation of a cadmium-inducible reporter gene. Microarray studies identified a high-affinity sulfate transporter (SULTR1;2) among the most robust and rapid cadmium-inducible transcripts. The SULTR1;2 promoter (2.2 kb) was fused with the firefly luciferase reporter gene to quantitatively report the transcriptional response of plants exposed to cadmium. Stably transformed luciferase reporter lines were ethyl methanesulfonate (EMS) mutagenized, and stable M(2) seedlings were screened for an abnormal luciferase response during exposure to cadmium. The screen identified non-allelic mutant lines that fell into one of three categories: (i) super response to cadmium (SRC) mutants; (ii) constitutive response to cadmium (CRC) mutants; or (iii) non-response and reduced response to cadmium (NRC) mutants. Two nrc mutants, nrc1 and nrc2, were mapped, cloned and further characterized. The nrc1 mutation was mapped to the γ-glutamylcysteine synthetase gene and the nrc2 mutation was identified as the first viable recessive mutant allele in the glutathione synthetase gene. Moreover, genetic, HPLC mass spectrometry, and gene expression analysis of the nrc1 and nrc2 mutants, revealed that intracellular glutathione depletion alone would be insufficient to induce gene expression of sulfate uptake and assimilation mechanisms. Our results modify the glutathione-depletion driven model for sulfate assimilation gene induction during cadmium stress, and suggest that an enhanced oxidative state and depletion of upstream thiols, in addition to glutathione depletion

  18. The inhibition effect of 2,3,7,8-tetrachlorinated dibenzo-p-dioxin-induced aryl hydrocarbon receptor activation in human hepatoma cells with the treatment of cadmium chloride

    Energy Technology Data Exchange (ETDEWEB)

    Chao, How-Ran [Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan (China); Emerging Compounds Research Center, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan (China); Tsou, Tsui-Chun [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 350, Taiwan (China); Chen, Hung-Ta [Sustainable Environment Research Center, National Cheng Kung University, Tainan 701, Taiwan (China); Chang, Eddy Essen; Tsai, Feng-Yuan [Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 350, Taiwan (China); Lin, Ding-Yan [Department of Environmental Science and Engineering, National Pingtung University of Science and Technology, Neipu, Pingtung 912, Taiwan (China); Chen, Fu-An [Graduate Institute of Pharmaceutical Science, Department of Pharmacy, Tajen University, Yan-Pu, Pingtung 907, Taiwan (China); Wang, Ya-Fen, E-mail: yfwang@cycu.edu.tw [Department of Bioenvironmental Engineering, Chung Yuan Christian University, Chungli, Taoyuan 320, Taiwan (China); R and D Center of Membrane Technology, Chung Yuan Christian University, Chungli 320, Taiwan (China)

    2009-10-15

    Polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), considered as endocrine disruptors, tend to accumulate in fatty tissues. Dioxin-responsive element chemical activated luciferase gene expression assay (DRE-luciferase assay) has been recognized as a semi-quantitative method for screening dioxins for its fast and low-cost as compared with HRGC/HRMS. However, some problems with the bioassay, including specificity, detection variation resulted from different cleanup strategies, and uncertainty of false-negative or false-positive results, remain to be overcome. Cadmium is a prevalent environmental contaminant around the world. This study was aimed to examine the effects of cadmium on the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced activation of aryl hydrocarbon receptor (AhR)-mediated gene expression in human hepatoma cells (Huh7-DRE-Luc cells and Huh7 cells). Ethoxyresorufin-O-deethylase (EROD) and DRE-luciferase assay were employed to determine the enzyme activity of cytochrome P450 1A1 (CYP1A1) and activation of AhR, respectively. The results showed that Cd{sup 2+} levels significantly inhibited the induction of TCDD-induced CYP1A1 and DRE luciferase activation in hepatoma cells. The 50% inhibited concentrations (IC{sub 50}) of CdCl{sub 2} were 0.414 {mu}M (95% confidence interval (C.I.): 0.230-0.602 {mu}M) in Huh7-DRE-Luc cells and 23.2 {mu}M (95% C.I.: 21.7-25.4 {mu}M) in Huh7 cells. Accordingly, prevention of interference with non-dioxin-like compounds in a DRE-luciferase assay is of great importance in an extensive cleanup procedure.

  19. Sex-related differences in cadmium-induced alteration of drug action in the rat

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    Schnell, R.C.; Pence, D.H.; Prosser, T.D.; Miya, T.S.

    1976-01-01

    Three days after pretreatment of rats of both sexes with cadmium (2 mg/kg, i.p.), the duration of hypnosis induced by hexobarbital (75 mg/kg, i.p.) was potentiated in males but not females. Likewise, similar treatment with cadmium leads to significant inhibition of the metabolism of hexobarbital by hepatic microsomal enzymes obtained from male but not female animals. These data suggest that there is a sex-related difference in the ability of cadmium to alter drug action in rats.

  20. induced by cadmium using random amplified polymorphic DNA

    African Journals Online (AJOL)

    darya

    2013-04-17

    Apr 17, 2013 ... Jin YH, Clark AB, Slebos, RJC, Al-Refai H, Taylor JA, Kunkel TA,. Resnick MA, Gordenin DA (2003). Cadmium is a mutagen that acts by inhibiting mismatch repair. Nat. Genet. 34(3):326-329. Joseph P (2009). Mechanisms of cadmium carcinogenesis. Toxicol. Appl. Pharmacol. 238:272-279. Azimi et al.

  1. Cadmium ion inhibition of quorum signalling in Chromobacterium violaceum.

    Science.gov (United States)

    Thornhill, Starla G; Kumar, Manish; Vega, Leticia M; McLean, Robert J C

    2017-10-01

    Single-celled bacteria are capable of acting as a community by sensing and responding to population density via quorum signalling. Quorum signalling in Chromobacterium violaceum, mediated by the luxI/R homologue, cviI/R, regulates a variety of phenotypes including violacein pigmentation, virulence and biofilm formation. A number of biological and organic molecules have been described as quorum signalling inhibitors but, to date, metal-based inhibitors have not been widely tested. In this study, we show that quorum sensing is inhibited in C. violaceum in the presence of sub-lethal concentrations of cadmium salts. Notable Cd2+-inhibition was seen against pigmentation, motility, chitinase production and biofilm formation. Cd-inhibition of quorum-signalling genes occurred at the level of transcription. There was no direct inhibition of chitinase activity by Cd2+ at the concentrations tested. Addition of the cognate quorum signals, N-hexanoyl homoserine lactone or N-decanoyl homoserine lactone, even at concentrations in excess of physiological levels, did not reverse the inhibition, suggesting that Cd-inhibition of quorum signaling is irreversible. This study represents the first description of heavy metal-based quorum inhibition in C. violaceum.

  2. Role of nitric oxide synthase inhibition in the acute hypertensive response to intracerebroventricular cadmium

    Science.gov (United States)

    Demontis, Maria Piera; Varoni, Maria Vittoria; Volpe, Anna Rita; Emanueli, Costanza; Madeddu, Paolo

    1998-01-01

    ability to attenuate the cadmium-induced pressure effect, L-Arg and its isomer exerted differential biochemical changes in brain L-citrulline, as L-Arg normalized cadmium-induced reduction in L-citrulline levels, whereas i.c.v. D-Arg did not.We conclude that the pressor effect of i.c.v. cadmium is due, at least in part, to reduced NO formation, consequent to inhibition of brain NO synthase. Accumulation of cadmium in the central nervous system could interfere with central mechanisms (including NO synthase) implicated in the regulation of cardiovascular function. PMID:9484863

  3. Cadmium induces transcription independently of intracellular calcium mobilization.

    Directory of Open Access Journals (Sweden)

    Brooke E Tvermoes

    Full Text Available BACKGROUND: Exposure to cadmium is associated with human pathologies and altered gene expression. The molecular mechanisms by which cadmium affects transcription remain unclear. It has been proposed that cadmium activates transcription by altering intracellular calcium concentration ([Ca(2+](i and disrupting calcium-mediated intracellular signaling processes. This hypothesis is based on several studies that may be technically problematic; including the use of BAPTA chelators, BAPTA-based fluorescent sensors, and cytotoxic concentrations of metal. METHODOLOGY/PRINCIPAL FINDING: In the present report, the effects of cadmium on [Ca(2+](i under non-cytotoxic and cytotoxic conditions was monitored using the protein-based calcium sensor yellow cameleon (YC3.60, which was stably expressed in HEK293 cells. In HEK293 constitutively expressing YC3.60, this calcium sensor was found to be insensitive to cadmium. Exposing HEK293::YC3.60 cells to non-cytotoxic cadmium concentrations was sufficient to induce transcription of cadmium-responsive genes but did not affect [Ca(2+](i mobilization or increase steady-state mRNA levels of calcium-responsive genes. In contrast, exposure to cytotoxic concentrations of cadmium significantly reduced intracellular calcium stores and altered calcium-responsive gene expression. CONCLUSIONS/SIGNIFICANCE: These data indicate that at low levels, cadmium induces transcription independently of intracellular calcium mobilization. The results also support a model whereby cytotoxic levels of cadmium activate calcium-responsive transcription as a general response to metal-induced intracellular damage and not via a specific mechanism. Thus, the modulation of intracellular calcium may not be a primary mechanism by which cadmium regulates transcription.

  4. Cadmium inhibits testis and epididymal acidification in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Caflisch, C.r.p; DuBose, T.D. Jr.

    1986-03-01

    The testis is known to be highly sensitive to functional impairment by cadmium, a widely distributed trace metal. Both vascular compromise and inhibition of Leydig cell androgen production may result in impaired sperm maturation and motility. Recent studies by our laboratory have confirmed the presence of an acid mileau in the testis and epididymis which may play an important role in sperm maturation. In this study the effect of cadmium on luminal acidification was assessed in rat seminiferous tubules, caput and cauda epididymis by glass membrane double-barrelled pH microelectrodes in vivo. Four Sprague-Dawley rats received CdCl/sub 2/ (0.015 mM/kg s.c.) 24 hrs. prior to micropuncture and 4 rats served as controls. Arterial blood gas values were within the normal range and were not different in the two groups. Cadmium resulted in marked alkalinization of seminiferous tubule fluid compared to controls (7.30 +/- 0.01 (15) vs 6.97 +/- 0.01 (25)) (p < 0.001). Similarly, the pH in proximal caput after CdCl/sub 2/ was 7.07 +/- 0.02 (19) a value significantly more alkaline (p < 0.001) than 6.58 +/- 0.02 (24) in untreated animals. In contrast, however, pH in the distal caput was 6.90 +/- 0.03 (19), a value indistinguishable from that observed in controls. In summary, CdCl/sub 2/ administration is associated with marked impairment of acidification in the testis and proximal epididymus while acidification in the distal epididymus remains intact.

  5. Cytoprotective effects of dietary flavonoids against cadmium-induced toxicity.

    Science.gov (United States)

    Li, Xia; Jiang, Xinwei; Sun, Jianxia; Zhu, Cuijuan; Li, Xiaoling; Tian, Lingmin; Liu, Liu; Bai, Weibin

    2017-06-01

    Cadmium (Cd) damages the liver, kidney, bones, reproductive system, and other organs. Flavonoids, such as anthocyanins and flavonols, which are commonly found in plant foods, have shown protective effects against Cd-induced damage. The cytoprotective effects of flavonoids against Cd-induced diseases are mainly attributable to three mechanisms. First, flavonoids clear reactive oxygen species, thereby reducing lipid peroxide production and improving the activity of antioxidation enzymes. Second, flavonoids chelate Cd, thus reducing the accumulation of Cd and altering the levels of other essential metal ions in vivo. Third, flavonoids reduce DNA damage and inhibit apoptosis. In addition, flavonoids were found to inhibit inflammation and fibrosis and improve glycometabolism and the secretion of reproductive hormones. We introduce the daily dosage and absorption rate of flavonoids and then focus on their bioactive effects against Cd-induced toxicity and reveal the underlying metabolic pathway, which provides a basis for further study of the nutritional prevention of Cd-induced injury. In particular, a better understanding is needed of the structure-activity relationship of flavonoids against Cd toxicity, which has not yet been reported. © 2017 New York Academy of Sciences.

  6. Cadmium-induced oxidative stress in potato tuber

    OpenAIRE

    Andrzej Stroiński; Monika Kozłowska

    2014-01-01

    Short-term treatment of tuber discs of potato (Solanum tuberosum L.) with cadmium chloride elevated the concentration of active oxygen species (.O-2, H202) and activated the antioxidative system. Two cultivars, Bintje and Bzura, susceptible and tolerant, respectively, to cadmium were examined. In more tolerant, control tissues the activity of ascorbic acid peroxidase (AAP) and catalase (CAT) was higher than in the sensitive ones. During first hours of stress, the inhibition of superoxide dism...

  7. Cadmium exposure induces hematuria in Korean adults

    Energy Technology Data Exchange (ETDEWEB)

    Han, Seung Seok [Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Kim, Myounghee, E-mail: dkkim73@gmail.com [Department of Dental Hygiene, College of Health Science, Eulji University, Gyeonggi-do 461-713 (Korea, Republic of); Lee, Su Mi [Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Lee, Jung Pyo [Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul 156-707 (Korea, Republic of); Kim, Sejoong [Department of Internal Medicine, Seoul National University Bundang Hospital, Gyeonggi-do 463-707 (Korea, Republic of); Joo, Kwon Wook [Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of); Lim, Chun Soo [Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul 156-707 (Korea, Republic of); Kim, Yon Su; Kim, Dong Ki [Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-744 (Korea, Republic of)

    2013-07-15

    Introduction: Toxic heavy metals have adverse effects on human health. However, the risk of hematuria caused by heavy metal exposure has not been evaluated. Methods: Data from 4701 Korean adults were obtained in the Korean National Health and Nutritional Examination Survey (2008–2010). Blood levels of the toxic heavy metals cadmium, lead, and mercury were measured. Hematuria was defined as a result of ≥+1 on a urine dipstick test. The odds ratios (ORs) for hematuria were measured according to the blood heavy metal levels after adjusting for multiple variables. Results: Individuals with blood cadmium levels in the 3rd and 4th quartiles had a greater OR for hematuria than those in the 1st quartile group: 3rd quartile, 1.35 (1.019–1.777; P=0.037); 4th quartile, 1.52 (1.140–2.017; P=0.004). When blood cadmium was considered as a log-transformed continuous variable, the correlation between blood cadmium and hematuria was significant: OR, 1.97 (1.224–3.160; P{sub trend}=0.005). In contrast, no significant correlations between hematuria and blood lead or mercury were found in the multivariate analyses. Discussion: The present study shows that high cadmium exposure is associated with a risk of hematuria. -- Highlights: • A high level of blood cadmium is associated with a high risk of hematuria. • This correlation is independent of several confounding factors. • Blood levels of lead and mercury are not associated with risk of hematuria. • This is the first study on the correlation between cadmium exposure and hematuria risk.

  8. Influence of cadmium on ketamine-induced anesthesia and brain microsomal Na[sup +], K[sup +]-ATPase in mice

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Y.; Sangiah, S. (Oklahoma State Univ., Stillwater, OK (United States))

    1994-10-01

    Cadmium is a rare metallic element, present in almost all types of food. Shellfish, wheat and rice accumulate very high amounts. Occupational and environmental pollutants are the main sources of cadmium exposure. Cadmium has a very long biologic half-life. Exposure to Cadmium causes anemia, hypertension, hepatic, renal, pulmonary and cardiovascular disorders as well as being a possible mutagen, teratogen and carcinogen. Acute cadmium treatment increased the hexobarbital sleeping time and inhibited hepatic microsomal drug metabolism due to a decrease in cytochrome P[sub 450] content. Cadmium potentiated ethanol-induced sleep in a dose-dependent manner. Cadmium has been shown to inhibit brain microsomal Na[sup +], K[sup +]-ATPase activity in vitro and in vivo. Cadmium and ethanol additively inhibited brain Na[sup +], K[sup +]-ATPase. This might be a direct interaction between cadmium and ethanol in the central nervous system. Ketamine is an intravenous anesthetic agent. It acts on central nervous system and produces [open quotes]dissociative anaesthesia.[close quotes] Ketamine provides adequate surgical anesthesia and is used alone in humans and/or combination with xylazine, an [alpha][sub 2]-adrenergic agonist in animals. It produces CNS depression, analgesia, amnesia, immobility and a feeling of dissociation from the environment. Ketamine is a non-competitive antagonist of the NMDA subset of the glutamate receptor. This perhaps results in an increase in neuronal activity leading to disorganization of normal neurotransmission and produces dissociative anesthetic state. Because it is different from most other anesthetics, ketamine may be expected to have a unique effect on brain biochemical parameters and enzymes. The purpose of this study was to examine the interactions between cadmium and ketamine on the central nervous system and ATPase, in an attempt to further understand the mechanism of action. 12 refs., 3 figs.

  9. Cadmium-induced oxidative stress in potato tuber

    Directory of Open Access Journals (Sweden)

    Andrzej Stroiński

    2014-01-01

    Full Text Available Short-term treatment of tuber discs of potato (Solanum tuberosum L. with cadmium chloride elevated the concentration of active oxygen species (.O-2, H202 and activated the antioxidative system. Two cultivars, Bintje and Bzura, susceptible and tolerant, respectively, to cadmium were examined. In more tolerant, control tissues the activity of ascorbic acid peroxidase (AAP and catalase (CAT was higher than in the sensitive ones. During first hours of stress, the inhibition of superoxide dismutase (SOD, CAT and AAP was observed and it comes from inactivation of enzymes by cadmium ions. A subsequent activity increase of the enzymes aroused earlier in tolerant tissues. It seems therefore, that tolerant tissues possess a more efficient antioxidative system.

  10. Oral cadmium chloride intoxication in mice

    DEFF Research Database (Denmark)

    Andersen, O; Nielsen, J B; Svendsen, P

    1988-01-01

    Diethyldithiocarbamate (DDC) is known to alleviate acute toxicity due to injection of cadmium salts. However, when cadmium chloride was administered by the oral route, DDC enhanced rather than alleviated the acute toxicity; both oral and intraperitoneal (i.p.) administration of DDC had this effect....... Thus, orally administered DDC enhanced cadmium-induced duodenal and ileal tissue damage and inhibition of peristalsis, as indicated by an increased intestinal transit time. At low cadmium doses, the whole-body retention of cadmium was increased by oral DDC administration. Intraperitoneally administered...... DDC increased cadmium-induced acute mortality and testicular necrosis, and it enhanced cadmium-induced reduction of intestinal motility and increased the whole-body retention of cadmium, indicating increased intestinal cadmium absorption. Also, DDC changed the organ distribution of absorbed cadmium...

  11. Cadmium

    NARCIS (Netherlands)

    Meulenbelt, Jan

    2017-01-01

    Together with zinc and mercury, cadmium belongs to group IIb of the periodic table. It can be found in rocks, soil, water, coal, zinc ore, lead ore, and copper ore. In the environment, cadmium is present predominantly as the oxide or as the chloride, sulfide, or sulfate salt. It has no recognizable

  12. Effects of vitamins C and E pretreatments on cadmium- induced ...

    African Journals Online (AJOL)

    GREGORY

    2010-09-27

    Sep 27, 2010 ... Animals were given single doses of vitamins C (1.5 mg/kg) and E (50 mg/kg) per oral and (0 - 8 mg Cd/kg ip) for 24 h. Animals were sacrificed and the serum ... effects of pretreatments with vitamins C and E on Cd-induced serum levels of the parameters were ... Furthermore, cadmium-induced toxicity is.

  13. Cadmium induces carcinogenesis in BEAS-2B cells through ROS-dependent activation of PI3K/AKT/GSK-3β/β-catenin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Son, Young-Ok; Wang, Lei; Poyil, Pratheeshkumar; Budhraja, Amit; Hitron, J. Andrew; Zhang, Zhuo [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY (United States); Lee, Jeong-Chae [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY (United States); School of Dentistry and Institute of Oral Biosciences (BK21 program), Research Center of Bioactive Materials, Chonbuk National University, Jeonju 561-756 (Korea, Republic of); Shi, Xianglin, E-mail: xshi5@email.uky.edu [Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY (United States)

    2012-10-15

    Cadmium has been widely used in industry and is known to be carcinogenic to humans. Although it is widely accepted that chronic exposure to cadmium increases the incidence of cancer, the mechanisms underlying cadmium-induced carcinogenesis are unclear. The main aim of this study was to investigate the role of reactive oxygen species (ROS) in cadmium-induced carcinogenesis and the signal transduction pathways involved. Chronic exposure of human bronchial epithelial BEAS-2B cells to cadmium induced cell transformation, as evidenced by anchorage-independent growth in soft agar and clonogenic assays. Chronic cadmium treatment also increased the potential of these cells to invade and migrate. Injection of cadmium-stimulated cells into nude mice resulted in the formation of tumors. In contrast, the cadmium-mediated increases in colony formation, cell invasion and migration were prevented by transfection with catalase, superoxide dismutase-1 (SOD1), or SOD2. In particular, chronic cadmium exposure led to activation of signaling cascades involving PI3K, AKT, GSK-3β, and β-catenin and transfection with each of the above antioxidant enzymes markedly inhibited cadmium-mediated activation of these signaling proteins. Inhibitors specific for AKT or β-catenin almost completely suppressed the cadmium-mediated increase in total and active β-catenin proteins and colony formation. Moreover, there was a marked induction of AKT, GSK-3β, β-catenin, and carcinogenic markers in tumor tissues formed in mice after injection with cadmium-stimulated cells. Collectively, our findings suggest a direct involvement of ROS in cadmium-induced carcinogenesis and implicate a role of AKT/GSK-3β/β-catenin signaling in this process. -- Highlights: ► Chronic exposure to cadmium induces carcinogenic properties in BEAS-2B cells. ► ROS involved in cadmium-induced tumorigenicity of BEAS-2B cells. ► Cadmium activates ROS-dependent AKT/GSK-3β/β-catenin-mediated signaling. ► ROS

  14. Ethylene potentiates sulfur-mediated reversal of cadmium inhibited photosynthetic responses in mustard

    Directory of Open Access Journals (Sweden)

    Nafees A Khan

    2016-11-01

    Full Text Available The potential of exogenous ethylene and sulfur (S in reversal of cadmium (Cd-inhibited photosynthetic and growth responses in mustard (Brassica juncea L. cv. Pusa Jai Kisan were studied. Plants grown with 50 µM Cd showed increased superoxide and H2O2 accumulation and lipid peroxidation together with increased activity of 1-aminocyclopropane carboxylic acid synthase (ACS and ethylene production and inhibition of photosynthesis and growth. Application of 1 mM SO42− or 200 µL L−1 ethephon (ethylene source influenced photosynthetic and growth performance equally in presence or absence of Cd. However, their combined application synergistically improved photosynthetic performance more in presence of Cd and reduced oxidative stress (lower superoxide and H2O2 accumulation by decreasing ethylene and glucose sensitivity with the increase in cysteine and methionineand a non-proteinogenic thiol (reduced glutathione; GSH contents. The central role of ethylene in potentiating S-mediated reversal of Cd-induced oxidative stress was evident with the use ethylene action inhibitor, norbornadiene (NBD. The application of NBD resulted in decreased thiol production and photosynthetic responses. This suggests that ethylene promotes the effects of S in reversal of adverse effects of Cd, and thus, ethylene modulation may be considered as potential tool to substantiate the S effects in reversal of Cd inhibited photosynthesis and growth in mustard.

  15. Inhibition of sulfate reduction by iron, cadmium and sulfide in granular sludge

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Silva, Blanca M. [Division de Ciencias Ambientales, Instituto Potosino de Investigacion Cientifica y Tecnologica, Camino a la Presa San Jose 2055, Lomas 4a. Seccion, 78216, San Luis Potosi, S.L.P. (Mexico); Briones-Gallardo, Roberto [Facultad de Ingenieria-Instituto de Metalurgia, Universidad Autonoma de San Luis Potosi, Sierra Leona 550, Lomas 2a. Seccion, 78210, San Luis Potosi, S.L.P. (Mexico); Razo-Flores, Elias [Division de Ciencias Ambientales, Instituto Potosino de Investigacion Cientifica y Tecnologica, Camino a la Presa San Jose 2055, Lomas 4a. Seccion, 78216, San Luis Potosi, S.L.P. (Mexico); Celis, Lourdes B., E-mail: celis@ipicyt.edu.mx [Division de Ciencias Ambientales, Instituto Potosino de Investigacion Cientifica y Tecnologica, Camino a la Presa San Jose 2055, Lomas 4a. Seccion, 78216, San Luis Potosi, S.L.P. (Mexico)

    2009-12-15

    This study investigated the inhibition effect of iron, cadmium and sulfide on the substrate utilization rate of sulfate reducing granular sludge. A series of batch experiments in a UASB reactor were conducted with different concentrations of iron (Fe{sup 2+}, 4.0-8.5 mM), cadmium (Cd{sup 2+}, 0.53-3.0 mM) and sulfide (4.2-10.6 mM), the reactor was fed with ethanol at 1 g chemical oxygen demand (COD)/L and sulfate to yield a COD/SO{sub 4}{sup 2-} (g/g) ratio of 0.5. The addition of iron, up to a concentration of 8.1 mM, had a positive effect on the substrate utilization rate which increased 40% compared to the rate obtained without metal addition (0.25 g COD/g VSS-d). Nonetheless, iron concentration of 8.5 mM inhibited the specific substrate utilization rate by 57% compared to the substrate utilization rate obtained in the batch amended with 4.0 mM Fe{sup 2+} (0.44 g COD/g VSS-d). Cadmium had a negative effect on the specific substrate utilization rate at the concentrations tested; at 3.0 mM Cd{sup 2+} the substrate utilization rate was inhibited by 44% compared with the substrate utilization rate without metal addition. Cadmium precipitation with sulfide did not decrease the inhibition of cadmium on sulfate reduction. These results could have important practical implications mainly when considering the application of the sulfate reducing process to treat effluents with high concentrations of sulfate and dissolved metals such as iron and cadmium.

  16. Stress-induced stimulation of choline transport in cultured choroid plexus epithelium exposed to low concentrations of cadmium

    Science.gov (United States)

    Young, Robin K.

    2013-01-01

    The choroid plexus epithelium forms the blood-cerebrospinal fluid barrier and accumulates essential minerals and heavy metals. Choroid plexus is cited as being a “sink” for heavy metals and excess minerals, serving to minimize accumulation of these potentially toxic agents in the brain. An understanding of how low doses of contaminant metals might alter transport of other solutes in the choroid plexus is limited. Using primary cultures of epithelial cells isolated from neonatal rat choroid plexus, our objective was to characterize modulation of apical uptake of the model organic cation choline elicited by low concentrations of the contaminant metal cadmium (CdCl2). At 50–1,000 nM, cadmium did not directly decrease or increase 30-min apical uptake of 10 μM [3H]choline. However, extended exposure to 250–500 nM cadmium increased [3H]choline uptake by as much as 75% without marked cytotoxicity. In addition, cadmium induced heat shock protein 70 and heme oxygenase-1 protein expression and markedly induced metallothionein gene expression. The antioxidant N-acetylcysteine attenuated stimulation of choline uptake and induction of stress proteins. Conversely, an inhibitor of glutathione synthesis l-buthionine-sulfoximine (BSO) enhanced stimulation of choline uptake and induction of stress proteins. Cadmium also activated ERK1/2 MAP kinase. The MEK1 inhibitor PD98059 diminished ERK1/2 activation and attenuated stimulation of choline uptake. Furthermore, inhibition of ERK1/2 activation abated stimulation of choline uptake in cells exposed to cadmium with BSO. These data indicate that in the choroid plexus, exposure to low concentrations of cadmium may induce oxidative stress and consequently stimulate apical choline transport through activation of ERK1/2 MAP kinase. PMID:24401988

  17. Ribosomal genes as early targets of cadmium-induced toxicity in Chironomus riparius larvae

    Energy Technology Data Exchange (ETDEWEB)

    Planello, R. [Biologia Ambiental, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia, Senda del Rey 9, 28040, Madrid (Spain); Martinez-Guitarte, J.L. [Biologia Ambiental, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia, Senda del Rey 9, 28040, Madrid (Spain); Morcillo, G. [Biologia Ambiental, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia, Senda del Rey 9, 28040, Madrid (Spain)]. E-mail: gmorcillo@ccia.uned.es

    2007-02-01

    Cadmium is a widespread environmental pollutant that causes severe impacts in organisms. Although the effects of cadmium on aquatic insects have been studied in terms of their toxicity and changes in developmental parameters, little is known about its molecular and genetic effects. We have investigated the alterations in the pattern of gene expression provoked by acute exposure to cadmium in Chironomus riparius Mg. (Diptera, Chironomidae), a sentinel organism widely used in aquatic toxicity testing. The early cytotoxic effects were evaluated using immunocytochemistry and specific fluorescent probes in fourth instar larvae after 12 h of 10 mM cadmium treatments; under these conditions no significant effect on larvae mortality was detected until after 36 h of exposure. The changes in the pattern of gene expression were analysed by means of DNA/RNA hybrid antibodies in the polytene chromosomes from salivary gland cells. A decrease in the activity of the nucleolus is especially remarkable, accompanied by a significant reduction in size and the modification in nucleolar architecture, as shown by FISH. The inhibition of rDNA transcription was further evaluated by Northern blot analysis, which showed a marked decrease in the level of preribosomal rRNA (54% 45S 12 h). However, the BR genes, whose products are the giant polypeptides that constitute the silk-like secretion for constructing housing tubes, remain active. Simultaneously, decondensation and activation take place at some chromosomal regions, especially at the centromeres. The changes observed in the pattern of gene expression do not resemble those found after heat shock or other cell stressors. These data provide the first evidence that cadmium interacts with ribosomal genes and results in a drastic impairment of the functional activity of the nucleolus, an essential organelle for cellular survival. Therefore, the depletion of ribosomes would be a long-term effect of Cd-induced cellular damage. These findings may

  18. Sexual dimorphism of cadmium-induced toxicity in rats: involvement of sex hormones.

    Science.gov (United States)

    Shimada, Hideaki; Hashiguchi, Takashi; Yasutake, Akira; Waalkes, Michael P; Imamura, Yorishige

    2012-09-01

    The toxic effect of cadmium varies with sex in experimental animals. Previous studies have demonstrated that pretreatment of male Fischer 344 (F344) rats with the female sex hormone progesterone markedly enhances the susceptibility to cadmium, suggesting a role for progesterone in the sexual dimorphism of cadmium toxicity. In the present study, we attempted to further elucidate the mechanism for sex differences in cadmium-induced toxicity in F344 rats. A single exposure to cadmium (5.0 mg Cd/kg, sc) was lethal in 10/10 (100 %) female compared with 6/10 (60 %) male rats. Using a lower dose of cadmium (3.0 mg Cd/kg), circulating alanine aminotransferase activity, indicative of hepatotoxicity, was highly elevated in the cadmium treated females but not in males. However, no gender-based differences occurred in the hepatic cadmium accumulation, metallothionein or glutathione levels. When cadmium (5.0 mg Cd/kg) was administered to young rats at 5 weeks of age, the sex-related difference in lethality was minimal. Furthermore, although ovariectomy blocked cadmium-induced lethality, the lethal effects of the metal were restored by pretreatment with progesterone (40 mg/kg, sc, 7 consecutive days) or β-estradiol (200 μg/kg, sc, 7 consecutive days) to ovariectomized rats. These results provide further evidence that female sex hormones such as progesterone and β-estradiol are involved in the sexual dimorphism of cadmium toxicity in rats.

  19. Apoptosis and necroptosis are induced in rainbow trout cell lines exposed to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Krumschnabel, Gerhard, E-mail: Gerhard.Krumschnabel@i-med.ac.at [Division of Developmental Immunology, Biocenter, Medical University Innsbruck, Fritz-Preglstr. 3, Innsbruck (Austria); Ebner, Hannes L.; Hess, Michael W. [Division of Histology and Embryology, Medical University Innsbruck, Innsbruck (Austria); Villunger, Andreas [Division of Developmental Immunology, Biocenter, Medical University Innsbruck, Fritz-Preglstr. 3, Innsbruck (Austria)

    2010-08-01

    Cadmium is an important environmental toxicant that can kill cells. A number of studies have implicated apoptosis as well as necrosis and, most recently, a form of programmed necrosis termed necroptosis in the process of cadmium-mediated toxicity, but the exact mechanism remains ill-defined and may depend on the affected cell type. This study investigated which mode of cell death may be responsible for cell death induction in cadmium-exposed trout cell lines from gill and liver and if this cell death was sensitive to inhibitors of necroptosis or apoptosis, respectively. It was observed that intermediate levels of cadmium that killed approximately 50% of the cells over 96-120 h of exposure caused cell death that morphologically resembled apoptosis and was associated with an increase of apoptotic markers such as the number of cells with diminished DNA content (sub-G1 cells), condensed or fragmented nuclei, and elevation of caspase-3 activity. At the same time, however, cells also lost plasma membrane integrity, as indicated by uptake of propidium iodide, showed a decrease of ATP levels and mitochondrial membrane potential, and displayed cell swelling, signs associated with secondary necrosis, or equally possible, necroptotic cell death. Importantly, many of these alterations were at least partly inhibited by the necroptosis inhibitor necrostatin-1 and were to a lesser extent also sensitive to the pan-caspase inhibitor zVAD-fmk, indicating that multiple modes of cell death are concurrently induced in cadmium-exposed trout cells, including necroptosis and apoptosis. Cell death appeared to lack concurrent radical formation, consistent with genetically regulated necroptotic cell death, but was characterized by the rapid induction of DNA damage markers, and the early onset of disintegration of the Golgi complex. Comparative experiments evaluating copper-toxicity indicated that in comparison to cadmium much higher concentrations of this metal were required to induce cell

  20. Oxidative stress and DNA damage induced by cadmium in the human keratinocyte HaCaT cell line: role of glutathione in the resistance to cadmium.

    Science.gov (United States)

    Nzengue, Yves; Steiman, Régine; Garrel, Catherine; Lefèbvre, Emmanuel; Guiraud, Pascale

    2008-01-14

    Cadmium affects the cellular homeostasis and generates damage via complex mechanisms involving interactions with other metals and oxidative stress induction. In this work we used a human keratinocyte cell line (HaCaT) as a model to study the oxidative damage induced by cadmium to cellular macromolecules, its effect on the antioxidant systems and the role of glutathione in cell protection toward cadmium toxicity. The cells were incubated for 24 and 48 h with cadmium (3, 15, 50 and 100 microM). High doses of cadmium were required to induce a cytotoxicity: 100 microM lead to 30% mortality after 24h and 50% after 48 h. The oxidation of lipids and proteins and the DNA damage, respectively, assessed by thiobarbituric acid reactants determination, thiol group measurement and comet assay, were observed for 50-100 microM cadmium. The cytotoxic effects were strongly correlated to the cellular cadmium content. The glutathione peroxidase and the catalase activities were decreased, while the glutathione reductase activity and the glutathione concentration were increased after cadmium treatment. The superoxide dismutases activities were unchanged. A depletion in glutathione prior to cadmium exposure increased the cytotoxic effects and provoked DNA damage. Our results suggested that the hydroxyl radical could be the major compound involved in the oxidative stress generated by cadmium and that glutathione could play a major role in the protection of HaCaT cells from cytotoxicity but mostly from DNA damage induced by cadmium.

  1. Studies on antioxidative enzymes induced by cadmium in pea plants (Pisum sativum).

    Science.gov (United States)

    Pandey, Nalini; Singh, Gaurav Kumar

    2012-03-01

    Pea plants (Pisum sativum cv. Swati) exposed to different concentration of cadmium (50,100, 200 microM Cd) under controlled glass house conditions were quantified for different physiological parameters and antioxidative enzymes. In pea plants, Cd produced a significant inhibition of growth and induced chlorosis, marginal yellowing and necrosis in young leaves, the effect being most pronounced at 200 microM Cd supply. An alteration in the activated oxygen metabolism of pea plants were also detected as evidenced by an increase in concentration of H2O2 and TBARS along with decrease in the chlorophyll and carotenoid concentration in leaves. Cadmium toxicity induced an increase in non-protein thiol, ascorbate, proline and cysteine concentration. A significant increment in the activity of SOD, APX and GR, and a decrease in CAT was observed as a result of Cd treatment. The enhanced activity of SOD and inhibition of CAT and POD produces a high build up of H2O2 which appears to be the main cause of oxidative stress due to Cd toxicity in pea plants.

  2. Sexual dimorphism of cadmium-induced toxicity in rats: involvement of sex hormones

    OpenAIRE

    Shimada, Hideaki; Hashiguchi, Takashi; Yasutake, Akira; Waalkes, Michael P.; Imamura, Yorishige; シマダ, ヒデアキ; ハシグチ, タカシ; ヤスタケ, アキラ; イマムラ, ヨリシゲ; 島田, 秀昭; 橋口, 敬志; 安武 章; 今村, 順茂

    2012-01-01

    The toxic effect of cadmium varies with sex in experimental animals.Previous studies have demonstrated that pretreatment of male Fischer 344 (F344) ratswith the female sex hormone progesterone markedly enhances the susceptibility tocadmium, suggesting a role for progesterone in the sexual dimorphism of cadmiumtoxicity. In the present study, weattempted to furtherelucidate the mechanism for sexdifferencesin cadmium-induced toxicity in F344 rats. A single exposure to cadmium(5.0 mg Cd/kg, s.c.)...

  3. Nickel and cadmium-induced SLBP depletion: A potential pathway to metal mediated cellular transformation.

    Directory of Open Access Journals (Sweden)

    Ashley Jordan

    Full Text Available Both nickel and cadmium compounds have been established as group I carcinogens for several decades. Despite over-whelming evidence of these compounds' carcinogenicity in humans, the specific underlying molecular mechanisms that govern metal induced cellular transformation remain unclear. In this study, we found that there were slightly different effects on decreased SLBP mRNA and protein as well as increased polyA H3.1 in our nickel exposed cells. This suggested that nickel and arsenic have similar effects on canonical histone mRNA transcription and translation. We also saw that the depletion of SLBP protein was reversed by inhibiting the proteosome. Finally, we showed that inhibiting the SLBP mRNA and protein levels were rescued by epigenetic modifiers suggesting that nickel's effects on SLBP may be mediated via epigenetic mechanisms. Taken together these results suggest a similar mechanism by which both arsenic and nickel may exert their carcinogenic effects.

  4. Ethylene signalling is mediating the early cadmium-induced oxidative challenge in Arabidopsis thaliana.

    Science.gov (United States)

    Schellingen, Kerim; Van Der Straeten, Dominique; Remans, Tony; Vangronsveld, Jaco; Keunen, Els; Cuypers, Ann

    2015-10-01

    Cadmium (Cd) induces the generation of reactive oxygen species (ROS) and stimulates ethylene biosynthesis. The phytohormone ethylene is a regulator of many developmental and physiological plant processes as well as stress responses. Previous research indicated various links between ethylene signalling and oxidative stress. Our results support a correlation between the Cd-induced oxidative challenge and ethylene signalling in Arabidopsis thaliana leaves. The effects of 24 or 72 h exposure to 5 μM Cd on plant growth and several oxidative stress-related parameters were compared between wild-type (WT) and ethylene insensitive mutants (etr1-1, ein2-1, ein3-1). Cadmium-induced responses observed in WT plants were mainly affected in etr1-1 and ein2-1 mutants, of which the growth was less inhibited by Cd exposure as compared to WT and ein3-1 mutants. Both etr1-1 and ein2-1 showed a delayed response in the glutathione (GSH) metabolism, including GSH levels and transcript levels of GSH synthesising and recycling enzymes. Furthermore, the expression of different oxidative stress marker genes was significantly lower in Cd-exposed ein2-1 mutants, evidencing that ethylene signalling is involved in early responses to Cd stress. A model for the cross-talk between ethylene signalling and oxidative stress is proposed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Cadmium-Induced Hydrogen Accumulation Is Involved in Cadmium Tolerance in Brassica campestris by Reestablishment of Reduced Glutathione Homeostasis.

    Science.gov (United States)

    Wu, Qi; Su, Nana; Chen, Qin; Shen, Wenbiao; Shen, Zhenguo; Xia, Yan; Cui, Jin

    2015-01-01

    Hydrogen gas (H2) was recently proposed as a therapeutic antioxidant and signaling molecule in clinical trials. However, the underlying physiological roles of H2 in plants remain unclear. In the present study, hydrogen-rich water (HRW) was used to characterize the physiological roles of H2 in enhancing the tolerance of Brassica campestris against cadmium (Cd). The results showed that both 50 μM CdCl2 and 50%-saturated HRW induced an increase of endogenous H2 in Brassica campestris seedlings, and HRW alleviated Cd toxicity related to growth inhibition and oxidative damage. Seedlings supplied with HRW exhibited increased root length and reduced lipid peroxidation, similar to plants receiving GSH post-treatment. Additionally, seedlings post-treated with HRW accumulated higher levels of reduced glutathione (GSH) and ascorbic acid (AsA) and showed increased GST and GPX activities in roots. Molecular evidence illustrated that the expression of genes such as GS, GR1 and GR2, which were down-regulated following the addition of Cd, GSH or BSO, could be reversed to varying degrees by the addition of HRW. Based on these results, it could be proposed that H2 might be an important regulator for enhancing the tolerance of Brassica campestris seedlings against Cd, mainly by governing reduced glutathione homeostasis.

  6. Essential roles of Cdc42 and MAPK in cadmium-induced apoptosis in Litopenaeus vannamei

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Ting; Wang, Wei-Na, E-mail: weina63@aliyun.com; Gu, Mei-Mei; Xie, Chen-Ying; Xiao, Yu-Chao; Liu, Yuan; Wang, Lei

    2015-06-15

    Highlights: • Cd{sup 2+} induces Cdc42 and MAPKs pathway related gene of Litopenaeus vannamei up-regulation. • Reduction of THC, increase of ROS production and apoptotic cell rate were observed when the shrimps exposure to Cd{sup 2+}. • DsRNA-suppression of LvCdc42 and MAPKs during Cd{sup 2+} stress reduces the ROS production and apoptosis. • We conclude that LvCdc42 and MAPKs play key roles in Cd{sup 2+} stress responses of shrimps. - Abstract: Cadmium, one of the most toxic heavy metals in aquatic environments, has severe effects on marine invertebrates and fishes. The MAPK signaling pathway plays a vital role in stress responses of animals. The mitogen-activated protein kinase (MAPK) signaling pathway plays a vital role in animals’ stress responses, including mediation of apoptosis induced by the Rho GTPase Cdc42. However, there is limited knowledge about its function in shrimps, although disorders exacerbated by environmental stresses (including heavy metal pollution) have caused serious mortality in commercially cultured shrimps. Thus, we probed roles of Cdc42 in Litopenaeus vannamei shrimps (LvCdc42) during cadmium exposure by inhibiting its expression using dsRNA-mediated RNA interference. The treatment successfully reduced expression levels of MAPKs (including p38, JNK, and ERK). Cadmium exposure induced significant increases in expression levels of LvCdc42 and MAPKs, accompanied by reductions in total hemocyte counts (THC) and increases in apoptotic hemocyte ratios and ROS production. However, all of these responses were much weaker in LvCdc42-suppressed shrimps, in which mortality rates were higher than in controls. Our results suggest that the MAPK pathway plays a vital role in shrimps’ responses to Cd{sup 2+}. They also indicate that LvCdc42 in shrimps participates in its regulation, and thus plays key roles in ROS production, regulation of apoptosis and associated stress responses.

  7. Cadmium exposure inhibits MMP2 and MMP9 activities in the prostate and testis

    Energy Technology Data Exchange (ETDEWEB)

    Lacorte, Livia M.; Rinaldi, Jaqueline C.; Justulin, Luis A.; Delella, Flávia K. [Univ Estadual Paulista – UNESP, Institute of Biosciences, Department of Morphology, Extracellular Matrix Laboratory, Botucatu, SP (Brazil); Moroz, Andrei [Univ Estadual Paulista – UNESP, School of Pharmaceutical Sciences, Department of Bioprocess and Biotechnology, Cell Culture Laboratory, Araraquara, SP (Brazil); Felisbino, Sérgio L., E-mail: felisbin@ibb.unesp.br [Univ Estadual Paulista – UNESP, Institute of Biosciences, Department of Morphology, Extracellular Matrix Laboratory, Botucatu, SP (Brazil)

    2015-02-20

    Matrix metalloproteinases (MMPs) are zinc (Zn{sup 2+}) and calcium (Ca{sup 2+}) dependant endopeptidases, capable of degradation of numerous components of the extracellular matrix. Cadmium (Cd{sup 2+}) is a well known environmental contaminant which could impair the activity of MMPs. In this sense, this study was conducted to evaluate if Cd{sup 2+} intake inhibits these endopeptidases activities at the rat prostate and testicles and if it directly inhibits the activity of MMP2 and MMP9 at gelatinolytic assays when present in the incubation buffer. To investigate this hypothesis, Wistar rats (5 weeks old), were given tap water (untreated, n = 9), or 15 ppm CdCl{sub 2} diluted in drinking water, during 10 weeks (n = 9) and 20 weeks (n = 9). The animals were euthanized and their ventral prostate, dorsal prostate, and testicles were removed. These tissue samples were processed for protein extraction and subjected to gelatin zymography evaluation. Additionally, we performed an experiment of gelatin zymography in which 5 μM or 2 mM cadmium chloride (CdCl{sub 2}) was directly dissolved at the incubation buffer, using the prostatic tissue samples from untreated animals that exhibited the highest MMP2 and MMP9 activities in the previous experiment. We have found that CdCl{sub 2} intake in the drinking water led to the inhibition of 35% and 30% of MMP2 and MMP9 (p < 0.05) at the ventral prostate and testis, respectively, in Cd{sup 2+} treated animals when compared to controls. Moreover, the activities of the referred enzymes were 80% and 100% inhibited by 5 μM and 2 mM of CdCl{sub 2}, respectively, even in the presence of 10 mM of CaCl{sub 2} within the incubation buffer solution. These important findings demonstrate that environmental cadmium contamination may deregulate the natural balance in the extracellular matrix turnover, through MMPs downregulation, which could contribute to the toxic effects observed in prostatic and testicular tissue after its

  8. Involvement of galectin-3 in cadmium-induced cardiac toxicity.

    Science.gov (United States)

    Yazıhan, Nuray; Koçak, Mehtap Kaçar; Akçıl, Ethem; Erdem, Onur; Sayal, Ahmet; Güven, Cengiz; Akyürek, Nalan

    2011-09-01

    Accumulation of the wide spread environmental toxin cadmium (Cd) in tissues results in toxicity. Heart is one of the most effected tissues. Cd exposure induces inflammation in effected tissues. The present study was focused to evaluate roles of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) in Cd toxicity and their relationships with galectin-3 levels. In this experimental study, male Wistar rats were divided randomly to control and experimental groups. Experimental group was exposed to Cd at the dose of 15 ppm for 8 weeks (n=10/group). Inflammatory status in hearts was evaluated with measurement of tissue TNF-α and IL-6 levels. Histopathological examination of heart was carried out by light microscopy. Heart tissue caspase-3 level was used to identify apoptosis. Tissue galectin-3 level was evaluated by ELISA. Statistical difference between groups was evaluated by unpaired Student t-test, correlation was analyzed by Pearson's test. Heart sizes were increased after Cd toxicity. A significant increase in galectin-3 tissue levels was seen after Cd toxicity, this was accompanied with a significant increase in the TNF-α (control: 402±39, Cd: 793±26 pg/g tissue, ptoxicity (control: 12±2, Cd: 18±3 pmol/µg/min, pCadmium causes increased galectin-3 production from heart tissue. The formation of TNF-α due to Cd exposure may likely trigger this mechanism.

  9. Cadmium-induced physiological response and antioxidant enzyme changes in the novel cadmium accumulator, Tagetes patula

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yu-Ting; Chen, Zueng-Sang [Department of Agricultural Chemistry, National Taiwan University, Taipei 10617, Taiwan (China); Hong, Chwan-Yang, E-mail: cyhong@ntu.edu.tw [Department of Agricultural Chemistry, National Taiwan University, Taipei 10617, Taiwan (China)

    2011-05-30

    The accumulation and effect of cadmium (Cd) on the growth and enzymatic activities changes of antioxidants in Tagetes patula, French marigold, were investigated to reveal the physiological mechanisms corresponding to its Cd tolerance and accumulation. Hydroponically grown T. patula plants were treated with different concentrations of Cd (0, 10, 25, 50 {mu}M CdCl{sub 2}) at various regime of times. T. patula accumulated Cd to a maximum of 450 mg Cd kg{sup -1} dry weight (DW) in shoot and 3500 mg Cd kg{sup -1} DW in root after 14 days' exposure at 10 and 50 {mu}M CdCl{sub 2}, respectively. The translocation factors of Cd were greater than 1 in plants exposed to 10 {mu}M CdCl{sub 2}. Toxic effects were gradually observed with increasing Cd concentration (25 and 50 {mu}M) accompanied with the reduction of biomass, chlorophyll content, decrease of cell viability and the increase level of lipid peroxidation. In leaves of T. patula, the activities of ascorbate peroxidase (APX), glutathione reductase (GR) and superoxide dismutase (SOD) were induced by Cd. However, in roots, activities of APX, GR, SOD and catalase (CAT) were significantly reduced by 25 and 50 {mu}M Cd treatment but not 10 {mu}M Cd. In-gel zymography analysis revealed that Cd induced the enzymatic activities of APX, MnSOD, CuZnSOD and different isozymes of GR in leaves. These results indicate that T. patula is a novel Cd accumulator and able to tolerate with Cd-induced toxicity by activation of its antioxidative defense system.

  10. Cadmium-induced physiological response and antioxidant enzyme changes in the novel cadmium accumulator, Tagetes patula.

    Science.gov (United States)

    Liu, Yu-Ting; Chen, Zueng-Sang; Hong, Chwan-Yang

    2011-05-30

    The accumulation and effect of cadmium (Cd) on the growth and enzymatic activities changes of antioxidants in Tagetes patula, French marigold, were investigated to reveal the physiological mechanisms corresponding to its Cd tolerance and accumulation. Hydroponically grown T. patula plants were treated with different concentrations of Cd (0, 10, 25, 50 μM Cd Cl(2)) at various regime of times. T. patula accumulated Cd to a maximum of 450 mg Cd kg(-1) dry weight (DW) in shoot and 3500 mg Cd kg(-1) DW in root after 14 days' exposure at 10 and 50 μM Cd Cl(2), respectively. The translocation factors of Cd were greater than 1 in plants exposed to 10 μM Cd Cl(2). Toxic effects were gradually observed with increasing Cd concentration (25 and 50 μM) accompanied with the reduction of biomass, chlorophyll content, decrease of cell viability and the increase level of lipid peroxidation. In leaves of T. patula, the activities of ascorbate peroxidase (APX), glutathione reductase (GR) and superoxide dismutase (SOD) were induced by Cd. However, in roots, activities of APX, GR, SOD and catalase (CAT) were significantly reduced by 25 and 50 μM Cd treatment but not 10 μM Cd. In-gel zymography analysis revealed that Cd induced the enzymatic activities of APX, MnSOD, CuZnSOD and different isozymes of GR in leaves. These results indicate that T. patula is a novel Cd accumulator and able to tolerate with Cd-induced toxicity by activation of its antioxidative defense system. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Effects of cadmium(II) on (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide-induced DNA damage response in human fibroblasts and DNA repair: a possible mechanism of cadmium's cogenotoxicity.

    Science.gov (United States)

    Mukherjee, Jagat J; Gupta, Suresh K; Kumar, Subodh; Sikka, Harish C

    2004-03-01

    Cadmium, a widespread environmental pollutant and a cigarette smoke constituent, enhances the genotoxicity of benzo[a]pyrene (BP). The mechanism(s) underlying the potentiation of BP-induced genotoxicity by Cd2+ is not clearly understood. Our studies of the effects of noncytotoxic concentrations of Cd2+ on the levels of p53 and p21 in (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-treated human fibroblasts showed that Cd2+ decreased BPDE-induced p21 levels in a dose-dependent manner whereas p53 accumulation is attenuated only at higher noncytotoxic concentrations of cadmium. These findings suggest that both the activity and the accumulation of p53 in response of BPDE treatment are inhibited by Cd2+ although the possibility of p53-independent p21 transactivation cannot be ruled out. Exposure of synchronized human fibroblast cells to 0.5 microM of BPDE caused 72% of the cells remaining in G1 phase as compared to 52% in the case of untreated cells. Treatment of the cells with CdCl2 prior to exposing them to BPDE caused a decrease in the G1 population (72 to 54%) in a dose-dependent manner. An in vitro repair assay of BPDE-damaged pUC18 plasmid DNA using untreated and cadmium-treated nucleotide excision repair (NER) proficient HeLa extract showed that cadmium impaired the ability of HeLa cell extract to repair BPDE-damaged pUC18 DNA. Our findings indicate that cadmium not only inhibits NER pathway-dependent repair of BPDE-damaged DNA but also impairs p53 and p21 responses and overrides BPDE-induced G1-S cell cycle arrest. The effect of cadmium on these processes may explain, at least partly, the potentiating effect of the metal on the genotoxicity of BP.

  12. Cadmium-induced glutathionylation of actin occurs through a ROS-independent mechanism: Implications for cytoskeletal integrity

    Energy Technology Data Exchange (ETDEWEB)

    Choong, Grace; Liu, Ying; Xiao, Weiqun; Templeton, Douglas M., E-mail: doug.templeton@utoronto.ca

    2013-10-15

    Cadmium disrupts the actin cytoskeleton in rat mesangial cells, and we have previously shown that this involves a complex interplay involving activation of kinase signaling, protein translocation, and disruption of focal adhesions. Here we investigate the role that glutathionylation of actin plays in Cd{sup 2+}-associated cytoskeletal reorganization. Low concentrations of Cd{sup 2+} (0.5–2 μM) caused an increase in actin glutathionylation by 6 h, whereas at higher concentrations glutathionylation remained at basal levels. Although oxidation with diamide increased glutathionylation, reactive oxygen species (ROS) were not involved in the Cd{sup 2+}-dependent effect, as only Cd{sup 2+} concentrations above 2 μM were sufficient to increase ROS. However, low [Cd{sup 2+}] increased total glutathione levels without affecting the ratio of reduced/oxidized glutathione, and inhibition of glutathione synthesis suppressed actin glutathionylation. Cadmium increased the activity of the enzyme glutaredoxin, which influences the equilibrium between glutathionylated and deglutathionylated proteins and thus may influence levels of glutathionylated actin. Together these observations show that cadmium-dependent effects on actin glutathionylation are affected by glutathione metabolism and not by direct effects of ROS on thiol chemistry. In vitro polymerization assays with glutathionylated actin show a decreased rate of polymerization. In contrast, immunofluorescence of cytoskeletal structure in intact cells suggests that increases in actin glutathionylation accompanying increased glutathione levels occurring under low Cd{sup 2+} exposure are protective in vivo, with cytoskeletal disruption ensuing only when higher Cd{sup 2+} concentrations increase ROS levels and prevent an increase in actin–glutathione conjugates. - Highlights: • Cadmium disrupts the actin cytoskeleton in mesangial cells. • Cadmium induces glutathionylation of actin at low concentrations.

  13. Cadmium toxicity to ringed seals (Phoca hispida): an epidemiological study of possible cadmium-induced nephropathy and osteodystrophy in ringed seals (Phoca hispida) from Qaanaaq in Northwest Greenland

    DEFF Research Database (Denmark)

    Sonne-Hansen, C; Dietz, R; Leifsson, P S

    2002-01-01

    The Greenland marine food chains contain high levels of cadmium, mercury and selenium. Concentrations of cadmium in the kidney of ringed seals (Phoca hispida) from the municipalities of Qaanaaq and Upernavik (Northwest Greenland) are among the highest recorded in the Arctic. The purpose of the st......The Greenland marine food chains contain high levels of cadmium, mercury and selenium. Concentrations of cadmium in the kidney of ringed seals (Phoca hispida) from the municipalities of Qaanaaq and Upernavik (Northwest Greenland) are among the highest recorded in the Arctic. The purpose....... Experience from cadmium-poisoned humans and laboratory mammals indicates that concentrations above 50-200 microg/g wet wt. may induce histopathological changes. Overall, 31 of the ringed seals had cadmium concentrations in the kidney cortex above 50 microg/g wet wt., 11 had concentrations above 100 and one...

  14. Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress

    National Research Council Canada - National Science Library

    Skipper, Anthony; Sims, Jennifer N; Yedjou, Clement G; Tchounwou, Paul B

    2016-01-01

    ... mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG₂) cells...

  15. Cadmium Chloride Induces DNA Damage and Apoptosis of Human Liver Carcinoma Cells via Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Anthony Skipper

    2016-01-01

    Full Text Available Cadmium is a heavy metal that has been shown to cause its toxicity in humans and animals. Many documented studies have shown that cadmium produces various genotoxic effects such as DNA damage and chromosomal aberrations. Ailments such as bone disease, renal damage, and several forms of cancer are attributed to overexposure to cadmium.  Although there have been numerous studies examining the effects of cadmium in animal models and a few case studies involving communities where cadmium contamination has occurred, its molecular mechanisms of action are not fully elucidated. In this research, we hypothesized that oxidative stress plays a key role in cadmium chloride-induced toxicity, DNA damage, and apoptosis of human liver carcinoma (HepG2 cells. To test our hypothesis, cell viability was determined by MTT assay. Lipid hydroperoxide content stress was estimated by lipid peroxidation assay. Genotoxic damage was tested by the means of alkaline single cell gel electrophoresis (Comet assay. Cell apoptosis was measured by flow cytometry assessment (Annexin-V/PI assay. The result of MTT assay indicated that cadmium chloride induces toxicity to HepG2 cells in a concentration-dependent manner, showing a 48 hr-LD50 of 3.6 µg/mL. Data generated from lipid peroxidation assay resulted in a significant (p < 0.05 increase of hydroperoxide production, specifically at the highest concentration tested. Data obtained from the Comet assay indicated that cadmium chloride causes DNA damage in HepG2 cells in a concentration-dependent manner. A strong concentration-response relationship (p < 0.05 was recorded between annexin V positive cells and cadmium chloride exposure. In summary, these in vitro studies provide clear evidence that cadmium chloride induces oxidative stress, DNA damage, and programmed cell death in human liver carcinoma (HepG2 cells.

  16. Aqueous extract of Monodora myristica ameliorates cadmium-induced hepatotoxicity in male rats

    OpenAIRE

    Oyinloye, Babatunji Emmanuel; Adenowo, Abiola Fatimah; Osunsanmi, Foluso Oluwagbemiga; Ogunyinka, Bolajoko Idiat; Nwozo, Sarah Onyenibe; Kappo,Abidemi Paul

    2016-01-01

    In recent years, indigenous medicinal plants exhibiting diverse biological activities have been explored in the amelioration of hepatotoxicity. This study investigates the protective effect of Monodora myristica (MM) on cadmium-induced liver damage in experimental animals. Male Wistar albino rats were maintained on 200?mg/L cadmium: Cd (Cd as CdCl2) in the animals? main drinking water to induce hepatotoxicity. Added to this, the animals received aqueous extracts of MM at a dose of 200 or 400 ...

  17. nitrosoguanidine-induced cadmium resistant mutants of Aspergillus ...

    Indian Academy of Sciences (India)

    Unknown

    of S. cerevisiae (Inouhe et al 1989) were used for under- standing the molecular genetics of cadmium toxicity and ... The pH of the medium was adjusted to 6⋅4 before autoclaving. Cadmium-resistant mutants after isolation ..... Saccharomyces cerevisiae; Biochem. Biophys. Acta 993 51–55. Kimura M, Otaki N and Imano M ...

  18. Induced Positron Annihiliation Investigation of Cadmium Zinc Telluride Crystal Microstructures

    Energy Technology Data Exchange (ETDEWEB)

    D. W. Akers

    2005-06-01

    Cadmium-Zinc-Telluride (CZT) crystals are used in semiconductor radiation detectors for the detection of x-ray and gamma radiation. However, production of detector grade crystals is difficult as small variations in compositional uniformity and primarily the zinc content can significantly affect the ability of the CZT crystal to function as a radiation detector. Currently there are no known nondestructive methods that can be used to identify detector grade crystals. The current test method is to fabricate and test the detector to determine if the crystal is sufficiently uniform and of the correct composition to be considered a detector grade crystal. Consequently, nondestructive detection methods are needed to identify detector grade crystals prior to the fabrication process. The purpose of this feasibility study was to perform a preliminary assessment of the ability of several new, nondestructive technologies based on Induced Positron Annihilation (IPA) to determine if detector grade CZT crystals can be identified. Results of measurements performed on specimens from Fisk University and EV Products, Inc. indicate that both the near surface Distributed Source Positron Annihilation (up to 3 mm penetration) and the volumetric Photon Induced Positron Annihilation methods may be suitable for determining CZT crystal quality. Further work on CZT crystals with a broader range of compositions and detector characteristics is needed to provide a well defined, calibrated, method for assessing CZT crystal quality.

  19. Effect of selenium on cadmium-induced oxidative stress and esterase activity in rat organs

    Directory of Open Access Journals (Sweden)

    Kevin Dzobo

    2013-05-01

    Full Text Available Metal toxicity is a threat mainly in the industrialised world where industry discharges many toxic metals into the environment. We investigated the effects of two metals cadmium and selenium on the cytosolic antioxidant enzymes and esterases in the liver, kidneys and testes of rats. Male Sprague-Dawley rats (n=28 were divided equally into four groups: control, cadmium, selenium and cadmium/selenium. Salts of the metals were administered intraperitoneally for 15 days. In the liver, cadmium treatment (1.67 mg/kg per day resulted in a decrease in catalase activity and an increase superoxide dismutase (SOD activity. Selenium treatment (0.23 mg/kg per day resulted in increases in glutathione s-transferase, catalase and DT-diaphorase activities. Treatment with both cadmium and selenium resulted in an increase in glutathione peroxidase (GPx activity. Esterase activities were significantly lower in the presence of cadmium. In the kidney, cadmium treatment caused a decrease in catalase, DT-diaphorase, and SOD activities and selenium supplementation reversed the cadmium-induced decrease in these enzyme activities. Selenium treatment increased catalase and SOD activities in the kidney. In the testis, cadmium treatment decreased GPx and SOD activities, but at the same time increased catalase and DT-diaphorase activities. Esterase activities increased in the presence of selenium in both the kidney and testis. These results suggest that selenium might be toxic to the liver while at the same time play a protective role against cadmium-induced oxidative stress and toxicity in the kidney and testis.

  20. Foliar application with nano-silicon reduced cadmium accumulation in grains by inhibiting cadmium translocation in rice plants.

    Science.gov (United States)

    Chen, Rui; Zhang, Changbo; Zhao, Yanling; Huang, Yongchun; Liu, Zhongqi

    2017-11-09

    Nano-silicon (Si) may be more effective than regular fertilizers in protecting plants from cadmium (Cd) stress. A field experiment was conducted to study the effects of nano-Si on Cd accumulation in grains and other organs of rice plants (Oryza sativa L. cv. Xiangzaoxian 45) grown in Cd-contaminated farmland. Foliar application with 5~25 mM nano-Si at anthesis stage reduced Cd concentrations in grains and rachises at maturity stage by 31.6~64.9 and 36.1~60.8%, respectively. Meanwhile, nano-Si application significantly increased concentrations of potassium (K), magnesium (Mg), and iron (Fe) in grains and rachises, but imposed little effect on concentrations of calcium (Ca), zinc (Zn), and manganese (Mn) in them. Uppermost nodes under panicles displayed much higher Cd concentration (4.50~5.53 mg kg-1) than other aerial organs. After foliar application with nano-Si, translocation factors (TFs) of Cd ions from the uppermost nodes to rachises significantly declined, but TFs of K, Mg, and Fe from the uppermost nodes to rachises increased significantly. High dose of nano-Si (25 mM) was more effective than low dose of nano-Si in reducing TFs of Cd from roots to the uppermost nodes and from the uppermost nodes to rachises. These findings indicate that nano-Si supply reduces Cd accumulation in grains by inhibiting translocation of Cd and, meanwhile, promoting translocation of K, Mg, and Fe from the uppermost nodes to rachises in rice plants.

  1. Cadmium toxicity to ringed seals (Phoca hispida): an epidemiological study of possible cadmium-induced nephropathy and osteodystrophy in ringed seals (Phoca hispida) from Qaanaaq in Northwest Greenland

    DEFF Research Database (Denmark)

    Sonne-Hansen, C; Dietz, R; Leifsson, P S

    2002-01-01

    of the study was to determine whether cadmium-induced damage in the kidneys and the skeletal system could be detected among 100 ringed seals from Northwest Greenland. The cadmium concentrations in the kidney cortex ranged from 0 to 248 microg/g wet weight (mean=44.5, N=100) in the 99 kidneys examined...... or osteodystrophy. This might be explained by the composition of the ringed seals diet, which contains high levels of vitamin D, calcium, phosphorus, zinc, selenium and protein. These elements are all likely to counteract cadmium-induced damage. It is speculated that ringed seal are not particularly vulnerable......The Greenland marine food chains contain high levels of cadmium, mercury and selenium. Concentrations of cadmium in the kidney of ringed seals (Phoca hispida) from the municipalities of Qaanaaq and Upernavik (Northwest Greenland) are among the highest recorded in the Arctic. The purpose...

  2. Cadmium-induced olfactory dysfunction in rainbow trout: Effects of binary and quaternary metal mixtures

    Energy Technology Data Exchange (ETDEWEB)

    Dew, William A. [Biological Sciences, University of Lethbridge, Lethbridge, Alberta T1 K 3M4 (Canada); Department of Biology, Trent University, Peterborough, Ontario K9 J 7B8 (Canada); Veldhoen, Nik; Carew, Amanda C.; Helbing, Caren C. [Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia V8 P 5C2 Canada (Canada); Pyle, Greg G., E-mail: gregory.pyle@uleth.ca [Biological Sciences, University of Lethbridge, Lethbridge, Alberta T1 K 3M4 (Canada)

    2016-03-15

    Highlights: • Cadmium impairs the olfactory response of rainbow trout. • Nickel and zinc, but not copper, protect against Cd-induced olfactory dysfunction. • Calcium, sodium, and magnesium also protect against the effect of cadmium. • Protection from cadmium is most likely not due to metallothionein expression. - Abstract: A functioning olfactory response is essential for fish to be able to undertake essential behaviors. The majority of work investigating the effects of metals on the olfactory response of fish has focused on single-metal exposures. In this study we exposed rainbow trout to cadmium, copper, nickel, zinc, or a mixture of these four metals at or below the current Canadian Council of Ministers of the Environment guidelines for the protection of aquatic life. Measurement of olfactory acuity using an electro-olfactogram demonstrated that cadmium causes significant impairment of the entire olfactory system, while the other three metals or the mixture of all four metals did not. Binary mixtures with cadmium and each of the other metals demonstrated that nickel and zinc, but not copper, protect against cadmium-induced olfactory dysfunction. Testing was done to determine if the protection from cadmium-induced olfactory dysfunction could be explained by binding competition between cadmium and the other metals at the cell surface, or if the protection could be explained by an up-regulation of an intracellular detoxification pathway, namely metallothionein. This study is the first to measure the effects of binary and quaternary metal mixtures on the olfactory response of fish, something that will aid in future assessments of the effects of metals on the environment.

  3. Protective role of pectin against cadmium-induced testicular toxicity and oxidative stress in rats.

    Science.gov (United States)

    Koriem, Khaled M M; Fathi, Gamal E; Salem, Huda A; Akram, Nabil H; Gamil, Sofie A

    2013-05-01

    Cadmium has been classified as an environmental pollutant and human carcinogen. Pectin is a family of complex polysaccharides that function as hydrating agents and cementing materials for the cellulosic network. The aim of this study was to evaluate the protective role of pectin against cadmium-induced testicular toxicity and oxidative stress in rats. Forty male Wistar rats were divided into five equal groups. Groups 1 and 2 were injected intraperitoneally (i.p.) saline (1 mg/kg) and pectin (50 mg/kg), respectively, two days/weeks over three weeks period. Groups 3-5 were injected i.p. with 1 mg/kg cadmium two days/week while groups 4 and 5 co-administrated i.p. with 25 and 50 mg/kg pectin, respectively, three days/week over three weeks period. The results of the present work revealed that cadmium-exposed rats showed decrease in serum testosterone, dehydroepiandrosterone sulfate and lactate dehydrogenase. Testicular cholesterol, total protein, glucose-6-phosphate dehydrogenase, 3β-hydroxysteroid dehydrogenase, superoxide dismutase, glutathione peroxidase, catalase, glutathione S-transferase and reduced glutathione levels were also decreased while testicular malondialdehyde level was increased after cadmium injection. On the other hand, serum luteinizing hormone, follicle stimulating hormone, sex hormone binding globulin and γ-glutamyl transpeptidase were increased after cadmium exposure. Cadmium also induced sperms loss. Co-administration of pectin with cadmium restores all the above parameters and sperms to the normal levels where pectin at higher dose was more effective than lower one. These results were supported by histochemical investigations. In conclusion, pectin can counteract the testicular toxicity and oxidative stress induced by cadmium and the effect was dose-dependent.

  4. Inhibiting Cadmium Transport Process in Root Cells of Plants: A Review

    Directory of Open Access Journals (Sweden)

    ZHAO Yan-ling

    2016-05-01

    Full Text Available Cadmium(Cd is the most common element found in the heavy-metal contaminated soils in China. Roots of rice and vegetables can concentrate Cd from acid soils, and then transport Cd to above-ground parts. Cd in edible part of plants directly influences the food safety. Cellwall, plasma membrane and organells of root cells in plant can discriminate Cd from other elements. A lot of Cd can be fixed in root cells by precipitation, complexation, compartmentation, and so on, to inhibit its transport from roots to shoot and guarantee the physiological activities in above-ground parts carrying out normally. This paper summarized recent advance on inhibiting Cd transport process in subcellular fractions of root cells of plants, which is in advantage of exploring excellent germplasms and gene resources in the future.

  5. Hydrogen sulfide - cysteine cycle system enhances cadmium tolerance through alleviating cadmium-induced oxidative stress and ion toxicity in Arabidopsis roots.

    Science.gov (United States)

    Jia, Honglei; Wang, Xiaofeng; Dou, Yanhua; Liu, Dan; Si, Wantong; Fang, Hao; Zhao, Chen; Chen, Shaolin; Xi, Jiejun; Li, Jisheng

    2016-12-22

    Cadmium (Cd2+) is a common toxic heavy metal ion. We investigated the roles of hydrogen sulfide (H2S) and cysteine (Cys) in plant responses to Cd2+ stress. The expression of H2S synthetic genes LCD and DES1 were induced by Cd2+ within 3 h, and endogenous H2S was then rapidly released. H2S promoted the expression of Cys synthesis-related genes SAT1 and OASA1, which led to endogenous Cys accumulation. The H2S and Cys cycle system was stimulated by Cd2+ stress, and it maintained high levels in plant cells. H2S inhibited the ROS burst by inducing alternative respiration capacity (AP) and antioxidase activity. H2S weakened Cd2+ toxicity by inducing the metallothionein (MTs) genes expression. Cys promoted GSH accumulation and inhibited the ROS burst, and GSH induced the expression of phytochelatin (PCs) genes, counteracting Cd2+ toxicity. In summary, the H2S and Cys cycle system played a key role in plant responses to Cd2+ stress. The Cd2+ tolerance was weakened when the cycle system was blocked in lcddes1-1 and oasa1 mutants. This paper is the first to describe the role of the H2S and Cys cycle system in Cd2+ stress and to explore the relevant and specificity mechanisms of H2S and Cys in mediating Cd2+ stress.

  6. Cadmium(II) inhibition of human uracil-DNA glycosylase by catalytic water supplantation

    Science.gov (United States)

    Gokey, Trevor; Hang, Bo; Guliaev, Anton B.

    2016-12-01

    Toxic metals are known to inhibit DNA repair but the underlying mechanisms of inhibition are still not fully understood. DNA repair enzymes such as human uracil-DNA glycosylase (hUNG) perform the initial step in the base excision repair (BER) pathway. In this work, we showed that cadmium [Cd(II)], a known human carcinogen, inhibited all activity of hUNG at 100 μM. Computational analyses based on 2 μs equilibrium, 1.6 μs steered molecular dynamics (SMD), and QM/MM MD determined that Cd(II) ions entered the enzyme active site and formed close contacts with both D145 and H148, effectively replacing the catalytic water normally found in this position. Geometry refinement by density functional theory (DFT) calculations showed that Cd(II) formed a tetrahedral structure with D145, P146, H148, and one water molecule. This work for the first time reports Cd(II) inhibition of hUNG which was due to replacement of the catalytic water by binding the active site D145 and H148 residues. Comparison of the proposed metal binding site to existing structural data showed that D145:H148 followed a general metal binding motif favored by Cd(II). The identified motif offered structural insights into metal inhibition of other DNA repair enzymes and glycosylases.

  7. Sensitivity to cadmium-induced genotoxicity in rat testicular cells is associated with minimal expression of the metallothionein gene.

    Science.gov (United States)

    Shiraishi, N; Hochadel, J F; Coogan, T P; Koropatnick, J; Waalkes, M P

    1995-02-01

    Cadmium is a carcinogenic metal. Although the mechanism of tumor induction is unknown, DNA/metal interactions may be involved. Metallothionein can protect against cadmium toxicity in our previous work it was shown to reduce cadmium genotoxicity in cultured cells. To extend these results, the genotoxicity of cadmium was studied in R2C cells, a rat testicular Leydig cell line. The R2C cells were very sensitive to cadmium-induced single-strand DNA damage (SSD), as measured by alkaline elution. SSD occurred in R2C cells after treatment with 25 and 50 microM CdCl2 for 2 hr. Prior work showed other cells required much higher levels of cadmium (approximately 500 microM) to induce genotoxicity. The genotoxic levels of cadmium (25-50 microM) were not cytotoxic in R2C cells as assessed by a metabolic activity (MTT) assay. Pretreatment of R2C cells with a low cadmium dose (2 microM, 24 hr) had no effect on cadmium-induced SSD, in contrast to prior work in other cells where such pretreatments reduced SSD through metallothionein gene activation. In fact, cadmium or zinc treatments resulted in little or no increase in metallothionein gene expression in R2C cells as determined by Northern blot analysis for metallothionein mRNA using cDNA or oligonucleotide probes and radioimmunoassay for metallothionein protein production. Basal metallothionein mRNA was essentially nondetectable. Induction of a cadmium-binding protein in R2C cells did occur, as determined by Cd-heme assay, but did not induce tolerance to SSD. In vivo, the Leydig cell is a target for cadmium carcinogenicity and its cadmium-binding protein is thought not to be a true metallothionein. These results indicate that R2C cells are sensitive to cadmium-induced genotoxicity and that this sensitivity is associated with minimal expression of the metallothionein gene.

  8. Influence of combined antioxidants against cadmium induced testicular damage.

    Science.gov (United States)

    Koyuturk, Meral; Yanardag, Refiye; Bolkent, Sehnaz; Tunali, Sevim

    2006-05-01

    Acute effects of cadmium (Cd) and combined antioxidants were evaluated in Sprague-Dawley rat testes. The rats were subdivided into four groups. Cadmium chloride (2mg/kgday) injected intraperitoneally during 8 days. Vitamin C (250mg/kgday), vitamin E (250mg/kgday) and sodium selenate (0.25mg/kgday) were pretreated by gavage in both of control and cadmium injected rats. Testis lipid peroxidation and glutathione levels were determined by spectrophotometrically. In Cd treated rats, lipid peroxidation levels were increased and glutathione levels were decreased and combined antioxidants treatment was effective in preventing of lipid peroxidation and normalizing glutathione. In Cd treated animals, the degenerative changes were observed, but not observed in the administrated rats with Cd and antioxidants under the light microscope. Proliferating cell nuclear antigen, metallothionein and caspase-3 activities were evaluated by immunohistochemically. Proliferation activity was not seen in the spermatogonial cells of cadmium treated testis. Treatment with antioxidants in cadmium administrated testis leads to pronounced increase in proliferation activity. Cytoplasmic caspase-3 activity was determined in the spermatogenic cells but not spermatogonia in treatment of antioxidants with Cd. In control and treated with antioxidants animals, metallothionein expressions were localized in the cells of seminiferous tubules, although the expression only was observed in the interstitial cells of cadmium treated rats. Results demonstrated beneficial effects of combined vitamin C, vitamin E and selenium treatment in Cd toxicity.

  9. Stimulation of p38 mitogen-activated protein kinase is an early regulatory event for the cadmium-induced apoptosis in human promonocytic cells.

    Science.gov (United States)

    Galán, A; García-Bermejo, M L; Troyano, A; Vilaboa, N E; de Blas, E; Kazanietz, M G; Aller, P

    2000-04-14

    Pulse treatment of U-937 promonocytic cells with cadmium chloride (2 h at 200 microM) provoked apoptosis and induced a rapid phosphorylation of p38 mitogen-activated protein kinase (p38(MAPK)) as well as a late phosphorylation of extracellular signal-regulated protein kinases (ERK1/2). However, although the p38(MAPK)-specific inhibitor SB203580 attenuated apoptosis, the process was not affected by the ERK-specific inhibitor PD98059. The attenuation of the cadmium-provoked apoptosis by SB203580 was a highly specific effect. In fact, the kinase inhibitor did not prevent the generation of apoptosis by heat shock and camptothecin, nor the generation of necrosis by cadmium treatment of glutathione-depleted cells, nor the cadmium-provoked activation of the stress response. The generation of apoptosis was preceded by intracellular H(2)O(2) accumulation and was accompanied by the disruption of mitochondrial transmembrane potential, both of which were inhibited by SB203580. On the other hand, the antioxidant agent butylated hydroxyanisole-inhibited apoptosis but did not prevent p38(MAPK) phosphorylation. In a similar manner, p38(MAPK) phosphorylation was not affected by the caspase inhibitors Z-VAD and DEVD-CHO, which nevertheless prevented apoptosis. These results indicate that p38(MAPK) activation is an early and specific regulatory event for the cadmium-provoked apoptosis in promonocytic cells.

  10. Salidroside Protects against Cadmium-Induced Hepatotoxicity in Rats via GJIC and MAPK Pathways

    Science.gov (United States)

    Han, Tao; Hu, Di; Wang, Yi; Yuan, Yan; Gu, Jianhong; Bian, Jianchun; Zhu, Jiaqiao; Liu, Zong-ping

    2015-01-01

    It is known that cadmium (Cd) induces cytotoxicity in hepatocytes; however, the underlying mechanism is unclear. Here, we studied the molecular mechanisms of Cd-induced hepatotoxicity in rat liver cells (BRL 3A) and in vivo. We observed that Cd treatment was associated with a time- and concentration-dependent decrease in the cell index (CI) of BRL 3A cells and cellular organelle ultrastructure injury in the rat liver. Meanwhile, Cd treatment resulted in the inhibition of gap junction intercellular communication (GJIC) and activation of mitogen-activated protein kinase (MAPK) pathways. Gap junction blocker 18-β-glycyrrhetinic acid (GA), administered in combination with Cd, exacerbated cytotoxic injury in BRL 3A cells; however, GA had a protective effect on healthy cells co-cultured with Cd-exposed cells in a co-culture system. Cd-induced cytotoxic injury could be attenuated by co-treatment with an extracellular signal-regulated kinase (ERK) inhibitor (U0126) and a p38 inhibitor (SB202190) but was not affected by co-treatment with a c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results indicate that ERK and p38 play critical roles in Cd-induced hepatotoxicity and mediate the function of gap junctions. Moreover, MAPKs induce changes in GJIC by controlling connexin gene expression, while GJIC has little effect on the Cd-induced activation of MAPK pathways. Collectively, our study has identified a possible mechanistic pathway of Cd-induced hepatotoxicity in vitro and in vivo, and identified the participation of GJIC and MAPK-mediated pathways in Cd-induced hepatotoxicity. Furthermore, we have shown that salidroside may be a functional chemopreventative agent that ameliorates the negative effects of Cd via GJIC and MAPK pathways. PMID:26070151

  11. Salidroside Protects against Cadmium-Induced Hepatotoxicity in Rats via GJIC and MAPK Pathways.

    Directory of Open Access Journals (Sweden)

    Hui Zou

    Full Text Available It is known that cadmium (Cd induces cytotoxicity in hepatocytes; however, the underlying mechanism is unclear. Here, we studied the molecular mechanisms of Cd-induced hepatotoxicity in rat liver cells (BRL 3A and in vivo. We observed that Cd treatment was associated with a time- and concentration-dependent decrease in the cell index (CI of BRL 3A cells and cellular organelle ultrastructure injury in the rat liver. Meanwhile, Cd treatment resulted in the inhibition of gap junction intercellular communication (GJIC and activation of mitogen-activated protein kinase (MAPK pathways. Gap junction blocker 18-β-glycyrrhetinic acid (GA, administered in combination with Cd, exacerbated cytotoxic injury in BRL 3A cells; however, GA had a protective effect on healthy cells co-cultured with Cd-exposed cells in a co-culture system. Cd-induced cytotoxic injury could be attenuated by co-treatment with an extracellular signal-regulated kinase (ERK inhibitor (U0126 and a p38 inhibitor (SB202190 but was not affected by co-treatment with a c-Jun N-terminal kinase (JNK inhibitor (SP600125. These results indicate that ERK and p38 play critical roles in Cd-induced hepatotoxicity and mediate the function of gap junctions. Moreover, MAPKs induce changes in GJIC by controlling connexin gene expression, while GJIC has little effect on the Cd-induced activation of MAPK pathways. Collectively, our study has identified a possible mechanistic pathway of Cd-induced hepatotoxicity in vitro and in vivo, and identified the participation of GJIC and MAPK-mediated pathways in Cd-induced hepatotoxicity. Furthermore, we have shown that salidroside may be a functional chemopreventative agent that ameliorates the negative effects of Cd via GJIC and MAPK pathways.

  12. Cadmium Induces Apoptosis in Freshwater Crab Sinopotamon henanense through Activating Calcium Signal Transduction Pathway.

    Directory of Open Access Journals (Sweden)

    Jinxiang Wang

    Full Text Available Calcium ion (Ca2+ is one of the key intracellular signals, which is implicated in the regulation of cell functions such as impregnation, cell proliferation, differentiation and death. Cadmium (Cd is a toxic environmental pollutant that can disturb cell functions and even lead to cell death. Recently, we have found that Cd induced apoptosis in gill cells of the freshwater crab Sinopotamon henanense via caspase activation. In the present study, we further investigated the role of calcium signaling in the Cd-induced apoptosis in the animals. Our data showed that Cd triggered gill cell apoptosis which is evidenced by apoptotic DNA fragmentation, activations of caspases-3, -8 and -9 and the presence of apoptotic morphological features. Moreover, Cd elevated the intracellular concentration of Ca2+, the protein concentration of calmodulin (CaM and the activity of Ca2+-ATPase in the gill cells of the crabs. Pretreatment of the animals with ethylene glycol-bis-(b-aminoethyl ether-N,N,N',N'-tetraacetic acid (EGTA, Ca2+ chelator, inhibited Cd-induced activation of caspases-3, -8 and -9 as well as blocked the Cd-triggered apoptotic DNA fragmentation. The apoptotic morphological features were no longer observed in gill cells pretreated with the Ca2+ signaling inhibitors before Cd treatment. Our results indicate that Cd evokes gill cell apoptosis through activating Ca2+-CaM signaling transduction pathway.

  13. The role of intracellular oxidation in death induction (apoptosis and necrosis) in human promonocytic cells treated with stress inducers (cadmium, heat, X-rays).

    Science.gov (United States)

    Galán, A; García-Bermejo, L; Troyano, A; Vilaboa, N E; Fernández, C; de Blas, E; Aller, P

    2001-04-01

    Treatment of U-937 human promonocytic cells with the stress inducers cadmium chloride (2 h at 200 microM), heat (2 h at 42.5 C) or X-rays (20 Gy), followed by recovery, caused death by apoptosis and stimulated caspase-3 activity. In addition, all stress agents caused intracellular oxidation, as measured by peroxide and/or anion superoxide accumulation. However, while pre-incubation with antioxidants (N-acetyl-L-cysteine or butylated hydroxyanisole) inhibited the induction of apoptosis by cadmium and X-rays, it did not affect the induction by heat-shock. Pre-incubation for 24 h with the GSH-depleting agent L-buthionine-[S,R]-sulfoximine (BSO) switched the mode of death from apoptosis to necrosis in cadmium-treated cells. By contrast, BSO only caused minor modifacions in the rate of apoptosis without affecting the mode of death in heat- and X-rays-treated cells. BSO potentiated peroxide accumulation in cells treated with both cadmium and X-rays. However, while the accumulation of peroxides was stable in the case of cadmium, it was transient in the case of X-rays. Moreover, the administration of antioxidants during the recovery period sufficed to prevent necrosis and restore apoptosis in BSO plus cadmium-treated cells. Cadmium and X-rays caused a decrease in intracellular ATP levels, but the decrease was similar in both apoptotic and necrotic cells. Taken together, these results demonstrate that (i) stress inducers cause intracellular oxidation, but oxidation is not a general requirement for apoptosis; and (ii) the duration of the oxidant state seems to be critical in determining the mode of death.

  14. Cadmium-induced programmed cell death signaling in tomato suspension cells

    NARCIS (Netherlands)

    Yakimova, E.T.; Woltering, E.J.; Kapchina-Toteva, V.M.

    2009-01-01

    Here we present a summary of our study on cadmium-induced cell death signaling in a model system of suspension-cultured tomato cells. Exposure of the cells to CdSO4 induced typical for PCD (cytoplasm shrinkage and nuclear condensation) morphological changes of the dead cells. Ethylene and hydrogen

  15. Cadmium restores in vitro splicing activity inhibited by zinc-depletion

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myeong Jin; Ayaki, Hitoshi; Kitamura, Keiko; Nishio, Hisahide [Kobe University Graduate School of Medicine, Department of Public Health, Kobe (Japan); Goji, Junko [Hyogo College of Medicine, Department of Public Health, Hyogo (Japan)

    2006-10-15

    Zinc (Zn)-depletion inhibits the second step of RNA splicing, namely exon-ligation. To investigate the effects of cadmium (Cd) and other metal ions on RNA splicing inhibited by Zn-depletion, we measured in vitro splicing activities in the presence of these metals. Zn-depletion in the splicing reaction mixture was achieved by addition of a Zn-chelator, 1,10-phenanthroline. Cd(II) at 1, 5 and 10 {mu}M restored the splicing activity to 2, 24 and 72% of that in the control reaction mixture, while higher concentrations of Cd(II) decreased the splicing activity, and more than 50 {mu}M Cd(II) showed a complete absence of spliced products. Hg(II) also restored the splicing activity, albeit to a lesser extent, since 5 and 10 {mu}M Hg(II) restored the splicing activity to 3 and 4% of the control value. The other metal ions examined in this study, Co(II), Cu(II), Mg(II) and Mn(II), did not show any restoration of the splicing activity. We concluded that Cd(II) could restore the in vitro splicing activity inhibited by Zn-depletion, although higher concentrations of Cd(II) prevented progress of the RNA splicing reaction. These results suggest that Cd(II) has a bifunctional property regarding RNA splicing, and is stimulatory at low concentrations and inhibitory at high concentrations. (orig.)

  16. Cadmium induced oxidative stress in kidney epithelia cells

    DEFF Research Database (Denmark)

    Bjerregaard, Henning F.

    2007-01-01

    . To minimize DCF photo-oxidation, illumination was limited to 100 ms exposures at 30 s intervals. ROS production rate was determined by linear regression analysis of change in the fluorescence intensity (FI) and expressed as increase in fluorescence intensity units (FIU) per min.    In order to evaluate...... that the Cd induced increase in ROS production was inhibited by the antioxidant N-acetylcysteine, by uncoupling of mitochondrial oxidative phosphorylation from respiration with CCCP and by buffering of intracellular calcium with BAPTA. These results indicate that Cd generate a prompt initiation of ROS...

  17. Cadmium induced oxidative stress in Dunaliella salina | Moradshahi ...

    African Journals Online (AJOL)

    The unicellular green algae Dunaliella salina contains various antioxidants which protect the cell from oxidative damage due to environmental stresses such as heavy metal stress. In the present study, the response of D. salina at the stationary growth phase to oxidative stress generated by cadmium chloride was ...

  18. Histopathological changes in the head kidney induced by cadmium ...

    African Journals Online (AJOL)

    We evaluated the effect of cadmium (Cd) on the structure and function of the head kidney in the freshwater fish Colossoma macropomum (C. macropomum). Juveniles were exposed to 0.1 mg/L CdCl2 for 31 days. Blood samples were examined using hematological tests and head kidney histology was determined by light ...

  19. Antioxidants, cadmium-induced toxicity, serum biochemical and the ...

    African Journals Online (AJOL)

    While the ACP and ACPT changed from 32.6±0.72 and 7 ±Units in the control to 54 and 17 units respectively at 40mg/kg of CD. Furthermore Cadmium also caused positively correlated dose- and time-dependent destruction of the histology of the liver, kidney and testes. These were characterized by vascular congestion, ...

  20. Phosphate-induced cadmium adsorption in a tropical savannah soil ...

    African Journals Online (AJOL)

    The influence of phosphate (P) on cadmium (Cd) adsorption was examined in a savanna soil with long history of different fertilizer amendment. The soil was incubated with P at 0, 250 and 500 mg P kg-1 soil and left to equilibrate for 2 weeks. Cd was added to the P-incubated soil at concentrations ranging from 27, 49 and ...

  1. Cadmium induced MTs synthesis via oxidative stress in yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Liu, Jianghai; Zhang, Yingmei; Huang, Dejun; Song, Gang

    2005-12-01

    Yeast, Saccharomyces cerevisiae, exposed to CdCl2 for 17 h was analysed with reference to survival, MTs and oxidative stress biomarkers. An enhanced accumulation of MDA and the increased activities of SOD and GPx in the Cd-treated yeasts under aerobic condition indicated CdCl2-caused oxidative stress in S. cerevisiae. MTs were significantly induced by CdCl2 under aerobic condition and the induced MTs contents were positively correlated with the accumulation of MDA in this study. However, MTs induction can be prominently inhibited by coincubation with NAC or anaerobic culture via eliminating ROS. This oxidative stress reduction was reflected by the decreases in MDA level and SOD and GPx activities. The results suggest that MTs inductive activity of cadmium in yeast cells was mediated by oxidative stress. In addition, increase of MTs contents was observed in cells untreated with CdCl2 under anaerobic conditions or coincubation with NAC, suggesting MTs are also susceptive to reductive stress.

  2. Gene networks and toxicity pathways induced by acute cadmium exposure in adult largemouth bass (Micropterus salmoides)

    Energy Technology Data Exchange (ETDEWEB)

    Mehinto, Alvine C., E-mail: alvinam@sccwrp.org [Southern California Coastal Water Research Project, Costa Mesa, CA 92626 (United States); Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Prucha, Melinda S. [Department of Human Genetics, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30322 (United States); Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Colli-Dula, Reyna C.; Kroll, Kevin J.; Lavelle, Candice M.; Barber, David S. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States); Vulpe, Christopher D. [Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA 94720 (United States); Denslow, Nancy D. [Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611 (United States)

    2014-07-01

    Highlights: • Low-level acute cadmium exposure elicited tissue-specific gene expression changes. • Molecular initiating events included oxidative stress and disruption of DNA repair. • Metallothionein, a marker of metal exposure, was not significantly affected. • We report effects of cadmium on cholesterol metabolism and steroid synthesis. • Diabetic complications and impaired reproduction are potential adverse outcomes. - Abstract: Cadmium is a heavy metal that can accumulate to toxic levels in the environment leading to detrimental effects in animals and humans including kidney, liver and lung injuries. Using a transcriptomics approach, genes and cellular pathways affected by a low dose of cadmium were investigated. Adult largemouth bass were intraperitoneally injected with 20 μg/kg of cadmium chloride (mean exposure level – 2.6 μg of cadmium per fish) and microarray analyses were conducted in the liver and testis 48 h after injection. Transcriptomic profiles identified in response to cadmium exposure were tissue-specific with the most differential expression changes found in the liver tissues, which also contained much higher levels of cadmium than the testis. Acute exposure to a low dose of cadmium induced oxidative stress response and oxidative damage pathways in the liver. The mRNA levels of antioxidants such as catalase increased and numerous transcripts related to DNA damage and DNA repair were significantly altered. Hepatic mRNA levels of metallothionein, a molecular marker of metal exposure, did not increase significantly after 48 h exposure. Carbohydrate metabolic pathways were also disrupted with hepatic transcripts such as UDP-glucose, pyrophosphorylase 2, and sorbitol dehydrogenase highly induced. Both tissues exhibited a disruption of steroid signaling pathways. In the testis, estrogen receptor beta and transcripts linked to cholesterol metabolism were suppressed. On the contrary, genes involved in cholesterol metabolism were highly

  3. Aloe Vera Extract Effect on Sperm Quality and Testicular Tissue of Rats Induced by Cadmium Chloride

    Directory of Open Access Journals (Sweden)

    F Farhangdoost

    2014-04-01

    Full Text Available Background & aim: A lot of physical and chemical factors cause infertility disorders. Cadmium is a chemical agent which damages the cell structure of the reproductive system. For reducing the effects of various factors, new traditional methods have been used. The aim of this study was to investigate the effects of Aloe vera extract on testicular tissue of rats induced by cadmium chloride. Methods: In this experimental study, 40 male Wistar rats (180-200 gr were randomly divided into four groups. Groups 1 and 2 received Cadmium chloride (1/5 mg / kg/ IP. Mice induced by cadmium chloride were treated with Aloe vera. Control and normal rats were treated with 400 mg/kg of Aloe vera extracts. After 25 days, these rats were weighed and then anesthetized using ether. Blood samples were collected from each individual to assess the level of testosterone and then the animals were debriefed. The testes were removed and transferred to 10% formalin solution. After tissue processing, 5 micron sections were prepared and stained with heamatoxillin-eosin and investigated by light microscope. Data were analyzed by one-way ANOVA test. Results: Mean seminiferous tubular diameter, number of spermatogonia, Leydig and Sertoli cell of cadmium control group compared to the healthy control group showed a significant decrease (p<0.05. The mean sperm count and sperm motility in extract cadmium group and healthy control group was close to normal and displayed a significant difference (p< 0.05. Conclusion: Hydroalcoholic extract of Aloe vera increases the number of spermatogonia, Leydig and Sertoli testicular tissue of mice contaminated with cadmium chloride

  4. Epigallocatechin-3-gallate attenuates cadmium-induced chronic renal injury and fibrosis.

    Science.gov (United States)

    Chen, Jinglou; Du, Lifen; Li, Jingjing; Song, Hongping

    2016-10-01

    Cadmium (Cd) pollution is a serious environmental problem. Kidney is a main target organ of Cd toxicity. This study was undertaken to investigate the potential protective effects of epigallocatechin-3-gallate (EGCG) against chronic renal injury and fibrosis induced by CdCl2. Rat model was induced by exposing to 250 mg/L CdCl2 through drinking water. The renal function was evaluated by detecting the levels of blood urea nitrogen (BUN) and serum creatinine (SCR). The oxidative stress was measured by detecting the levels of malondialdehyde (MDA), nitric oxide (NO), reduced glutathione/oxidized glutathione (GSH/GSSG) and renal enzymatic antioxidant status. Additionally, the renal levels of transforming growth factor-β1 (TGF-β1), Smad3, phosphorylation-Smad3 (pp-Smad3), α-smooth muscle actin (α-SMA), vimentin and E-cadherin were measured by western blot assay. Renal levels of microRNA-21 (miR-21), miR-29a/b/c and miR-192 were measured by quantitative RT-PCR. It was found that EGCG ameliorated the CdCl2-induced renal injury, inhibited the level of oxidative stress, normalized renal enzymatic antioxidant status and E-cadherin level, as well as attenuated the over generation of TGF-β1, pp-Smad3, vimentin and α-SMA. EGCG also decreased the production of miR-21 and miR-192, and enhanced the levels of miR-29a/b/c. These results showed that EGCG could attenuate Cd induced chronic renal injury. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Combined protective effect of vitamins C and E on cadmium induced ...

    African Journals Online (AJOL)

    Our study pertains to the potential ability of vitamin C and/or vitamin E, used as nutritional supplements, to alleviate oxidative stress induced by cadmium. Male rats were randomly divided into five groups of eight each. Group I served as the controls; group II received in their drinking water CdCl2 (200 mg/L); group III ...

  6. Evaluation of laser induced breakdown spectroscopy for cadmium determination in soils

    Science.gov (United States)

    Santos, Dario, Jr.; Nunes, Lidiane C.; Trevizan, Lilian C.; Godoi, Quienly; Leme, Flavio O.; Braga, Jez Willian B.; Krug, Francisco José

    2009-10-01

    Cadmium is known to be a toxic agent that accumulates in the living organisms and present high toxicity potential over lifetime. Efforts towards the development of methods for microanalysis of environmental samples, including the determination of this element by graphite furnace atomic absorption spectrometry (GFAAS), inductively coupled plasma optical emission spectrometry (ICP OES), and inductively coupled plasma-mass spectrometry (ICP-MS) techniques, have been increasing. Laser induced breakdown spectroscopy (LIBS) is an emerging technique dedicated to microanalysis and there is a lack of information dealing with the determination of cadmium. The aim of this work is to demonstrate the feasibility of LIBS for cadmium detection in soils. The experimental setup was designed using a laser Q-switched (Nd:YAG, 10 Hz, λ = 1064 nm) and the emission signals were collimated by lenses into an optical fiber coupled to a high-resolution intensified charge-coupled device (ICCD)-echelle spectrometer. Samples were cryogenically ground and thereafter pelletized before LIBS analysis. Best results were achieved by exploring a test portion (i.e. sampling spots) with larger surface area, which contributes to diminish the uncertainty due to element specific microheterogeneity. Calibration curves for cadmium determination were achieved using certified reference materials. The metrological figures of merit indicate that LIBS can be recommended for screening of cadmium contamination in soils.

  7. Cadmium chloride inhibits lactate gluconeogenesis in mouse renal proximal tubules: An in vitro metabolomic approach with (13)C NMR.

    Science.gov (United States)

    Faiz, Hassan; Boghossian, Michelle; Martin, Guy; Baverel, Gabriel; Ferrier, Bernard; Conjard-Duplany, Agnès

    2015-11-04

    Using isolated mouse renal proximal tubules incubated with lactate as substrate, we have found that the addition of 1-50 μM cadmium chloride (CdCl2) caused a concentration-dependent decrease in lactate utilization, in glucose production and in the cellular level of ATP, coenzyme A, acetyl-coenzyme A and glutathione (reduced and oxidized forms). Combining enzymatic and (13)C NMR measurements in a cellular metabolomic approach, we have shown that, in the presence of 10 μM CdCl2, fluxes through the key-enzymes of gluconeogenesis, phosphoenolpyruvate carboxykinase and glucose-6-phosphatase were greatly depressed by cadmium. This was accompanied by a reduction in fluxes through the enzymes of the tricarboxylic acid cycle. Comparing the mouse and human renal metabolic responses to cadmium, it is interesting to observe that the mouse renal proximal tubule was much more sensitive than the human renal proximal tubule to the adverse effects of CdCl2. As far as renal gluconeogenesis is concerned, the mouse seems to be an appropriate and convenient animal model to study the mechanism of cadmium nephrotoxicity. However, the data obtained in the mouse should be extrapolated to humans with caution because the inhibition of fluxes through the enzymes of the tricarboxylic acid cycle in mouse tubules were not observed in human tubules. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  8. Inhibition of Yap2 activity by MAPKAP kinase Rck1 affects yeast tolerance to cadmium.

    Science.gov (United States)

    Mazzola, Daiane; Pimentel, Catarina; Caetano, Soraia; Amaral, Catarina; Menezes, Regina; Santos, Claudia N; Eleutherio, Elis; Rodrigues-Pousada, Claudina

    2015-09-14

    Yap2 is a cadmium responsive transcription factor that interacts with MAPK-activated protein (MAPKAP) kinase Rck1. We show that Rck1 deletion confers protection against cadmium toxicity and that the mechanism underlying this observation relies on Yap2. Rck1 removal from the yeast genome potentiates Yap2 activity by increasing protein half-life and delaying its nuclear export. As a consequence, several Yap2 antioxidant targets are over-activated by a mechanism that also requires Yap1. Several genes of the cell wall integrity (CWI) pathway are upregulated under cadmium stress in a Yap2 dependent way. We showed that deletion of CWI genes renders yeast cells more sensitive to cadmium. These findings led us to suggest that in response to cadmium stress Yap2 may serve a dual purpose: oxidative stress attenuation and cell wall maintenance. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  9. Cadmium-induced oxidative stress and apoptosis in the testes of frog Rana limnocharis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Hangjun; Cai Chenchen; Shi Cailei; Cao Hui; Han Ziliu [Department of Environmental Sciences, Hangzhou Normal University, Xuelin Road 16, Xiasha Gaojiao Dongqu, Hangzhou, Zhejiang Province, 310036 (China); Jia Xiuying, E-mail: hznujiaxiuying@126.com [Department of Environmental Sciences, Hangzhou Normal University, Xuelin Road 16, Xiasha Gaojiao Dongqu, Hangzhou, Zhejiang Province, 310036 (China)

    2012-10-15

    Highlights: Black-Right-Pointing-Pointer Cd can cause vacuoles and deformity of the spermatogenic cells in the frog testes. Black-Right-Pointing-Pointer Cd can result in oxidative stress in the frog testes. Black-Right-Pointing-Pointer Cd can induce significantly increase of ROS contents triggered DNA damages in the frog testes. Black-Right-Pointing-Pointer Cd can cause apoptosis in the testes of male R. limnocharis. Black-Right-Pointing-Pointer Apoptosis by Cd in the frog testes is related to Caspase-3, Bax and Bcl-2 genes. - Abstract: This study explored the genetic damage induced by cadmium exposure in the testes of Rana limnocharis. Healthy adult frogs were exposed to 2.5, 5, 7.5, or 10 mg/L of cadmium solution for 14 days. The results showed that exposure to these concentrations increased the levels of reactive oxygen species and malondialdehyde content in the testes, clearly indicating a dose-effect relationship. Moreover, the same dosages of Cd{sup 2+} solution increased glutathione (reduced) content, with the values being significantly different from those observed in the control group (P < 0.01). The comet assay results demonstrated that the DNA damage rate, tail length, and tail moment of samples obtained from frogs exposed to 2.5-7.5 mg/L of cadmium solution significantly increased compared with those of samples obtained from the control group (P < 0.01). These findings suggest that cadmium can induce free radical generation, followed by lipid peroxidation and DNA damage. Ultrastructural observation revealed vacuoles in the spermatogenic cells, cell dispersion, incomplete cell structures, and deformed nucleoli. Moreover, cadmium exposure induced significant down-regulation of Bcl-2 expression and up-regulation of Bax and caspase-3 expressions. Taken together, these data indicate that cadmium can induce testicular cell apoptosis in R. limnocharis. Exploring the effects of cadmium on the mechanism of reproductive toxicity in amphibians will help provide a

  10. A hemicellulose-bound form of silicon inhibits cadmium ion uptake in rice (Oryza sativa) cells.

    Science.gov (United States)

    Ma, Jie; Cai, Hongmei; He, Congwu; Zhang, Wenjun; Wang, Lijun

    2015-05-01

    Silicon (Si) alleviates cadmium (Cd) toxicity in rice (Oryza sativa). However, the chemical mechanisms at the single-cell level are poorly understood. Here, a suspension of rice cells exposed to Cd and/or Si treatments was investigated using a combination of plant cell nutritional, molecular biological, and physical techniques including in situ noninvasive microtest technology (NMT), polymerase chain reaction (PCR), inductively coupled plasma mass spectroscopy (ICP-MS), and atomic force microscopy (AFM) in Kelvin probe mode (KPFM). We found that Si-accumulating cells had a significantly reduced net Cd(2+) influx, compared with that in Si-limited cells. PCR analyses of the expression levels of Cd and Si transporters in rice cells showed that, when the Si concentration in the medium was increased, expression of the Si transporter gene Low silicon rice 1 (Lsi1) was up-regulated, whereas expression of the gene encoding the transporter involved in the transport of Cd, Natural resistance-associated macrophage protein 5 (Nramp5), was down-regulated. ICP-MS results revealed that 64% of the total Si in the cell walls was bound to hemicellulose constituents following the fractionation of the cell walls, and consequently inhibited Cd uptake. Furthermore, AFM in KPFM demonstrated that the heterogeneity of the wall surface potential was higher in cells cultured in the presence of Si than in those cultured in its absence, and was homogenized after the addition of Cd. These results suggest that a hemicellulose-bound form of Si with net negative charges is responsible for inhibition of Cd uptake in rice cells by a mechanism of [Si-hemicellulose matrix]Cd complexation and subsequent co-deposition. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  11. Prophylactic Effects of Ethanolic Extract of Irvingia gabonensis Stem Bark against Cadmium-Induced Toxicity in Albino Rats

    Directory of Open Access Journals (Sweden)

    Oluwafemi Adeleke Ojo

    2014-01-01

    Full Text Available The prophylactic effect of ethanolic extract of Irvingia gabonensis stem bark on cadmium-induced oxidative damage in male albino rats’ liver was investigated. Male Wistar rats were divided into control, cadmium, and treatment groups. In the prophylactic experiment, Irvingia gabonensis (200 and 400 mg/kg body weight was administered by oral gavage for 21 days before exposure to cadmium. Antioxidant marker enzymes such as reduced glutathione (GSH levels, catalase (CAT, glutathione peroxidase (GPx, superoxide dismutase (SOD, and lipid peroxidation (LPO were determined in the liver and heart alanine aminotransferase (ALT and aspartate aminotransferase (AST activities were monitored and histological examination was carried out. Results indicate that cadmium-induced rats had significantly increased relative weight of liver and heart when compared to controls. Treatment with Irvingia gabonensis at 200 and 400 mg/kg caused a significant decrease in relative weight of the organs. In cadmium-induced rats, serum ALT and AST activities and levels of LPO were increased whereas hepatic and cardiac marker enzymes significantly decreased. Furthermore, histological alteration in liver and aorta was observed in cadmium untreated rats and was ameliorated in cadmium rats treated with Irvingia gabonensis. In conclusion, the extract indicates antioxidant and hepatoprotective properties that eliminate the deleterious effects of toxic metabolites of cadmium.

  12. Cadmium-induced changes in the growth and oxidative metabolism of pea plants.

    Science.gov (United States)

    Sandalio, L M; Dalurzo, H C; Gómez, M; Romero-Puertas, M C; del Río, L A

    2001-11-01

    The effect of growing pea (Pisum sativum L.) plants with CdCl(2) (0-50 microM) on different plant physiological parameters and antioxidative enzymes of leaves was studied in order to know the possible involvement of this metal in the generation of oxidative stress. In roots and leaves of pea plants Cd produced a significant inhibition of growth as well as a reduction in the transpiration and photosynthesis rate, chlorophyll content of leaves, and an alteration in the nutrient status in both roots and leaves. The ultrastructural analysis of leaves from plants grown with 50 microM CdCl(2), showed cell disturbances characterized by an increase of mesophyll cell size, and a reduction of intercellular spaces, as well as severe disturbances in chloroplast structure. Alterations in the activated oxygen metabolism of pea plants were also detected, as evidenced by an increase in lipid peroxidation and carbonyl-groups content, as well as a decrease in catalase, SOD and, to a lesser extent, guaiacol peroxidase activities. Glutathione reductase activity did not show significant changes as a result of Cd treatment. A strong reduction of chloroplastic and cytosolic Cu,Zn-SODs by Cd was found, and to a lesser extent of Fe-SOD, while Mn-SOD was only affected by the highest Cd concentrations. Catalase isoenzymes responded differentially, the most acidic isoforms being the most sensitive to Cd treatment. Results obtained suggest that growth of pea plants with CdCl(2) can induce a concentration-dependent oxidative stress situation in leaves, characterized by an accumulation of lipid peroxides and oxidized proteins as a result of the inhibition of the antioxidant systems. These results, together with the ultrastructural data, point to a possible induction of leaf senescence by cadmium.

  13. Modulation of cadmium-induced mitochondrial dysfunction and volume changes by temperature in rainbow trout (Oncorhynchus mykiss)

    Energy Technology Data Exchange (ETDEWEB)

    Onukwufor, John O. [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada); Kibenge, Fred [Department of Pathology and Microbiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada); Stevens, Don [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada); Kamunde, Collins, E-mail: ckamunde@upei.ca [Department of Biomedical Sciences, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada C1A 4P3 (Canada)

    2015-01-15

    Highlights: • Interactions of Cd and temperature exacerbate mitochondrial dysfunction and enhance Cd accumulation. • Cd uptake by mitochondria occurs through the Ca uniporter. • Temperature exacerbates Cd-induced mitochondrial volume changes. • Low concentrations of Cd inhibit mitochondrial swelling. - Abstract: We investigated how temperature modulates cadmium (Cd)-induced mitochondrial bioenergetic disturbances, metal accumulation and volume changes in rainbow trout (Oncorhynchus mykiss). In the first set of experiments, rainbow trout liver mitochondrial function and Cd content were measured in the presence of complex I substrates, malate and glutamate, following exposure to Cd (0–100 μM) at three (5, 13 and 25 °C) temperatures. The second set of experiments assessed the effect of temperature on Cd-induced mitochondrial volume changes, including the underlying mechanisms, at 15 and 25 °C. Although temperature stimulated both state 3 and 4 rates of respiration, the coupling efficiency was reduced at temperature extremes due to greater inhibition of state 3 at low temperature and greater stimulation of state 4 at the high temperature. Cadmium exposure reduced the stimulatory effect of temperature on state 3 respiration but increased that on state 4, consequently exacerbating mitochondrial uncoupling. The interaction of Cd and temperature yielded different responses on thermal sensitivity of state 3 and 4 respiration; the Q{sub 10} values for state 3 respiration increased at low temperature (5–13 °C) while those for state 4 increased at high temperature (13–25 °C). Importantly, the mitochondria accumulated more Cd at high temperature suggesting that the observed greater impairment of oxidative phosphorylation with temperature was due, at least in part, to a higher metal burden. Cadmium-induced mitochondrial volume changes were characterized by an early phase of contraction followed by swelling, with temperature changing the kinetics and

  14. Protection of cadmium chloride induced DNA damage by Lamiaceae plants.

    Science.gov (United States)

    Thirugnanasampandan, Ramaraj; Jayakumar, Rajarajeswaran

    2011-10-01

    To analyze the total phenolic content, DNA protecting and radical scavenging activity of ethanolic leaf extracts of three Lamiaceae plants, i.e. Anisomelos malabarica (A. malabarica), Leucas aspera (L. aspera) and Ocimum basilicum (O. basilicum). The total polyphenols and flavonoids were analyzed in the ethanolic leaf extracts of the lamiaceae plants. To determine the DNA protecting activity, various concentrations of the plant extracts were prepared and treated on cultured HepG2 human lung cancer cells. The pretreated cells were exposed to H2O2 to induce DNA damage through oxidative stress. Comet assay was done and the tail length of individual comets was measured. Nitric oxide and superoxide anion scavenging activities of lamiaceae plants were analyzed. Among the three plant extracts, the highest amount of total phenolic content was found in O. basilicum (189.33 mg/g), whereas A. malabarica showed high levels of flavonoids (10.66 mg/g). O. basilicum also showed high levels of DNA protecting (85%) and radical scavenging activity. The results of this study shows that bioactive phenols present in lamiaceae plants may prevent carcinogenesis through scavenging free radicals and inhibiting DNA damage.

  15. Protective effects of blueberries (Vaccinium corymbosum L.) extract against cadmium-induced hepatotoxicity in mice.

    Science.gov (United States)

    Gong, Pin; Chen, Fu-xin; Wang, Lan; Wang, Jing; Jin, Sai; Ma, Yang-min

    2014-05-01

    The oxidative status and morphological changes of mouse liver exposed to cadmium chloride (Cd(II)) and therapeutic potential of blueberry (Vaccinium corymbosum L.) extract against Cd(II)-induced hepatic injury were investigated. A variety of parameters were evaluated, including lipid peroxidation (LPO), protein carbonyl (PCO) level, DNA fragment, as well as antioxidative defense system (i.e., superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH)). Elemental analysis and evaluation of morphological changes and NO levels were also performed. Exposure to Cd(II) led to increased LPO and PCO as well as DNA fragment and a reduction of SOD and CAT activities, however, the content of GSH elevated probably due to biological adaptive-response. In contrast, co-treatment of anthocyanin (Ay) inhibited the increased oxidative parameters as well as restored the activities of antioxidative defense system in a dose-dependent manner. Ay administration regained these morphological changes caused by intoxication of Cd(II) to nearly normal levels. Moreover, the accumulation of Cd(II) in liver may be one of the reasons for Cd(II) toxicity and Ay can chelate with Cd(II) to reduce Cd(II) burden. The influence of Cd(II) on the Zn and Ca levels can also be adjusted by the co-administration of Ay. Exposure to Cd(II) led to an increase of NO and Ay reduced NO contents probably by directly scavenging. Potential mechanisms for the protective effect of Ay have been proposed, including its anti-oxidative and anti-inflammatory effect along with the metal-chelating capacity. These results suggest that blueberry extract may be valuable as a therapeutic agent in combating Cd(II)-induced tissue injury. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. The hepatoprotective effect of putrescine against cadmium-induced acute liver injury

    Energy Technology Data Exchange (ETDEWEB)

    Tzirogiannis, Konstantinos N.; Panoutsopoulos, Georgios I.; Papadimas, George K.; Kondyli, Vasiliki G.; Kourentzi, Kalliopi T.; Hereti, Rosa I.; Mykoniatis, Michael G. [Department of Experimental Pharmacology, Medical School, Athens University, 75 Mikras Asias St., 115 27, Athens (Greece); Demonakou, Maria D. [Histopathology Laboratory, Sismanoglion G.D. Hospital, Sismanogliou 1, Marousi 151 27, Attiki (Greece)

    2004-06-01

    The hepatoprotective effect of putrescine against cadmium liver injury was investigated. Male Wistar rats were injected with a dose of cadmium (6.5 mg CdCl{sub 2}/kg bodyweight, intraperitoneally). Normal saline (group I) or putrescine (300 {mu}mol/kg bodyweight; group II) were injected 2, 5 and 8 h later. A number of animals of both groups were killed 0, 12, 16, 24, 48 or 60 h after cadmium intoxication. Liver tissue was histologically assessed for necrosis, apoptosis, peliosis, mitoses, and inflammatory infiltration. Apoptosis was also quantified by the TUNEL assay for hepatocytes and nonparenchymal liver cells. The discrimination between hepatic cell subpopulations was achieved histochemically. The mitotic index in hematoxylin-eosin-stained sections and by the immunochemical detection of Ki67 nuclear antigen, {sup 3}H-thymidine incorporation into hepatic DNA, and hepatic thymidine kinase activity were all used as indices of liver regeneration. Both hepatocyte apoptosis and liver necrosis evolved in a biphasic temporal pattern. Nonparenchymal cell apoptosis and peliosis hepatis evolved in a monophasic pattern and were correlated closely. Putrescine administration totally reversed liver necrosis and hepatocyte apoptosis. The time profile of nonparenchymal apoptosis was altered and peliosis hepatis was also totally attenuated. In conclusion, putrescine protected hepatocytes and modulated the mechanism of cadmium-induced acute hepatotoxicity. (orig.)

  17. Ameliorating potential of Ashwagandha on cadmium chloride induced changes in weights of visceral organs

    Directory of Open Access Journals (Sweden)

    M.K.

    Full Text Available The present study was carried out to evaluate the protective effect of Ashwagandha on Cadmium chloride induced changes in weights of visceral organs of male rats. Thirty male Wistar rats were divided equally into three groups. Group I was fed on balanced diet of rat pellets for a period of sixty days. The rats in group II were given freshly prepared cadmium chloride solution in the deionised drinking water @200 ppm daily for 60 days. The rats in Group III were fed on Ashwagandha plant powder thoroughly mixed in rat feed at the concentration of 0.5g/Kg (w/w corresponding to 500 ppm level. Simultaneously the rats were given cadmium-chloride @200 ppm in deionised drinking water throughout the experimental period. It is concluded that oral administration of Ashwagandha (Withania somnifera plant powder for 60 days significantly improved the weights of testes, accessory sex organs, liver and kidney in male rats. Simultaneous medication of Ashwagandha (500 ppm in feed reduced the severity of cadmium chloride toxicity in male Wistar rats. [Veterinary World 2008; 1(11.000: 343-345

  18. Halenaquinone inhibits RANKL-induced osteoclastogenesis.

    Science.gov (United States)

    Tsukamoto, Sachiko; Takeuchi, Tomoharu; Kawabata, Tetsuro; Kato, Hikaru; Yamakuma, Michiko; Matsuo, Kanae; El-Desoky, Ahmed H; Losung, Fitje; Mangindaan, Remy E P; de Voogd, Nicole J; Arata, Yoichiro; Yokosawa, Hideyoshi

    2014-11-15

    Halenaquinone was isolated from the marine sponge Petrosia alfiani as an inhibitor of osteoclastogenic differentiation of murine RAW264 cells. It inhibited the RANKL (receptor activator of nuclear factor-κB ligand)-induced upregulation of TRAP (tartrate-resistant acid phosphatase) activity as well as the formation of multinuclear osteoclasts. In addition, halenaquinone substantially suppressed RANKL-induced IκB degradation and Akt phosphorylation. Thus, these results suggest that halenaquinone inhibits RANKL-induced osteoclastogenesis at least by suppressing the NF-κB and Akt signaling pathways. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Comparative analysis of antioxidants against cadmium induced reproductive toxicity in adult male rats.

    Science.gov (United States)

    Jahan, Sarwat; Khan, Mehreen; Ahmed, Shakeel; Ullah, Hizb

    2014-02-01

    The present study was conducted to compare and evaluate the potential benefits of three different antioxidants in reversing cadmium (Cd)-induced reproductive toxicity in adult male rats. Rats (n = 5) weighing 180 +/- 20 gm were divided into five groups (control, Cd, Cd + sulforaphane, Cd + vitamin E, and Cd + plant extract). Treated groups received CdCl2 (0.2 mg/kg), sulforaphane (25 µg/rat), vitamin E (75 mg/kg), and plant extract (100 mg/kg) for 15 days. Blood samples and testicular tissues were obtained for estimation of testosterone, Zn, and Cd concentration and daily sperm production/efficiency of sperm production. Cadmium exposure caused a significant decrease in final body weight (p Cadmium exposure caused a significant decrease (p toxicity. Present findings suggest that Ficus religiosa and sulforaphane are more powerful antioxidants as compared to vitamin E in reversing the oxidative stress and can have a protective role against Cd induced reproductive toxicity in adult male rats. Part of the mechanism involved in this protective role seems to be associated with the antioxidant properties of these agents in reducing reproductive damage.

  20. Protective effect of Lycium barbarum polysaccharides against cadmium-induced testicular toxicity in male mice.

    Science.gov (United States)

    Zhang, Lili; Li, Qin; Zheng, Gaoli; Chen, Yunxiang; Huang, Mincong; Zhang, Lijiang; Lin, Xiaoyan

    2017-06-01

    The present study was performed to determine whether Lycium barbarum polysaccharides (LBPs) would protect mice against cadmium (Cd)-induced testicular toxicity. Seventy-two male mice were randomly divided into six groups with twelve mice per group. Four groups were administered orally with cadmium chloride (5.0 mg per kg body weight) for 35 days and treated in combination with LBPs (0, 10.0, 33.3 or 100 mg kg(-1)) from one week before exposure to Cd until the end of the experiment. The other two groups were administered orally with vehicle or LBP (100 mg kg(-1)) only. Pretreatment with LBP ameliorated the Cd-induced reduction in the body weights, sperm motility as well as the level of testosterone in serum. Moreover, Cd-induced increase in the abnormal sperms was reduced and effects of Cd on the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were reversed. Histopathological examination further confirmed that the LBPs effectively attenuated Cd-induced degeneration of seminiferous tubules. Thus, LBPs attenuated Cd-induced testicular injury by improving the activity of antioxidant enzymatic activity and lowering the oxidative stress, so it could be a potential auxiliary therapeutic agent for Cd-induced testicular toxicity.

  1. The Effects of Agaricus blazei Murill Polysaccharides on Cadmium-Induced Apoptosis and the TLR4 Signaling Pathway of Peripheral Blood Lymphocytes in Chicken.

    Science.gov (United States)

    Liu, Wenjing; Ge, Ming; Hu, Xuequan; Lv, Ai; Ma, Dexing; Huang, Xiaodan; Zhang, Ruili

    2017-11-01

    In this study, we investigated the effects of Agaricus blazei Murill polysaccharides (ABP) on cadmium (Cd)-induced apoptosis and the TLR4 signaling pathway of chicken peripheral blood lymphocytes (PBLs). Seven-day-old healthy chickens were randomly divided into four groups, and each group contained 20 males. The cadmium-supplemented diet group (Cd group) was fed daily with full feed that contained 140 mg cadmium chloride (CdCl2)/kg and 0.2 mL saline. The A. blazei Murill polysaccharide diet group (ABP group) was fed daily with full feed with 0.2 mL ABP solution (30 mg/mL) by oral gavage. The cadmium-supplemented plus A. blazei Murill polysaccharide diet group (Cd + ABP group) was fed daily with full feed containing 140 mg CdCl2/kg and 0.2 mL ABP solution (30 mg/mL) by gavage. The control group was fed daily with full feed with 0.2 mL saline per day. We measured the apoptosis rate and messenger RNA (mRNA) levels of apoptosis genes (caspase-3, Bax, and Bcl-2), the mRNA levels of TLR4 and TLR4 signaling pathway-related factors (MyD88, TRIF, NF-κB, and IRF3), the TLR4 protein expression, and the concentrations of inflammatory cytokines (IL-1β, IL-6, and TNF-α) in chicken PBLs. The results showed that the PBL apoptosis rate was significantly increased, the mRNA levels of caspase-3 and Bax were significantly increased, while that of Bcl-2 was significantly reduced. The Bax/Bcl-2 ratio was significantly increased in the Cd group at 20, 40, and 60 days after treatment compared with that in the control group. After treatment with ABP, the above changes were clearly suppressed. At the same time, ABP reduced the concentrations of IL-1β, IL-6, and TNF-α induced by Cd. We also found that ABP inhibited the TLR4 mRNA level and protein expression and inhibited the mRNA levels of MyD88, TRIF, NF-κB, and IRF3. The results demonstrated that Cd could induce apoptosis, activate the TLR4 signaling pathway, and induce the expression of inflammatory cytokines in chicken

  2. Planarians as models of cadmium-induced neoplasia provide measurable benchmarks for mechanistic studies.

    Science.gov (United States)

    Voura, Evelyn B; Montalvo, Melissa J; Dela Roca, Kevin T; Fisher, Julia M; Defamie, Virginie; Narala, Swami R; Khokha, Rama; Mulligan, Margaret E; Evans, Colleen A

    2017-08-01

    Bioassays of planarian neoplasia highlight the potential of these organisms as useful standards to assess whether environmental toxins such as cadmium promote tumorigenesis. These studies complement other investigations into the exceptional healing and regeneration of planarians - processes that are driven by a population of active stem cells, or neoblasts, which are likely transformed during planarian tumor growth. Our goal was to determine if planarian tumorigenesis assays are amenable to mechanistic studies of cadmium carcinogenesis. To that end we demonstrate, by examining both counts of cell populations by size, and instances of mitosis, that the activity of the stem cell population can be monitored. We also provide evidence that specific biomodulators can affect the potential of planarian neoplastic growth, in that an inhibitor of metalloproteinases effectively blocked the development of the lesions. From these results, we infer that neoblast activity does respond to cadmium-induced tumor growth, and that metalloproteinases are required for the progression of cancer in the planarian. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Cadmium chloride-induced testicular toxicity in male wistar rats; prophylactic effect of quercetin, and assessment of testicular recovery following cadmium chloride withdrawal.

    Science.gov (United States)

    Nna, Victor U; Ujah, Godwin A; Mohamed, Mahaneem; Etim, Kingsley B; Igba, Benedict O; Augustine, Ele R; Osim, Eme E

    2017-10-01

    This study assessed the effect of quercetin (QE) on cadmium chloride (CdCl2) - induced testicular toxicity, as well as the effect of withdrawal of CdCl2 treatment on same. Thirty male Wistar rats aged 10 weeks old and weighing 270-300g were assigned into 5 groups and used for this study. Rats in groups 1-4 were administered vehicle, CdCl2 (5mg/kg bwt), CdCl2+QE (5mg/kg bwt and 20mg/kg bwt, respectively) or QE (20mg/kg bwt) orally for 4 weeks. Group 5 rats received CdCl2, with 4 weeks recovery period. Results showed that cadmium accumulated in serum, testis and epididymis, decreased body weight, testicular and epididymal weights, sperm count, motility and viability. Cadmium decreased serum concentrations of reproductive hormones, but increased testicular glucose, lactate and lactate dehydrogenase activity. Cadmium decreased testicular enzymatic (superoxide dismutase, catalase and glutathione peroxidase) and non-enzymatic (glutathione, vitamins C and E) antioxidants, and increased malondialdehyde and hydrogen peroxide. Cadmium down-regulated Bcl-2 protein, up-regulated Bax protein, increased Bax/Bcl-2 ratio and cleaved caspase-3 activity. Histopathology of the testis showed decreased Johnsen's score and Leydig cell count. These negative effects were attenuated by QE administration, while withdrawal of CdCl2 did not appreciably reverse toxicity. We conclude that QE better protected the testis from CdCl2 toxicity than withdrawal of CdCl2 administration. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Cadmium-induced disruption of environmental exploration and chemical communication in matrinxa, Brycon amazonicus

    Energy Technology Data Exchange (ETDEWEB)

    Honda, R.T. [Centro Universitario Nilton Lins - CUNL, Laboratory of Toxicology, Av. Prof. Nilton Lins 3259, Parque das Laranjeiras, Zip 69058-040 Manaus, AM (Brazil)], E-mail: rhonda@niltonlins.br; Fernandes-de-Castilho, M. [Universidade Federal do Parana - UFPR, Research Center on Animal Welfare (RECAW), Laboratory of Studies on Animal Stress, Department of Physiology, Sector of Biological Science, Jardim das Americas, Zip 81531-970 Curitiba, PR (Brazil); Val, A.L. [Instituto Nacional de Pesquisas da Amazonia - INPA, Laboratory of Ecophysiology and Molecular Evolution, Av. Andre Araujo 2936, Aleixo, Zip 69083-000 Manaus, AM (Brazil)

    2008-09-17

    The effects of cadmium exposure on both environment exploration and behavioral responses induced by alarm substance in matrinxa (Brycon amazonicus), a fish species endemic to the Amazon basin, were investigated. Fish exposed to 9.04 {+-} 0.07 {mu}g/L waterborne cadmium for 96 h followed by 24 h depuration period in clean water, were video-recorded for 15 min, followed by immediate introduction of conspecific skin extract to the tank and a new 30 min period of fish video-recording. Cd-exposed matrinxa showed a significantly lowered locomotor activity (t-test t{sub 12} = 2.7; p = 0.025) and spatial distribution (t-test t{sub 12} = 2.4; p = 0.03) relative to the unexposed control fish prior to the alarm substance introduction, and did not present any significant reaction when the skin extract was introduced. The control fish, in opposite, showed a higher level of activity and spatial distribution prior the skin extract contact and significantly decreased their response after the chemical stimulus (locomotion-repeated-measure ANOVA F{sub 1,11} = 5.6; p = 0.04; spatial distribution F{sub 1,11} = 19.4; p = 0.001). In conclusion, exposure to a low level of cadmium affects both the environment exploration performance and the conspecific chemical communication in matrinxa. If the reduced environmental exploration performance of Cd-exposed fish is an adjustment to the compromised chemical communication or an independent effect of cadmium is the next step to be investigated.

  5. Tubulin posttranslational modifications induced by cadmium in the sponge Clathrina clathrus.

    Science.gov (United States)

    Ledda, F D; Ramoino, P; Ravera, S; Perino, E; Bianchini, P; Diaspro, A; Gallus, L; Pronzato, R; Manconi, R

    2013-09-15

    As sessile filter feeders, sponges are exposed to environmental stress due to pollutants of both anthropogenic and natural origins and are able to accumulate harmful substances. Thus, sponges are considered a good tool for the biomonitoring of coastal areas. In this study, we used biochemical and immunocytochemical analyses to provide new data on the cadmium-related changes in sponge cells. In particular, we analyzed the effects of different concentrations of cadmium on the microtubule network in the calcisponge Clathrina clathrus. Quantitative densitometry of the immunoblots showed that, while the levels of α- and β-tubulin remained relatively constant in C. clathrus when exposed to 1 and 5 μM CdCl2, there were progressive shifts in the levels of some tubulin isoforms. Exposure for 24h to sublethal concentrations of cadmium reduced the level of tyrosinated α-tubulin and enhanced the levels of acetylated and detyrosinated α-tubulin relative to the levels in controls. Confocal microscopy analysis of immunolabeled tissue sections showed that the inhibitory effect of cadmium was associated with a decrease in the labeling of the cells with a monoclonal antibody that recognizes tyrosinated α-tubulin. By contrast, the reactivity with a monoclonal antibody that recognizes acetylated α-tubulin and with a polyclonal antibody specific for detyrosinated α-tubulin was enhanced at the same time points. Because the acetylation and detyrosination of α-tubulin occur on stable microtubules, the marked enhancement of α-tubulin acetylation and detyrosination in Cd(2+)-treated cells indicates that divalent Cd ions stabilize microtubules. The possibility that Cd(2+) may increase the stability of cytoplasmic microtubules was tested by exposing Cd(2+)-treated cells to a cold temperature (0°C). As shown, the microtubule bundles induced by Cd(2+), which were labeled by the monoclonal antibodies against acetylated and detyrosinated α-tubulin, were resistant to cold. Copyright

  6. Protective effect of aqueous Curry leaf (Murraya koenigii) extract against cadmium-induced oxidative stress in rat heart.

    Science.gov (United States)

    Mitra, Elina; Ghosh, Arnab K; Ghosh, Debosree; Mukherjee, Debasri; Chattopadhyay, Aindrila; Dutta, Santanu; Pattari, Sanjib Kumar; Bandyopadhyay, Debasish

    2012-05-01

    Treatment of rats with a low dose of cadmium chloride caused a significant damage in the rat cardiac tissue indicated by the increase in the level of serum glutamate oxaloacetate transaminase and lactate dehydrogenase1 activities. Histological studies confirmed the damage due to cadmium. That cadmium-induced tissue damage was caused due to oxidative stress was evident from the changes observed in the levels of lipid peroxidation and reduced glutathione, the protein carbonyl content, and the alterations in the activities of cardiac antioxidant and pro-oxidant enzymes. Treatment of rats with cadmium also caused alterations in the activities of mitochondrial Kreb's cycle as well as respiratory chain enzymes. All these changes were ameliorated when the rats were pre-treated with an aqueous extract of Curry leaf (Murraya koenigii). The studies indicated that the aqueous extract of Curry leaf protects the rat cardiac tissue against cadmium-induced oxidative stress possibly through its antioxidant activity. As curry leaf is consumed by people as part of their diet in India and South-East Asian and some European countries as well, and, as it has no reported side-effects, the results seem to have relevance at places where humans are exposed to cadmium environmentally or occupationally. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Cadmium-induced immune abnormality is a key pathogenic event in human and rat models of preeclampsia.

    Science.gov (United States)

    Zhang, Qiong; Huang, Yinping; Zhang, Keke; Huang, Yanjun; Yan, Yan; Wang, Fan; Wu, Jie; Wang, Xiao; Xu, Zhangye; Chen, Yongtao; Cheng, Xue; Li, Yong; Jiao, Jinyu; Ye, Duyun

    2016-11-01

    With increased industrial development, cadmium is an increasingly important environmental pollutant. Studies have identified various adverse effects of cadmium on human beings. However, the relationships between cadmium pollution and the pathogenesis of preeclampsia remain elusive. The objective of this study is to explore the effects of cadmium on immune system among preeclamptic patients and rats. The results showed that the cadmium levels in the peripheral blood of preeclamptic patients were significantly higher than those observed in normal pregnancy. Based on it, a novel rat model of preeclampsia was established by the intraperitoneal administration of cadmium chloride (CdCl2) (0.125 mg of Cd/kg body weight) on gestational days 9-14. Key features of preeclampsia, including hypertension, proteinuria, placental abnormalities and small foetal size, appeared in pregnant rats after the administration of low-dose of CdCl2. Cadmium increased immunoglobulin production, mainly angiotensin II type 1-receptor-agonistic autoantibodies (AT1-AA), by increasing the expression of activation-induced cytosine deaminase (AID) in B cells. AID is critical for the maturation of antibody and autoantibody responses. In addition, angiotensin II type 1-receptor-agonistic autoantibody, which emerged recently as a potential pathogenic contributor to PE, was responsible for the deposition of complement component 5 (C5) in kidneys of pregnant rats via angiotensin II type 1 receptor (AT1R) activation. C5a is a fragment of C5 that is released during C5 activation. Selectively interfering with C5a signalling by a complement C5a receptor-specific antagonist significantly attenuated hypertension and proteinuria in Cd-injected pregnant rats. Our results suggest that cadmium induces immune abnormalities that may be a key pathogenic contributor to preeclampsia and provide new insights into treatment strategies of preeclampsia. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Preferential Elimination of Older Erythrocytes in Circulation and Depressed Bone Marrow Erythropoietic Activity Contribute to Cadmium Induced Anemia in Mice.

    Science.gov (United States)

    Chatterjee, Sreoshi; Saxena, Rajiv K

    2015-01-01

    Feeding cadmium chloride (50 or 1000 ppm CdCl2 in drinking water, ad libitum) to C57BL/6 mice resulted in a significant and sustained fall in blood erythrocyte count and hemoglobin levels that started 4 and 3 weeks after the start of 50 and 1000 ppm cadmium doses respectively. A transient yet significant reticulocytosis occurred during the first 4 weeks of cadmium treatment. Using the recently developed double in vivo biotinylation (DIB) technique, turnover of erythrocyte cohorts of different age groups was simultaneously monitored in control and cadmium treated mice. A significant accumulation of younger erythrocytes and a concomitant decline in the relative proportions of older erythrocytes in circulation was observed in both 50 and 1000 ppm cadmium groups indicating that older erythrocytes were preferentially eliminated in cadmium induced anemia. A significant increase in the erythropoietin levels in plasma was seen in mice exposed to 1000 ppm cadmium. Levels of inflammatory cytokines (IL1A, IL6, TNFα, IFNγ) were however not significantly altered in cadmium treated mice. A significant increase in cellular levels of reactive oxygen species (ROS) was observed in older erythrocytes in circulation but not in younger erythrocytes. Erythropoietic activity in the bone marrows and spleens of cadmium treated mice was examined by monitoring the relative proportion of cells belonging to the erythroid line of differentiation in these organs. Erythroid cells in bone marrow declined markedly (about 30%) in mice in the 1000 ppm cadmium group but the decline was not significant in the 50 ppm cadmium group. Cells representing various stages of erythroid differentiation in bone marrow and spleen were enumerated flow cytometrically by double staining with anti-Ter119 and anti-transferrin receptor (CD71) monoclonal antibodies. Decline of erythroid cells was essentially confined to pro-erythroblast and erythroblast-A, along with a concurrent increase in the splenic erythroid

  9. Protective effect of boric acid on lead- and cadmium-induced genotoxicity in V79 cells.

    Science.gov (United States)

    Ustündağ, Aylin; Behm, Claudia; Föllmann, Wolfram; Duydu, Yalçin; Degen, Gisela H

    2014-06-01

    The toxic heavy metals cadmium (Cd) and lead (Pb) are important environmental pollutants which can cause serious damage to human health. As the metal ions (Cd(2+) and Pb(2+)) accumulate in the organism, there is special concern regarding chronic toxicity and damage to the genetic material. Metal-induced genotoxicity has been attributed to indirect mechanisms, such as induction of oxidative stress and interference with DNA repair. Boron is a naturally occurring element and considered to be an essential micronutrient, although the cellular activities of boron compounds remain largely unexplored. The present study has been conducted to evaluate potential protective effects of boric acid (BA) against genotoxicity induced by cadmium chloride (CdCl2) and lead chloride (PbCl2) in V79 cell cultures. Cytotoxicity assays (neutral red uptake and cell titer blue assay) served to determine suitable concentrations for subsequent genotoxicity assays. Chromosomal damage and DNA strand breaks were assessed by micronucleus tests and comet assays. Both PbCl2 and CdCl2 (at 3, 5 and 10 µM) were shown to induce concentration-dependent increases in micronucleus frequencies and DNA strand breaks in V79 cells. BA itself was not cytotoxic (up to 300 µM) and showed no genotoxic effects. Pretreatment of cells with low levels of BA (2.5 and 10 µM) was found to strongly reduce the genotoxic effects of the tested metals. Based on the findings of this in vitro study, it can be suggested that boron provides an efficient protection against the induction of DNA strand breaks and micronuclei by lead and cadmium. Further studies on the underlying mechanisms for the protective effect of boron are needed.

  10. Interactive effects of cadmium and Microcystis aeruginosa (cyanobacterium) on the growth, antioxidative responses and accumulation of cadmium and microcystins in rice seedlings.

    Science.gov (United States)

    Kuang, Xiaolin; Gu, Ji-Dong; Tie, BaiQing; Yao, Bangsong; Shao, Jihai

    2016-10-01

    Cadmium pollution and harmful cyanobacterial blooms are two prominent environmental problems. The interactive effects of cadmium(II) and harmful cyanobacteria on rice seedlings remain unknown. In order to elucidate this issue, the interactive effects of cadmium(II) and Microcystis aeruginosa FACHB905 on the growth and antioxidant responses of rice seedling were investigated in this study, as well as the accumulation of cadmium(II) and microcystins. The results showed that the growth of rice seedlings was inhibited by cadmium(II) stress but promoted by inoculation of M. aeruginosa FACHB905. cadmium(II) stress induced oxidative damage on rice seedlings. Inoculation of M. aeruginosa FACHB905 alleviated the toxicity of cadmium(II) on rice seedlings. The accumulation of cadmium(II) in rice seedlings was decreased by M. aeruginosa FACHB905, but the translocation of cadmium(II) from root to shoot was increased by this cyanobacterium. The accumulation of microcystins in rice seedlings was decreased by cadmium(II). Results presented in this study indicated that cadmium(II) and M. aeruginosa had antagonistic toxicity on rice seedlings. The findings of this study throw new light on evaluation of ecological- and public health-risks for the co-contamination of cadmium(II) and harmful cyanobacteria.

  11. Cadmium-induced malignant transformation in rat liver cells: role of aberrant oncogene expression and minimal role of oxidative stress.

    Science.gov (United States)

    Qu, Wei; Diwan, Bhalchandra A; Reece, Jeffrey M; Bortner, Carl D; Pi, Jingbo; Liu, Jie; Waalkes, Michael P

    2005-04-10

    Our study examined the role of oxidative stress and aberrant gene expression in malignant transformation induced by chronic, low-level cadmium exposure in non-tumorigenic rat liver epithelial cell line, TRL 1215. Cells were cultured in 1.0 microM cadmium (as CdCl(2)) for up to 28 weeks and compared to passage-matched control cells. The level of cadmium used for transformation produced no evidence of increased superoxide (O(2) (-*.)) or hydrogen peroxide (H(2)O(2)) levels in the early stages of exposure (hr). The chronic cadmium exposed liver epithelial cells (CCE-LE) were hyperproliferative with a growth rate about 3-fold higher than control cells. CCE-LE cells produced highly aggressive tumors upon inoculation into mice confirming malignant transformation. Analysis of cellular reactive oxygen species (ROS) showed that CCE-LE cells possessed markedly lower basal levels of intracellular O(2) (-*.)and H(2)O(2) and were very tolerant to high-dose (50 microM) cadmium-induced ROS. Time course studies showed the production of ROS by high-dose cadmium was abolished well in advance of malignant transformation. In contrast, marked overexpression of the oncogenes c-myc and c-jun occurred in transformed CCE-LE cells as evidenced by up to 10-fold increases in both transcript and protein. A significant increase in DNA-binding activity of the transcription factors AP-1 and NF-kappaB occurred in CCE-LE cells. Increases in oncogene expression and transcription factor activity occurred concurrently with malignant transformation. Thus, cadmium-induced ROS occurs as an early, high-dose event but is abolished well in advance of malignant transformation. Low-level chronic cadmium triggers oncogene overexpression possibly by altering critical transcription factor activity. Such changes in cellular gene expression likely culminate in the loss of growth control and cadmium-induced neoplastic transformation in CCE-LE cells, whereas generation of ROS by cadmium seemed to play a minimal role

  12. Protective effect of an aphrodisiac herb Tribulus terrestris Linn on cadmium-induced testicular damage

    OpenAIRE

    Rajendar, B.; K Bharavi; Rao, G S; P.V.S Kishore; Kumar, P. Ravi; Kumar, C. S. V. Satish; Patel, T. Pankaj

    2011-01-01

    Aim: The aim of the present study was to investigate whether Tribulus terrestris Linn (TT) could protect the cadmium (Cd)-induced testicular tissue peroxidation in rats and to explore the underlying mechanism of the same. Materials and Methods: In vitro and in vivo studies were conducted to know the protective effect of ethanolic extract of TT (eTT) in Cd toxicity. In in vitro studies, total antioxidant and ferrous metal ion chelating activity of TT was studied. In vivo studies were conducted...

  13. Laser-induced photodynamic effects at silica nanocomposite based on cadmium sulphide quantum dots.

    Science.gov (United States)

    Voznesenskiy, S S; Sergeev, A A; Galkina, A N; Kulchin, Yu N; Shchipunov, Yu A; Postnova, I V

    2014-01-27

    In this paper we study the laser-induced modification of optical properties of nanocomposite based on cadmium sulphide quantum dots encapsulated into thiomalic acid shell which were embedded into a porous silica matrix. We found red shift of luminescence of the nanocomposite when exposed to laser radiation at λ = 405 nm. Using pump-probe method and Small-Angle X-ray Scattering technique it was found that laser radiation at λ = 405 nm also increases the absorption coefficient of the nanocomposite in 15 times due to agglomeration of quantum dots. The modification of absorption properties is fully reversible.

  14. Cadmium-induced changes in vacuolar aspects of Arabidopsis thaliana.

    Science.gov (United States)

    Sharma, Shanti S; Yamamoto, Kotaro; Hamaji, Kohei; Ohnishi, Miwa; Anegawa, Aya; Sharma, Shashi; Thakur, Sveta; Kumar, Vijay; Uemura, Tomohiro; Nakano, Akihiko; Mimura, Tetsuro

    2017-05-01

    We have examined the changes due to Cd treatment in the vacuolar form in root tip cortical cells in Arabidopsis thaliana employing a transformant with GFP fused to a tonoplast protein. A Cd-induced enhancement in complexity with general expansion of vacuolar system within 24 h was evident. The changes in the vacuolar form were dependent on the applied Cd concentrations. Concomitantly, as revealed through dithizone staining, Cd accumulated in the seedling roots exhibiting abundance of Cd-dithizone complexes in root tip, root hairs and vasculature. To get insight into the involvement of SNARE protein-mediated vesicle fusion in Cd detoxification, the magnitude of Cd toxicity in a couple of knock out mutants of the vacuolar Qa-SNARE protein VAM3/SYP22 was compared with that in the wild type. The Cd toxicity appeared to be comparable in the mutants and the wild type. In order to analyze the Cd effects at cellular level, we treated the Arabidopsis suspension-cultured cells with Cd. Cd, however, did not induce a change in the vacuolar form in suspension-cultured cells although Cd measured with ICP-MS was obviously taken up into the cell. The V-ATPase activity in the microsomal fractions from vacuoles isolated from A. thaliana suspension cultured cells remained unaffected by Cd. Changes in the levels of certain metabolites of Cd-treated cells were also not so distinct except for those of glutathione. The significance of findings is discussed. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  15. Can zinc supplementation ameliorate cadmium-induced alterations in the bioelement content in rabbits?

    Science.gov (United States)

    Bulat, Zorica; Đukić-Ćosić, Danijela; Antonijević, Biljana; Buha, Aleksandra; Bulat, Petar; Pavlović, Zoran; Matović, Vesna

    2017-03-01

    The study was designed to investigate the influence of zinc (Zn) supplementation on cadmium-induced alterations in zinc, copper (Cu), and magnesium (Mg) status in rabbits. For this purpose, the concentrations of cadmium (Cd), Zn, Cu, and Mg were estimated in the blood, liver, kidney, and bone. The rabbits were divided in a control group, a Cd group-animals intoxicated orally with Cd (10 mg kg-1 bw, as aqueous solution of Cd-chloride), and a Cd+Zn group-animals intoxicated with the same dose of Cd and co-treated with Zn (20 mg kg-1 bw, as aqueous solution of Zn-sulphate). Solutions were administered orally, every day for 28 days. Sample mineralisation was performed with concentrated nitric acid (HNO3) and perchloric acid (HClO4) (4:1) and metal concentrations were determined by atomic absorption spectrophotometry (AAS). Zinc supplementation improved some of Cd-induced disturbances in bioelement levels in the investigated tissues. Beneficial effects of Zn on Zn and Cu levels were observed in blood, as well as on the Cu kidney level. The calculated values for Cu/Zn, Mg/Zn, and Mg/Cu ratios in blood suggest that Zn co-treatment reduces Cd-induced changes in bioelement ratios in blood.

  16. In Vitro Inhibition of Human Sperm Creatine Kinase by Nicotine,Cotinine and Cadmium, as a Mechanism in Smoker Men Infertility

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Ghaffari

    2009-01-01

    Full Text Available Background: Nicotine, cotinine and cadmium are harmful components of cigarettes that have aneffect on human reproductive function. Although the effects of cigarette smoke on male reproductivefunction is characterized in several articles its mechanism of action is still unknown.In the present study, we investigate the effect of nicotine, cotinine and cadmium on human spermcreatine kinase activity in vitro.Materials and Methods: Total creatine kinase activity is measured in sperm homogenates afterchromatography on a diethylaminoethyl cellulose (DEAE-32 column.Results: We show that creatine kinase activity is significantly inhibited by nicotine (44%, cotinine(39% and cadmium (65% at a concentration of 60 μg/ml. Kinetic studies reveal that the inhibitoryeffect of nicotine, cotinine and cadmium are competitive in relation to creatine phosphate.Conclusion: Considering the importance of creatine kinase activity for normal sperm energymetabolism, our results suggest that inhibition of this enzyme by nicotine, cotinine and cadmium maybe an important mechanism in infertility amongst male smokers. However, further investigationsare needed to elucidate the exact mechanism of cigarette effect on male reproductive function atthe molecular level.

  17. Cadmium-induced proteome remodeling regulated by Spc1/Sty1 and Zip1 in fission yeast.

    Science.gov (United States)

    Guo, Lan; Ghassemian, Majid; Komives, Elizabeth A; Russell, Paul

    2012-09-01

    Stress-activated protein kinases and transcription factors are crucial for surviving exposure to cadmium and other environmental toxicants, but their effects on the proteome remain largely unexplored. In this study, isobaric tag for relative and absolute quantitation reveals that cadmium stress triggers rapid proteome remodeling in the fission yeast Schizosaccharomyces pombe. Spc1/Sty1, a mitogen/stress-activated protein kinase homologous to human p38 and Saccharomyces cerevisiae Hog1, controls many of these changes, including enzymes of the oxidative phase of the pentose phosphate pathway and trehalose metabolism. Genetic studies indicate that control of carbohydrate metabolism by Spc1 is required for cadmium tolerance. The bZIP transcription factor Zip1, which is functionally related to human Nrf2 and S. cerevisiae Met4, has a smaller effect on cadmium-induced proteome remodeling, but it is required for production of key proteins involved in sulfur metabolism, which are essential for cadmium resistance. These studies reveal how Spc1 and Zip1 independently reshape the proteome to modulate cellular defense mechanisms against the toxic effects of cadmium.

  18. G9a-mediated histone methylation regulates cadmium-induced male fertility damage in pubertal mice.

    Science.gov (United States)

    Li, Min; Liu, Chuan; Yang, Lingling; Zhang, Lei; Chen, Chunhai; He, Mindi; Lu, Yonghui; Feng, Wei; Pi, Huifeng; Zhang, Yanwen; Zhong, Min; Yu, Zhengping; Zhou, Zhou

    2016-06-11

    Increasing evidence suggests that cadmium (Cd) is associated with male fertility damage. However, the effects of histone modification on Cd-induced male fertility damage remain obscure. This study aims to evaluate the roles of histone methylation mediated by euchromatin histone methyltransferase (EHMT2/G9a) in regulating Cd-induced male fertility damage. We exposed 4-week-old male C57BL/6J mice to Cd by intraperitoneal injection at 2mg/kg for 1, 3 and 5days. Our data showed that Cd exposure decreased the numbers of impregnated females and litter sizes, which was concomitant with sperm count reduction, histological changes in the cauda epididymal ducts and seminiferous epithelium, and testicular cell apoptosis as evaluated by terminal dUTP nick-end labeling (TUNEL) assay and immunoblotting with increased levels of cleaved caspase 3, PARP and Bax and a decreased level of Bcl-2. Cd-induced male fertility damage was accompanied by enhanced G9a activity followed by increased histone H3 lysine 9 monomethylation (H3K9me1) and dimethylation (H3K9me2) in testes. Furthermore, inhibition of G9a by BIX-01294 normalized H3K9me1 and H3K9me2 to basal levels and prevented Cd-induced male fertility damage and testicular cell apoptosis. Our present study revealed that G9a-mediated histone methylation plays a critical role in Cd-induced male fertility damage and testicular cell apoptosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. Livolin Forte Ameliorates Cadmium-Induced Kidney Injury in Wistar Rats

    Directory of Open Access Journals (Sweden)

    Akomolafe Rufus O.

    2016-06-01

    Full Text Available The kidney, which is an integral part of the drug excretion system, was reported as one of the targets of cadmium toxicity. Early events of cadmium toxicity in the cell include a decrease in cell membrane fluidity, breakdown of its integrity, and impairment of its repair mechanisms. Phosphatidylcholine and vitamin E have a marked fluidizing effect on cellular membranes. We hypothesized that Livolin forte (LIV could attenuate kidney damage induced by cadmium in rats. Twenty-five adult male Wistar rats were divided into five groups of five rats each: group I (control group received 0.3 ml/kg/day of propylene glycol for six weeks; group II was given 5 mg/kg/day of cadmium (Cd i.p for 5 consecutive days; group III rats were treated in a similar way as group II but were allowed a recovery period of 4 weeks; group IV was treated with LIV (5.2 mg/kg/day for a period of 4 weeks after inducing renal injury with Cd similarly to group II; and group V was allowed a recovery period of 2 weeks after a 4-week LIV treatment (5.2 mg/kg/day following Cd administration. A significant increase in plasma creatinine, urea, uric acid, and TBARS were observed in groups II and III compared to the control rats. Significant reductions in total protein, glucose, and GSH activity were also recorded. The urine concentrations of creatinine, urea, and uric acid in groups II and III were significantly lower than the control group. Th is finding was accompanied by a significant decrease in creatinine and urea clearance. Post-treatment with LIV caused significant decreases in plasma creatinine, urea, uric acid, and TBARS. Significant increases in total protein, glucose, and GSH activity of groups IV and V were observed compared to group II. A significant increase in urine concentrations of creatinine, urea, and uric acid and significant decreases in total protein, glucose, and GSH activity were observed in groups IV and V compared to group II. Photomicrographs of the rat kidneys

  20. Reversal of Cadmium-induced Oxidative Stress in Chicken by Herbal Adaptogens Withania Somnifera and Ocimum Sanctum

    Science.gov (United States)

    Bharavi, K.; Reddy, A. Gopala; Rao, G. S.; Reddy, A. Rajasekhara; Rao, S. V. Rama

    2010-01-01

    The present study was carried out to evaluate the herbal adaptogens Withania somnifera and Ocimum sanctum on cadmium-induced oxidative toxicity in broiler chicken. Cadmium administration at the rate of 100 ppm orally along with feed up to 28 days produced peroxidative damage, as indicated by increase in TBARS, reduction in glutathione (GSH) concentration in liver and kidney, and increase in catalase (CAT) and superoxide dismutase (SOD) of erythrocytes. Herbal adaptogens Withania somnifera roots and Ocimum sanctum leaf powder administration at the rate of 0.1% through feed reversed the antioxidant enzyme of RBC, i.e., CAT and SOD, nonenzymatic antioxidants GSH and lipid peroxidation marker TBARS of liver and kidney. Liver and kidney tissue repair and normal function was assessed by alanine aminotransaminase for liver and creatinine and blood urea nitrogen for kidney. In conclusion, oral administration of Withania somnifera root and Ocimum sanctum leaf powder prevented cadmium-induced peroxidation of tissues. PMID:21170246

  1. Sulforaphane mitigates cadmium-induced toxicity pattern in human peripheral blood lymphocytes and monocytes.

    Science.gov (United States)

    Alkharashi, Nouf Abdulkareem Omer; Periasamy, Vaiyapuri Subbarayan; Athinarayanan, Jegan; Alshatwi, Ali A

    2017-10-01

    Cadmium (Cd) is a highly toxic and widely distributed heavy metal that induces various diseases in humans through environmental exposure. Therefore, alleviation of Cd-induced toxicity in living organisms is necessary. In this study, we investigated the protective role of sulforaphane on Cd-induced toxicity in human peripheral blood lymphocytes and monocytes. Sulforaphane did not show any major reduction in the viability of lymphocytes and monocytes. However, Cd treatment at a concentration of 50μM induced around 69% cell death. Treatment of IC10-Cd and 100μM sulforaphane combination for 24 and 48h increased viability by 2 and 9% in cells subjected to Cd toxicity, respectively. In addition, IC25 of Cd and 100μM sulforaphane combination recovered 17-20% of cell viability. Cd induced apoptotic and necrotic cell death. Sulforaphane treatment reduced Cd-induced cell death in lymphocytes and monocytes. Our results clearly indicate that when the cells were treated with Cd+sulforaphane combination, sulforaphane decreased the Cd-induced cytotoxic effect in lymphocytes and monocytes. In addition, sulforaphane concentration plays a major role in the alleviation of Cd-induced toxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Attenuation of cadmium-induced decline in spatial, habituation and recognition memory by long-term administration of almond and walnut supplementation: Role of cholinergic function.

    Science.gov (United States)

    Batool, Zehra; Agha, Faiza; Ahmad, Saara; Liaquat, Laraib; Tabassum, Saiqa; Khaliq, Saima; Anis, Lubna; Sajid, Irfan; Emad, Shaista; Perveen, Tahira; Haider, Saida

    2017-01-01

    Excessive exposure of cadmium which is regarded as a neurotoxin can stimulate aging process by inducing abnormality in neuronal function. It has been reported that supplementation of almond and walnut attenuate age-related memory loss. Present study was designed to investigate the weekly administration of cadmium for one month on learning and memory function with relation to cholinergic activity. Cadmium was administered at the dose of 50 mg/kg/week. Whereas, almond and walnut was supplemented at the dose of 400 mg/kg/day along with cadmium administration to separate set of rats. At the end of experiment, memory function was assessed by Morris water maze, open field test and novel object recognition test. Results of the present study showed that cadmium administration significantly reduced memory retention. Reduced acetylcholine levels and elevated acetyl cholinesterase activity were also observed in frontal cortex and hippocampus of cadmium treated rats. Malondialdehyde levels were also significantly increased following the administration of cadmium. Daily supplementation of almond and walnut for 28 days significantly attenuated cadmium-induced memory impairment in rats. Results of the present study are discussed in term of cholinergic activity in cadmium-induced memory loss and its attenuation by nuts supplementation in rats.

  3. Effect of selenium on cadmium-induced oxidative stress and esterase activity in rat organs

    OpenAIRE

    Kevin Dzobo; Yogeshkumar S. Naik

    2013-01-01

    Metal toxicity is a threat mainly in the industrialised world where industry discharges many toxic metals into the environment. We investigated the effects of two metals cadmium and selenium on the cytosolic antioxidant enzymes and esterases in the liver, kidneys and testes of rats. Male Sprague-Dawley rats (n=28) were divided equally into four groups: control, cadmium, selenium and cadmium/selenium. Salts of the metals were administered intraperitoneally for 15 days. In the liver, cadmium tr...

  4. Mitigation of cadmium-induced lung injury by Nigella sativa oil.

    Science.gov (United States)

    El-Ebiary, Ahmad A; El-Ghaiesh, Sabah; Hantash, Ehab; Alomar, Suliman

    2016-12-01

    Induction of oxidative stress and inflammation are considered the primary mechanism of cadmium (Cd) toxicity. Nigella sativa (NS) seeds and their oil (NSO) have been reported to possess antioxidant and anti-inflammatory potential. This study was conducted to assess the protective effect of NSO on Cd-induced lung damage in rat. Forty adult male Wistar rats were divided equally into 4 groups. Animals in groups I, II, and III received 1 ml of isotonic saline intraperitoneally (IP), 2 mg/kg of cadmium chloride (CdCl2) dissolved in isotonic saline IP, and 1 ml/kg of NSO by gastric gavage, respectively. Group IV rats received NSO an hour prior to CdCl2 administration via the same routes and doses as previously described. All animals were treated for 28 days. At the end of the study, animals were sacrificed; lungs were harvested for histopathological studies using light and electron microscopy. Saline-treated and NSO-treated rats showed normal lung parenchyma. However, CdCl2-treated rats showed massive degenerative changes in alveolar epithelial lining, disrupted interalveolar septa, and hemolytic debris in alveoli. Rats treated with both NSO and CdCl2 (group IV) showed amelioration of most Cd-induced lung damage with minimal histopathological changes in lung architecture. This study elucidates the protective effects of NSO on Cd-induced lung injury in rats and highlights the possibility of using NSO as a protective agent in individuals at high risk of Cd-induced lung toxicity.

  5. Opiatergic participation in the thirst-inhibiting effect of acute third ventricle injections of cadmium (Cd2+ and lead (Pb2+

    Directory of Open Access Journals (Sweden)

    E. De-Castro-e-Silva

    1998-06-01

    Full Text Available We have previously demonstrated that acute third ventricle injections of both lead and cadmium prevent the dipsogenic response elicited by dehydration or by central injections of dipsogenic agents such as angiotensin II, carbachol and isoproterenol in rats. We have also shown that the antidipsogenic action of cadmium may be due, at least in part, to activation of thirst-inhibitory central serotonergic pathways. In the present paper we show that in Wistar male rats the antidipsogenic effect of both lead acetate (3.0 nmol/rat and cadmium chloride (3.0 nmol/rat may be partially dependent on the activation of brain opiatergic pathways since central injections of naloxone (82.5 nmol/rat, a non-selective opioid antagonist, blunt the thirst-inhibiting effect of these metals. One hundred and twenty minutes after the second third ventricle injections, dehydrated animals (14 h overnight receiving saline + sodium acetate displayed a high water intake (7.90 ± 0.47 ml/100 g body weight whereas animals receiving saline + lead acetate drank 3.24 ± 0.47 ml/100 g body weight. Animals receiving naloxone + lead acetate drank 6.94 ± 0.60 ml/100 g body weight. Animals receiving saline + saline drank 8.16 ± 0.66 ml/100 g body weight whilst animals receiving saline + cadmium chloride drank 1.63 ± 0.37 ml/100 g body weight. Animals receiving naloxone + cadmium chloride drank 8.01 ± 0.94 ml/100 g body weight. It is suggested that acute third ventricle injections of both lead and cadmium exert their antidipsogenic effect by activating thirst-inhibiting opioid pathways in the brain.

  6. Tubulin posttranslational modifications induced by cadmium in the sponge Clathrina clathrus

    Energy Technology Data Exchange (ETDEWEB)

    Ledda, F.D., E-mail: f.ledda@hotmail.it [Dipartimento di Scienze della Terra, dell’Ambiente e della Vita (DISTAV), Università di Genova, Corso Europa 26, I-16132 Genova (Italy); Dipartimento di Scienze della Natura e del Territorio (DIPNET), Università di Sassari, Via Muroni 25, I-07100 Sassari (Italy); Ramoino, P. [Dipartimento di Scienze della Terra, dell’Ambiente e della Vita (DISTAV), Università di Genova, Corso Europa 26, I-16132 Genova (Italy); Ravera, S. [Dipartimento di Farmacia (DIFAR), Viale Cembrano 4, I-16147 Genova (Italy); Perino, E. [Dipartimento di Scienze della Terra, dell’Ambiente e della Vita (DISTAV), Università di Genova, Corso Europa 26, I-16132 Genova (Italy); Bianchini, P. [Istituto Italiano di Tecnologia (IIT), Dipartimento di Nanofisica, Via Morego 30, I-16163 Genova (Italy); Diaspro, A. [Istituto Italiano di Tecnologia (IIT), Dipartimento di Nanofisica, Via Morego 30, I-16163 Genova (Italy); Dipartimento di Fisica (DIFI), Università di Genova, Via Dodecaneso 33, I-16146 Genova (Italy); Gallus, L.; Pronzato, R. [Dipartimento di Scienze della Terra, dell’Ambiente e della Vita (DISTAV), Università di Genova, Corso Europa 26, I-16132 Genova (Italy); Manconi, R. [Dipartimento di Scienze della Natura e del Territorio (DIPNET), Università di Sassari, Via Muroni 25, I-07100 Sassari (Italy)

    2013-09-15

    Highlights: •The effect of Cd{sup 2+} on Clathrina clathrus microtubule network was studied. •Cd{sup 2+} exposure increases acetylated and detyrosinated α-tubulin levels. •Microtubules enriched in acetylated/detyrosinated α-tubulin were resistant to cold. •Clathrina clathrus exposed to Cd{sup 2+} showed cytoplasmic microtubules with an enhanced stability. -- Abstract: As sessile filter feeders, sponges are exposed to environmental stress due to pollutants of both anthropogenic and natural origins and are able to accumulate harmful substances. Thus, sponges are considered a good tool for the biomonitoring of coastal areas. In this study, we used biochemical and immunocytochemical analyses to provide new data on the cadmium-related changes in sponge cells. In particular, we analyzed the effects of different concentrations of cadmium on the microtubule network in the calcisponge Clathrina clathrus. Quantitative densitometry of the immunoblots showed that, while the levels of α- and β-tubulin remained relatively constant in C. clathrus when exposed to 1 and 5 μM CdCl{sub 2}, there were progressive shifts in the levels of some tubulin isoforms. Exposure for 24 h to sublethal concentrations of cadmium reduced the level of tyrosinated α-tubulin and enhanced the levels of acetylated and detyrosinated α-tubulin relative to the levels in controls. Confocal microscopy analysis of immunolabeled tissue sections showed that the inhibitory effect of cadmium was associated with a decrease in the labeling of the cells with a monoclonal antibody that recognizes tyrosinated α-tubulin. By contrast, the reactivity with a monoclonal antibody that recognizes acetylated α-tubulin and with a polyclonal antibody specific for detyrosinated α-tubulin was enhanced at the same time points. Because the acetylation and detyrosination of α-tubulin occur on stable microtubules, the marked enhancement of α-tubulin acetylation and detyrosination in Cd{sup 2+}-treated cells

  7. Cadmium stress disrupts the endomembrane organelles and endocytosis during Picea wilsonii pollen germination and tube growth.

    Directory of Open Access Journals (Sweden)

    Xiaoxia Wang

    Full Text Available As one of the most severe pollutants, cadmium has been reported to be harmful to plant cells, but the effects of cadmium on gymnosperm pollen germination and tube growth and the mechanism of this involvement are still unclear. Here, we report that cadmium not only strongly inhibited P. wilsonii pollen germination and tube growth, but also significantly altered tube morphology in a dose-dependent manner. Time-lapse images obtained with a laser scanning confocal microscope revealed that endocytosis was dramatically inhibited by cadmium stress. Further investigation with ER-Tracker dye indicated that cadmium stress reduced the number of the Golgi apparatus, and induced dilation of ER. Additionally, Lyso-Tracker staining showed that cadmium distinctly promoted the formation of acidic organelles in pollen tubes, likely derived from the dilated ER. Taken together, our studies indicated that P. wilsonii pollens were highly susceptible to cadmium stress, and that cadmium stress strongly inhibited pollen germination and tube growth by disrupting the endomembrane organelles, inhibiting endo/exocytosis, and forming acidic vacuoles, resulting in swollen tube tips and irregularly broadened tube diameters. These findings provide a new insight into the effects of cadmium toxicity on the tip growth of pollen tubes.

  8. Testicular toxicity induced by dietary cadmium in cocks and ameliorative effect by selenium.

    Science.gov (United States)

    Li, Jin-Long; Gao, Rui; Li, Shu; Wang, Jin-Tao; Tang, Zhao-Xin; Xu, Shi-Wen

    2010-08-01

    Cadmium (Cd) is an ubiquitous environmental pollutant that has been associated with male reproductive toxicity in animal models. However, little is known about the reproductive toxicity of Cd in birds. To investigate the toxicity of Cd on male reproduction in birds and the protective effects of selenium (Se) against subchronic exposure to dietary Cd, 100-day-old cocks received either Se (as 10 mg Na(2)SeO(3) per kg of diet), Cd (as 150 mg CdCl(2) per kg of diet) or Cd + Se in their diets for 60 days. Histological and ultrastructural changes in the testis, the concentrations of Cd and Se, amount of lipid peroxidation (LPO), the activities of the antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GPx), and apoptosis and serum testosterone levels were determined. Exposure to Cd significantly lowered SOD and GPx activity, Se content in the testicular tissue, and serum testosterone levels. It increased the amount of LPO, the numbers of apoptotic cells and Cd concentration and caused obvious histopathological changes in the testes. Concurrent treatment with Se reduced the Cd-induced histopathological changes in the testis, oxidative stress, endocrine disorder and apoptosis, suggesting that the toxic effects of cadmium on the testes is ameliorated by Se. Se supplementation also modified the distribution of Cd in the testis.

  9. Insulin-Inducible SMILE Inhibits Hepatic Gluconeogenesis.

    Science.gov (United States)

    Lee, Ji-Min; Seo, Woo-Young; Han, Hye-Sook; Oh, Kyoung-Jin; Lee, Yong-Soo; Kim, Don-Kyu; Choi, Seri; Choi, Byeong Hun; Harris, Robert A; Lee, Chul-Ho; Koo, Seung-Hoi; Choi, Hueng-Sik

    2016-01-01

    The role of a glucagon/cAMP-dependent protein kinase-inducible coactivator PGC-1α signaling pathway is well characterized in hepatic gluconeogenesis. However, an opposing protein kinase B (PKB)/Akt-inducible corepressor signaling pathway is unknown. A previous report has demonstrated that small heterodimer partner-interacting leucine zipper protein (SMILE) regulates the nuclear receptors and transcriptional factors that control hepatic gluconeogenesis. Here, we show that hepatic SMILE expression was induced by feeding in normal mice but not in db/db and high-fat diet (HFD)-fed mice. Interestingly, SMILE expression was induced by insulin in mouse primary hepatocyte and liver. Hepatic SMILE expression was not altered by refeeding in liver-specific insulin receptor knockout (LIRKO) or PKB β-deficient (PKBβ(-/-)) mice. At the molecular level, SMILE inhibited hepatocyte nuclear factor 4-mediated transcriptional activity via direct competition with PGC-1α. Moreover, ablation of SMILE augmented gluconeogenesis and increased blood glucose levels in mice. Conversely, overexpression of SMILE reduced hepatic gluconeogenic gene expression and ameliorated hyperglycemia and glucose intolerance in db/db and HFD-fed mice. Therefore, SMILE is an insulin-inducible corepressor that suppresses hepatic gluconeogenesis. Small molecules that enhance SMILE expression would have potential for treating hyperglycemia in diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  10. Tunisian radish (Raphanus sativus) extract prevents cadmium-induced immunotoxic and biochemical alterations in rats.

    Science.gov (United States)

    ben Salah-Abbès, Jalila; Abbès, Samir; Zohra, Haous; Oueslati, Ridha

    2015-01-01

    Cadmium (Cd), a known carcinogen and potent immunotoxicant in humans and animals, is dispersed throughout the environment as a result of pollution from a variety of sources. Tunisian radish (Raphanus sativus) extract (TRE) is a known anti-oxidant and free radical scavenger that has been shown to help alleviate immune system disorders, including some induced by environmental toxicants. The present study was undertaken to investigate potential protective effects of TRE against Cd-induced immunotoxicities (and general toxicities) in situ. Cadmium chloride (at 2.5 mg CdCl2/kg BW) and TRE (5, 10, or 15 mg/kg BW) were given (alone or in combination [actually, in sequence of Cd and then TRE]) to rats daily by oral gavage for 2 weeks. Results indicated that treatment with CdCl2 alone resulted in significant decreases in plasma levels of total protein, triglycerides, creatine kinase, creatinine, IgG and IgA, T-lymphocyte sub-types (CD4(+), CD3(+), CD56(+), and CD8(+)), and in thymic and hepatic indices (relative weights). In contrast, CdCl2 treatment caused significant increases in serum LDH, AST, and ALT, in the formation/release of pro-inflammatory cytokines (IL-1 and TNFα), and in the relative weights of host spleen and kidneys. Rats treated with TRE alone had no discernable changes compared to the controls with regard to all test parameters. Combined treatment of CdCl2 and TRE-at any dose-resulted in a significant improvement of all test parameters compared to those seen with Cd alone. These results illustrated (and provided further support for a continuing belief in) the beneficial effects of TRE in reducing the harmful outcomes of commonly encountered toxicants (like Cd) on the immune system and on overall host health status.

  11. Inhibition of Inducible Nitric Oxide Synthase, Cycleooxygenase-2 ...

    African Journals Online (AJOL)

    Inhibition of Inducible Nitric Oxide Synthase, Cycleooxygenase-2 and Lipid Peroxidation by Methanol Extract of Pericarpium Zanthoxyli. ... Production of iNOS induced by LPS was significantly (p < 0.05) inhibited by the extract, suggesting that the extract inhibits nitric oxide (NO) production by suppressing iNOS expression.

  12. Roles of hydrogen sulfide and nitric oxide in the alleviation of cadmium-induced oxidative damage in alfalfa seedling roots.

    Science.gov (United States)

    Li, Le; Wang, Yanqin; Shen, Wenbiao

    2012-06-01

    Despite hydrogen sulfide (H(2)S) and nitric oxide (NO) are important endogenous signals or bioregulators involved in many vital aspects of plant growth and responses against abiotic stresses, little information was known about their interaction. In the present study, we evaluated the effects of H(2)S and NO on alfalfa (Medicago sativa L.) plants exposed to cadmium (Cd) stress. Pretreatment with an H(2)S donor sodium hydrosulfide (NaHS) and well-known NO donor sodium nitroprusside (SNP) decreased the Cd toxicity. This conclusion was supported by the decreases of lipid peroxidation as well as the amelioration of seedling growth inhibition and Cd accumulation, in comparison with the Cd-stressed alone plants. Total activities and corresponding transcripts of antioxidant enzymes, including superoxide dismutase, peroxidase and ascorbate peroxidase were modulated differentially, thus leading to the alleviation of oxidative damage. Effects of H(2)S above were reversed by 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (cPTIO), the specific scavenger of NO. By using laser confocal scanning microscope combined with Greiss reagent method, further results showed that NO production increased significantly after the NaHS pretreatment regardless of whether Cd was applied or not, all of which were obviously inhibited by cPTIO. These decreases of NO production were consistent with the exaggerated syndromes associated with Cd toxicity. Together, above results suggested that NO was involved in the NaHS-induced alleviation of Cd toxicity in alfalfa seedlings, and also indicated that there exists a cross-talk between H(2)S and NO responsible for the increased abiotic stress tolerance.

  13. Oxidative stress parameters induced by exposure to either cadmium or 17β-estradiol on Mytilus galloprovincialis hemocytes. The role of signaling molecules

    Energy Technology Data Exchange (ETDEWEB)

    Koutsogiannaki, Sophia [Laboratory of Animal Physiology, Zoology Department, School of Biology, Faculty of Science, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Franzellitti, Silvia [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); Fabbri, Elena [University of Bologna, Interdepartment Centre for Environmental Science Research, via S. Alberto 163, 48123 Ravenna (Italy); University of Bologna, Department of Biological, Geological, and Environmental Sciences, via Selmi 3, 40100 Bologna (Italy); Kaloyianni, Martha, E-mail: kaloyian@bio.auth.gr [Laboratory of Animal Physiology, Zoology Department, School of Biology, Faculty of Science, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece)

    2014-01-15

    cyclic adenosine-3′-5′-monophosphate (cAMP). Our results also attribute a protective role to cAMP, since pre-elevated intracellular cAMP levels inhibited the signal induced by each exposure. Finally, since aquatic invertebrates have been the most widely used monitoring organisms for pollution impact evaluation in marine environments and taking under consideration the positive correlation obtained between the studied parameters, we can suggest the simultaneous use of these oxidative stress parameters offering an effective early warning system in biomonitoring of aquatic environments.

  14. Protective effect of theaflavins on cadmium-induced testicular toxicity in male rats.

    Science.gov (United States)

    Wang, Wenxiang; Sun, Yan; Liu, Jin; Wang, Jieying; Li, Yuchen; Li, Hong; Zhang, Wenchang; Liao, Huizhen

    2012-09-01

    Male Sprague-Dawley rats were treated with cadmium (Cd) (0.4 mg/kg body weight, s.c., once a day) and three concentrations of theaflavins (50, 100 or 200mg/kg body weight, orally, once a day) for five weeks to evaluate the protective role of theaflavins on Cd-induced testicular toxicity. After five weeks, serum sex hormone levels, sperm characteristics, DNA damage, oxidant-antioxidant status, Cd content in several organs were measured. The results showed that a low dose of Cd caused testicular toxicity, which was represented by decreased serum testosterone levels, induction of DNA damage, increased malondialdehyde (MDA) content, Cd accumulation in several organs. Administration of theaflavins led to a dose-dependent alleviation Cd-induced damage in testis, including enhanced serum testosterone levels, improved sperm characteristics and abrogation of DNA damage. Theaflavins may also reduce the production of Cd-induced MDA content, decrease Cd concentration in liver, testis and blood, increase Cd content in urine and feces. These findings suggest the use of theaflavins as a potential therapeutic agent for Cd-induced testicular toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Protective effects of selenium against cadmium induced hematological disturbances, immunosuppressive, oxidative stress and hepatorenal damage in rats.

    Science.gov (United States)

    El-Boshy, Mohamed E; Risha, Engy F; Abdelhamid, Fatma M; Mubarak, Mohammad S; Hadda, Taibi Ben

    2015-01-01

    increased IFN-γ, GSH level, CAT, and GPx activities, as well as lymphocyte count while IL-10 was decreased. Selenium in combination with cadmium, significantly improved the elevation of serum IL-1β, IL-6, TNF α, IL-10 and malondialdehyde in addition to enhancing the antioxidant enzyme activities of GSH, CAT, GPx and SOD. Moreover, selenium has ameliorated the cadmium-induced liver and kidney damage by improving hepatic and renal markers. The results of this investigation demonstrated that selenium has the potential to countermeasure the immunosuppressive as well as hepatic and renal oxidative damage induced by cadmium in rats; selenium has shown promising effects against Cd toxicity. Copyright © 2014 Elsevier GmbH. All rights reserved.

  16. Effects of ?-Tocopherol on Cadmium-Induced Toxicity in Rat Testis and Spermatogenesis

    OpenAIRE

    Yang, Hoe Saeng; Han, Dong Keun; Kim, Jung Ran; Sim, Jae Chul

    2006-01-01

    Cadmium is known to exert toxic effects on multiple organs, including the testes. To determine if ?-Tocopherol, an antioxidant, could protect testicular tissues and spermatogenesis from the toxic effects of cadmium, six-week old male Sprague-Dawley rats were randomized to receive cadmium at doses of 0 (control), 1, 2, 4 or 8 mg/kg by the intraperitoneal route (Group A) or ?-tocopherol for 5 days before being challenged with cadmium (Group B) in an identical dose-dependent manner. When both gr...

  17. Cadmium induced-oxidative stress in pituitary gland is reversed by removing the contamination source.

    Science.gov (United States)

    Miler, Eliana A; Nudler, Silvana I; Quinteros, Fernanda A; Cabilla, Jimena P; Ronchetti, Sonia A; Duvilanski, Beatriz H

    2010-10-01

    Cadmium (Cd(2+)) is one of the most important environmental contaminants and acts as an endocrine disruptor. Previously, we have demonstrated that the simultaneous administration of Cd(2+) and melatonin (Mel) in drinking water impaired metal-induced oxidative stress in rat anterior pituitary gland. The aim of this study was to investigate if a treatment started after the toxic manifestations of Cd( 2+) became evident could reverse the effects of the metal. Animals exposed to Cd(2+) (5 parts per million [ppm], 30 days) were treated with Mel or without the metal during the next 1 or 2 months. Cd(2+) exposure increased the expression of heme oxygenase-1 (HO-1), a biomarker of oxidative stress, and an a posteriori Mel treatment reversed oxidative stress induced by Cd(2+). This effect was also observed 1 month after metal removal. The Cd(2+)-induced increase in metallothionein-1 (MT-1) and nitric oxide synthase 1 (NOS1) expression were also reversed by metal removal. In addition, serum prolactin and luteinizing hormone levels affected by Cd( 2+) exposure were normalized. Considering that the manifestations of Cd(2+) intoxication become evident only after a certain period of metal accumulation, these results show that metal removal is enough to reverse Cd(2+) effects in anterior pituitary gland and bring to light the relevance of moving away the individual from the contamination source.

  18. Multiple biomarkers of biological effects induced by cadmium in clam Ruditapes philippinarum.

    Science.gov (United States)

    Ji, Chenglong; Wu, Huifeng; Zhou, Mo; Zhao, Jianmin

    2015-06-01

    Cadmium (Cd) is a known heavy metal pollutant in the Bohai Sea. Manila clam Ruditapes philippinarum is an important fishery species along the Bohai coast. In this study, the biological effects induced by two concentrations (20 and 200 μg/L) of Cd were characterized using multiple biochemical indices in the digestive glands of clam R. philippinarum. The total hemocyte counts, reactive oxygen species productions and antioxidant enzyme activities exhibited that Cd induced dose-dependent immune and oxidative stresses in clam digestive glands. Metabolic responses indicated that both Cd exposures caused immune stress marked by the elevated branched chain amino acids (valine, leucine and isoleucine), together with the disturbance in energy metabolism. The differential metabolic biomarkers related to osmotic stress, including homarine, betaine, tyrosine and phenylalanine, suggested the differential responsive mechanisms in clam digestive glands induced by Cd exposures. In addition, both Cd treatments enhanced the anaerobiosis metabolism in clam digestive glands via differential metabolic pathways. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. MAPK/JNK1 activation protects cells against cadmium-induced autophagic cell death via differential regulation of catalase and heme oxygenase-1 in oral cancer cells.

    Science.gov (United States)

    So, Keum-Young; Kim, Sang-Hun; Jung, Ki-Tae; Lee, Hyun-Young; Oh, Seon-Hee

    2017-10-01

    Antioxidant enzymes are related to oral diseases. We investigated the roles of heme oxygenase-1 (HO-1) and catalase in cadmium (Cd)-induced oxidative stress and the underlying molecular mechanism in oral cancer cells. Exposing YD8 cells to Cd reduced the expression levels of catalase and superoxide dismutase 1/2 and induced the expression of HO-1 as well as autophagy and apoptosis, which were reversed by N-acetyl-l-cysteine (NAC). Cd-exposed YD10B cells exhibited milder effects than YD8 cells, indicating that Cd sensitivity is associated with antioxidant enzymes and autophagy. Autophagy inhibition via pharmacologic and genetic modulations enhanced Cd-induced HO-1 expression, caspase-3 cleavage, and the production of reactive oxygen species (ROS). Ho-1 knockdown increased autophagy and apoptosis. Hemin treatment partially suppressed Cd-induced ROS production and apoptosis, but enhanced autophagy and CHOP expression, indicating that autophagy induction is associated with cellular stress. Catalase inhibition by pharmacological and genetic modulations increased Cd-induced ROS production, autophagy, and apoptosis, but suppressed HO-1, indicating that catalase is required for HO-1 induction. p38 inhibition upregulated Cd-induced phospho-JNK and catalase, but suppressed HO-1, autophagy, apoptosis. JNK suppression exhibited contrary results, enhancing the expression of phospho-p38. Co-suppression of p38 and JNK1 failed to upregulate catalase and procaspase-3, which were upregulated by JNK1 overexpression. Overall, the balance between the responses of p38 and JNK activation to Cd appears to have an important role in maintaining cellular homeostasis via the regulation of antioxidant enzymes and autophagy induction. In addition, the upregulation of catalase by JNK1 activation can play a critical role in cell protection against Cd-induced oxidative stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. Phytosiderophores determine thresholds for iron and zinc accumulation in biofortified rice endosperm while inhibiting the accumulation of cadmium.

    Science.gov (United States)

    Banakar, Raviraj; Alvarez Fernandez, Ana; Díaz-Benito, Pablo; Abadia, Javier; Capell, Teresa; Christou, Paul

    2017-10-13

    Nicotianamine (NA) and 2'-deoxymugenic acid (DMA) are metal-chelating ligands that promote the accumulation of metals in rice endosperm, but it is unclear how these phytosiderophores regulate the levels of different metals and limit their accumulation. In this study, transgenic rice plants producing high levels of NA and DMA accumulated up to 4-fold more iron (Fe) and 2-fold more zinc (Zn) in the endosperm compared with wild-type plants. The distribution of Fe and Zn in vegetative tissues suggested that both metals are sequestered as a buffering mechanism to avoid overloading the seeds. The buffering mechanism involves the modulation of genes encoding metal transporters in the roots and aboveground vegetative tissues. As well as accumulating more Fe and Zn, the endosperm of the transgenic plants accumulated less cadmium (Cd), suggesting that higher levels of Fe and Zn competitively inhibit Cd accumulation. Our data show that although there is a strict upper limit for Fe (~22.5 µg g-1 dry weight) and Zn (~84 µg g-1 dry weight) accumulation in the endosperm, the careful selection of strategies to increase endosperm loading with essential minerals can also limit the accumulation of toxic metals such as Cd, thus further increasing the nutritional value of rice. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  1. Preventive effects of β-cryptoxanthin against cadmium-induced oxidative stress in the rat testis

    Directory of Open Access Journals (Sweden)

    Xiao-Ran Liu

    2016-01-01

    Full Text Available β-cryptoxanthin (CRY, a major carotenoid of potential interest for health, is obtained naturally from orange vegetables and fruits. A few research studies have reported that CRY could decrease oxidative stress and germ cell apoptosis. The purpose of this study was to examine the effects of CRY on acute cadmium chloride (CdCl 2 -induced oxidative damage in rat testes. For this study, 24 rats were divided into four groups, one of which serves as a control group that received intraperitoneal (i.p. injections of corn oil and physiological saline. The other rats were i.p. injected with CRY (10 μg kg−1 every 8 h, beginning 8 h before CdCl 2 (2.0 mg kg−1 treatment. The pathological and TUNEL findings revealed that CRY ameliorated the Cd-induced testicular histological changes and germ cell apoptosis in the rats. Furthermore, the Cd-induced decrease in the testicular testosterone (T level was attenuated after CRY administration (P < 0.05. The administration of CRY significantly reversed the Cd-induced increases in the lipid peroxide (LPO and malondialdehyde (MDA levels (P < 0.01. The testicular antioxidants superoxide dismutase (SOD, catalase (CAT and glutathione (GSH were decreased by treatment with Cd alone but were restored by CRY co-treatment. These results demonstrated that the application of CRY can enhance the tolerance of rats to Cd-induced oxidative damage and suggest that it has promised as a pharmacological agent to protect against Cd-induced testicular toxicity.

  2. Toxicity of cadmium to grapevine

    Energy Technology Data Exchange (ETDEWEB)

    Rupp, D.; Ruehl, E.; Alleweldt, G.

    1985-01-01

    Cuttings of the cv. Riesling were cultivated in nutrient solutions with different amounts of cadmium. Cadmium inhibited the growth of shoot and of leaf area and produced chlorosis, necroses and leaf deformations. Old leaves showed no symptoms at all, but with high cadmium levels leaf fall occurred. The threshold of cadmium damage was beneath a level of 0.1 ppm Cd of the nutrient solution. The dry matter production of the plants was reduced by cadmium: 0.66 mg Cd/l of nutrient solution caused an inhibition of 50%. Cadmium reduced the chlorophyll content of the leaves. The transport of iron from roots to leaves was inhibited nearly completely by medium to high levels of cadmium (1.0, 3.0, 10.0 ppm). Iron was accumulated in the roots. Thus cadmium may have caused an iron deficiency chlorosis in grapevines. The uptake of cadmium showed a clear dependence on the amount of cadmium in the nutrient solution. Within the plants, decreasing amounts of cadmium were found following the pattern roots - stem - leaves.

  3. Role of Nrf2 antioxidant defense in mitigating cadmium-induced oxidative stress in the olfactory system of zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Lu; Gallagher, Evan P., E-mail: evang3@uw.edu

    2013-01-15

    Exposure to trace metals can disrupt olfactory function in fish leading to a loss of behaviors critical to survival. Cadmium (Cd) is an olfactory toxicant that elicits cellular oxidative stress as a mechanism of toxicity while also inducing protective cellular antioxidant genes via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, the molecular mechanisms of Cd-induced olfactory injury have not been characterized. In the present study, we investigated the role of the Nrf2-mediated antioxidant defense pathway in protecting against Cd-induced olfactory injury in zebrafish. A dose-dependent induction of Nrf2-regulated antioxidant genes associated with cellular responses to oxidative stress was observed in the olfactory system of adult zebrafish following 24 h Cd exposure. Zebrafish larvae exposed to Cd for 3 h showed increased glutathione S-transferase pi (gst pi), glutamate–cysteine ligase catalytic subunit (gclc), heme oxygenase 1 (hmox1) and peroxiredoxin 1 (prdx1) mRNA levels indicative of Nrf2 activation, and which were blocked by morpholino-mediated Nrf2 knockdown. The inhibition of antioxidant gene induction in Cd-exposed Nrf2 morphants was associated with disruption of olfactory driven behaviors, increased cell death and loss of olfactory sensory neurons (OSNs). Nrf2 morphants also exhibited a downregulation of OSN-specific genes after Cd exposure. Pre-incubation of embryos with sulforaphane (SFN) partially protected against Cd-induced olfactory tissue damage. Collectively, our results indicate that oxidative stress is an important mechanism of Cd-mediated injury in the zebrafish olfactory system. Moreover, the Nrf2 pathway plays a protective role against cellular oxidative damage and is important in maintaining zebrafish olfactory function. -- Highlights: ► Oxidative stress is an important mechanism of Cd-mediated olfactory injury. ► Cd induces antioxidant gene expression in the zebrafish olfactory system. ► The

  4. Molecular responses during cadmium-induced stress in Daphnia magna: Integration of differential gene expression with higher-level effects

    Energy Technology Data Exchange (ETDEWEB)

    Soetaert, Anneleen [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium)]. E-mail: anneleen.soetaert@ua.ac.be; Vandenbrouck, Tine [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Ven, Karlijn van der [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Maras, Marleen [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Remortel, Piet van [Department of Mathematics and Informatics, Intelligent Systems Laboratory, University of Antwerp, Middelheimlaan 1, B-2020 Antwerp (Belgium); Blust, Ronny [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Coen, Wim M. de [Department of Biology, Laboratory for Ecophysiology, Biochemistry and Toxicology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium)

    2007-07-20

    DNA microarrays offer great potential in revealing insight into mechanistic toxicity of contaminants. The aim of the present study was (i) to gain insight in concentration- and time-dependent cadmium-induced molecular responses by using a customized Daphnia magna microarray, and (ii) to compare the gene expression profiles with effects at higher levels of biological organization (e.g. total energy budget and growth). Daphnids were exposed to three cadmium concentrations (nominal value of 10, 50, 100 {mu}g/l) for two time intervals (48 and 96 h). In general, dynamic expression patterns were obtained with a clear increase of gene expression changes at higher concentrations and longer exposure duration. Microarray analysis revealed cadmium affected molecular pathways associated with processes such as digestion, oxygen transport, cuticula metabolism and embryo development. These effects were compared with higher-level effects (energy budgets and growth). For instance, next to reduced energy budgets due to a decline in lipid, carbohydrate and protein content, we found an up-regulated expression of genes related to digestive processes (e.g. {alpha}-esterase, cellulase, {alpha}-amylase). Furthermore, cadmium affected the expression of genes coding for proteins involved in molecular pathways associated with immune response, stress response, cell adhesion, visual perception and signal transduction in the present study.

  5. Analysis of metal profile in soybean after cadmium-induced oxidative damage

    Directory of Open Access Journals (Sweden)

    Emiliano Felici

    2014-06-01

    Full Text Available Objective: To analyze the effect of cadmium (Cd on soybean seedlings growth and the relationship with the distribution and concentration of macro-microelements. Methods: The ions concentrations were determined by ICP-MS. The extraction efficiency and digestion time were optimized. Also, oxidative stress parameters were determined and related with metal content. Results: The accumulated amount of dry matter in roots and leaves was lower in the Cd-treated group. Regression analysis showed that the exposure to Cd affected the accumulated amount of dry matter as well as the content of mineral elements in the analysis samples. In Cd treated plants, electrical conductivity increased respect to the controls, indicating that ionic permeability became altered. A strong inhibition of the chlorophylls (chl biosynthesis in the Cd-treated group was also demonstrated by a decrease of chla and chlb concentration. This result was related with the observed significant decrease in the Mg uptake at the roots and leaves level. Conclusions: The stress caused by Cd exposure, evidenced by significantly high hydrogen peroxide levels in roots and leaves after 24 h and the content of specific macro-microelements is a factor that affects the accumulation of dry matter, electrical conductivity and chlorophylls concentration

  6. Ameliorative effect of propolis on the cadmium-induced reproductive toxicity in male albino rats.

    Science.gov (United States)

    Çilenk, Kübra Tuğçe; Öztürk, İsmet; Sönmez, Mehmet Fatih

    2016-10-01

    Propolis is a potent antioxidant and a free radical scavenger. The present study aimed to investigate protective effects of propolis extract on cadmium-induced testicular damage, apoptosis, HIF-1α expression and toxicity in rat's testis tissue. A total of 32 male rats were equally divided into four study groups namely, control, Cd (1mg/kg/day), Cd+propolis (50mg/kg/day) and propolis. The rats were decapitated under ketamine anesthesia and their testes tissues were removed. Serum testosterone, tissue malondialdehyde and HIF-1α levels, HIF-1α expression, apoptosis and histopathological damage scores were then compared. In the Cd group, the diameters of seminiferous tubules, tubular biopsy score of Johnsen and serum testosterone levels were decreased compared control group, but tissue HIF-1α and tissue MDA levels was higher than control group. The immunoreactivity of HIF-1α and the number of apoptotic cells were increased in Cd group. Furthermore, the propolis treated group showed an improved histological appearance in the Cd group. Thus, the results suggest that propolis acts as a potent protective agent against Cd-induced testicular toxicity in rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Enoxacin directly inhibits osteoclastogenesis without inducing apoptosis.

    Science.gov (United States)

    Toro, Edgardo J; Zuo, Jian; Ostrov, David A; Catalfamo, Dana; Bradaschia-Correa, Vivian; Arana-Chavez, Victor; Caridad, Aliana R; Neubert, John K; Wronski, Thomas J; Wallet, Shannon M; Holliday, L Shannon

    2012-05-18

    Enoxacin has been identified as a small molecule inhibitor of binding between the B2-subunit of vacuolar H+-ATPase (V-ATPase) and microfilaments. It inhibits bone resorption by calcitriol-stimulated mouse marrow cultures. We hypothesized that enoxacin acts directly and specifically on osteoclasts by disrupting the interaction between plasma membrane-directed V-ATPases, which contain the osteoclast-selective a3-subunit of V-ATPase, and microfilaments. Consistent with this hypothesis, enoxacin dose-dependently reduced the number of multinuclear cells expressing tartrate-resistant acid phosphatase (TRAP) activity produced by RANK-L-stimulated osteoclast precursors. Enoxacin (50 μM) did not induce apoptosis as measured by TUNEL and caspase-3 assays. V-ATPases containing the a3-subunit, but not the "housekeeping" a1-subunit, were isolated bound to actin. Treatment with enoxacin reduced the association of V-ATPase subunits with the detergent-insoluble cytoskeleton. Quantitative PCR revealed that enoxacin triggered significant reductions in several osteoclast-selective mRNAs, but levels of various osteoclast proteins were not reduced, as determined by quantitative immunoblots, even when their mRNA levels were reduced. Immunoblots demonstrated that proteolytic processing of TRAP5b and the cytoskeletal protein L-plastin was altered in cells treated with 50 μM enoxacin. Flow cytometry revealed that enoxacin treatment favored the expression of high levels of DC-STAMP on the surface of osteoclasts. Our data show that enoxacin directly inhibits osteoclast formation without affecting cell viability by a novel mechanism that involves changes in posttranslational processing and trafficking of several proteins with known roles in osteoclast function. We propose that these effects are downstream to blocking the binding interaction between a3-containing V-ATPases and microfilaments.

  8. Enoxacin Directly Inhibits Osteoclastogenesis without Inducing Apoptosis*

    Science.gov (United States)

    Toro, Edgardo J.; Zuo, Jian; Ostrov, David A.; Catalfamo, Dana; Bradaschia-Correa, Vivian; Arana-Chavez, Victor; Caridad, Aliana R.; Neubert, John K.; Wronski, Thomas J.; Wallet, Shannon M.; Holliday, L. Shannon

    2012-01-01

    Enoxacin has been identified as a small molecule inhibitor of binding between the B2-subunit of vacuolar H+-ATPase (V-ATPase) and microfilaments. It inhibits bone resorption by calcitriol-stimulated mouse marrow cultures. We hypothesized that enoxacin acts directly and specifically on osteoclasts by disrupting the interaction between plasma membrane-directed V-ATPases, which contain the osteoclast-selective a3-subunit of V-ATPase, and microfilaments. Consistent with this hypothesis, enoxacin dose-dependently reduced the number of multinuclear cells expressing tartrate-resistant acid phosphatase (TRAP) activity produced by RANK-L-stimulated osteoclast precursors. Enoxacin (50 μm) did not induce apoptosis as measured by TUNEL and caspase-3 assays. V-ATPases containing the a3-subunit, but not the “housekeeping” a1-subunit, were isolated bound to actin. Treatment with enoxacin reduced the association of V-ATPase subunits with the detergent-insoluble cytoskeleton. Quantitative PCR revealed that enoxacin triggered significant reductions in several osteoclast-selective mRNAs, but levels of various osteoclast proteins were not reduced, as determined by quantitative immunoblots, even when their mRNA levels were reduced. Immunoblots demonstrated that proteolytic processing of TRAP5b and the cytoskeletal protein l-plastin was altered in cells treated with 50 μm enoxacin. Flow cytometry revealed that enoxacin treatment favored the expression of high levels of DC-STAMP on the surface of osteoclasts. Our data show that enoxacin directly inhibits osteoclast formation without affecting cell viability by a novel mechanism that involves changes in posttranslational processing and trafficking of several proteins with known roles in osteoclast function. We propose that these effects are downstream to blocking the binding interaction between a3-containing V-ATPases and microfilaments. PMID:22474295

  9. Cadmium-induced teratogenicity: Association with ROS-mediated endoplasmic reticulum stress in placenta

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhen; Wang, Hua; Xu, Zhong Mei; Ji, Yan-Li; Chen, Yuan-Hua; Zhang, Zhi-Hui; Zhang, Cheng; Meng, Xiu-Hong; Zhao, Mei; Xu, De-Xiang, E-mail: xudex@126.com

    2012-03-01

    The placenta is essential for sustaining the growth of the fetus. An increased endoplasmic reticulum (ER) stress has been associated with the impaired placental and fetal development. Cadmium (Cd) is a potent teratogen that caused fetal malformation and growth restriction. The present study investigated the effects of maternal Cd exposure on placental and fetal development. The pregnant mice were intraperitoneally injected with CdCl{sub 2} (4.5 mg/kg) on gestational day 9. As expected, maternal Cd exposure during early limb development significantly increased the incidences of forelimb ectrodactyly in fetuses. An obvious impairment in the labyrinth, a highly developed tissue of blood vessels, was observed in placenta of mice treated with CdCl{sub 2}. In addition, maternal Cd exposure markedly repressed cell proliferation and increased apoptosis in placenta. An additional experiment showed that maternal Cd exposure significantly upregulated the expression of GRP78, an ER chaperone. Moreover, maternal Cd exposure induced the phosphorylation of placental eIF2α, a downstream molecule of PERK signaling. In addition, maternal Cd exposure significantly increased the level of placental CHOP, another target of PERK signaling, indicating that the unfolded protein response (UPR) signaling was activated in placenta of mice treated with CdCl{sub 2}. Interestingly, alpha-phenyl-N-t-butylnitrone, a free radical spin-trapping agent, significantly alleviated Cd-induced placental ER stress and UPR. Taken together, these results suggest that reactive oxygen species (ROS)-mediated ER stress might be involved in Cd-induced impairment on placental and fetal development. Antioxidants may be used as pharmacological agents to protect against Cd-induced fetal malformation and growth restriction. -- Highlights: ► Cd induces fetal malformation and growth restriction. ► Cd induced placental ER stress and UPR. ► PBN alleviates Cd-induced ER stress and UPR in placenta. ► ROS-mediated ER

  10. Solanum torvum Swartz. fruit attenuates cadmium-induced liver and kidney damage through modulation of oxidative stress and glycosylation.

    Science.gov (United States)

    Ramamurthy, C H; Subastri, A; Suyavaran, A; Subbaiah, K C V; Valluru, L; Thirunavukkarasu, C

    2016-04-01

    Increased levels of environmental pollutants are linked to almost all human disorders; the efficient method to manage the human health is through naturally available dietary molecule. Solanum torvum (ST) Swartz (Solanaceae) commonly called Turkey Berry is found in Africa, Asia, and South America. Its fruit, part of traditional Indian cuisine, is a widely consumed nutritious herb, acclaimed for its medicinal value. ST aqueous extract (STAe) (250, 500, and 1000 mg/kg b.w., 6 days; oral) against acute Cadmium (Cd) (6.3 mg/kg b.w., single dose; oral) toxicity was evaluated in rats. Protective effect was assessed using serum markers, tissue antioxidants, oxidant derivatives, glycoprotein, and histopathological studies. The activities of serum marker enzymes were increased (40-60 %); antioxidant enzymes such as SOD and CAT, GSH, and its metabolic enzyme activities were decreased (50-80 %) in the liver and kidney upon Cd intoxication. During STAe pre-treatment, at doses of 250 and 500 mg/kg b.w., the above changes were brought to near normal (25-63 %). Tissue 4-hydroxynonenal, 3-nitrotyrosine, and protein carbonyls were increased (8-15 fold) in Cd-alone-treated rats, whereas pre-supplementation of STAe significantly decreased their levels and inhibited the protein glycosylation effectively. The pharmacological effect of STAe was confirmed by histopathological observations. Based on previous literature and present investigation, we conclude that ST may serve as a potential functional food against environmental contaminant such as heavy metal-induced oxidative stress.

  11. Emodin inhibits proliferation and invasion, and induces apoptosis in ...

    African Journals Online (AJOL)

    Emodin inhibits proliferation and invasion, and induces apoptosis in human esophageal cancer cell line ECA109. ... Tropical Journal of Pharmaceutical Research ... Conclusion: These results suggest that emodin inhibits cell proliferation and cell invasion, but induces cell apoptosis in human esophageal cancer cell line ...

  12. Low Doses of Cadmium Chloride and Methallothionein-1-Bound Cadmium Display Different Accumulation Kinetics and Induce Different Genes in Cells of the Human Nephron

    Directory of Open Access Journals (Sweden)

    Dana Cucu

    2011-08-01

    Full Text Available Background/Aims: The present study was conducted to investigate the renal tubular handling of inorganic cadmium (Cd2+ by exposing primary human tubular cell cultures to physiologically relevant doses of cadmium chloride (CdCl2. Furthermore, the cellular accumulation of Cd2+ was compared to that of metallothionein-1-bound Cd (Cd7MT-1. Finally, this study aimed to investigate the effect of the accumulation of Cd (both Cd2+ and Cd7MT-1 in renal cells on the expression of genes relevant to nephrotoxic processes. Methods: Cd concentration was measured using atomic absorption spectrometry. mRNA expression was evaluated by quantitative real-time RT-PCR. Results: Cd2+ accumulated into human tubular cells in a concentration- and time-dependent way. Furthermore, cellular accumulation of Cd2+ was different from the cellular accumulation of Cd7MT-1, indicative for different uptake routes. Finally, mRNA expression of the genes encoding the anti-oxidative proteins metallothionein-1 (MT-1 and heme-oxygenase-1 (HO-1 as well as the pro-apoptotic Bcl-2-associated X protein (Bax were upregulated by CdCl2 and not by Cd7MT1. Conclusion: In the presence of physiologically relevant Cd concentrations, tubular accumulation of the element in its inorganic form is different from that of Cd7MT-1. Furthermore, the tubular accumulation of inorganic Cd induces mRNA expression of genes of which the protein products may play a role in Cd-associated renal toxicity.

  13. Long-term cadmium exposure induces anemia in rats through hypoinduction of erythropoietin in the kidneys

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, Hyogo [Department of Public Health, Fukushima Medical College, Fukushima (Japan); Sato, Masao [Department of Biomolecular Sciences, Institute of Biomedical Sciences, Fukushima Medical College, Fukushima (Japan); Konno, Nobuhiro [Department of Public Health, Fukushima Medical College, Fukushima (Japan); Fukushima, Masaaki [Department of Public Health, Fukushima Medical College, Fukushima (Japan)

    1996-11-01

    Cadmium (Cd), a highly toxic heavy metal, is distributed widely in the general environment of today. The characteristic clinical manifestations of chronic Cd intoxication include renal proximal tubular dysfunction, general osteomalacia with severe pains, and anemia. We have recently reported that the serum level of erythropoietin (EPO) remained low despite the severe anemia in patients with Itai-itai disease, the most severe form of chronic Cd intoxication. In order to prove that the anemia observed in chronic Cd intoxication arises from low production of EPO in the kidneys following the renal injury, we administered Cd to rats for a long period and performed the analysis of EPO mRNA inducibility in the kidneys. The rats administered Cd for 6 and 9 months showed anemia with low levels of plasma EPO as well as biochemical and histological renal tubular damage, and also hypoinduction of EPO mRNA in the kidneys. The results indicate that chronic Cd intoxication causes anemia by disturbing the EPO-production capacity of renal cells. (orig.). With 4 figs., 4 tabs.

  14. In Posidonia oceanica cadmium induces changes in DNA methylation and chromatin patterning.

    Science.gov (United States)

    Greco, Maria; Chiappetta, Adriana; Bruno, Leonardo; Bitonti, Maria Beatrice

    2012-01-01

    In mammals, cadmium is widely considered as a non-genotoxic carcinogen acting through a methylation-dependent epigenetic mechanism. Here, the effects of Cd treatment on the DNA methylation patten are examined together with its effect on chromatin reconfiguration in Posidonia oceanica. DNA methylation level and pattern were analysed in actively growing organs, under short- (6 h) and long- (2 d or 4 d) term and low (10 μM) and high (50 μM) doses of Cd, through a Methylation-Sensitive Amplification Polymorphism technique and an immunocytological approach, respectively. The expression of one member of the CHROMOMETHYLASE (CMT) family, a DNA methyltransferase, was also assessed by qRT-PCR. Nuclear chromatin ultrastructure was investigated by transmission electron microscopy. Cd treatment induced a DNA hypermethylation, as well as an up-regulation of CMT, indicating that de novo methylation did indeed occur. Moreover, a high dose of Cd led to a progressive heterochromatinization of interphase nuclei and apoptotic figures were also observed after long-term treatment. The data demonstrate that Cd perturbs the DNA methylation status through the involvement of a specific methyltransferase. Such changes are linked to nuclear chromatin reconfiguration likely to establish a new balance of expressed/repressed chromatin. Overall, the data show an epigenetic basis to the mechanism underlying Cd toxicity in plants.

  15. Cadmium-induced oxidative stress and apoptotic changes in the testis of freshwater crab, Sinopotamon henanense.

    Directory of Open Access Journals (Sweden)

    Lan Wang

    Full Text Available Cadmium (Cd, one of the most toxic environmental and industrial pollutants, is known to exert gonadotoxic and spermiotoxic effects. In the present study, we examined the toxic effect of Cd on the testis of freshwater crab, Sinopotamon henanense. Crabs were exposed to different Cd concentrations (from 0 to 116.00 mg·L(-1 for 7 d. Oxidative stress and apoptotic changes in the testes were detected. The activities of SOD, GPx and CAT initially increased and subsequently decreased with increasing Cd concentrations, which was accompanied with the increase in malondialdehyde (MDA and H(2O(2 content in a concentration-dependent manner. Typical morphological characteristic and physiological changes of apoptosis were observed using a variety of methods (HE staining, AO/EB double fluorescent staining, Transmission Electron Microscope observation and DNA fragmentation analysis, and the activities of caspase-3 and caspase-9 were increased in a concentration-dependent manner after Cd exposure. These results led to the conclusion that Cd could induced oxidative damage as well as apoptosis in the testis, and the apoptotic processes may be mediated via mitochondria-dependent apoptosis pathway by regulating the activities of caspase-3 and caspase-9.

  16. Activation cross sections on cadmium: Deuteron induced nuclear reactions up to 40 MeV

    Science.gov (United States)

    Tárkányi, F.; Király, B.; Ditrói, F.; Takács, S.; Csikai, J.; Hermanne, A.; Uddin, M. S.; Hagiwara, M.; Baba, M.; Ido, T.; Shubin, Yu. N.; Kovalev, S. F.

    2007-06-01

    Cross sections of deuteron induced nuclear reactions were measured up to 40 MeV using the standard stacked-foil irradiation method and high-resolution gamma-ray spectroscopy. Experimental cross sections and derived integral yields are reported for the reactions natCd(d,x)107g,108g,108m,109g,110g,110m,111g,112m,113m,114m,115m,116m1In, natCd(d,x)111m,115g,115m,117g,117mCd and natCd(d,x)105g,106m,110m,111gAg. No experimental data measured on natural cadmium have been found in the literature for the isotopes 107g,108g,108m,112m,115mIn, 111m,115m,117g,117mCd and 105g,106m,110m,111gAg. The experimental data are analyzed with and compared to the results of the theoretical model code ALICE-IPPE. Applications of the cross sections for data validation, medical radioisotope production, thin-layer activation and dose calculation are discussed.

  17. Investigation of activation cross-sections of alpha-induced nuclear reactions on natural cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Khandaker, Mayeen Uddin [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Department of Physics, University of Malaya, 50603 Kuala Lumpur (Malaysia); Kim, Kwangsoo [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Lee, Manwoo [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Research Center, Dongnam Institute of Radiological and Medical Science, Busan 619-953 (Korea, Republic of); Kim, Guinyun, E-mail: gnkim@knu.ac.kr [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of)

    2014-08-15

    We measured production cross-sections of Sn, In, and Cd radionuclides from alpha-induced reactions on {sup nat}Cd from their respective threshold to 45 MeV by using a stacked-foil activation technique at the MC-50 cyclotron of the Korea Institute of Radiological and Medical Sciences. The results were compared with the earlier measurements as well as with the theoretical values obtained from the TENDL-2012 library based on the TALYS 1.4 code. Our measurements for the {sup 110,113g,117m}Sn, {sup 108m,108g,109g,110m,110g,111g,113m,114m,115m,116m,117m,117g}In, and {sup 111m,115g}Cd radionuclides in the energy region from the threshold energy to 45 MeV are in general good agreement with the other experimental data and calculated results. The integral yields for thick target were also deduced using the measured cross-sections and the stopping power of natural cadmium target and found in agreement with the directly measured yields available in the literature. The measured cross-sections find importance in various practical applications including nuclear medicine and improvement of nuclear model calculations.

  18. Investigation of activation cross-sections of alpha-induced nuclear reactions on natural cadmium

    Science.gov (United States)

    Khandaker, Mayeen Uddin; Kim, Kwangsoo; Lee, Manwoo; Kim, Guinyun

    2014-08-01

    We measured production cross-sections of Sn, In, and Cd radionuclides from alpha-induced reactions on natCd from their respective threshold to 45 MeV by using a stacked-foil activation technique at the MC-50 cyclotron of the Korea Institute of Radiological and Medical Sciences. The results were compared with the earlier measurements as well as with the theoretical values obtained from the TENDL-2012 library based on the TALYS 1.4 code. Our measurements for the 110,113g,117mSn, 108m,108g,109g,110m,110g,111g,113m,114m,115m,116m,117m,117gIn, and 111m,115gCd radionuclides in the energy region from the threshold energy to 45 MeV are in general good agreement with the other experimental data and calculated results. The integral yields for thick target were also deduced using the measured cross-sections and the stopping power of natural cadmium target and found in agreement with the directly measured yields available in the literature. The measured cross-sections find importance in various practical applications including nuclear medicine and improvement of nuclear model calculations.

  19. Protective effects of thymoquinone and l-cysteine on cadmium-induced reproductive toxicity in rats

    Directory of Open Access Journals (Sweden)

    Manal M. Sayed

    2014-01-01

    Full Text Available This study was conducted to investigate the possible protective role of thymoquinone (TQ and l-cysteine on the reproductive toxicity of male rats induced by cadmium chloride (CdCl2. Forty rats were divided into four even groups. The first group served as untreated control. The second, third and fourth groups received CdCl2, CdCl2 and TQ, and CdCl2 and l-cysteine, respectively for 56 days. Cd exposure caused spermatological damage (decrease sperm count and motility and increased the rates of sperm abnormalities, decrease serum testosterone level and increased oxidative stress. Histological alterations were also observed in the form of vascular and cellular changes in CdCl2 treated rats. The vascular changes were congestion of the blood vessels with interstitial edema in the testes, epididymis, seminal vesicle and prostate. The cellular changes were in the form of degenerative changes with presence of multinucleated giant cells in the lumen of seminiferous tubules, vacuolation and sloughing of the lining epithelium of the epididymis, seminal vesiculitis and prostatitis. Co-administration of TQ and l-cysteine with CdCl2 increased glutathione (GSH, superoxide dismutase (SOD, catalase (CAT and testosterone and reduced lipid peroxidation (LPO activity. In conclusion, our results showed that TQ and l-cysteine can ameliorate the deleterious effects of CdCl2 probably by activating testicular endocrine and antioxidant systems.

  20. Influence of injection timing on severity of cadmium-induced testicular toxicity in mice.

    Science.gov (United States)

    Ohtani, Katsumi; Yanagiba, Yukie; Ashimori, Atsushige; Takeuchi, Asuka; Takada, Naoko; Togawa, Masako; Hasegawa, Tatsuya; Ikeda, Masayuki; Miura, Nobuhiko

    2013-02-01

    Cadmium (Cd) is one of the endocrine disrupter and is a well-known testicular toxicant. Recently, we reported that Cd-induced mortality was markedly different by injection timing. In this report, we investigated whether severity of testicular toxicity was affected by injection timing of Cd. C57BL/6J mice (male, 7 w) were received single intraperitoneal injection of CdCl(2) (4.5 mg/kg) at zeitgeber time 6 (ZT6) or ZT18; these injection timings showed highest (ZT6) or lowest (ZT18) mortality in our previous study (Miura, 2012). After one week of the injection, several parameters for testicular toxicity such as epididymal sperm motility and numbers of sperm head both in cauda epididymidis and testis were measured. At ZT6 injection group, all parameters examined were significantly reduced compared to the control group. However, very interestingly, no significant changes were observed at ZT18 injection group. We obtained similar results by another experiment in which mice were received single subcutaneous injection of CdCl(2) (4 or 6 mg/kg) followed by measuring the parameters ten days after the injection. This diurnal variation was not contradictory to the result of the lethal toxicity which we showed earlier. Therefore, our results indicate that the testicular toxicity of Cd is also influenced by the injection timing.

  1. Reproductive toxicity and gender differences induced by cadmium telluride quantum dots in an invertebrate model organism

    Science.gov (United States)

    Yan, Si-Qi; Xing, Rui; Zhou, Yan-Feng; Li, Kai-Le; Su, Yuan-Yuan; Qiu, Jian-Feng; Zhang, Yun-Hu; Zhang, Ke-Qin; He, Yao; Lu, Xiao-Ping; Xu, Shi-Qing

    2016-09-01

    Sexual glands are key sites affected by nanotoxicity, but there is no sensitive assay for measuring reproductive toxicity in animals. The aim of this study was to investigate the toxic effects of cadmium telluride quantum dots (CdTe-QDs) on gonads in a model organism, Bombyx mori. After dorsal vein injection of 0.32 nmol of CdTe-QDs per individual, the QDs passed through the outer membranes of gonads via the generation of ROS in the membranes of spermatocysts and ovarioles, as well as internal germ cells, thereby inducing early germ cell death or malformations via complex mechanisms related to apoptosis and autophagy through mitochondrial and lysosomal pathways. Histological observations of the gonads and quantitative analyses of germ cell development showed that the reproductive toxicity was characterized by obvious male sensitivity. Exposure to QDs in the early stage of males had severe adverse effects on the quantity and quality of sperm, which was the main reason for the occurrence of unfertilized eggs. Ala- or Gly-conjugated QDs could reduce the nanotoxicity of CdTe-QDs during germ cell development and fertilization of their offspring. The results demonstrate that males are preferable models for evaluating the reproductive toxicity of QDs in combined in vivo/in vitro investigations.

  2. The Protective Roles of Zinc and Magnesium in Cadmium-Induced Renal Toxicity in Male Wistar Rats

    National Research Council Canada - National Science Library

    Nasim Babaknejad; Ali Asghar Moshtaghie; Kahin Shahanipour; Somaye Bahrami

    2014-01-01

    .... Cadmium can cause dysfunction of different body organs. Zinc (Zn) and magnesium (Mg) supplementation can have protective effects against cadmium toxicity due to their antagonistic and antioxidants properties...

  3. Cadmium Induces Apoptosis in Freshwater Crab Sinopotamon henanense through Activating Calcium Signal Transduction Pathway: e0144392

    National Research Council Canada - National Science Library

    Jinxiang Wang; Pingping Zhang; Na Liu; Qian Wang; Jixian Luo; Lan Wang

    2015-01-01

      Calcium ion (Ca2+) is one of the key intracellular signals, which is implicated in the regulation of cell functions such as impregnation, cell proliferation, differentiation and death. Cadmium (Cd...

  4. Reciprocal Interactions between Cadmium-Induced Cell Wall Responses and Oxidative Stress in Plants

    Science.gov (United States)

    Loix, Christophe; Huybrechts, Michiel; Vangronsveld, Jaco; Gielen, Marijke; Keunen, Els; Cuypers, Ann

    2017-01-01

    Cadmium (Cd) pollution renders many soils across the world unsuited or unsafe for food- or feed-orientated agriculture. The main mechanism of Cd phytotoxicity is the induction of oxidative stress, amongst others through the depletion of glutathione. Oxidative stress can damage lipids, proteins, and nucleic acids, leading to growth inhibition or even cell death. The plant cell has a variety of tools to defend itself against Cd stress. First and foremost, cell walls might prevent Cd from entering and damaging the protoplast. Both the primary and secondary cell wall have an array of defensive mechanisms that can be adapted to cope with Cd. Pectin, which contains most of the negative charges within the primary cell wall, can sequester Cd very effectively. In the secondary cell wall, lignification can serve to immobilize Cd and create a tougher barrier for entry. Changes in cell wall composition are, however, dependent on nutrients and conversely might affect their uptake. Additionally, the role of ascorbate (AsA) as most important apoplastic antioxidant is of considerable interest, due to the fact that oxidative stress is a major mechanism underlying Cd toxicity, and that AsA biosynthesis shares several links with cell wall construction. In this review, modifications of the plant cell wall in response to Cd exposure are discussed. Focus lies on pectin in the primary cell wall, lignification in the secondary cell wall and the importance of AsA in the apoplast. Regarding lignification, we attempt to answer the question whether increased lignification is merely a consequence of Cd toxicity, or rather an elicited defense response. We propose a model for lignification as defense response, with a central role for hydrogen peroxide as substrate and signaling molecule. PMID:29163592

  5. Reciprocal Interactions between Cadmium-Induced Cell Wall Responses and Oxidative Stress in Plants

    Directory of Open Access Journals (Sweden)

    Christophe Loix

    2017-10-01

    Full Text Available Cadmium (Cd pollution renders many soils across the world unsuited or unsafe for food- or feed-orientated agriculture. The main mechanism of Cd phytotoxicity is the induction of oxidative stress, amongst others through the depletion of glutathione. Oxidative stress can damage lipids, proteins, and nucleic acids, leading to growth inhibition or even cell death. The plant cell has a variety of tools to defend itself against Cd stress. First and foremost, cell walls might prevent Cd from entering and damaging the protoplast. Both the primary and secondary cell wall have an array of defensive mechanisms that can be adapted to cope with Cd. Pectin, which contains most of the negative charges within the primary cell wall, can sequester Cd very effectively. In the secondary cell wall, lignification can serve to immobilize Cd and create a tougher barrier for entry. Changes in cell wall composition are, however, dependent on nutrients and conversely might affect their uptake. Additionally, the role of ascorbate (AsA as most important apoplastic antioxidant is of considerable interest, due to the fact that oxidative stress is a major mechanism underlying Cd toxicity, and that AsA biosynthesis shares several links with cell wall construction. In this review, modifications of the plant cell wall in response to Cd exposure are discussed. Focus lies on pectin in the primary cell wall, lignification in the secondary cell wall and the importance of AsA in the apoplast. Regarding lignification, we attempt to answer the question whether increased lignification is merely a consequence of Cd toxicity, or rather an elicited defense response. We propose a model for lignification as defense response, with a central role for hydrogen peroxide as substrate and signaling molecule.

  6. Function of a novel cadmium-induced yodA protein in Escherichia coli.

    Science.gov (United States)

    Stojnev, Tatjana; Harichová, Jana; Ferianc, Peter; Nyström, Thomas

    2007-08-01

    Cells of Escherichia coli increase greatly the synthesis of a small primarily cytoplasmic protein as soon as the cell growth rate falls below the maximal growth rate supported by cadmium exposure, after which the mature product is exported to the periplasm. This protein was previously identified as the product of the E. coli yodA open reading frame. We now report the isolation of an E. coli mutant defective in YodA synthesis because of insertional inactivation of the corresponding gene. In experiments to test the ability of both the wild-type and yodA mutant E. coli cells to bind cadmium, we have used gamma-labeled [(109)Cd]. Whereas the wild-type E. coli strain was able to bind metal, the yodA mutant strain failed to do so. In addition, analysis of such a mutant demonstrated that it grows at a rate distinguishable from that of the isogenic parent in the presence of cadmium ions. However, challenging cells with hydrogen peroxide and additional metals such as zinc, copper, cobalt, and nickel did not significantly affect the growth rate of the mutant. This growth phenotype was found to be the result of the loss of its ability to bind cadmium. These results suggest that the role of YodA protein might be to decrease the concentration level of cadmium ions in E. coli cells during cadmium stress by its ability to bind heavy metal.

  7. Is the capacity of lead acetate and cadmium chloride to induce genotoxic damage due to direct DNA-metal interaction?

    Science.gov (United States)

    Valverde, M; Trejo, C; Rojas, E

    2001-05-01

    Even though the toxic effects of lead and cadmium compounds have been studied over many years, inconsistent results have been obtained about their mutagenic, clastogenic and carcinogenic properties. However, these metals are considered to be potential human carcinogens. The mechanism of metal-induced carcinogenesis is still unknown, but one possible pathway may involve the interaction of metals with DNA, either directly or indirectly. In this work we explore the capacity of lead, cadmium or a mixture of both metals to interact with acellular DNA, by employing a variant of the comet assay. Our results, using low non-cytotoxic metal concentrations (0.01, 0.1 and 1.0 microM) with the standard protocol for the acellular assay, showed an induction of DNA damage in cells of all organs studied; however, basal DNA damage was different in each organ. To confirm that we were working with pure DNA, proteinase K was added to the lysis solution. With this enriched-lysis solution we found a negative response in the induction of DNA damage in cells derived from the liver, kidney and lung of CD-1 male mice. To support the results obtained by the enriched-acellular assay, we studied the capacity of lead and cadmium (0.1 microM) to induce breaks in pooled genomic DNA in cells of the same organs, with negative results. Consistent with these findings, these metals do not induce DNA breaks in the plasmid pUSE amp+. On the whole, we did not detect direct induction of DNA strand breaks by lead acetate, cadmium chloride or a mixture of both metals, all at low non-cytotoxic concentrations. However, we found an induction of lipid peroxidation and an increase in free radical levels in the different organs of CD-1 male mice after inhalation of lead acetate (0.0068 microg/cc) or cadmium chloride (0.08 microg/cc) for 1 h, suggesting the induction of genotoxicity and carcinogenicity by indirect interactions, such as oxidative stress.

  8. Mitochondrial Electron Transport Chain in Heavy Metal-Induced Neurotoxicity: Effects of Cadmium, Mercury, and Copper

    Directory of Open Access Journals (Sweden)

    Elena A. Belyaeva

    2012-01-01

    Full Text Available To clarify the role of mitochondrial electron transport chain (mtETC in heavy-metal-induced neurotoxicity, we studied action of Cd2+, Hg2+, and Cu2+ on cell viability, intracellular reactive oxygen species formation, respiratory function, and mitochondrial membrane potential of rat cell line PC12. As found, the metals produced, although in a different way, dose- and time-dependent changes of all these parameters. Importantly, Cd2+ beginning from 10 [mu]M and already at short incubation time (3 h significantly inhibited the FCCP-uncoupled cell respiration; besides, practically the complete inhibition of the respiration was reached after 3 h incubation with 50 [mu]M Hg2+ or 500 [mu]M Cd2+, whereas even after 48 h exposure with 500 [mu]M Cu2+, only a 50% inhibition of the respiration occurred. Against the Cd2+-induced cell injury, not only different antioxidants and mitochondrial permeability transition pore inhibitors were protective but also such mtETC effectors as FCCP and stigmatellin (complex III inhibitor. However, all mtETC effectors used did not protect against the Hg2+- or Cu2+-induced cell damage. Notably, stigmatellin was shown to be one of the strongest protectors against the Cd2+-induced cell damage, producing a 15–20% increase in the cell viability. The mechanisms of the mtETC involvement in the heavy-metal-induced mitochondrial membrane permeabilization and cell death are discussed.

  9. Development of a Method for the Determination of Chromium and Cadmium in Tannery Wastewater Using Laser-Induced Breakdown Spectroscopy

    Directory of Open Access Journals (Sweden)

    Mahwish Bukhari

    2012-01-01

    Full Text Available This paper illustrates systematic development of a convenient analytical method for the determination of chromium and cadmium in tannery wastewater using laser-induced breakdown spectroscopy (LIBS. A new approach was developed by which liquid was converted into solid phase sample surface using absorption paper for subsequent LIBS analysis. The optimized values of LIBS parameters were 146.7 mJ for chromium and 89.5 mJ for cadmium (laser pulse energy, 4.5 μs (delay time, 70 mm (lens to sample surface distance, and 7 mm (light collection system to sample surface distance. Optimized values of LIBS parameters demonstrated strong spectrum lines for each metal keeping the background noise at minimum level. The new method of preparing metal standards on absorption papers exhibited calibration curves with good linearity with correlation coefficients, R2 in the range of 0.992 to 0.998. The developed method was tested on real tannery wastewater samples for determination of chromium and cadmium.

  10. Inhibitory effect of plant-originated glycoprotein (27 kDa) on expression of matrix metalloproteinase-9 in cadmium chloride-induced BNL CL.2 cells.

    Science.gov (United States)

    Lee, Jin; Lim, Kye-Taek

    2011-12-01

    Cadmium is very harmful to the environment and to human beings because of its long lifetime. The toxicity of cadmium as an industrial pollutant and a food contaminant, and as one of the major components in cigarette smoke is well known. Cadmium can cause a number of lesions in many organs, such as the kidney, the lung, the liver, the brain, the blood system. However, the mechanism of toxicity of cadmium is not yet clear. Also, it has been well known as human carcinogen which is indirectly caused inflammation-mediated hepatocarcinoma. In the present study it was demonstrated that glycoprotein (27 kDa) isolated from Gardenia jasminoides Ellis (GJE) protects BNL CL.2 cells from expression of inflammation-related factors stimulated by cadmium chloride (10 μM). Intracellular ROS and intracellular Ca(2+) using fluorescence, activities of activator protein (AP)-1, cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-9, and arachidonic acid (AA) using immunoblot analysis or radioactivity were evaluated. The results obtained from this experiment indicated that GJE glycoprotein (100 μg/mL) inhibits the production of intracellular ROS, and intracellular Ca(2+) mobilization. Also, it significantly suppressed inflammatory factors [expression of AP-1 (c-Jun and c-Fos), arachidonic acid, COX-2, and MMP-9]. Taken together, these findings suggest that GJE glycoprotein might be used for protection of inflammation caused by cadmium ion as one of natural compounds. Copyright © 2011 Elsevier GmbH. All rights reserved.

  11. Mechanisms of cadmium carcinogenicity in the gastrointestinal tract.

    Science.gov (United States)

    Bishak, Yaser Khaje; Payahoo, Laleh; Osatdrahimi, Alireza; Nourazarian, Alireza

    2015-01-01

    Cancer, a serious public health problem in worldwide, results from an excessive and uncontrolled proliferation of the body cells without obvious physiological demands of organs. The gastrointestinal tract, including the esophagus, stomach and intestine, is a unique organ system. It has the highest cancer incidence and cancer- related mortality in the body and is influenceed by both genetic and environmental factors. Among the various chemical elements recognized in the nature, some of them including zinc, iron, cobalt, and copper have essential roles in the various biochemical and physiological processes, but only at low levels and others such as cadmium, lead, mercury, arsenic, and nickel are considered as threats for human health especially with chronic exposure at high levels. Cadmium, an environment contaminant, cannot be destroyed in nature. Through impairment of vitamin D metabolism in the kidney it causes nephrotoxicity and subsequently bone metabolism impairment and fragility. The major mechanisms involved in cadmium carcinogenesis could be related to the suppression of gene expression, inhibition of DNA damage repair, inhibition of apoptosis, and induction of oxidative stress. In addition, cadmium may act through aberrant DNA methylation. Cadmium affects multiple cellular processes, including signal transduction pathways, cell proliferation, differentiation, and apoptosis. Down-regulation of methyltransferases enzymes and reduction of DNA methylation have been stated as epigenetic effects of cadmium. Furthermore, increasing intracellular free calcium ion levels induces neuronal apoptosis in addition to other deleterious influence on the stability of the genome.

  12. Hydrogen sulfide alleviates cadmium-induced morpho-physiological and ultrastructural changes in Brassica napus.

    Science.gov (United States)

    Ali, Basharat; Gill, Rafaqat A; Yang, Su; Gill, Muhammad B; Ali, Shafaqat; Rafiq, Muhammad T; Zhou, Weijun

    2014-12-01

    In the present study, role of hydrogen sulfide (H2S) in alleviating cadmium (Cd) induced stress in oilseed rape (Brassica napus L.) was studied under greenhouse conditions. Plants were grown hydroponically under three levels (0, 100, and 500µM) of Cd and three levels (0, 100 and 200µM) of H2S donor, sodium hydrosulfide (NaHS). Results showed that application of H2S significantly improved the plant growth, root morphology, chlorophyll contents, elements uptake and photosynthetic activity in B. napus plants under Cd stress. Moreover, addition of H2S reduced the Cd concentration in the leaves and roots of B. napus plants under Cd-toxicity. Exogenously applied H2S decreased the production of malondialdehyde and reactive oxygen species in the leaves and roots by improving the enzymatic antioxidant activities under Cd stress conditions. The microscopic examination indicated that application of exogenous H2S improved the cell structures and enabled a clean mesophyll cell having a well developed chloroplast with thylakoid membranes, and a number of mitochondria could be observed in the micrographs. A number of modifications could be found in root tip cell i.e. mature mitochondria, long endoplasmic reticulum and golgibodies under combined application of H2S and Cd. On the basis of these findings, it can be concluded that application of exogenous H2S has a protective role on plant growth, photosynthetic parameters, elements uptake, antioxidants enzyme activities and ultrastructural changes in B. napus under high Cd stress conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Oxidative injury induced by cadmium sulfide nanoparticles in A549 cells and rat lungs.

    Science.gov (United States)

    Wang, Junfeng; Jiang, Chunyang; Alattar, Mohamed; Hu, Xiaoli; Ma, Dong; Liu, Huibin; Meng, Chunyan; Cao, Fuyuan; Li, Weihong; Li, Qingzhao

    2015-01-01

    Rod-shaped cadmium sulfide nanoparticles (CdS NPs) are becoming increasingly important in many industrial fields, but their potential hazards remain unknown. This study aimed to explore the patterns and mechanisms of lung injury induced by CdS NPs. A549 cells and rats were exposed to two types of CdS NPs with a same diameter of 20-30 nm but different lengths, CdS1 (80-100 nm) and CdS2 (110-130 nm). The using doses were included 10 μg/ml and 20 μg/ml two types of CdS NPs for cellular experiments and five times dose of 20 mg/kg body weight for rats' exposure. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and trypan blue staining were used to detect the A549 cell mortality percentage. The levels of reactive oxygen species (ROS) were determined in A549 cell. The vigor of superoxide dismutase (SOD) and the contents of catalase (CAT) and malondialdehyde (MDA) were detected both in A549 cells and in rats' serum and lung tissues. The cellular morphological changes were observed under transmission electron microscopy (TEM) and the pathological changes were observed in rats' lung tissue. CdS NPs significantly increased A549 cell mortality percentage. The CdS NPs also increased the levels of ROS and MDA content, whereas they decreased SOD and CAT activities. In parallel, similar changes of the contents of MDA, SOD and CAT were also observed in the sera and lung tissues of CdS NP-treated rats. The cellular TEM detection revealed that two types of CdS nanorods appeared as orderly arranged rounded fat droplets separately and leading to nucleus condensation (CdS1). These cellular and rats' tissues changes in the group treated with CdS1 were more significant than the CdS2 groups. Furthermore, CdS NPs induced many pathological changes, including emphysematous changes in rat lung tissue. Especially visible lung consolidation can be observed in the CdS1 group. CdS NPs induce oxidative injury in the respiratory system, and their toxic effects may be related to grain length.

  14. Inhibition of ethylene production by putrescine alleviates aluminium-induced root inhibition in wheat plants.

    Science.gov (United States)

    Yu, Yan; Jin, Chongwei; Sun, Chengliang; Wang, Jinghong; Ye, Yiquan; Zhou, Weiwei; Lu, Lingli; Lin, Xianyong

    2016-01-08

    Inhibition of root elongation is one of the most distinct symptoms of aluminium (Al) toxicity. Although putrescine (Put) has been identified as an important signaling molecule involved in Al tolerance, it is yet unknown how Put mitigates Al-induced root inhibition. Here, the possible mechanism was investigated by using two wheat genotypes differing in Al resistance: Al-tolerant Xi Aimai-1 and Al-sensitive Yangmai-5. Aluminium caused more root inhibition in Yangmai-5 and increased ethylene production at the root apices compared to Xi Aimai-1, whereas the effects were significantly reversed by ethylene biosynthesis inhibitors. The simultaneous exposure of wheat seedlings to Al and ethylene donor, ethephon, or ethylene biosynthesis precursor, 1-aminocyclopropane-1-carboxylic acid (ACC), increased ethylene production and aggravated root inhibition, which was more pronounced in Xi Aimai-1. In contrast, Put treatment decreased ethylene production and alleviated Al-induced root inhibition in both genotypes, and the effects were more conspicuous in Yangmai-5. Furthermore, our results indicated that Al-induced ethylene production was mediated by ACC synthase (ACS) and ACC oxidase, and that Put decreased ethylene production by inhibiting ACS. Altogether, these findings indicate that ethylene is involved in Al-induced root inhibition and this process could be alleviated by Put through inhibiting ACS activity.

  15. Haem oxygenase-1 is involved in salicylic acid-induced alleviation of oxidative stress due to cadmium stress in Medicago sativa.

    Science.gov (United States)

    Cui, Weiti; Li, Le; Gao, Zhaozhou; Wu, Honghong; Xie, Yanjie; Shen, Wenbiao

    2012-09-01

    This work examines the involvement of haem oxygenase-1 (HO-1) in salicylic acid (SA)-induced alleviation of oxidative stress as a result of cadmium (Cd) stress in alfalfa (Medicago sativa L.) seedling roots. CdCl(2) exposure caused severe growth inhibition and Cd accumulation, which were potentiated by pre-treatment with zinc protoporphyrin (ZnPPIX), a potent HO-1 inhibitor. Pre-treatment of plants with the HO-1 inducer haemin or SA, both of which could induce MsHO1 gene expression, significantly reduced the inhibition of growth and Cd accumulation. The alleviation effects were also evidenced by a decreased content of thiobarbituric acid-reactive substances (TBARS). The antioxidant behaviour was confirmed by histochemical staining for the detection of lipid peroxidation and the loss of plasma membrane integrity. Furthermore, haemin and SA pre-treatment modulated the activities of ascorbate peroxidase (APX), superoxide dismutase (SOD), and guaiacol peroxidase (POD), or their corresponding transcripts. Significant enhancement of the ratios of reduced/oxidized homoglutathione (hGSH), ascorbic acid (ASA)/dehydroascorbate (DHA), and NAD(P)H/NAD(P)(+), and expression of their metabolism genes was observed, consistent with a decreased reactive oxygen species (ROS) distribution in the root tips. These effects are specific for HO-1, since ZnPPIX blocked the above actions, and the aggravated effects triggered by SA plus ZnPPIX were differentially reversed when carbon monoxide (CO) or bilirubin (BR), two catalytic by-products of HO-1, was added. Together, the results suggest that HO-1 is involved in the SA-induced alleviation of Cd-triggered oxidative stress by re-establishing redox homeostasis.

  16. Purification and characterization of a cadmium-induced metallothionein from the shore crab Carcinus maenas (L.)

    DEFF Research Database (Denmark)

    Pedersen, K L; Pedersen, S N; Højrup, P

    1994-01-01

    Two metallothionein variants were purified from the midgut gland of crabs (Carcinus maenas) exposed to a high cadmium concentration (2 p.p.m.). One of the variants was purified from crabs exposed to a low cadmium concentration (0.5 p.p.m.). The purification method involved acetone precipitation......, gel filtration and reversed-phase h.p.l.c. The complete amino acid sequences of both variants have been elucidated by m.s. and automated sequence analysis on S-methylated proteins or fragments produced by cleavage of the S-methylated proteins with Staphylococcus aureus proteinase. The two variants...

  17. Inhibition of lipopolysaccharide-induced neuroinflammatory events ...

    African Journals Online (AJOL)

    tetrazolium bromide (MTT) assay. Lipopolysaccharide (LPS) is used to activate BV-2 microglia. Nitric oxide (NO) levels were measured using Griess assay. Inducible NO synthase (iNOS) expressional levels were measured by Western blot analysis.

  18. Hepatoprotective effect of grape seed proanthocyanidins on Cadmium-induced hepatic injury in rats: Possible involvement of mitochondrial dysfunction, inflammation and apoptosis

    Directory of Open Access Journals (Sweden)

    Selvaraj Miltonprabu

    2016-01-01

    Full Text Available The present study was undertaken to evaluate the possible ameliorative role of grape seed proanthocyanidins (GSP against Cadmium (Cd induced hepatic inflammation, apoptosis and hepatic mitochondrial toxicity in rats. Male Wistar rats were distributed in four experimental groups: control, GSP, Cd and Cd + GSP. Exposure to a hepatotoxic dose of Cd (5 mg/kg BW caused liver damage, coupled with enhanced reactive oxygen species (ROS generation, increased inflammation and apoptosis in liver with increased DNA damage in hepatocytes of rats. Mitochondria were isolated from the hepatic tissues of rats from each group. Our results showed significant decrease in the tri-carboxylic acid cycle enzymes, increased mitochondrial swelling, inhibition of cytochrome c oxidase activity and complex I–III, II–III and IV mediated electron transfer, decreased mitochondrial ATPases, a reduction in calcium content and mitochondrial oxygen consumption in Cd treated rats. All these molecular changes caused by Cd were alleviated by the pre-supplementation with GSP (100 mg/kg BW. The ultra structural changes in the liver also support our findings. From our results, it is clearly indicated that the free radical scavenging, metal chelating and antioxidant potentials of GSP might be the possible reason, responsible for the rescue action against Cd induced mitochondrial damage in the liver of rats.

  19. Aspirin augments hyaluronidase induced adhesion inhibition ...

    African Journals Online (AJOL)

    Postoperative adhesions occur after virtually all abdomino-pelvic surgery and are the leading cause of intestinal obstruction and other gynaecologic problems. We used an animal model to test the efficacy of combined administration of aspirin and hyaluronidase on adhesion formation. Adhesions were induced using ...

  20. Caspase-Dependent and Caspase-Independent Pathways Are Involved in Cadmium-Induced Apoptosis in Primary Rat Proximal Tubular Cell Culture.

    Science.gov (United States)

    Liu, Gang; Zou, Hui; Luo, Tongwang; Long, Mengfei; Bian, Jianchun; Liu, Xuezhong; Gu, Jianhong; Yuan, Yan; Song, Ruilong; Wang, Yi; Zhu, Jiaqiao; Liu, Zongping

    2016-01-01

    We designed this study to investigate whether cadmium induces caspase-independent apoptosis and to investigate the relationship between the caspase-dependent and caspase-independent apoptotic pathways. Cadmium (1.25-2.5 μM) induced oxidative stress in rat proximal tubular (rPT) cells, as seen in the reactive oxygen species levels; N-acetylcysteine prevented this. Cyclosporin A (CsA) prevented mitochondrial permeability transition pore opening and apoptosis; there was mitochondrial ultrastructural disruption, mitochondrial cytochrome c (cyt c) translocation to the cytoplasm, and subsequent caspase-9 and caspase-3 activation. Z-VAD-FMK prevented caspase-3 activation and apoptosis and decreased BNIP-3 (Bcl-2/adenovirus E1B 19-kDa interacting protein 3) expression levels and apoptosis-inducing factor/endonuclease G (AIF/Endo G) translocation. Simultaneously, cadmium induced prominent BNIP-3 expression in the mitochondria and cytoplasmic AIF/Endo G translocation to the nucleus. BNIP-3 silencing significantly prevented AIF and Endo G translocation and decreased the apoptosis rate, cyt c release, and caspase-9 and caspase-3 activation. These results suggest that BNIP-3 is involved in the caspase-independent apoptotic pathway and is located upstream of AIF/Endo G; both the caspase-dependent and caspase-independent pathways are involved in cadmium-induced rPT cell apoptosis and act synergistically.

  1. Effect of Ocimum basilicum extract on cadmium-induced testicular histomorphometric and immunohistochemical alterations in albino rats

    Science.gov (United States)

    Nooh, Hanna Z.

    2013-01-01

    The present study examined the efficacy of Ocimum basilicum (basil) extract, a natural herb, with antioxidant properties, against testicular toxicity induced by cadmium (Cd), which is one of the most important toxic heavy metals. The intoxicated rats showed significant alterations in the testicular tissue including decreased seminiferous epithelium height and changes in the arrangement of spermatogenic layers. Hypospermatogensis with cytoplasmic vacuolization and pyknotic nuclei were observed. Intertubular hemorrahage and absence of spermatozoa were noted. Decreased cell proliferation was reflected by a decrease in Ki-67 expression, whereas the increase in apoptotic rate was associated with a decrease in the Bcl/Bax ratio. Concomitant treatment with aqueous basil extract led to an improvement in histological, morphometrical and immunohistochemical changes induced by Cd. The beneficial effects of basil extract could be attributed to its antioxidant properties. PMID:23869259

  2. Heme oxygenase-1-mediated apoptosis under cadmium-induced oxidative stress is regulated by autophagy, which is sensitized by tumor suppressor p53.

    Science.gov (United States)

    So, Keum-Young; Oh, Seon-Hee

    2016-10-07

    Heme oxygenase-1 (HO-1) is a stress-inducible cytoprotective enzyme. It is often overexpressed in different types of cancers and promotes cell survival. However, the role of HO-1 and the underlying molecular mechanism of cadmium (Cd)-induced oxidative stress in cancer cells remain undefined. Here we show that the role of HO-1 under Cd-induced oxidative stress is dependent upon autophagy, which is sensitized by the tumor suppressor p53. The sensitivity to Cd was 3.5- and 14-fold higher in p53-expressing YD8 and H460 cells than in p53-null YD10B and H1299 cells, respectively. The levels of p53 in YD8 and H460 cells decreased in a Cd concentration-dependent manner, which was inhibited by pretreatment with N-acetylcysteine. In both cell lines, Cd exposure resulted in caspase-3-mediated PARP-1 cleavage and the induction of CHOP, LC3-II, and HO-1, which were limited in YD10B and H1299 cells exposed to high concentrations of Cd. Cd exposure to p53-overexpressing YD10B cells enhanced Cd-induced HO-1 and LC3-II levels, whereas genetic knockdown of p53 in YD8 cells resulted in the suppression of Cd-induced levels of HO-1 and LC3-II, indicating that p53 is required in the sensing of HO-1 and induction of autophagy. The inhibition of autophagy using small interfering RNA (siRNA) for the autophagy-related gene atg5 enhanced HO-1, CHOP, and PARP-1 cleavage induced by Cd. However, transfection with HO-1 siRNA increased Cd-induced LC3-II, and suppressed the expression of CHOP and cleavage of PARP-1. Collectively, the role of HO-1 in apoptosis could be modulated by autophagy, which is sensitized by p53 expression in human cancer cell lines. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Cadmium-induced oxidative stress and antioxidative enzyme response in water hyacinth and salvinia

    OpenAIRE

    Vestena, Silvane; Cambraia, Jose; Ribeiro, Cleberson; Oliveira, Juraci A.; Oliva, Marco A.

    2011-01-01

    The reactive oxygen species generation, lipid peroxidation and antioxidative enzyme response of water hyacinth and salvinia to Cd were evaluated. Cadmium was absorbed/accumulated mainly in the roots, but significant amounts also translocated to the leaves. No Cd effect on dry weight was detected, although toxicity symptoms were visible. Superoxide and H2O2 concentrations increased, in addition to lipid peroxidation in both species, especially in the leaves of salvinia. In general, antioxidati...

  4. Effect of Cadmium Ion on alpha-Glucosidase: An Inhibition Kinetics and Molecular Dynamics Simulation Integration Study.

    Science.gov (United States)

    Luo, Tao; Lee, Jinhyuk; Lü, Zhi-Rong; Mu, Hang; Yue, Li-Mei; Park, Yong-Doo; Ye, Zhuo-Ming

    2016-06-01

    α-Glucosidase is a critical metabolic enzyme that produces glucose molecules by catalyzing carbohydrates. The aim of this study is to elucidate biological toxicity of Cd(2+) based on α-glucosidase activity and conformational changes. We studied Cd(2+)-mediated inactivation as well as conformational modulation of α-glucosidase by using kinetics coupled with simulation of molecular dynamics. The enzyme was significantly inactivated by Cd(2+) in a reversibly binding behavior, and Cd(2+) binding induced a non-competitive type of inhibition reaction (the K i was calculated as 0.3863 ± 0.033 mM). Cd(2+) also modulated regional denaturation of the active site pocket as well as overall partial tertiary structural change. In computational simulations using molecular dynamics, simulated introduction of Cd(2+) induced in a depletion of secondary structure by docking Cd(2+) near the saccharides degradation at the active site, suggesting that Cd(2+) modulating enzyme denaturation. The present study elucidated that the binding of Cd(2+) triggers conformational changes of α-glucosidase as well as inactivates catalytic function, and thus suggests an explanation of the deleterious effects of Cd(2+) on α-glucosidase.

  5. Epidermal growth factor inhibits cysteamine-induced duodenal ulcers

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1983-01-01

    mg/kg, s.c.). Furthermore, measurements on tissue extracts of the pouches revealed that 5 h after cysteamine treatment, Brunner's glands were depleted of epidermal growth factor. The effect on ulcer development of intraduodenally applied exogenous epidermal growth factor (1 micrograms/kg . h) also...... was studied. Luminal epidermal growth factor significantly inhibited the formation of cysteamine-induced duodenal ulcer, compared with controls receiving saline. The effect was not due to inhibition of gastric acid secretion or stimulation of duodenal bicarbonate secretion since the dose of epidermal growth...... of synthesis and secretion of endogenous epidermal growth factor may be a pathogenetic factor in cysteamine-induced duodenal ulcer....

  6. Cadmium-induced calcium release and prostaglandin E[sub 2] production in neonatal mouse calvaria are dependent on cox-2 induction and protein kinase C activation

    Energy Technology Data Exchange (ETDEWEB)

    Romare, A. (Department of Pharmacology, Faculty of Health Sciences, Univ. of Linkoeping (Sweden)); Lundholm, C.E. (Department of Pharmacology, Univ. of Linkoeping (Sweden) Astra Haessle AB, Regulatory Affairs, Moendal (Sweden))

    The mechanisms by which cadmium (Cd) causes skeletal impairment have not been fully clarified. Release of calcium from neonatal mouse calvaria in organ culture is stimulated by submicromolar concentrations of Cd, an effect that is associated with increased production of prostaglandin E[sub 2] (PGE[sub 2]). The prostaglandin-synthesising enzyme cyclooxygenase (cox) exists in two forms, one constitutive (cox-1) and the other inducible (cox-2). Cox-2 can be induced by mitogenic stimuli and inflammatory cytokines, such as parathyroid hormone (PTH), interleukin-1[alpha] and tumour necrosis factor-[alpha]. Cd potently activates protein kinase C (PKC), which in turn induces cox-2 production in several cell types. Our aim was to determine whether Cd-induced Ca release and PGE[sub 2] production in neonatal mouse calvaria involve induction of cox-2 and, if so, to ascertain whether that effect is mediated by activation of PKC. Cd dose-dependently stimulated Ca release from cultured neonatal mouse calvaria, with a maximal effect at 0.4-0.8 [mu]M. Different sensitivity was observed to Cd-induced Ca release between two breeds of mice suggesting that the susceptibility to Cd may be genetically determined. Dexamethasone (10 [mu]M) added to the culture medium abolished the Ca releasing effect of Cd, an effect not overcome by addition of arachidonic acid (10 [mu]M). The cox-2-selective inhibitors NS-398 and DFU and the less selective inhibitor meloxicam, potently impeded Cd-induced Ca release (IC[sub 50] of 1 nM, 41 nM and 7 nM, respectively) and calvarial production of PGE[sub 2]. Cd-induced and phorbol 12-myristate 13-acetate (PMA; 20 nM)-induced Ca release was inhibited by the PKC inhibitor calphostin C (0.5 [mu]M) and by NS-398. The effects of PMA and Cd on Ca release were not additive, suggesting that both operated via the PKC pathway. We suggest that Cd-induced Ca release from neonatal mouse calvaria in culture depends on induction of cox-2 that occurs via the PKC signalling

  7. Cadmium-induced calcium release and prostaglandin E{sub 2} production in neonatal mouse calvaria are dependent on cox-2 induction and protein kinase C activation

    Energy Technology Data Exchange (ETDEWEB)

    Romare, A. [Department of Pharmacology, Faculty of Health Sciences, Univ. of Linkoeping (Sweden); Lundholm, C.E. [Department of Pharmacology, Univ. of Linkoeping (Sweden)]|[Astra Haessle AB, Regulatory Affairs, Moendal (Sweden)

    1999-06-01

    The mechanisms by which cadmium (Cd) causes skeletal impairment have not been fully clarified. Release of calcium from neonatal mouse calvaria in organ culture is stimulated by submicromolar concentrations of Cd, an effect that is associated with increased production of prostaglandin E{sub 2} (PGE{sub 2}). The prostaglandin-synthesising enzyme cyclooxygenase (cox) exists in two forms, one constitutive (cox-1) and the other inducible (cox-2). Cox-2 can be induced by mitogenic stimuli and inflammatory cytokines, such as parathyroid hormone (PTH), interleukin-1{alpha} and tumour necrosis factor-{alpha}. Cd potently activates protein kinase C (PKC), which in turn induces cox-2 production in several cell types. Our aim was to determine whether Cd-induced Ca release and PGE{sub 2} production in neonatal mouse calvaria involve induction of cox-2 and, if so, to ascertain whether that effect is mediated by activation of PKC. Cd dose-dependently stimulated Ca release from cultured neonatal mouse calvaria, with a maximal effect at 0.4-0.8 {mu}M. Different sensitivity was observed to Cd-induced Ca release between two breeds of mice suggesting that the susceptibility to Cd may be genetically determined. Dexamethasone (10 {mu}M) added to the culture medium abolished the Ca releasing effect of Cd, an effect not overcome by addition of arachidonic acid (10 {mu}M). The cox-2-selective inhibitors NS-398 and DFU and the less selective inhibitor meloxicam, potently impeded Cd-induced Ca release (IC{sub 50} of 1 nM, 41 nM and 7 nM, respectively) and calvarial production of PGE{sub 2}. Cd-induced and phorbol 12-myristate 13-acetate (PMA; 20 nM)-induced Ca release was inhibited by the PKC inhibitor calphostin C (0.5 {mu}M) and by NS-398. The effects of PMA and Cd on Ca release were not additive, suggesting that both operated via the PKC pathway. We suggest that Cd-induced Ca release from neonatal mouse calvaria in culture depends on induction of cox-2 that occurs via the PKC signalling

  8. Cadmium-induced ethylene production and responses in Arabidopsis thaliana rely on ACS2 and ACS6 gene expression.

    Science.gov (United States)

    Schellingen, Kerim; Van Der Straeten, Dominique; Vandenbussche, Filip; Prinsen, Els; Remans, Tony; Vangronsveld, Jaco; Cuypers, Ann

    2014-08-01

    Anthropogenic activities cause metal pollution worldwide. Plants can absorb and accumulate these metals through their root system, inducing stress as a result of excess metal concentrations inside the plant. Ethylene is a regulator of multiple plant processes, and is affected by many biotic and abiotic stresses. Increased ethylene levels have been observed after exposure to excess metals but it remains unclear how the increased ethylene levels are achieved at the molecular level. In this study, the effects of cadmium (Cd) exposure on the production of ethylene and its precursor 1-aminocyclopropane-1-carboxylic acid (ACC), and on the expression of the ACC Synthase (ACS) and ACC Oxidase (ACO) multigene families were investigated in Arabidopsis thaliana. Increased ethylene release after Cd exposure was directly measurable in a system using rockwool-cultivated plants; enhanced levels of the ethylene precursor ACC together with higher mRNA levels of ethylene responsive genes: ACO2, ETR2 and ERF1 also indicated increased ethylene production in hydroponic culture. Regarding underlying mechanisms, it was found that the transcript levels of ACO2 and ACO4, the most abundantly expressed members of the ACO multigene family, were increased upon Cd exposure. ACC synthesis is the rate-limiting step in ethylene biosynthesis, and transcript levels of both ACS2 and ACS6 showed the highest increase and became the most abundant isoforms after Cd exposure, suggesting their importance in the Cd-induced increase of ethylene production. Cadmium induced the biosynthesis of ACC and ethylene in Arabidopsis thaliana plants mainly via the increased expression of ACS2 and ACS6. This was confirmed in the acs2-1acs6-1 double knockout mutants, which showed a decreased ethylene production, positively affecting leaf biomass and resulting in a delayed induction of ethylene responsive gene expressions without significant differences in Cd contents between wild-type and mutant plants.

  9. Cadmium-induced ethylene production and responses in Arabidopsis thaliana rely on ACS2 and ACS6 gene expression

    Science.gov (United States)

    2014-01-01

    Background Anthropogenic activities cause metal pollution worldwide. Plants can absorb and accumulate these metals through their root system, inducing stress as a result of excess metal concentrations inside the plant. Ethylene is a regulator of multiple plant processes, and is affected by many biotic and abiotic stresses. Increased ethylene levels have been observed after exposure to excess metals but it remains unclear how the increased ethylene levels are achieved at the molecular level. In this study, the effects of cadmium (Cd) exposure on the production of ethylene and its precursor 1-aminocyclopropane-1-carboxylic acid (ACC), and on the expression of the ACC Synthase (ACS) and ACC Oxidase (ACO) multigene families were investigated in Arabidopsis thaliana. Results Increased ethylene release after Cd exposure was directly measurable in a system using rockwool-cultivated plants; enhanced levels of the ethylene precursor ACC together with higher mRNA levels of ethylene responsive genes: ACO2, ETR2 and ERF1 also indicated increased ethylene production in hydroponic culture. Regarding underlying mechanisms, it was found that the transcript levels of ACO2 and ACO4, the most abundantly expressed members of the ACO multigene family, were increased upon Cd exposure. ACC synthesis is the rate-limiting step in ethylene biosynthesis, and transcript levels of both ACS2 and ACS6 showed the highest increase and became the most abundant isoforms after Cd exposure, suggesting their importance in the Cd-induced increase of ethylene production. Conclusions Cadmium induced the biosynthesis of ACC and ethylene in Arabidopsis thaliana plants mainly via the increased expression of ACS2 and ACS6. This was confirmed in the acs2-1acs6-1 double knockout mutants, which showed a decreased ethylene production, positively affecting leaf biomass and resulting in a delayed induction of ethylene responsive gene expressions without significant differences in Cd contents between wild-type and

  10. Blueberry (Vaccinium ashei Reade) extract ameliorates ovarian damage induced by subchronic cadmium exposure in mice: Potential δ-ALA-D involvement.

    Science.gov (United States)

    Izaguirry, Aryele Pinto; Soares, Melina Bucco; Vargas, Laura Musacchio; Spiazzi, Cristiano Chiapinotto; Dos Santos Brum, Daniela; Noremberg, Simone; Mendez, Andreas Sebastian Loureiro; Santos, Francielli Weber

    2017-01-01

    Females are born with a finite number of oocyte-containing follicles and ovary damage results in reduced fertility. Cadmium accumulates in the reproductive system, damaging it, and the cigarette smoke is a potential exposure route. Natural therapies are relevant to health benefits and disease prevention. This study verified the effect of cadmium exposure on the ovaries of mice and the blueberry extract as a potential therapy. Blueberry therapy was effective in restoring reactive species levels and δ-aminolevulinate dehydratase activity, and partially improved the viability of cadmium-disrupted follicles. This therapy was not able to restore the 17 β-hydroxysteroid dehydrogenase activity. Extract HPLC evaluation indicated the presence of quercetin, quercitrin, isoquercetin, and ascorbic acid. Ascorbic acid was the major substance and its concentration was 620.24 µg/mL. Thus, cadmium accumulates in the ovaries of mice after subchronic exposure, inducing cellular damage, and the blueberry extract possesses antioxidant properties that could protect, at least in part, the ovarian tissue from cadmium toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 32: 188-196, 2017. © 2015 Wiley Periodicals, Inc.

  11. Madecassoside Inhibits Melanin Synthesis by Blocking Ultraviolet-Induced Inflammation

    OpenAIRE

    Eunsun Jung; Jung-A Lee; Seoungwoo Shin; Kyung-Baeg Roh; Jang-Hyun Kim; Deokhoon Park

    2013-01-01

    Madecassoside (MA), a pentacyclic triterpene isolated from Centella asitica (L.), is used as a therapeutic agent in wound healing and also as an anti-inflammatory and anti-aging agent. However, the involvement of MA in skin-pigmentation has not been reported. This study was conducted to investigate the effects of MA on ultraviolet (UV)-induced melanogenesis and mechanisms in a co-culture system of keratinocytes and melanocytes. MA significantly inhibited UVR-induced melanin synthesis and mel...

  12. Lead (Pb2+ and cadmium (Cd2+ inhibit the dipsogenic action of central beta-adrenergic stimulation by isoproterenol

    Directory of Open Access Journals (Sweden)

    J.B. Fregoneze

    1997-03-01

    Full Text Available We have previously demonstrated that acute third ventricle injections of both Pb2+ and Cd2+ impair the dipsogenic response elicited by three different situations: dehydration and central cholinergic or angiotensinergic stimulation. ß-Adrenergic activation is part of the multifactorial integrated systems operating in drinking behavior control in the central nervous system. In the present study acute third ventricle injections of Pb2+ (3, 30 and 300 pmol/rat or Cd2+ (0.3, 3 and 30 pmol/rat blocked the dipsogenic response induced by third ventricle injections of isoproterenol (ISO; 160 nmol/rat in a dose-dependent manner. Normohydrated animals receiving ISO + NaAc (sodium acetate or saline (controls displayed a high water intake after 120 min (ISO + saline = 5.78 ± 0.54 ml/100 g; ISO + NaAc = 6.00 ± 0.6 ml/100 g. After the same period, animals receiving ISO but pretreated with PbAc at the highest dose employed (300 pmol/rat drank 0.78 ± 0.23 ml/100 g while those receiving ISO and pretreated with the highest dose of CdCl2 (30 pmol/rat presented a water intake of 0.7 ± 0.30 ml/100 g. Third ventricle injections of CdCl2 (3 nmol/rat or PbAc (3 nmol/rat did not modify food intake in rats deprived of food for 24 h. Thus, general central nervous system depression explaining the antidipsogenic action of the metals can be safely excluded. It is concluded that both Pb2+ and Cd2+ inhibit water intake induced by central ß-adrenergic stimulation

  13. Autophagy contributes to gefitinib-induced glioma cell growth inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Cheng-Yi [Department of Surgery, Fong-Yuan Hospital, Taichung 420, Taiwan (China); Graduate Institute of Pharmaceutical Science and Technology, Central Taiwan University of Science and Technology, Taichung 406, Taiwan (China); Kuan, Yu-Hsiang [Department of Pharmacology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Pharmacy, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China); Ou, Yen-Chuan; Li, Jian-Ri [Division of Urology, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Wu, Chih-Cheng [Department of Anesthesiology, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Department of Financial and Computational Mathematics, Providence University, Taichung 433, Taiwan (China); Pan, Pin-Ho [Department of Pediatrics, Tungs’ Taichung MetroHarbor Hospital, Taichung 435, Taiwan (China); Chen, Wen-Ying [Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Huang, Hsuan-Yi [Department of Surgery, Fong-Yuan Hospital, Taichung 420, Taiwan (China); Chen, Chun-Jung, E-mail: cjchen@vghtc.gov.tw [Department of Medical Research, Taichung Veterans General Hospital, Taichung 407, Taiwan (China); Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan (China); Rong Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan (China); Center for General Education, Tunghai University, Taichung 407, Taiwan (China); Department of Nursing, HungKuang University, Taichung 433, Taiwan (China)

    2014-09-10

    Epidermal growth factor receptor tyrosine kinase inhibitors, including gefitinib, have been evaluated in patients with malignant gliomas. However, the molecular mechanisms involved in gefitinib-mediated anticancer effects against glioma are incompletely understood. In the present study, the cytostatic potential of gefitinib was demonstrated by the inhibition of glioma cell growth, long-term clonogenic survival, and xenograft tumor growth. The cytostatic consequences were accompanied by autophagy, as evidenced by monodansylcadaverine staining of acidic vesicle formation, conversion of microtubule-associated protein-1 light chain 3-II (LC3-II), degradation of p62, punctate pattern of GFP-LC3, and conversion of GFP-LC3 to cleaved-GFP. Autophagy inhibitor 3-methyladenosine and chloroquine and genetic silencing of LC3 or Beclin 1 attenuated gefitinib-induced growth inhibition. Gefitinib-induced autophagy was not accompanied by the disruption of the Akt/mammalian target of rapamycin signaling. Instead, the activation of liver kinase-B1/AMP-activated protein kinase (AMPK) signaling correlated well with the induction of autophagy and growth inhibition caused by gefitinib. Silencing of AMPK suppressed gefitinib-induced autophagy and growth inhibition. The crucial role of AMPK activation in inducing glioma autophagy and growth inhibition was further supported by the actions of AMP mimetic AICAR. Gefitinib was shown to be capable of reducing the proliferation of glioma cells, presumably by autophagic mechanisms involving AMPK activation. - Highlights: • Gefitinib causes cytotoxic and cytostatic effect on glioma. • Gefitinib induces autophagy. • Gefitinib causes cytostatic effect through autophagy. • Gefitinib induces autophagy involving AMPK.

  14. HDAC6 inhibition effectively reverses chemotherapy-induced peripheral neuropathy.

    Science.gov (United States)

    Krukowski, Karen; Ma, Jiacheng; Golonzhka, Olga; Laumet, Geoffroy O; Gutti, Tanuja; van Duzer, John H; Mazitschek, Ralph; Jarpe, Matthew B; Heijnen, Cobi J; Kavelaars, Annemieke

    2017-06-01

    Chemotherapy-induced peripheral neuropathy is one of the most common dose-limiting side effects of cancer treatment. Currently, there is no Food and Drug Administration-approved treatment available. Histone deacetylase 6 (HDAC6) is a microtubule-associated deacetylase whose function includes regulation of α-tubulin-dependent intracellular mitochondrial transport. Here, we examined the effect of HDAC6 inhibition on established cisplatin-induced peripheral neuropathy. We used a novel HDAC6 inhibitor ACY-1083, which shows 260-fold selectivity towards HDAC6 vs other HDACs. Our results show that HDAC6 inhibition prevented cisplatin-induced mechanical allodynia, and also completely reversed already existing cisplatin-induced mechanical allodynia, spontaneous pain, and numbness. These findings were confirmed using the established HDAC6 inhibitor ACY-1215 (Ricolinostat), which is currently in clinical trials for cancer treatment. Mechanistically, treatment with the HDAC6 inhibitor increased α-tubulin acetylation in the peripheral nerve. In addition, HDAC6 inhibition restored the cisplatin-induced reduction in mitochondrial bioenergetics and mitochondrial content in the tibial nerve, indicating increased mitochondrial transport. At a later time point, dorsal root ganglion mitochondrial bioenergetics also improved. HDAC6 inhibition restored the loss of intraepidermal nerve fiber density in cisplatin-treated mice. Our results demonstrate that pharmacological inhibition of HDAC6 completely reverses all the hallmarks of established cisplatin-induced peripheral neuropathy by normalization of mitochondrial function in dorsal root ganglia and nerve, and restoration of intraepidermal innervation. These results are especially promising because one of the HDAC6 inhibitors tested here is currently in clinical trials as an add-on cancer therapy, highlighting the potential for a fast clinical translation of our findings.

  15. Galectin-3 inhibition ameliorates hypoxia-induced pulmonary artery hypertension.

    Science.gov (United States)

    Hao, Mingwen; Li, Miaomiao; Li, Wenjun

    2017-01-01

    Galectin-3 (Gal-3) is a β-galactoside-binding lectin, which is important in inflammation, fibrosis and heart failure. The present study aimed to investigate the role and mechanism of Gal-3 in hypoxia-induced pulmonary arterial hypertension (PAH). Male C57BL/6J and Gal‑3‑/‑ mice were exposed to hypoxia, then the right ventricular systolic pressure (RVSP) and Fulton's index were measured, and Gal‑3 mRNA and protein expression in the pulmonary arteries was analyzed by reverse transcription‑quantitative polymerase chain reaction and western blotting. Compared with the control, hypoxia increased the mRNA and protein expression levels of Gal‑3 in wild type murine pulmonary arteries. Gal‑3 deletion reduced the hypoxia‑induced upregulation of RVSP and Fulton's index. Furthermore, human pulmonary arterial endothelial cells (HPAECs) and human pulmonary arterial smooth muscle cells (HPASMCs) were stimulated by hypoxia in vitro, and Gal‑3 expression was inhibited by small interfering RNA. The inflammatory response of HPAECs, and the proliferation and cell cycle distribution of HPASMCs was also analyzed. Gal‑3 inhibition alleviated the hypoxia‑induced inflammatory response in HPAECs, including tumor necrosis factor‑α and interleukin‑1 secretion, expression of intercellular adhesion molecule‑1 and adhesion of THP‑1 monocytes. Gal‑3 inhibition also reduced hypoxia‑induced proliferation of HPASMCs, partially by reducing cyclin D1 expression and increasing p27 expression. Furthermore, Gal‑3 inhibition suppressed HPASMC switching from a 'contractile' to a 'synthetic' phenotype. In conclusion, Gal‑3 serves a fundamental role in hypoxia‑induced PAH, and inhibition of Gal‑3 may represent a novel therapeutic target for the treatment of hypoxia-induced PAH.

  16. Inhibition of autophagy protects against PAMAM dendrimers-induced hepatotoxicity.

    Science.gov (United States)

    Li, Yubin; Zeng, Xian; Wang, Shaofei; Sun, Yun; Wang, Ziyu; Fan, Jiajun; Song, Ping; Ju, Dianwen

    2015-05-01

    Toxicity of nanomaterials is one of the biggest challenges in their medicinal applications. Although toxicities of nanomaterials have been widely reported, the exact mechanisms of toxicities are still not well elucidated. Consequently, the exploration of approaches to attenuate toxicities of nanomaterials is limited. In this study, we reported that poly-amidoamine (PAMAM) dendrimers, a widely used nanomaterial in the pharmaceutical industry, caused toxicity of human liver cells by inducing cell growth inhibition, mitochondria damage, and apoptosis. Meanwhile, autophagy was activated in PAMAM dendrimers-induced toxicity and inhibition of autophagy-rescued viability of hepatic cells, indicating that autophagy played a key role in PAMAM dendriemrs-induced hepatotoxicity. To further explore approaches to attenuate PAMAM dendrimers-induced liver injury, effects of autophagic inhibitors on PAMAM dendrimers' hepatotoxicity were investigated in an in vivo model. Autophagy blockage in PAMAM dendrimers-administered mice led to weight restoration, damage reversion of liver tissue, and protection against changes of serum biochemistry parameters. Moreover, inhibition of Akt/mTOR and activation of Erk1/2 signaling pathways were involved in PAMAM dendrimers-induced autophagy. Collectively, these findings indicated that autophagy was associated with PAMAM dendrimers-induced hepatotoxicity, and supported the possibility that autophagy inhibitors could be used to reduce hepatotoxicity of PAMAM dendrimers.

  17. Cadmium Alternatives

    Science.gov (United States)

    2012-08-01

    using for commercial applications Other zinc alloys Zinc cobalt , tin zinc, zinc iron Passivation Cadmium, ZnNi, SnZn, ZnCo, ZnFe, and...for Change Cadmium passivated with hexavalent chromium has been in use for many decades Cadmium is toxic, and is classified as a priority...Executive Orders 13514 & 13423 DoD initiatives – Young memo (April 2009) DFAR restricting use of hexavalent chromium Allows the use of hexavalent

  18. Ameliorating effects of green tea extract on cadmium induced reproductive injury in male Wistar rats with respect to androgen receptors and caspase- 3.

    Science.gov (United States)

    Abdelrazek, Heba M A; Helmy, Seham A; Elsayed, Doaa H; Ebaid, Hala M; Mohamed, Racha M

    2016-12-01

    Cadmium is one of the potent environmental endocrine disruptors that has adverse effects on male fertility. This study was conducted to investigate the protective role of green tea extract (GTE) on cadmium chloride (CdCl2) induced reproductive toxicities in male Wistar rats. Thirty-six male Wistar rats were divided to 4 groups, each one contained 9 rats. Control group, they were gavaged distilled water, meanwhile the treated groups gavaged CdCl2 (3mg/kg), GTE (70mg/kg) and CdCl2+GTE (3mg/kg and 70mg/kg) for 63days. In GTE+ CdCl2 treated rats, the final body weight, relative testicular weight, epididymal weight, seminal and prostate glands weights were significantly (P<0.05) increased compared to CdCl2 intoxicated rats. Sperm cell concentration was significantly (P<0.05) increased in CdCl2+GTE group, while sperm morphological abnormalities were significantly (P<0.05) decreased than CdCl2 group. The levels of superoxide dismutase (SOD) and reduced glutathione (GSH) were elevated significantly (P<0.05) in CdCl2+GTE group, meanwhile catalase activity was significantly (P<0.05) declined than CdCl2 group. Hypercholesterolemia was observed in CdCl2 group than control one while GTE+CdCl2 group revealed significant (P<0.05) reduction in cholesterol level than CdCl2 treated group. Testicular androgen receptors and caspase-3 protein expression showed marked reduction and increase (P<0.05) in CdCl2 group than control, respectively. Treatment with GTE with CdCl2 significantly (P<0.05) increased androgen receptors, while decreased caspase-3 protein than CdCl2 group. In conclusion, GTE exhibited protective effect on testes by inhibiting CdCl2 induced oxidative damage and cellular apoptosis. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

  19. Chloroquinone Inhibits Cell Proliferation and Induces Apoptosis in ...

    African Journals Online (AJOL)

    Original Research Article. Chloroquinone Inhibits Cell Proliferation and Induces. Apoptosis in Nasopharyngeal Carcinoma Cell Lines. Xin-Qing Yang, Hao Zheng, Qing Ye, Rui-Yu Li* and Yong Chen. Department of Otolaryngology Head and Neck Surgery, Fujian Provincial Clinical College, Fujian Medical University, China.

  20. Crude extract of Nigella sativa inhibits proliferation and induces ...

    African Journals Online (AJOL)

    admin

    2012-08-09

    Aug 9, 2012 ... including p53 and p21. These findings demonstrate that EENS inhibits proliferation and induces apoptosis in HeLa cells and suggest this extract may be a promising agent for the prevention/treatment of human cervical cancer. Key words: Nigella sativa, cervical cancers, apoptosis, caspases, cell cycle.

  1. Glycation inhibits trichloroacetic acid (TCA)-induced whey protein precipitation

    Science.gov (United States)

    Four different WPI saccharide conjugates were successfully prepared to test whether glycation could inhibit WPI precipitation induced by trichloroacetic acid (TCA). Conjugates molecular weights after glycation were analyzed with SDS-PAGE. No significant secondary structure change due to glycation wa...

  2. Crude extract of Nigella sativa inhibits proliferation and induces ...

    African Journals Online (AJOL)

    Crude extract of Nigella sativa inhibits proliferation and induces apoptosis in human cervical carcinoma HeLa cells. ... African Journal of Biotechnology ... Cervical cancer is a major cause of morbidity in women worldwide and chemotherapy for this cancer seems unsatisfactory, which demands exploring new therapeutic ...

  3. Cadmium suppresses the proliferation of piglet Sertoli cells and causes their DNA damage, cell apoptosis and aberrant ultrastructure

    Directory of Open Access Journals (Sweden)

    Zhang Ming

    2010-08-01

    Full Text Available Abstract Objective Very little information is known about the toxic effects of cadmium on somatic cells in mammalian testis. The objective of this study is to explore the toxicity of cadmium on piglet Sertoli cells. Methods Sertoli cells were isolated from piglet testes using a two-step enzyme digestion and followed by differential plating. Piglet Sertoli cells were identified by oil red O staining and Fas ligand (FasL expression as assayed by immunocytochemistry and expression of transferrin and androgen binding protein by RT-PCR. Sertoli cells were cultured in DMEM/F12 supplemented with 10% fetal calf serum in the absence or presence of various concentrations of cadmium chloride, or treatment with p38 MAPK inhibitor SB202190 and with cadmium chloride exposure. Apoptotic cells in seminiferous tubules of piglets were also performed using TUNEL assay in vivo. Results Cadmium chloride inhibited the proliferation of Piglet Sertoli cells as shown by MTT assay, and it increased malondialdehyde (MDA but reduced superoxide dismutase (SOD and Glutathione peroxidase (GSH-Px activity. Inhibitor SB202190 alleviated the proliferation inhibition of cadmium on piglet Sertoli cells. Comet assay revealed that cadmium chloride caused DNA damage of Piglet Sertoli cells and resulted in cell apoptosis as assayed by flow cytometry. The in vivo study confirmed that cadmium induced cell apoptosis in seminiferous tubules of piglets. Transmission electronic microscopy showed abnormal and apoptotic ultrastructure in Piglet Sertoli cells treated with cadmium chloride compared to the control. Conclusion cadmium has obvious adverse effects on the proliferation of piglet Sertoli cells and causes their DNA damage, cell apoptosis, and aberrant morphology. This study thus offers novel insights into the toxicology of cadmium on male reproduction.

  4. Cadmium suppresses the proliferation of piglet Sertoli cells and causes their DNA damage, cell apoptosis and aberrant ultrastructure

    Science.gov (United States)

    2010-01-01

    Objective Very little information is known about the toxic effects of cadmium on somatic cells in mammalian testis. The objective of this study is to explore the toxicity of cadmium on piglet Sertoli cells. Methods Sertoli cells were isolated from piglet testes using a two-step enzyme digestion and followed by differential plating. Piglet Sertoli cells were identified by oil red O staining and Fas ligand (FasL) expression as assayed by immunocytochemistry and expression of transferrin and androgen binding protein by RT-PCR. Sertoli cells were cultured in DMEM/F12 supplemented with 10% fetal calf serum in the absence or presence of various concentrations of cadmium chloride, or treatment with p38 MAPK inhibitor SB202190 and with cadmium chloride exposure. Apoptotic cells in seminiferous tubules of piglets were also performed using TUNEL assay in vivo. Results Cadmium chloride inhibited the proliferation of Piglet Sertoli cells as shown by MTT assay, and it increased malondialdehyde (MDA) but reduced superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px) activity. Inhibitor SB202190 alleviated the proliferation inhibition of cadmium on piglet Sertoli cells. Comet assay revealed that cadmium chloride caused DNA damage of Piglet Sertoli cells and resulted in cell apoptosis as assayed by flow cytometry. The in vivo study confirmed that cadmium induced cell apoptosis in seminiferous tubules of piglets. Transmission electronic microscopy showed abnormal and apoptotic ultrastructure in Piglet Sertoli cells treated with cadmium chloride compared to the control. Conclusion cadmium has obvious adverse effects on the proliferation of piglet Sertoli cells and causes their DNA damage, cell apoptosis, and aberrant morphology. This study thus offers novel insights into the toxicology of cadmium on male reproduction. PMID:20712887

  5. Comparative effects of repeated administration of cadmium chloride during pregnancy and lactation and selenium protection against cadmium toxicity on some organs in immature rats' offsprings.

    Science.gov (United States)

    Bekheet, Souad H M

    2011-12-01

    This research comprises studies on the transfer of cadmium (CdCl(2)) from the lactating dam to the pup via milk and absorbed in the suckling, showing that cadmium is transferred to the testes, ovary, cerebellum, and thyroid gland during development. The present studies were carried out in order to assess the protective effects of selenium against cadmium toxicity in pregnant rats. On the sixth day of gestation, the females were dosed subcutaneously either with cadmium or with cadmium and selenium in the following doses (mg/kg of body weight): 0, 1 Cd, 1 Cd + 1 Se, 2 Cd, 2 Cd + 2 Se. In groups treated with cadmium, no maternal or embryonic toxicities were observed; however, an increase in testes diameters of seminiferous tubules, a progressive sloughing of germ cells, vacuolization of Sertoli cells, and Leydig cells hyperplasia were noted. The reduction in the ovary size and inhibited folliculogenesis resulted in diminution of the numbers of primordial, growing, and tertiary follicles. The pathological change in the cerebellum, the migration of granular cells from the external germinal layer to the internal granular layer, was strongly retarded. Also, the formation of many microfollicles in the thyroid gland which mimic the changes was seen in thyrotoxicosis. It also appears that selenium used at a low-enough dose could be a very effective protection against cadmium-induced developmental toxicity in the testes, ovary, cerebellum, and thyroid gland but not in the higher dose in the ovary and cerebellum.

  6. Thymol Ameliorates Cadmium-Induced Phytotoxicity in the Root of Rice (Oryza sativa) Seedling by Decreasing Endogenous Nitric Oxide Generation.

    Science.gov (United States)

    Wang, Ting-Ting; Shi, Zhi Qi; Hu, Liang-Bin; Xu, Xiao-Feng; Han, Fengxiang X; Zhou, Li-Gang; Chen, Jian

    2017-08-30

    Thymol has been developed as medicine and food preservative due to its immune-regulatory effect and antimicrobial activity, respectively. However, little is currently known about the role of thymol in the modulation of plant physiology. In the present study, we applied biochemical and histochemical approaches to investigate thymol-induced tolerance in rice (Oryza sativa) seedlings against Cd (cadmium) stress. Thymol at 20 μM recovered root growth completely upon CdCl2 exposure. Thymol pronouncedly decreased Cd-induced ROS accumulation, oxidative injury, cell death, and Cd2+ accumulation in roots. Pharmaceutical experiments suggested that endogenous NO mediated Cd-induced phytotoxicity. Thymol decreased Cd-induced NO accumulation by suppressing the activity of NOS (nitric oxide synthase) and NR (nitrate reductase) in root. The application of NO donor (SNP, sodium nitroprusside) resulted in the increase in endogenous NO level, which in turn compromised the alleviating effects of thymol on Cd toxicity. Such findings may helpful to illustrate the novel role of thymol in the modulation of plant physiology, which may be applicable to improve crop stress tolerance.

  7. Tinospora cordifolia extract attenuates cadmium-induced biochemical and histological alterations in the heart of male Wistar rats.

    Science.gov (United States)

    Priya, Lohanathan Bharathi; Baskaran, Rathinasamy; Elangovan, Pitchai; Dhivya, Velumani; Huang, Chih-Yang; Padma, Viswanadha Vijaya

    2017-03-01

    Persistence of cadmium (Cd) in the environment causes serious ecological problems. Tinospora cordifolia is a medicinal herb used in Ayurveda for treating various metabolic disorders and toxic conditions. The present study investigates the protective effect of T. cordifolia stem methanolic extract (TCME) on a heavy metal, Cd-induced cardiotoxicity in male Wistar rats. Male albino Wistar rats were divided into four groups (n=6). The animals after treatment for 28days with Cd and TCME were analysed for biochemical and histological changes in the serum and heart tissues. Cd induced lipid peroxidation and protein carbonylation was significantly reduced by TCME. TCME also reduced the histological alterations induced by Cd treatment in the heart tissues with diminished loss of myocardial fibers. Administration of TCME effectively prevented the altered levels of serum marker enzymes (creatine kinase and lactate dehydrogenase), antioxidants, such as superoxide dismutase, catalase, glutathione, glutathione peroxidase and glutathione-S-transferase, and glycoproteins contents such as hexose, hexoseamine, fucose, and sialic acid by Cd intoxication. TCME also offered protection against the change in levels of Na(+)K(+)ATPase, Mg(2+)ATPase and Ca(2+)ATPase activities against Cd toxicity. The study suggests TCME as a potent cardioprotective agent against Cd induced toxicity. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin

    Science.gov (United States)

    Verespy III, Stephen; Mehta, Akul Y.; Afosah, Daniel; Al-Horani, Rami A.; Desai, Umesh R.

    2016-01-01

    Allosteric partial inhibition of soluble, monomeric proteases can offer major regulatory advantages, but remains a concept on paper to date; although it has been routinely documented for receptors and oligomeric proteins. Thrombin, a key protease of the coagulation cascade, displays significant conformational plasticity, which presents an attractive opportunity to discover small molecule probes that induce sub-maximal allosteric inhibition. We synthesized a focused library of some 36 sulfated coumarins to discover two agents that display sub-maximal efficacy (~50%), high potency (thrombin (>150-fold). Michaelis-Menten, competitive inhibition, and site-directed mutagenesis studies identified exosite 2 as the site of binding for the most potent sulfated coumarin. Stern-Volmer quenching of active site-labeled fluorophore suggested that the allosteric regulators induce intermediate structural changes in the active site as compared to those that display ~80–100% efficacy. Antithrombin inactivation of thrombin was impaired in the presence of the sulfated coumarins suggesting that allosteric partial inhibition arises from catalytic dysfunction of the active site. Overall, sulfated coumarins represent first-in-class, sub-maximal inhibitors of thrombin. The probes establish the concept of allosteric partial inhibition of soluble, monomeric proteins. This concept may lead to a new class of anticoagulants that are completely devoid of bleeding. PMID:27053426

  9. Oxime-Induced Reactivation of Carboxylesterase Inhibited by Organophosphorus Compounds

    Science.gov (United States)

    1993-05-13

    O.NOH C.l(H CII,- 0-(4 Ixonitroso acet0- 2-PAK M- phenofle (IN"P) O4."M C14.NW C-0 Nonoisontrou’- Diacetyl mono- T9 acetOne . (XINA) oxims (DAN) 823...Or AD-POOB 837111.1 IIII IN III EllNIH NI Oxime -induced Reactivation of Carboxylesterase Inhibited by Organophosphorus Compounds Donald M. Maxwell...ABSTRACT A structure-activity analysis of the ability of oximes to reactivate rat plasma carboxylesterase (CaE) that was inhibited by organophosphorus

  10. Ascorbic acid, garlic extract and taurine alleviate cadmium-induced oxidative stress in freshwater catfish (Clarias batrachus)

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Puneet, E-mail: puneetbiochem@gmail.com [Aquatic Biotechnology and Fish Pathology Laboratory, Department of Animal Science, M.J.P. Rohilkhand University, Bareilly-243 006 (India); Prasad, Y. [Aquatic Biotechnology and Fish Pathology Laboratory, Department of Animal Science, M.J.P. Rohilkhand University, Bareilly-243 006 (India); Patra, A.K. [West Bengal University of Animal and Fishery Sciences, Kolkata-700037 (India); Ranjan, R.; Swarup, D.; Patra, R.C. [Division of Medicine, Indian Veterinary Research Institute, Izatnagar-243122 (India); Pal, Satya [Env. Eng. Lab., Deptt. of Civil Engineering, I.I.T., Roorkee-247667 (India)

    2009-09-01

    An experiment was conducted to investigate bioaccumulation potential of cadmium (Cd) and changes in oxidative stress indices in liver and kidney tissues from Cd-exposed catfish (Clarias batrachus) with or without simultaneous treatment of water with ascorbic acid, garlic extract or taurine. C. batrachus (n = 324) with average length of 20 {+-} 4 cm and weight of 86 {+-} 5 g were used for the present investigation. Fishes were divided into nine groups (I to IX) each comprising 36 fishes. The fishes of groups II, III, IV and V were challenged with 5 ppm of cadmium chloride monohydrate (CdCl{sub 2}.H{sub 2}O), whereas groups VI, VII, VIII and IX were exposed to 10 ppm CdCl{sub 2}.H{sub 2}O solution for a period of 45 days. Group I was kept as negative control and the fishes of this group were maintained in water containing no added Cadmium. Group II and VI were maintained as Cd exposed non treated control to serve as positive controls. Fishes of III and VII, IV and VIII, V and IX received ascorbic acid (5 ppm), extract of dried garlic (5 ppm) or taurine (5 ppm), respectively during the entire experiment period. The concentrations of Cd in liver and kidney increased significantly following exposure to Cd and the level continued to rise with the increase in exposure duration. Treatment of tank water with ascorbic acid, garlic or taurine significantly reduced the Cd concentrations in tissues compared to the positive control group, but the level in Cd exposed groups was greater than the negative control group. Fishes exposed to Cd and treated with ascorbic acid, garlic or taurine had reduced oxidative stress as evidenced from lower concentration of lipid peroxides and higher activities of superoxide dismutase and catalase in liver, kidney and erythrocytes compared to fishes exposed to Cd. The reduction in Cd induced oxidative stress was highest in ascorbic acid treated group followed by garlic and taurine treatment. The results suggest that ascorbic acid, garlic and

  11. Madecassoside inhibits melanin synthesis by blocking ultraviolet-induced inflammation.

    Science.gov (United States)

    Jung, Eunsun; Lee, Jung-A; Shin, Seoungwoo; Roh, Kyung-Baeg; Kim, Jang-Hyun; Park, Deokhoon

    2013-12-16

    Madecassoside (MA), a pentacyclic triterpene isolated from Centella asitica (L.), is used as a therapeutic agent in wound healing and also as an anti-inflammatory and anti-aging agent. However, the involvement of MA in skin-pigmentation has not been reported. This study was conducted to investigate the effects of MA on ultraviolet (UV)-induced melanogenesis and mechanisms in a co-culture system of keratinocytes and melanocytes. MA significantly inhibited UVR-induced melanin synthesis and melanosome transfer in the co-culture system. These effects were further demonstrated by the MA-induced inhibition of protease-activated receptor-2 expression and its signaling pathway, cyclooxygenase-2, prostaglandin E2 and prostaglandin F2 alpha in keratinocytes. The clinical efficacy of MA was confirmed on artificially tanned human skin. MA significantly reduced UV-induced melanin index at 8 weeks after topical application. Overall, the study demonstrated significant benefits of MA use in the inhibition of hyperpigmentation caused by UV irradiation.

  12. Madecassoside Inhibits Melanin Synthesis by Blocking Ultraviolet-Induced Inflammation

    Directory of Open Access Journals (Sweden)

    Eunsun Jung

    2013-12-01

    Full Text Available Madecassoside (MA, a pentacyclic triterpene isolated from Centella asitica (L., is used as a therapeutic agent in wound healing and also as an anti-inflammatory and anti-aging agent. However, the involvement of MA in skin-pigmentation has not been reported. This study was conducted to investigate the effects of MA on ultraviolet (UV-induced melanogenesis and mechanisms in a co-culture system of keratinocytes and melanocytes. MA significantly inhibited UVR-induced melanin synthesis and melanosome transfer in the co-culture system. These effects were further demonstrated by the MA-induced inhibition of protease-activated receptor-2 expression and its signaling pathway, cyclooxygenase-2, prostaglandin E2 and prostaglandin F2 alpha in keratinocytes. The clinical efficacy of MA was confirmed on artificially tanned human skin. MA significantly reduced UV-induced melanin index at 8 weeks after topical application. Overall, the study demonstrated significant benefits of MA use in the inhibition of hyperpigmentation caused by UV irradiation.

  13. Impaired leaf CO2 diffusion mediates Cd-induced inhibition of photosynthesis in the Zn/Cd hyperaccumulator Picris divaricata.

    Science.gov (United States)

    Tang, Lu; Ying, Rong-Rong; Jiang, Dan; Zeng, Xiao-Wen; Morel, Jean-Louis; Tang, Ye-Tao; Qiu, Rong-Liang

    2013-12-01

    Mechanisms of cadmium (Cd)-induced inhibition of photosynthesis in the Zn/Cd hyperaccumulator Picris divaricata were investigated using photosynthesis limitation analysis. P. divaricata seedlings were grown in nutrient solution containing 0, 5, 10, 25, 50, or 75 μM Cd for 2 weeks. Total limitations to photosynthesis (TL) increased from 0% at 5 μM Cd to 68.8% at 75 μM Cd. CO2 diffusional limitation (DL) made the largest contribution to TL, accounting for 93-98% of TL in the three highest Cd treatments, compared to just 2-7% of TL attributable to biochemical limitation (BL). Microscopic imaging revealed significantly decreased stomatal density and mesophyll thickness in the three highest Cd treatments. Chlorophyll fluorescence parameters related to photosynthetic biochemistry (Fv/Fm, NPQ, ΦPSII, and qP) were not significantly decreased by increased Cd supply. Our results suggest that increased DL in leaves is the main cause of Cd-induced inhibition of photosynthesis in P. divaricata, possibly due to suppressed function of mesophyll and stomata. Analysis of chlorophyll fluorescence showed that Cd supply had little effect on photochemistry parameters, suggesting that the PSII reaction centers are not a main target of Cd inhibition of photosynthesis in P. divaricata. Copyright © 2013. Published by Elsevier Masson SAS.

  14. Sox9 potentiates BMP2-induced chondrogenic differentiation and inhibits BMP2-induced osteogenic differentiation.

    Directory of Open Access Journals (Sweden)

    Junyi Liao

    Full Text Available Bone morphogenetic protein 2 (BMP2 is one of the key chondrogenic growth factors involved in the cartilage regeneration. However, it also exhibits osteogenic abilities and triggers endochondral ossification. Effective chondrogenesis and inhibition of BMP2-induced osteogenesis and endochondral ossification can be achieved by directing the mesenchymal stem cells (MSCs towards chondrocyte lineage with chodrogenic factors, such as Sox9. Here we investigated the effects of Sox9 on BMP2-induced chondrogenic and osteogenic differentiation of MSCs. We found exogenous overexpression of Sox9 enhanced the BMP2-induced chondrogenic differentiation of MSCs in vitro. Also, it inhibited early and late osteogenic differentiation of MSCs in vitro. Subcutaneous stem cell implantation demonstrated Sox9 potentiated BMP2-induced cartilage formation and inhibited endochondral ossification. Mouse limb cultures indicated that BMP2 and Sox9 acted synergistically to stimulate chondrocytes proliferation, and Sox9 inhibited BMP2-induced chondrocytes hypertrophy and ossification. This study strongly suggests that Sox9 potentiates BMP2-induced MSCs chondrogenic differentiation and cartilage formation, and inhibits BMP2-induced MSCs osteogenic differentiation and endochondral ossification. Thus, exogenous overexpression of Sox9 in BMP2-induced mesenchymal stem cells differentiation may be a new strategy for cartilage tissue engineering.

  15. Whole-body aerosol exposure of cadmium chloride (CdCl{sub 2}) and tetrabromobisphenol A (TBBPA) induced hepatic changes in CD-1 male mice

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yuanhong; Hu, Yabing; Liu, Shuyun; Zheng, Huiying; Wu, Xiaojuan; Huang, Zhengyu; Li, Hao; Peng, Baoqi; Long, Jinlie [Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035 (China); Pan, Bishu [Taizhou Center for Disease Control and Prevention, Taizhou 318000 (China); Huang, Changjiang, E-mail: cjhuang5711@163.com [Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035 (China); Dong, Qiaoxiang, E-mail: dqxdong@163.com [Institute of Environmental Safety and Human Health, Wenzhou Medical University, Wenzhou 325035 (China)

    2016-11-15

    Highlights: • Hepatotoxicity of TBBPA and Cd aerosol co-exposure was evaluated in CD-1 male mice. • Hepatic changes include focal necrosis, increased organ weight, and elevated enzymes. • TBBPA group exhibited highest hepatic toxicity followed by co-exposure and Cd groups. • We did not observe any synergistic effect of hepatic toxicity between TBBPA and Cd. • TBBPA/Cd suppressed antioxidant defensive mechanisms and increased oxidative stress. - Abstract: Cadmium (Cd) and tetrabromobisphenol A (TBBPA) are two prevalent contaminants in e-waste recycling facilities. However, the potential adversely health effect of co-exposure to these two types of pollutants in an occupational setting is unknown. In this study, we investigated co-exposure of these two pollutants on hepatic toxicity in CD-1 male mice through a whole-body aerosol inhalation route. Specifically, mice were exposed to solvent control (5% DMSO), Cd (8 μg/m{sup 3}), TBBPA (16 μg/m{sup 3}) and Cd/TBBPA mixture for 8 h/day and 6 days a week for 60 days. Hepatic changes include increased organ weight, focal necrosis, and elevated levels of liver enzymes in serum. These changes were most severe in mice exposed to TBBPA, followed by Cd/TBBPA mixture and Cd. These chemicals also led to suppressed antioxidant defensive mechanisms and increased oxidative stress. Further, these chemicals induced gene expression of apoptosis-related genes, activated genes encoding for phase I detoxification enzymes and inhibited genes encoding for phase II detoxification enzymes. These findings indicate that the hepatic damages induced by subchronic aerosol exposure of Cd and TBBPA may result from the oxidative damages caused by excessive ROS production when these chemicals were metabolized in the liver.

  16. Amelioration of Cadmium-Induced Nephropathy using Polyphenol-rich Extract of Vernonia amygdalina (Del. Leaves in Rat Model

    Directory of Open Access Journals (Sweden)

    Christian E. Imafidon

    2015-11-01

    Full Text Available AIM: To determine the effects of polyphenol-rich extract of the leaves of Vernonia amygdalina (PEVA in rats with Cd-induced nephropathy. MATERIALS AND METHODS: Sixty five male Wistar rats were divided into five groups as follows; Group 1 received distilled water throughout the period of study. Group 2 received 5 mg/kg body weight of cadmium (Cd, in the form of CdSO4, for five consecutive days via intraperitoneal route. Groups 3, 4 and 5 were pretreated with Cd as group 2 and thereafter received oral treatment of PEVA for 4 weeks at 100 mg/kg, 200 mg/kg and 400 mg/kg body weight, respectively. RESULTS: Exposure to Cd toxicity significantly induced deleterious alterations in plasma and urine levels of creatinine, urea and glucose as well as creatinine and urea clearance (p < 0.05 in the rat model. There was a significant disturbance in the antioxidant system as revealed by the levels of thiobarbituric acid reactive substance (TBARS and reduced glutathione (GSH (p < 0.05 in the kidney tissue of the rats. With marked improvements in renal histoarchitecture, PEVA treatment showed a duration and non dose-dependent ameliorative potential. CONCLUSION: PEVA treatment reversed the compromise of renal function that was induced by Cd toxicity in rat model.

  17. Protective effect of probiotic bacteria against cadmium-induced genotoxicity in rat hepatocytes in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Đurašević Siniša F.

    2012-01-01

    Full Text Available The protective effect of probiotic bacteria against cadmium (Cd-induced genotoxicity was studied in rat hepatocytes in vivo and in vitro. Male Wistar rats, Rattus norvegicus, were treated for five weeks with (i CdCl2 (70 ppm in the drinking water, (ii a mixture of lyophilized probiotic bacteria Lactobacillus rhamnosus, L. acidophilus and Bifido-bacterium longum (5×108 cfu/g of food, or (iii CdCl2 and probiotic bacteria. In addition, single cells obtained from the untreated rat liver were exposed to CdCl2 (70 ppm, probiotic bacteria (1.28 mg/ml, or CdCl2 and probiotic bacteria, for 15 min at 22°C in the dark. The level of Cd-induced DNA damage in hepatocytes was determined by the comet assay. The obtained results show that probiotic bacteria significantly reduced Cd-induced genotoxicity, both in vivo and in vitro (20% and 48%, respectively. Moreover, the toxicity of Cd to lactobacilli in the gastrointestinal tracts of rats was significantly decreased in the probiotic-treated animals. The binding of Cd2+ to probiotic bacteria was proposed as the most probable protection mechanism. [Acknowledgments. This research was financially supported by the Ministry of Education and Science of the Government of Serbia, projects No 172058 and 173023

  18. N-acetylcysteine effectively mitigates cadmium-induced oxidative damage and cell death in Leydig cells in vitro.

    Science.gov (United States)

    Khanna, Smita; Mitra, Sumonto; Lakhera, Pramesh C; Khandelwal, Shashi

    2016-01-01

    Cadmium (Cd) is known to cause severe damage to various organs including lung, liver, kidney, brain and reproductive system. Several studies have reported the induction of oxidative stress pathways following Cd exposure. Since oxidative stress is also deemed responsible for inducing male infertility, a growing worldwide concern, we tried to understand whether the antioxidant N-acetylcysteine (NAC) can be a potential therapeutic agent to counter Cd toxicity using primary Leydig cells. This study highlights the initial cellular alterations which culminate in cell death induction. Primary Leydig cells were isolated from 28-day-old male Wistar rats, exposed to various concentrations of Cd in vitro and biochemical and cell death parameters were evaluated to understand the effect of Cd. NAC pre-treatment was done to understand its protective efficacy. Following Cd exposure to Leydig cells in vitro, we found simultaneous intracellular calcium (Ca(2+)) increase and reduction in mitochondrial membrane polarization at 30 min, followed by significant induction of reactive oxygen species and MAPK-extracellular-regulated kinases with concurrent glutathione depletion at 1 h, and significant cell death (both necrotic and apoptotic) at 6 and 18 h, respectively. Pre-treatment with NAC abrogated all these toxic manifestations and showed significantly reduced cell death. NAC also rescued the expression of 3-βHSD, a major steroidogenic protein. Taken together, these data illustrated that NAC can be used as a potential protective agent against Cd-induced testicular toxicity, especially with regards to oxidative stress-induced Leydig cell toxicity.

  19. Strain difference of cadmium-induced testicular toxicity in inbred Wistar-Imamichi and Fischer 344 rats

    Energy Technology Data Exchange (ETDEWEB)

    Shimada, Hideaki; Narumi, Rika [Kumamoto University, Faculty of Education, Kumamoto (Japan); Nagano, Masaaki; Yasutake, Akira [National Institute for Minamata Disease, Biochemistry Section, Kumamoto (Japan); Waalkes, Michael P. [National Cancer Institute at the National Institute of Environmental Health Sciences, Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, Research Triangle Park, NC (United States); Imamura, Yorishige [Kumamoto University, Graduate School of Pharmaceutical Sciences, Kumamoto (Japan)

    2009-07-15

    Previously, we reported that Wistar-Imamichi (WI) rats are highly resistant to cadmium (Cd)-induced lethality and hepatotoxicity compared to Fischer 344 (F344) rats. Since the testes are one of the most sensitive organs to acute Cd toxicity, we examined possible strain-related differences in Cd-induced testicular toxicity between inbred WI and F344 rats. Rats were treated with a single dose of 0.5, 1.0 or 2.0 mg Cd/kg, as CdCl{sub 2}, sc and killed 24 h later. Cd at doses of 1.0 and 2.0 mg/kg induced severe testicular hemorrhage, as assessed by pathological and testis hemoglobin content, in F344 rats, but not WI rats. After Cd treatment (2.0 mg/kg), the testicular Cd content was significantly lower in WI rats than in the F344 rats, indicating a toxiokinetic mechanism for the observed strain difference. Thus, the remarkable resistance to Cd-induced testicular toxicity in WI rats is associated, at least in part, with lower testicular accumulation of Cd. When zinc (Zn; 10 mg/kg, sc) was administered in combination with Cd (2.0 mg/kg) to F344 rats, the Cd-induced increase in testicular hemoglobin content, indicative of hemorrhage, was significantly reduced. Similarly, the testicular Cd content was significantly decreased with Zn co-treatment compared to Cd treatment alone. Thus, it can be concluded that the testicular Cd accumulation partly competes with Zn transport systems and that these systems may play an important role in the strain-related differences in Cd-induced testicular toxicity between WI and F344 rats. (orig.)

  20. Prevention of dipyrone (metamizole) induced inhibition of aspirin antiplatelet effects.

    Science.gov (United States)

    Polzin, Amin; Richter, Stefan; Schrör, Karsten; Rassaf, Tienush; Merx, Marc W; Kelm, Malte; Hohlfeld, Thomas; Zeus, Tobias

    2015-07-01

    We have recently shown that dipyrone (metamizole), a non-opioid analgesic, can nullify aspirin (acetylsalicylic acid; ASA) antiplatelet effects in patients with coronary artery disease (CAD). In this study, we analysed the aspirin and dipyrone drug-drug interaction in order to identify strategies to prevent the dipyrone induced inhibition of asprin antiplatelet effects. Platelet function was measured by arachidonic acid-induced light-transmission aggregometry, thromboxane (TX) B2- formation by immunoassay. Dipyrone metabolite plasma levels were determined by high-performance-liquid-chromatography (HPLC). In seven healthy individuals, in vitro ASA (30 µM/ 100 µM/ 300 µM/ 1,000 µM) and dipyrone (10 µM) coincubation revealed, that the aspirin and dipyrone interaction can be overcome by increasing doses of aspirin. In 36 aspirin and dipyrone comedicated CAD patients, addition of ASA (30 µM/ 100 µM) in vitro inhibited, but did not completely overcome the dipyrone induced reduction of aspirin antiplatelet effects. Notably, the inhibition of thromboxane formation in aspirin and dipyrone comedicated CAD patients coincided with dipyrone plasma levels. In a cross-over designed study in four healthy individuals, we were able to prove that inhibition of aspirin (100 mg/ day) effects by dipyrone (750 mg/ day) was reversible. Furthermore, aspirin (100 mg/ day) medication prior to dipyrone (750 mg/ day) intake prevented the inhibition of antiplatelet effects by dipyrone in 12 healthy individuals. In conclusion, aspirin medication prior to dipyrone intake preserves antiplatelet effects, circumventing the pharmacodynamic drug-drug interaction at the level of cyclooxygenase-1.

  1. Retrieval-Induced Inhibition in Short-Term Memory.

    Science.gov (United States)

    Kang, Min-Suk; Choi, Joongrul

    2015-07-01

    We used a visual illusion called motion repulsion as a model system for investigating competition between two mental representations. Subjects were asked to remember two random-dot-motion displays presented in sequence and then to report the motion directions for each. Remembered motion directions were shifted away from the actual motion directions, an effect similar to the motion repulsion observed during perception. More important, the item retrieved second showed greater repulsion than the item retrieved first. This suggests that earlier retrieval exerted greater inhibition on the other item being held in short-term memory. This retrieval-induced motion repulsion could be explained neither by reduced cognitive resources for maintaining short-term memory nor by continued inhibition between short-term memory representations. These results indicate that retrieval of memory representations inhibits other representations in short-term memory. We discuss mechanisms of retrieval-induced inhibition and their implications for the structure of memory. © The Author(s) 2015.

  2. Cadmium exposure in newborn rats ovary induces developmental disorders of primordial follicles and the differential expression of SCF/c-kit gene.

    Science.gov (United States)

    Zhang, Wenchang; Wu, Tingting; Zhang, Chenyun; Luo, Lingfeng; Xie, Meimei; Huang, Huiling

    2017-10-05

    Since the 1990s, the rising problem that gonad reproductive toxicity on adult female after exposing to cadmium (Cd), an environmental endocrine disruptor, has attracted high attention at home and abroad,and was systematically studied. Our research focuses on a further problem is that early cadmium exposure (during birth to before puberty) impact on development and function of ovarian cells and its possible mechanism. Our research focuses on the changes of ovarian cells growth and development after the newborn rat ovaries with cadmium exposure in vitro, and different expression of ovarian cells development-related factors, SCF/c-kit and changes of their DNA methylation status. We obtained ovaries from 4-day-old SD rats and cultured them in DMEM/F12 mixed with α-MEM media in vitro. Different doses of cadmium were designed as control, 0.5, 5, 10 and 50μM, and then the constituent ratio of ovarian follicle and follicular oocytes diameter were observed with microscope after 4-h exposure. We found that the increased constituent ratio of original follicle and decreased diameter of all levels of follicular oocytes(compared with control, with statistically significant differences, Pgrowth follicle and increased diameter of oocytes under the treatment of adding SCF in cell culture media. Finally, MALDI-TOF-MS method showed DNA-low methylation status of SCF/c-kit promoter region after Cd exposure. Overall, we concluded that the exposure of cadimium (5-50μM) on newborn rats ovaries could inhibit follicle development.SCF/c-kit system might mediate follicle development damage caused by cadmium, which is associated with DNA hypomethylation of SCF/c-kit promoter region may be worthy of further study. Copyright © 2017. Published by Elsevier B.V.

  3. Recovery of Saccharomyces cerevisiae from ethanol-induced growth inhibition.

    OpenAIRE

    Walker-Caprioglio, H M; Rodriguez, R J; Parks, L W

    1985-01-01

    Ethanol caused altered mobility of the lipophilic probe 1,6-diphenyl-1,3,5-hexatriene in plasma membrane preparations of Saccharomyces cerevisiae. Because lipids had been shown to protect yeast cells against ethanol toxicity, sterols, fatty acids, proteins, and combinations of these were tested; however, protection from growth inhibition was not seen. Ethanol-induced, prolonged lag periods and diminished growth rates in S. cerevisiae were reduced by an autoconditioning of the medium by the in...

  4. Linear ubiquitin chain induces apoptosis and inhibits tumor growth.

    Science.gov (United States)

    Qin, Zhoushuai; Jiang, Wandong; Wang, Guifen; Sun, Ying; Xiao, Wei

    2018-01-01

    Ubiquitination of proliferating cell nuclear antigen (PCNA) plays an important role in DNA damage response. Ectopic expression of PCNA fused at either terminus with ubiquitin (Ub) lacking two C-terminal glycine residues induces translesion DNA synthesis which resembles synthesis mediated by PCNA monoubiquitination. PCNA fused with Ub containing the C-terminal Gly residues at the C-terminus can be further polyubiquitinated in a Gly-dependent manner, which inhibits cell proliferation and induces ATR-dependent replication checkpoint. In this study, we surprisingly found that PCNA fused to a head-to-tail linear Ub chain induces apoptosis in a Ub chain length-dependent manner. Further investigation revealed that the apoptotic effect is actually induced by the linear Ub chain independently from PCNA, as the Ub chain fused to GFP or an epitope tag still efficiently induces apoptosis. It is revealed that the artificial linear Ub chain differs from endogenously encoded linear Ub chains in that its Ubs contain a Ub-G76S substitution, making the Ub chain resistant to cleavage by deubiquitination enzymes. We demonstrated in this study that ectopic expression of the artificial Ub chain alone in cultured human cancer cells is sufficient to inhibit tumor growth in a xenograft mouse model, making the linear Ub chain a putative anti-cancer agent.

  5. Adaptation strategies of two closely related Desmodesmus armatus (green alga) strains contained different amounts of cadmium: a study with light-induced synchronized cultures of algae.

    Science.gov (United States)

    Pokora, Wojciech; Baścik-Remisiewicz, Agnieszka; Tukaj, Stefan; Kalinowska, Renata; Pawlik-Skowrońska, Barbara; Dziadziuszko, Małgorzata; Tukaj, Zbigniew

    2014-01-15

    During the Desmodesmus armatus cell cycle, 8-celled coenobia of 276-4d strain accumulated a much lower amounts of cadmium than unicells of B1-76 strain. Cadmium reduced growth and photosynthesis in the cells of strain B1-76, but not those of 276-4d strain. Cells of 276-4d strain revealed a higher activity of superoxide dismutase (SOD) isoforms, in particular the activity and protein content of Fe-SOD. Cu/Zn-SOD was earlier and much stronger induced by cadmium in 276-4d than in B1-76 strain, whereas Fe- and Mn-SOD activity and Fe-SOD synthesis were induced only in 276-4d strain. Cadmium did not affect the heat shock protein 70 synthesis in B1-76 strain, but significantly stimulated this process in 276-4d strain. The level of glutathione increased 30-fold during cell development of Cd-exposed 276-4d strain, while in B1-76 it increased about 12 timed. Matured cells of both strains exposed to cadmium produced comparable amounts of phytochelatins and other thiol peptides, but their production in young cells of B1-76 strain was much higher than in 276-4d strain. In conclusion, a complex of internal detoxification mechanisms appeared to be more efficient in cells of 276-4d strain than B1-76 one. Copyright © 2013 Elsevier GmbH. All rights reserved.

  6. Ameliorative effects of Rosmarinus officinalis leaf extract and Vitamin C on cadmium-induced oxidative stress in Nile tilapia Oreochromis niloticus.

    Science.gov (United States)

    Al-Anazi, Marim Saleh; Virk, Promy; Elobeid, Mai; Siddiqui, Muzammil Iqbal

    2015-11-01

    The present studywas undertaken to assess the bioaccumulation potential of cadmium in liver, kidney, gills and muscles of freshwater fish, Nile tilapia Oreochromis niloticus and the changes in oxidative stress indices in liver and kidney with or without simultaneous treatment with waterborne vitamin C and rosemary leaf extract. Adult tilapia were divided into seven groups. Six groups were exposed to sublethal concentrations of Cd, three groups to 5 ppm, while other three to 10 ppm. Two groups from each of the Cd exposed groups were treated with Vitamin C (5ppm) and rosemary leaf extract (2.5 ppm) for a period of 21 days. Cadmium concentration in liver, kidneys and gills was significantly higher in the cadmium exposed groups being invariably high in the groups exposed to 10 ppm CdCl2.H2O.Treatment with Vitamin C and rosemary leaf extract significantly reduced cadmium concentration in comparison to non-treated Cd exposed groups. Treatment with Vitamin C and rosemary leaf extract significantly reduced oxidative stress in Cd exposed fish as evidenced from lower concentration of lipid peroxides and reduced activity of catalase and higher activity of superoxide dismutase in liver and kidney as compared to control fish. Reduction in Cd induced oxidative stress and bioaccumulation was comparable between the two antioxidant treatments, Vitamin C and rosemary leaf extract. The key findings suggest that both the antioxidants used showed ameliorative potential to reduce tissue accumulation of Cd and associated oxidative stress in fresh water fish, Nile tilapia.

  7. Cadmium Toxicity Induced Alterations in the Root Proteome of Green Gram in Contrasting Response towards Iron Supplement

    Directory of Open Access Journals (Sweden)

    Sowbiya Muneer

    2014-04-01

    Full Text Available Cadmium signifies a severe threat to crop productivity and green gram is a notably iron sensitive plant which shows considerable variation towards cadmium stress. A gel-based proteomics analysis was performed with the roots of green gram exposed to iron and cadmium combined treatments. The resulting data show that twenty three proteins were down-regulated in iron-deprived roots either in the absence (−Fe/−Cd or presence (−Fe/+Cd of cadmium. These down-regulated proteins were however well expressed in roots under iron sufficient conditions, even in the presence of cadmium (+Fe/+Cd. The functional classification of these proteins determined that 21% of the proteins are associated with nutrient metabolism. The other proteins in higher quantities are involved in either transcription or translation regulation, and the rest are involved in biosynthesis metabolism, antioxidant pathways, molecular chaperones and stress response. On the other hand, several protein spots were also absent in roots in response to iron deprivation either in absence (−Fe/−Cd or presence (−Fe/+Cd of cadmium but were well expressed in the presence of iron (+Fe/+Cd. Results suggest that green gram plants exposed to cadmium stress are able to change the nutrient metabolic balance in roots, but in the mean time regulate cadmium toxicity through iron supplements.

  8. Altered PITX2 and LEF1 gene expression in the cadmium-induced omphalocele in the chick model.

    Science.gov (United States)

    Doi, Takashi; Puri, Prem; Bannigan, John; Thompson, Jennifer

    2011-05-01

    Although, recent studies have suggested that disruption of somitogenesis may be involved in ventral body wall (VBW) defects; the molecular mechanisms of VBW defects remain unclear. In the chick embryo, the administration of cadmium (Cd) induces VBW defects similar to the human omphalocele. In this model, the earliest histological change in the somite occurs commencing at 4 h post-Cd treatment (4 h). PITX2 is expressed in somites, and PITX2 mutants have been shown to display VBW defects. PITX2 interacts with lymphoid enhancer factor-1 (LEF1) to regulate somite myogenesis. We designed this study to investigate the hypothesis that PITX2 and LEF1 genes are downregulated during the critical period of early embryogenesis in the Cd-induced omphalocele chick model. Chick embryos were exposed to Cd or saline after 60 h incubation and harvested at 1, 4, and 8 h posttreatment. Chicks were then divided into two groups: control (n = 24), and Cd (n = 24). RT-PCR was performed and analyzed statistically (significant difference was accepted at p PITX2 and LEF1 at 4 h were significantly decreased in the Cd group compared with controls, whereas there were no differences at the other time points. Immunoreactivity of those proteins at 4 h was also markedly decreased in somites in the Cd-treated embryos compared with controls. Downregulation of PITX2 and LEF1 genes may interfere with ventral body wall formation in Cd chick model causing omphalocele by disrupting somite myogenesis.

  9. Histological and immunohistochemical effects of Curcuma longa on activation of rat hepatic stellate cells after cadmium induced hepatotoxicity.

    Science.gov (United States)

    El-Mansy, A A; Mazroa, S A; Hamed, W S; Yaseen, A H; El-Mohandes, E A

    2016-01-01

    The liver is a target for toxic chemicals such as cadmium (Cd). When the liver is damaged, hepatic stellate cells (HSC) are activated and transformed into myofibroblast-like cells, which are responsible for liver fibrosis. Curcuma longa has been reported to exert a hepato-protective effect under various pathological conditions. We investigated the effects of C. longa administration on HSC activation in response to Cd induced hepatotoxicity. Forty adult male albino rats were divided into: group 1 (control), group 2 (Cd treated), group 3 (C. longa treated) and group 4 (Cd and C. longa treated). After 6 weeks, liver specimens were prepared for light and electron microscopy examination of histological changes and immunohistochemical localization of alpha smooth muscle actin (αSMA) as a specific marker for activated HSC. Activated HSC with a positive αSMA immune reaction were not detected in groups 1 and 3. Large numbers of activated HSC with αSMA immune reactions were observed in group 2 in addition to Cd induced hepatotoxic changes including excess collagen deposition in thickened portal triads, interlobular septa with hepatic lobulation, inflammatory cell infiltration, a significant increase in Kupffer cells and degenerated hepatocytes. In group 4, we observed a significant decrease in HSC that expressed αSMA with amelioration of the hepatotoxic changes. C. longa administration decreased HSC activation and ameliorated hepatotoxic changes caused by Cd in adult rats.

  10. Onion and garlic extracts as potential antidotes for cadmium-induced biochemical alterations in prostate glands of rats.

    Science.gov (United States)

    Ola-Mudathir, F K; Suru, S M

    2015-11-01

    Cadmium (Cd) has been implicated in increased prostate gland malignancy risk in both wildlife and humans. This study examines the chemoprotective roles of onion and garlic extracts on Cd-induced biochemical alterations in the prostate glands of rats. Adult male Wistar rats were randomly divided into nine groups: control group received double distilled water; Cd group received Cd alone (1.5 mg/100 g bwt per day); extract-treated groups were pre-treated with varied doses of onion and/or garlic extract (0.5 ml and 1.0 ml/100 g bwt per day) for 1 week and then co-treated with Cd (1.5 mg/100 g bwt per day) for additional 3 weeks. Oxidant/antioxidant status and acid phosphatase (ACPtotal and ACPprostatic ) activity were examined in prostate glands. Cd intoxication caused a marked (P garlic extract significantly minimised these alterations. The onion extract offered a dose-dependent protection. Our findings suggest a chemoprotective capability for onion and garlic extracts against Cd-induced biochemical alteration in the prostate glands. © 2014 Blackwell Verlag GmbH.

  11. Salvinorin A Inhibits Airway Hyperreactivity Induced by Ovalbumin Sensitization

    Science.gov (United States)

    Rossi, Antonietta; Caiazzo, Elisabetta; Bilancia, Rossella; Riemma, Maria A.; Pagano, Ester; Cicala, Carla; Ialenti, Armando; Zjawiony, Jordan K.; Izzo, Angelo A.; Capasso, Raffaele; Roviezzo, Fiorentina

    2017-01-01

    Salvinorin A, a neoclerodane diterpene isolated from Salvia divinorum, exerts a number of pharmacological actions which are not solely limited to the central nervous system. Recently it has been demonstrated that Salvinorin A inhibits acute inflammatory response affecting leukotriene (LT) production. Since LTs are potent lipid mediators implicated in allergic diseases, we evaluated the effect of Salvinorin A on allergic inflammation and on airways following sensitization in the mouse. Mice were sensitized with s.c. injection of ovalbumin (OVA) on days 1 and 8. Sensitized mice received on days 9 and 12 on the shaved dorsal surface air administration to induce the development of the air-pouches. On day 15 animals were challenged by injection of OVA into the air-pouch. Salvinorin A, administered (10 mg/kg) before each allergen exposure, significantly reduced OVA-induced LT increase in the air pouch. This effect was coupled to a reduction in cell recruitment and Th2 cytokine production. In another set of experiments, mice were sensitized with OVA and both bronchial reactivity and pulmonary inflammation were assessed. Salvinorin A abrogated bronchial hyperreactivity and interleukin (IL)-13 production, without effect on pulmonary inflammation. Indeed cell infiltration and peribronchial edema were still present following diterpenoid treatment. Similarly, pulmonary IL-4 and plasmatic IgE levels were not modulated. Conversely, Salvinorin A significantly reduced LTC4 production in the lung of sensitized mice. Finally mast cell activity was evaluated by means of toluidine blue staining. Data obtained evidenced that Salvinorin A significantly inhibited mast cell degranulation in the lung. Our study demonstrates that Salvinorin A inhibits airway hyperreactivity induced by sensitization by inhibition of LT production and mast cell degranulation. In conclusion Salvinorin A could represent a promising candidate for drug development in allergic diseases such as asthma. PMID

  12. Attenuation of cadmium chloride induced cytotoxicity in murine hepatocytes by a protein isolated from the leaves of the herb Cajanus indicus L.

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-06-15

    Cadmium has been recognized as a strong environmental pollutant. Exposure to this heavy metal occurs through the intake of foodstuffs, drinking water and also via the inhalation of air. Present study was conducted to evaluate the protective effect of a 43 kDa protein, isolated from the leaves of the herb Cajanus indicus, against cadmium-induced cytotoxicity in hepatocytes. For this study, cadmium chloride (CdCl{sub 2}) has been used as the source of cadmium. Treatment of hepatocytes with 800 {mu}M CdCl{sub 2} for 3 h caused significant reduction in cell viability in association with the increased levels of glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) leakage. The activities of the antioxidant enzymes, superoxide dismutase, catalase (CAT), glutathione-S-transferase and glutathione reductase, and the levels of cellular metabolites, reduced glutathione (GSH) as well as total thiols have also been decreased under the same treatment. In addition, the toxin enhanced the levels of the lipid peroxidation end products and oxidized glutathione (GSSG). Incubation of hepatocytes with the protein at a dose of 0.1 mg/ml for 3 h prior to the toxin treatment (at a dose of 800 {mu}M for 3 h) restored the activities of all the antioxidant enzymes, the levels of GSH, total thiols, cell viability and also attenuated the increased levels of GPT, ALP, lipid peroxidation and GSSG. In addition, the protein resisted CdCl{sub 2} induced alterations of all the parameters when applied in combination with CdCl{sub 2}. Effects of a known antioxidant, vitamin E, and a non-relevant protein, bovine serum albumin against CdCl{sub 2} induced cytotoxicity have also been included in the study. Combining all, we would like to say that the protein possessed protective activity against CdCl{sub 2} induced cytotoxicity in mouse hepatocytes probably via its antioxidant property. (orig.)

  13. Evidence of immunocompetence reduction induced by cadmium exposure in honey bees (Apis mellifera).

    Science.gov (United States)

    Polykretis, P; Delfino, G; Petrocelli, I; Cervo, R; Tanteri, G; Montori, G; Perito, B; Branca, J J V; Morucci, G; Gulisano, M

    2016-11-01

    In the last decades a dramatic loss of Apis mellifera hives has been reported in both Europe and USA. Research in this field is oriented towards identifying a synergy of contributing factors, i.e. pathogens, pesticides, habitat loss and pollution to the weakening of the hive. Cadmium (Cd) is a hazardous anthropogenic pollutant whose effects are proving to be increasingly lethal. Among the multiple damages related to Cd contamination, some studies report that it causes immunosuppression in various animal species. The aim of this paper is to determine whether contamination by Cd, may have a similar effect on the honey bees' immunocompetence. Our results, obtained by immune challenge experiments and confirmed by structural and ultrastructural observations show that such metal causes a reduction in immunocompetence in 3 days Cd exposed bees. As further evidence of honey bee response to Cd treatment, Energy Dispersive X-ray Spectroscopy (X-EDS) has revealed the presence of zinc (Zn) in peculiar electron-dense granules in fat body cells. Zn is a characteristic component of metallothioneins (MTs), which are usually synthesized as anti-oxidant and scavenger tools against Cd contamination. Our findings suggest that honey bee colonies may have a weakened immune system in Cd polluted areas, resulting in a decreased ability in dealing with pathogens. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Histopathological changes in the head kidney induced by cadmium in a neotropical fish Colossoma macropomum

    Directory of Open Access Journals (Sweden)

    R. Salazar-Lugo

    2013-12-01

    Full Text Available We evaluated the effect of cadmium (Cd on the structure and function of the head kidney in the freshwater fish Colossoma macropomum (C. macropomum. Juveniles were exposed to 0.1 mg/L CdCl2 for 31 days. Blood samples were examined using hematological tests and head kidney histology was determined by light microscopy. The concentration of Cd in the head and trunk kidneys was measured using an atomic absorption spectrophotometer. Cd produced histopathological changes in the head kidney, the most evident of these being: the thickening of the vein wall, an increase in the number of basophils/mast cells close to blood vessels and a severe depletion of hematopoietic precursors especially the granulopoietic series. In the blood, a decrease in the total leucocytes and hemoglobin concentration was observed. Cd-exposed fish showed higher Cd concentrations in the trunk kidney than the head kidney. In conclusion, exposure to Cd affected precursor hematopoietic cells in C. macropomum.

  15. Prevention of cadmium-induced sterility by zinc in the male rat.

    Science.gov (United States)

    Saksena, S; White, M J; Mertzlufft, J; Lau, I

    1983-05-01

    The potential of zinc (Zn) to antagonize the adverse effects of cadmium (Cd) on the male reproductive processes was studied. A significant reduction in the weights of the testis and epididymis, the testicular sperm population and oligospermia to azoospermia in the epididymis was recorded in rats treated once s.c. with 2 mg/kg Cd and sacrificed 20 days later. This was accompanied by a significantly reduced serum T and a loss of fertility. Administration of a single s.c. injection of Zn (80 mg/kg) did not alter significantly any of the reproductive parameters studied. On the other hand, Zn given 1/2 to 2 h after Cd resulted in partial recovery. Organ weights and sperm population in these groups were maintained and the fertility rate was 67% and 50% at 5 and 20 days as compared to 67% and 0% at corresponding period in Cd-exposed males. The protective effect diminished when Zn was given more than 2 h after Cd exposure. The most effective regimen of Zn therapy was an administration of a total dose of 80 mg/kg Zn given in 3 injections (15 mg/kg before, 50 mg/kg at the time and 15 mg/kg 2 h after Cd). The results provide evidence that Zn, if given before or within 2 h of Cd exposure, is capable of at least partially reversing its deleterious effects on spermatogenesis, steroidogenesis and fertility of the male rat.

  16. Cadmium sulfide quantum dots induce oxidative stress and behavioral impairments in the marine clam Scrobicularia plana.

    Science.gov (United States)

    Buffet, Pierre-Emmanuel; Zalouk-Vergnoux, Aurore; Poirier, Laurence; Lopes, Christelle; Risso-de-Faverney, Christine; Guibbolini, Marielle; Gilliland, Douglas; Perrein-Ettajani, Hanane; Valsami-Jones, Eugenia; Mouneyrac, Catherine

    2015-07-01

    Cadmium sulfide (CdS) quantum dots have a number of current applications in electronics and solar cells and significant future potential in medicine. The aim of the present study was to examine the toxic effects of CdS quantum dots on the marine clam Scrobicularia plana exposed for 14 d to these nanomaterials (10 µg Cd L(-1) ) in natural seawater and to compare them with soluble Cd. Measurement of labile Cd released from CdS quantum dots showed that 52% of CdS quantum dots remained in the nanoparticulate form. Clams accumulated the same levels of Cd regardless of the form in which it was delivered (soluble Cd vs CdS quantum dots). However, significant changes in biochemical responses were observed in clams exposed to CdS quantum dots compared with soluble Cd. Increased activities of catalase and glutathione-S-transferase were significantly higher in clams exposed in seawater to Cd as the nanoparticulate versus the soluble form, suggesting a specific nano effect. The behavior of S. plana in sediment showed impairments of foot movements only in the case of exposure to CdS quantum dots. The results show that oxidative stress and behavior biomarkers are sensitive predictors of CdS quantum dots toxicity in S. plana. Such responses, appearing well before changes might occur at the population level, demonstrate the usefulness of this model species and type of biomarker in the assessment of nanoparticle contamination in estuarine ecosystems. © 2015 SETAC.

  17. Evaluation of proteome alterations induced by cadmium stress in sunflower (Helianthus annuus L.) cultures.

    Science.gov (United States)

    Lopes Júnior, Cícero Alves; Barbosa, Herbert de Sousa; Moretto Galazzi, Rodrigo; Ferreira Koolen, Hector Henrique; Gozzo, Fábio Cesar; Arruda, Marco Aurélio Zezzi

    2015-09-01

    The present study evaluates, at a proteomic level, changes in protein abundance in sunflower leaves in the absence or presence (at 50 or 700mg) of cadmium (as CdCl2). At the end of the cultivation period (45 days), proteins are extracted from leaves with phenol, separated by two-dimensional difference gel electrophoresis (2-D DIGE), and excised from the gels. The differential protein abundances (for proteins differing by more than 1.8 fold, which corresponds to 90% variation) are characterized using nESI-LC-MS/MS. The protein content decreases by approximately 41% in plants treated with 700mg Cd compared with control plants. By comparing all groups of plants evaluated in this study (Control vs. Cd-lower, Control vs. Cd-higher and Cd-lower vs. Cd-higher), 39 proteins are found differential and 18 accurately identified; the control vs. Cd-higher treatment is that presenting the most differential proteins. From identified proteins, those involved in energy and disease/defense (including stress), are the ribulose bisphosphate carboxylase large chain, transketolase, and heat shock proteins are the most differential abundant proteins. Thus, at the present study, photosynthesis is the main process affected by Cd in sunflowers, although these plants are highly tolerant to Cd. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Low energy Ar+ ion irradiation induced surface modification in cadmium zinc telluride (CdZnTe)

    Science.gov (United States)

    Tripathi, J. K.; Harilal, S. S.; Hassanein, A.

    2014-09-01

    In this paper, we report on modifications in structural, stoichiometry, and optical properties of cadmium zinc telluride (CdZnTe) crystals due to 1 keV Ar+ ion irradiation as a function of ion fluence, using ion flux of 1.7 × 1017 ions cm-2 s-1. The CdZnTe crystals were irradiated at normal incidence, using fluence range of 8 × 1017-3 × 1019 ions cm-2. Atomic force microscopy studies show sequential change in surface structure as a function of ion fluence, from homogeneously populated nano-hole to micron sized holes on the entire CZT crystal surface. These holes are well geometrically defined and most of them are rectangular in shape. X-ray photoelectron spectroscopy studies show a reduction in Zn at % while Raman and photoluminescence studies show almost complete depletion of Te inclusions and slight red shifts, respectively, due to ion irradiations. Schottky diode radiation detectors fabricated from such defect free CZT crystals will show significantly higher energy resolution.

  19. Root-induced changes to cadmium speciation in the rhizosphere of two rice (Oryza sativa L.) genotypes

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Linfei [Institute of Soil and Water Resources and Environmental Science, Zhejiang University, Hangzhou 310029 (China); Zhejiang Provincial Key Laboratory of Subtropic Soil and Plant Nutrition, Hangzhou 310029 (China); Department of Crop and Soil Sciences, Bradfield Hall, Cornell University, Ithaca, NY 14853 (United States); McBride, Murray B. [Department of Crop and Soil Sciences, Bradfield Hall, Cornell University, Ithaca, NY 14853 (United States); Cheng, Hao [Institute of Soil and Water Resources and Environmental Science, Zhejiang University, Hangzhou 310029 (China); Zhejiang Provincial Key Laboratory of Subtropic Soil and Plant Nutrition, Hangzhou 310029 (China); Wu, Jianjun [Institute of Soil and Water Resources and Environmental Science, Zhejiang University, Hangzhou 310029 (China); Zhejiang Provincial Key Laboratory of Subtropic Soil and Plant Nutrition, Hangzhou 310029 (China); Ministry of Agriculture Key Laboratory of Nonpoint Source Pollution Control, Hangzhou 310029 (China); Shi, Jiachun, E-mail: jcshi@zju.edu.cn [Institute of Soil and Water Resources and Environmental Science, Zhejiang University, Hangzhou 310029 (China); Zhejiang Provincial Key Laboratory of Subtropic Soil and Plant Nutrition, Hangzhou 310029 (China); Ministry of Agriculture Key Laboratory of Nonpoint Source Pollution Control, Hangzhou 310029 (China); Xu, Jianming, E-mail: jmxu@zju.edu.cn [Institute of Soil and Water Resources and Environmental Science, Zhejiang University, Hangzhou 310029 (China); Zhejiang Provincial Key Laboratory of Subtropic Soil and Plant Nutrition, Hangzhou 310029 (China); Ministry of Agriculture Key Laboratory of Nonpoint Source Pollution Control, Hangzhou 310029 (China); Wu, Laosheng [Institute of Soil and Water Resources and Environmental Science, Zhejiang University, Hangzhou 310029 (China); Zhejiang Provincial Key Laboratory of Subtropic Soil and Plant Nutrition, Hangzhou 310029 (China); Ministry of Agriculture Key Laboratory of Nonpoint Source Pollution Control, Hangzhou 310029 (China)

    2011-04-15

    Our aim was to investigate rhizosphere effects on the chemical behavior of Cd. This was done in a glasshouse experiment, where two rice cultivars (Zhenong54 and Sixizhan) were grown in soil spiked with cadmium (Cd) at two levels, 3.9{+-}0.5 and 8.3{+-}0.5 mg kg{sup -1} soil, placed in a rhizobox until ripening stage. Chemical forms of cadmium near the root surface were then assessed using a sequential extraction procedure (SEP). There were significant differences in Cd species, especially exchangeable Cd (EXC-Cd) between the two rice cultivars as affected by rice roots. The lowest EXC-Cd with Zhenong54 appeared in the near-rhizosphere area with little difference between tillering stage and ripening stage while Sixizhan had its lowest EXC-Cd concentration in the root compartment. Both cultivars had slight changes in the Fe/Mn oxide-bound fraction of Cd (FMO-Cd) at the grain ripening stage while the control treatments without plants had a significant increase in FMO-Cd at the same time, indicating a transformation from a less bioavailable form (FMO-Cd) to more bioavailable forms (EXC-Cd). Soil microbial biomass in the vicinity of the root surface had opposite trends to some extent with EXC-Cd, partly because of the root-induced changes to bioavailable Cd. Unlike Zhenong54, Sixizhan had a higher Cd concentration in the root, but only a small proportion of Cd translocated from the root to grain. - Research highlights: {yields}We investigated genotypic effects on Cd speciation in the rhizosphere of rice. {yields}Zhenong54 (ZN) and Sixizhan (SX) were grown in rhizobox to show root-induced changes. {yields}Lowest exchangeable-Cd of ZN was in near-rhizosphere while SX in root compartment. {yields}Soil microbial biomass had opposite trends with exchangeable-Cd in both cultivars. {yields}Unlike ZN, SX had higher Cd content in roots, but lower Cd content in shoots.

  20. ERα inhibited myocardin-induced differentiation in uterine fibroids

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Xing-Hua, E-mail: xinghualiao@hotmail.com [Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065 (China); Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China); Li, Jun-Yan [Henan Vocational College of Applied Technology, Zhengzhou 450042 (China); Dong, Xiu-Mei [Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065 (China); Yuncheng County People' s Hospital, Shandong 274700 (China); Wang, Xiuhong [Xianning Central Hospital, Department of Obstetrics and Gynecology, Xianning, Hubei 437100 (China); Xiang, Yuan; Li, Hui; Yu, Cheng-Xi; Li, Jia-Peng; Yuan, Bai-Yin [Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065 (China); Zhou, Jun, E-mail: zhoujun@wust.edu.cn [Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065 (China); School of Medicine, Wuhan University of Science and Technology, Wuhan 430065 (China); Zhang, Tong-Cun, E-mail: zhangtongcun@wust.edu.cn [Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, 430065 (China); Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457 (China)

    2017-01-01

    Uterine fibroids, also known as uterine leiomyomas, are a benign tumor of the human uterus and the commonest estrogen-dependent benign tumor found in women. Myocardin is an important transcriptional regulator in smooth and cardiac muscle development. The role of myocardin and its relationship with ERα in uterine fibroids have barely been addressed. We noticed that the expression of myocardin was markedly reduced in human uterine fibroid tissue compared with corresponding normal or adjacent myometrium tissue. Here we reported that myocardin induced the transcription and expression of differentiation markers SM22α and alpha smooth muscle actin (α-SMA) in rat primary uterine smooth muscle cells (USMCs) and this effect was inhibited by ERα. Notably, we showed that, ERα induced expression of proliferation markers PCNA and ki-67 in rat primary USMCs. We also found ERα interacted with myocardin and formed complex to bind to CArG box and inhibit the SM22α promoter activity. Furthermore, ERα inhibited the transcription and expression of myocardin, and reduced the levels of transcription and expression of downstream target SM22α, a SMC differentiation marker. Our data thus provided important and novel insights into how ERα and myocardin interact to control the cell differentiation and proliferation of USMCs. Thus, it may provide potential therapeutic target for uterine fibroids.

  1. Docosahexaenoic Acid Inhibits Cerulein-Induced Acute Pancreatitis in Rats

    Directory of Open Access Journals (Sweden)

    Yoo Kyung Jeong

    2017-07-01

    Full Text Available Oxidative stress is an important regulator in the pathogenesis of acute pancreatitis (AP. Reactive oxygen species induce activation of inflammatory cascades, inflammatory cell recruitment, and tissue damage. NF-κB regulates inflammatory cytokine gene expression, which induces an acute, edematous form of pancreatitis. Protein kinase C δ (PKCδ activates NF-κB as shown in a mouse model of cerulein-induced AP. Docosahexaenoic acid (DHA, an ω-3 fatty acid, exerts anti-inflammatory and antioxidant effects in various cells and tissues. This study investigated whether DHA inhibits cerulein-induced AP in rats by assessing pancreatic edema, myeloperoxidase activity, levels of lipid peroxide and IL-6, activation of NF-κB and PKCδ, and by histologic observation. AP was induced by intraperitoneal injection (i.p. of cerulein (50 μg/kg every hour for 7 h. DHA (13 mg/kg was administered i.p. for three days before AP induction. Pretreatment with DHA reduced cerulein-induced activation of NF-κB, PKCδ, and IL-6 in pancreatic tissues of rats. DHA suppressed pancreatic edema and decreased the abundance of lipid peroxide, myeloperoxidase activity, and inflammatory cell infiltration into the pancreatic tissues of cerulein-stimulated rats. Therefore, DHA may help prevent the development of pancreatitis by suppressing the activation of NF-κB and PKCδ, expression of IL-6, and oxidative damage to the pancreas.

  2. Prolyl isomerase Pin1 regulates cadmium-induced autophagy via ubiquitin-mediated post-translational stabilization of phospho-Ser GSK3αβ in human hepatocellular carcinoma cells.

    Science.gov (United States)

    So, Keum-Young; Oh, Seon-Hee

    2015-12-01

    Accumulating evidence suggests that prolyl-isomerase (Pin1) is an important regulator of apoptosis. In the present study, Pin1 was shown to negatively regulate the stabilization of glycogen synthase kinase (GSK) 3αβ serine phosphorylation by inhibiting ubiquitin (Ub)-proteasome degradation, and to induce autophagy following cadmium (Cd) exposure. Cd-induced autophagy in human hepatoma (HepG2) cells has been demonstrated by green fluorescent protein (GFP)-LC3B plasmid DNA transfection, and LC3-II conversion by autophagy inhibitors. Atg5 silencing inhibited Cd-induced apoptosis, indicating that autophagy is involved in cell death. Exposing HepG2 cells to Cd (≤6 μM) initially increased p-Ser GSK3αβ, but then resulted in a gradual decrease, which correlated with polyubiquitinated protein levels, which is indicative of protein degradation. However, high Cd concentrations lead to p-Ser GSK3αβ and polyubiquitinated protein accumulation, indicating proteasome impairment. Cd-induced p-Ser GSK3αβ was enhanced by proteasome inhibition (MG132) and ubiquitin deficiency (cyclohexamide), but no ubiquitination of p-Ser GSK3αβ or GSK3αβ was detected. Cd exposure resulted in p-Ser GSK3αβ redistribution from the nucleus into the cytosol, and this along with autophagy, was inhibited by leptomycin B. Cd concentrations Ser GSK3αβ, autophagy, and polyubiquitinated protein levels, while its inhibition reversed the effects. Silencing and overexpression of GSK3αβ had no effect on Cd-induced Pin1 levels. Immunoprecipitation studies showed that Pin1 and p-Ser GSK3αβ interact. Collectively, Pin1 protects cells by inhibiting p-Ser GSK3αβ, and Pin1 decrease upregulates p-Ser GSK3αβ, through the inhibition of Ub-mediated proteasome degradation, and stimulates cell death via autophagy. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Dietary phosphorus exacerbates bone loss induced by cadmium in ovariectomized rats.

    Science.gov (United States)

    Bakhshalian, Neema; Johnson, Sarah A; Hooshmand, Shirin; Feresin, Rafaela G; Elam, Marcus L; Soung, Do Y; Payton, Mark E; Arjmandi, Bahram H

    2014-12-01

    Postmenopausal bone loss can be exacerbated by environmental contaminants, including the heavy metal cadmium (Cd). We hypothesized that incorporating phosphorus (P) into the diet would lead to the chelation of Cd into P, preventing its absorption and subsequent bone loss. To test this hypothesis, we used ovariectomized rats as a model of postmenopausal osteoporosis to examine the deleterious effects of Cd on bone with and without added P. Fifty 3-month-old ovariectomized Sprague-Dawley rats were assigned to five treatment groups (n = 10 per group) for 3 months as follows: (1) control; (2) 50 ppm Cd; (3) 50 ppm Cd plus 1.2% P; (4) 200 ppm Cd; and (5) 200 ppm Cd plus 1.2% P. Cd plus P caused a significant loss of whole body (P = 0.0001 and P < 0.001) and femoral (P = 0.0005 and P < 0.001) bone mineral density (BMD) and bone mineral content, respectively, and a loss of fourth lumbar vertebra BMD and bone mineral content (P < 0.0001 and P < 0.001, respectively). Nonetheless, 200 ppm Cd plus 1.2% P had the most deleterious effects on whole body and femoral BMD. For femoral neck microstructural properties, 50 ppm Cd plus 1.2% P caused an increase in trabecular separation, whereas 200 ppm Cd plus 1.2% P caused a decrease in bone volume-to-total volume ratio, a decrease in trabecular number, and an increase in trabecular separation and structural model index. Our findings indicate that Cd exposure, along with high intake of P, may be a public health hazard with respect to bone health.

  4. Cadmium delays non-homologous end joining (NHEJ) repair via inhibition of DNA-PKcs phosphorylation and downregulation of XRCC4 and Ligase IV

    Energy Technology Data Exchange (ETDEWEB)

    Li, Weiwei; Gu, Xueyan; Zhang, Xiaoning; Kong, Jinxin [Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000 (China); Ding, Nan [Gansu Key laboratory of Space Radiobiology, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Qi, Yongmei; Zhang, Yingmei [Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000 (China); Wang, Jufang [Gansu Key laboratory of Space Radiobiology, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou 730000 (China); Huang, Dejun, E-mail: huangdj@lzu.edu.cn [Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, School of Life Sciences, Lanzhou University, Lanzhou 730000 (China)

    2015-09-15

    Highlights: • Cadmium (Cd) exposure delayed the repair of DNA damage induced by X-ray. • Cd exposure altered the phosphorylation of DNA-PKcs on Thr-2609 and Ser-2056 sites. • Cd impaired the formation of XRCC4 and Ligase IV foci, and down-regulated their protein expression. • Zinc mitigated the effects of Cd on DDR by regulating pDNA-PKcs (Thr-2609), XRCC4 and Ligase IV. - Abstract: Although studies have shown that cadmium (Cd) interfered with DNA damage repair (DDR), whether Cd could affect non-homologous end joining (NHEJ) repair remains elusive. To further understand the effect of Cd on DDR, we used X-ray irradiation of Hela cells as an in vitro model system, along with γH2AX and 53BP1 as markers for DNA damage. Results showed that X-ray significantly increased γH2AX and 53BP1 foci in Hela cells (p < 0.01), all of which are characteristic of accrued DNA damage. The number of foci declined rapidly over time (1–8 h postirradiation), indicating an initiation of NHEJ process. However, the disappearance of γH2AX and 53BP1 foci was remarkably slowed by Cd pretreatment (p < 0.01), suggesting that Cd reduced the efficiency of NHEJ. To further elucidate the mechanisms of Cd toxicity, several markers of NHEJ pathway including Ku70, DNA-PKcs, XRCC4 and Ligase IV were examined. Our data showed that Cd altered the phosphorylation of DNA-PKcs, and reduced the expression of both XRCC4 and Ligase IV in irradiated cells. These observations are indicative of the impairment of NHEJ-dependent DNA repair pathways. In addition, zinc (Zn) mitigated the effects of Cd on NHEJ, suggesting that the Cd-induced NHEJ alteration may partly result from the displacement of Zn or from an interference with the normal function of Zn-containing proteins by Cd. Our findings provide a new insight into the toxicity of Cd on NHEJ repair and its underlying mechanisms in human cells.

  5. Molecular Mechanisms of Malignant Transformation by Low Dose Cadmium in Normal Human Bronchial Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Laura Cartularo

    Full Text Available Cadmium is a carcinogenic metal, the mechanisms of which are not fully understood. In this study, human bronchial epithelial cells were transformed with sub-toxic doses of cadmium (0.01, 0.05, and 0.1 μM and transformed clones were characterized for gene expression changes using RNA-seq, as well as other molecular measurements. 440 genes were upregulated and 47 genes were downregulated in cadmium clones relative to control clones over 1.25-fold. Upregulated genes were associated mostly with gene ontology terms related to embryonic development, immune response, and cell movement, while downregulated genes were associated with RNA metabolism and regulation of transcription. Several embryonic genes were upregulated, including the transcription regulator SATB2. SATB2 is critical for normal skeletal development and has roles in gene expression regulation and chromatin remodeling. Small hairpin RNA knockdown of SATB2 significantly inhibited growth in soft agar, indicating its potential as a driver of metal-induced carcinogenesis. An increase in oxidative stress and autophagy was observed in cadmium clones. In addition, the DNA repair protein O6-methylguanine-DNA-methyltransferase was depleted by transformation with cadmium. MGMT loss caused significant decrease in cell viability after treatment with the alkylating agent temozolomide, demonstrating diminished capacity to repair such damage. Results reveal various mechanisms of cadmium-induced malignant transformation in BEAS-2B cells including upregulation of SATB2, downregulation of MGMT, and increased oxidative stress.

  6. Equol inhibits growth, induces atresia, and inhibits steroidogenesis of mouse antral follicles in vitro.

    Science.gov (United States)

    Mahalingam, Sharada; Gao, Liying; Gonnering, Marni; Helferich, William; Flaws, Jodi A

    2016-03-15

    Equol is a non-steroidal estrogen metabolite produced by microbial conversion of daidzein, a major soy isoflavone, in the gut of some humans and many animal species. Isoflavones and their metabolites can affect endogenous estradiol production, action, and metabolism, potentially influencing ovarian follicle function. However, no studies have examined the effects of equol on intact ovarian antral follicles, which are responsible for sex steroid synthesis and further development into ovulatory follicles. Thus, the present study tested the hypothesis that equol inhibits antral follicle growth, increases follicle atresia, and inhibits steroidogenesis in the adult mouse ovary. To test this hypothesis, antral follicles isolated from adult CD-1 mice were cultured with vehicle control (dimethyl sulfoxide; DMSO) or equol (600 nM, 6 μM, 36 μM, and 100 μM) for 48 and 96 h. Every 24h, follicle diameters were measured to monitor growth. At 48 and 96 h, the culture medium was subjected to measurement of hormone levels, and the cultured follicles were subjected to gene expression analysis. Additionally, follicles were histologically evaluated for signs of atresia after 96 h of culture. The results indicate that equol (100 μM) inhibited follicle growth, altered the mRNA levels of bcl2-associated X protein and B cell leukemia/lymphoma 2, and induced follicle atresia. Further, equol decreased the levels of estradiol, testosterone, androstenedione, and progesterone, and it decreased mRNA levels of cholesterol side-chain cleavage, steroid 17-α-hydroxalase, and aromatase. Collectively, these data indicate that equol inhibits growth, increases atresia, and inhibits steroidogenesis of cultured mouse antral follicles. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Arginase Inhibition Reverses Monocrotaline-Induced Pulmonary Hypertension

    Science.gov (United States)

    Jung, Christian; Grün, Katja; Betge, Stefan; Pernow, John; Kelm, Malte; Masyuk, Maryna; Kuethe, Friedhelm; Ndongson-Dongmo, Bernadin; Bauer, Reinhard; Lauten, Alexander; Schulze, P. Christian; Berndt, Alexander

    2017-01-01

    Pulmonary hypertension (PH) is a heterogeneous disorder associated with a poor prognosis. Thus, the development of novel treatment strategies is of great interest. The enzyme arginase (Arg) is emerging as important player in PH development. The aim of the current study was to determine the expression of ArgI and ArgII as well as the effects of Arg inhibition in a rat model of PH. PH was induced in 35 Sprague–Dawley rats by monocrotaline (MCT, 60 mg/kg as single-dose). There were three experimental groups: sham-treated controls (control group, n = 11), MCT-induced PH (MCT group, n = 11) and MCT-induced PH treated with the Arg inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA; MCT/NorNoha group, n = 13). ArgI and ArgII expression was determined by immunohistochemistry and Western blot. Right ventricular systolic pressure (RVPsys) was measured and lung tissue remodeling was determined. Induction of PH resulted in an increase in RVPsys (81 ± 16 mmHg) compared to the control group (41 ± 15 mmHg, p = 0.002) accompanied by a significant elevation of histological sum-score (8.2 ± 2.4 in the MCT compared to 1.6 ± 1.6 in the control group, p < 0.001). Both, ArgI and ArgII were relevantly expressed in lung tissue and there was a significant increase in the MCT compared to the control group (p < 0.01). Arg inhibition resulted in a significant reduction of RVPsys to 52 ± 19 mmHg (p = 0.006) and histological sum-score to 5.8 ± 1.4 compared to the MCT group (p = 0.022). PH leads to increased expression of Arg. Arg inhibition leads to reduction of RVPsys and diminished lung tissue remodeling and therefore represents a potential treatment strategy in PH. PMID:28757567

  8. Improved Sensitization of Zinc Oxide Nanorods by Cadmium Telluride Quantum Dots through Charge Induced Hydrophilic Surface Generation

    Directory of Open Access Journals (Sweden)

    Karthik Laxman

    2014-01-01

    Full Text Available This paper reports on UV-mediated enhancement in the sensitization of semiconductor quantum dots (QDs on zinc oxide (ZnO nanorods, improving the charge transfer efficiency across the QD-ZnO interface. The improvement was primarily due to the reduction in the interfacial resistance achieved via the incorporation of UV light induced surface defects on zinc oxide nanorods. The photoinduced defects were characterized by XPS, FTIR, and water contact angle measurements, which demonstrated an increase in the surface defects (oxygen vacancies in the ZnO crystal, leading to an increase in the active sites available for the QD attachment. As a proof of concept, a model cadmium telluride (CdTe QD solar cell was fabricated using the defect engineered ZnO photoelectrodes, which showed ∼10% increase in photovoltage and ∼66% improvement in the photocurrent compared to the defect-free photoelectrodes. The improvement in the photocurrent was mainly attributed to the enhancement in the charge transfer efficiency across the defect rich QD-ZnO interface, which was indicated by the higher quenching of the CdTe QD photoluminescence upon sensitization.

  9. In vitro cadmium-induced alterations in growth and oxidative metabolism of upland cotton (Gossypium hirsutum L.).

    Science.gov (United States)

    Daud, M K; Mei, Lei; Najeeb, Ullah; Khan, Muhammad Azim; Deeba, Farah; Raza, Irum; Batool, Aliya; Zhu, S J

    2014-01-01

    Cadmium (Cd) is a toxic pollutant, which cause both dose- and time-dependent physiological and biochemical alterations in plants. The present in vitro study was undertaken to explore Cd-induced physiological and biochemical changes in cotton callus culture at 0, 550, 700, 850, and 1000 μM Cd for four different stress periods (7, 14, 21, and 28 days). At 1000 μM Cd, mean growth values were lower than their respective control. The cell protein contents decreased only after 7-day and 14-day stress treatment. At 550 μM Cd, malondialdehyde (MDA) contents decreased after various stress periods except 21-day period. Superoxide dismutase (SOD) activity at 1000 μM Cd improved relative to its respective controls in the first three stress regimes. Almost a decreasing trend in the hydrogen peroxide (H2O2) and peroxidase (POD) activities at all Cd levels after different stress periods was noticed. Ascorbate peroxidase (APX) activity descended over its relevant controls in the first three stress regimes except at 700 μM Cd after 14- and 21-day stress duration. Moreover, catalase (CAT) mean values significantly increased as a whole. From this experiment, it can be concluded that lipid peroxidation as well as reactive oxygen species (ROS) production was relatively higher as has been revealed by higher MDA contents and greater SOD, CAT activities.

  10. Proteomic analysis provides insights into the molecular bases of hydrogen gas-induced cadmium resistance in Medicago sativa.

    Science.gov (United States)

    Dai, Chen; Cui, Weiti; Pan, Jincheng; Xie, Yanjie; Wang, Jin; Shen, Wenbiao

    2017-01-30

    Recently, molecular hydrogen (H2) has emerged as a bio-regulator both in animals and plants. Normally, functions of endogenous generated H2 could be mimicked by exogenously applied hydrogen-rich water (HRW) or hydrogen-rich saline (particularly in animals). Although alfalfa seedlings showed more cadmium (Cd) resistance after the administration with HRW, corresponding molecular mechanism is still elusive. To address this gap, iTRAQ-based quantitative proteomics was used. The results showed that a total of 2377 proteins were identified with Medicago sativa is a widely used forage around the world. Recently, hydrogen gas (H2) was suggested as a candidate of signal molecule, and found to effectively attenuate Cd-induced damage in alfalfa seedlings. However, the underlying molecular mechanism still needs to be further elucidated. In the present work, an iTRAQ-based quantitative proteomics was firstly carried out, and the results revealed the main molecular targets and metabolic processes associated with Cd resistance conferred by H2. This study may expand our understanding of hydrogen gas-medicated heavy metal tolerance in plants. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Use of phosphorus to alleviate stress induced by cadmium and zinc ...

    African Journals Online (AJOL)

    Also, these results suggested that Cd and Zn exerted their toxic effects on the growth of E. nuttallii and H. verticillata, at least in part, by the induction of oxidative stress and inhibition of photosynthesis. Through comparing the response of the two plants to oxidative stress caused by Cd and Zn, it was found that E. nuttallii was ...

  12. Radiation-induced inhibition of RNA synthesis in Tetrahymena pyriformis.

    Science.gov (United States)

    Ernst, S G; Rustad, R C; Oleinick, N L

    1975-07-01

    Radiation-induced disturbances in RNA synthesis were investigated in exponentially growing Tetrahymena. Sub-lethal doses of gamma-radiation lead to a transient, dose-dependent decrease in the rate of total RNA synthesis measured by 3H-uridine incorporation, without an alteration of 3H-uridine uptake by the cells. The rate of 3H-uridine incorporation decreases exponentially with dose. In contrast, the duration of inhibition of RNA synthesis is linearly dependent on dose. Target-theory calculations suggest that the sensitive molecule has a molecular weight of about 2 X 10(7) Daltons.

  13. Genotoxic Effect of Atrazine, Arsenic, Cadmium and Nitrate ...

    African Journals Online (AJOL)

    ATZ), Cadmium (Cd), Arsenic (As) and Nitrate (NO3) have both estrogenic activity and carcinogenic potential. Atrazine has clastogenic effects and may also act as tumor promoter as it induces the aromatase enzyme. Arsenic and Cadmium ...

  14. Acute exposure to waterborne cadmium induced oxidative stress and immunotoxicity in the brain, ovary and liver of zebrafish (Danio rerio)

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jia-Lang, E-mail: zhengjialang@aliyun.com; Yuan, Shuang-Shuang; Wu, Chang-Wen; Lv, Zhen-Ming

    2016-11-15

    Highlights: • Cd induced oxidative stress and immunotoxicity by the generation of ROS. • The toxic effects depended on exposure time and different tissues. • Nrf2 and NF-κB mediated antioxidant and inflammatory responses. • Gene changed at transcriptional, translational, post-translational levels. - Abstract: Cadmium (Cd) is an environmental contaminant that poses serious risks to aquatic organisms and their associated ecosystem. The mechanisms underlying Cd-induced oxidative stress and immunotoxicity in fish remain largely unknown. In this study, adult female zebrafish were exposed to 0 (control), 1 mg L{sup −1} Cd for 24 h and 96 h, and the oxidative stress and inflammatory responses induced by Cd were evaluated in the brain, liver and ovary. Reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) increased in a time-dependent manner after treatment with Cd in the brain and liver. The increase may result from the disturbance of genes including copper and zinc superoxide dismutase (Cu/Zn-SOD), catalase (CAT), inducible nitric oxide synthase (iNOS), and ciclooxigenase-2 (COX-2) at mRNA, protein and activity levels. Although ROS, NO and MDA were not significantly affected by Cd in the ovary, the up-regulation of Cu/Zn-SOD, CAT, iNOS, and COX-2 was observed. Exposure to Cd induced a sharp increase in the protein levels of tumor necrosis factor alpha (TNF-α) in the brain, liver and ovary, possibly contributing to activate inflammatory responses. Furthermore, we also found a dramatic increase in mRNA levels of NF-E2-related factor 2 (Nrf2) and nuclear transcription factor κB (NF-κB) at 24 h in the liver and ovary. The corresponding changes in the mRNA levels of Kelch-like-ECH-associated protein 1 (Keap1a and Keap1b) and the inhibitor of κBα (IκBαa and IκBαb) may contribute to regulate the transcriptional activity of Nrf2 and NF-κB, respectively. Contrarily, mRNA levels of Nrf2, NF-κB, Keap1, Keap1b, IκBαa and IκBαb remained

  15. Gelsolin Inhibits the Inflammatory Process Induced by LPS

    Directory of Open Access Journals (Sweden)

    Ying Cheng

    2017-01-01

    Full Text Available Background/Aims: Endotoxemia is a life-threatening situation that signifies a key challenge in the field of intensive care medicine. Proinflammatory mediators produced by macrophages play a key role in endotoxemia. Gelsolin (GSN is involved in the process of inflammation. Methods: IL-6 and TNF-α in the supernatant were measured with an ELISA kit. NO production was assessed by measurement of nitrite concentration with the Griess assay. si-RNA directed against GSN (si-GSN was transfected by Lipofectamine. Results: LPS decreased the levels of GSN. Recombinant GSN inhibited the cytokines induced by LPS and rescued mice from LPS-induced death, and si-GSN increased death in the LPS-pretreated mice. Conclusion: GSN exhibited a protective role in endotoxemia.

  16. Use of Fourier Transform Infrared (FTIR) spectroscopy to study cadmium-induced changes in Padina tetrastromatica (Hauck)

    Digital Repository Service at National Institute of Oceanography (India)

    DeSouza, L.; PrabhaDevi; DivyaShridhar, M.P.; Naik, C.G.

    in their position towards lower wavenumber upon sugar-cadmium metalation. Because of the complexity of the absorption of various cellular polysaccharides, specifi c assign- ments are rather diffi cult. Although, it was earlier speculated that carbohydrates play... Learning). 115. Upatham, E., Benjaporn, B., Maleeya, K., Prayad, P. and Krisna, P. 2002. Biosorption of Cadmium and Chromium in Duckweed Wolffia globosa. Int. J. Phytoremediation, 4:73–86. Wehrheim, B. and Wettern, M. 1994. Comparative studies...

  17. Differential susceptibility to cadmium-induced liver and kidney injury in wild and laboratory-bred bank voles Myodes glareolus.

    Science.gov (United States)

    Salińska, Aneta; Włostowski, Tadeusz; Oleńska, Ewa

    2013-08-01

    The objective of the study was to compare the sensitivity of wild and laboratory-bred bank voles to cadmium (Cd)-induced histopathological changes in the liver and kidneys. For 4 weeks, the male bank voles-both wild and laboratory-bred-were provided with diet containing Cd in quantities factors during the development of Cd toxicity in the liver and kidneys-were carried out. Histopathological changes (focal hepatocyte swelling, vacuolation and inflammation [leukocyte infiltration] in the liver, and focal proximal tubule degeneration [including epithelial cell swelling] in the kidneys) occurred only in the wild bank voles fed a diet containing 60 μg Cd/g. There were no differences in concentrations of Cd, MT, GSH, Zn, and Cu in liver and kidney between the respective groups of wild and laboratory-bred animals. However, a decrease of hepatic Fe and lipid peroxidation was observed in the wild voles exhibiting histopathological changes. These data indicate the following: (1) wild bank voles are more susceptible to Cd-induced liver and kidney injury than those bred and raised in the laboratory; (2) the difference in sensitivity may be associated with a distinct decrease of hepatic Fe in response to Cd exposure between the two groups of bank voles; and (3) dietary Cd may produce histopathological changes indirectly through decreasing the hepatic Fe and Fe-dependent oxidative processes. These results also suggest that histopathology in the liver and kidney of wild bank voles living in a contaminated environment may occur at relatively low levels of tissue Cd.

  18. Modulation of cadmium-induced phytotoxicity in Cabomba caroliniana by urea involves photosynthetic metabolism and antioxidant status.

    Science.gov (United States)

    Huang, Wenmin; Shao, Hui; Zhou, Sining; Zhou, Qin; Li, Wei; Xing, Wei

    2017-10-01

    Urea is a widespread organic pollutant, which can be a nitrogen source, playing different roles in the growth of submerged macrophytes depending on concentrations, while high cadmium (Cd) concentrations are often toxic to macrophytes. In order to evaluate the combined effect of urea and Cd on a submerged macrophyte, Cabomba caroliniana, the morphological and physiological responses of C. caroliniana in the presence of urea and Cd were studied. The results showed that high concentrations of urea (400mgL-1) and Cd (500µmolL-1) had negative effects on C. caroliniana. There were strong visible symptoms of toxicity after 4 days of exposure under Cd-alone, 400mgL-1 urea, and Cd+400mgL-1 urea treatments. In addition, 400mgL-1 urea and Cd had adverse effects on C. caroliniana's pigment system. Significant losses in chlorophyll fluorescence and photosynthetic rates, as well as Rubisco activity were also observed under Cd-alone, 400mgL-1 urea, and Cd+400mgL-1 urea treatments. 400mgL-1 urea markedly enhanced Cd toxicity in C. caroliniana, reflected by a sharp decrease in photosynthetic activity and more visible toxicity symptoms. The results of thiobarbituric acid reactive substances (TBARS) pointed to extreme oxidative stress in C. caroliniana induced under Cd or 400mgL-1 urea exposure. Exogenous ascorbate (AsA) protected C. caroliniana from adverse damage in 400mgL-1 urea, which further corroborated the oxidative stress claim under 400mgL-1 urea. However, results also demonstrated that lower urea concentration (10mgL-1) alleviated Cd-induced phytotoxicity by stimulating chlorophyll synthesis and photosynthetic activity, as well as activating the activity of catalase (CAT) and glutathione-S-transferase (GST), which may explain the alleviating effect of urea on C. caroliniana under Cd stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Isoliquiritigenin Induces Autophagy and Inhibits Ovarian Cancer Cell Growth

    Directory of Open Access Journals (Sweden)

    Hsin-Yuan Chen

    2017-09-01

    Full Text Available Ovarian cancer is one of the commonest gynecologic malignancies, which has a poor prognosis for patients at the advanced stage. Isoliquiritigenin (ISL, an active flavonoid component of the licorice plant, previously demonstrated antioxidant, anti-inflammatory, and tumor suppressive effects. In this study, we investigated the antitumor effect of ISL on human ovarian cancer in vitro using the human ovarian cancer cell lines, OVCAR5 and ES-2, as model systems. Our results show that ISL significantly inhibited the viability of cancer cells in a concentration- and time-dependent manner. Flow cytometry analysis indicated that ISL induced G2/M phase arrest. Furthermore, the expression of cleaved PARP, cleaved caspase-3, Bax/Bcl-2 ratio, LC3B-II, and Beclin-1 levels were increased in western blot analysis. To clarify the role of autophagy and apoptosis in the effect of ISL, we used the autophagy inhibitor—3-methyladenine (3-MA to attenuate the punctate fluorescence staining pattern of the p62/sequestosome 1 (SQSTM1, red fluorescence and LC3 (green fluorescence proteins after ISL treatment, and 3-MA inhibited the cytotoxicity of ISL. These findings provide new information about the link between ISL-induced autophagy and apoptosis and suggest that ISL is a candidate agent for the treatment of human ovarian cancer.

  20. Ginger extract inhibits LPS induced macrophage activation and function

    Directory of Open Access Journals (Sweden)

    Bruch David

    2008-01-01

    Full Text Available Abstract Background Macrophages play a dual role in host defence. They act as the first line of defence by mounting an inflammatory response to antigen exposure and also act as antigen presenting cells and initiate the adaptive immune response. They are also the primary infiltrating cells at the site of inflammation. Inhibition of macrophage activation is one of the possible approaches towards modulating inflammation. Both conventional and alternative approaches are being studied in this regard. Ginger, an herbal product with broad anti inflammatory actions, is used as an alternative medicine in a number of inflammatory conditions like rheumatic disorders. In the present study we examined the effect of ginger extract on macrophage activation in the presence of LPS stimulation. Methods Murine peritoneal macrophages were stimulated by LPS in presence or absence of ginger extract and production of proinflammatory cytokines and chemokines were observed. We also studied the effect of ginger extract on the LPS induced expression of MHC II, B7.1, B7.2 and CD40 molecules. We also studied the antigen presenting function of ginger extract treated macrophages by primary mixed lymphocyte reaction. Results We observed that ginger extract inhibited IL-12, TNF-α, IL-1β (pro inflammatory cytokines and RANTES, MCP-1 (pro inflammatory chemokines production in LPS stimulated macrophages. Ginger extract also down regulated the expression of B7.1, B7.2 and MHC class II molecules. In addition ginger extract negatively affected the antigen presenting function of macrophages and we observed a significant reduction in T cell proliferation in response to allostimulation, when ginger extract treated macrophages were used as APCs. A significant decrease in IFN-γ and IL-2 production by T cells in response to allostimulation was also observed. Conclusion In conclusion ginger extract inhibits macrophage activation and APC function and indirectly inhibits T cell activation.

  1. Cadmium and Cadmium/Zinc Ratios and Tobacco-Related Morbidities

    Science.gov (United States)

    Richter, Patricia; Faroon, Obaid; Pappas, R. Steven

    2017-01-01

    Metals are one of five major categories of carcinogenic or toxic constituents in tobacco and tobacco smoke. Cadmium is highly volatile and a higher percentage of the total tobacco cadmium content is efficiently transferred to mainstream tobacco smoke than many other toxic metals in tobacco. Inhaled cadmium bioaccumulates in the lungs and is distributed beyond the lungs to other tissues, with a total body biological half-life of one to two decades. Chronic cadmium exposure through tobacco use elevates blood and urine cadmium concentrations. Cadmium is a carcinogen, and an inducer of proinflammatory immune responses. Elevated exposure to cadmium is associated with reduced pulmonary function, obstructive lung disease, bronchogenic carcinoma, cardiovascular diseases including myocardial infarction, peripheral arterial disease, prostate cancer, cervical cancer, pancreatic cancer, and various oral pathologies. Cadmium and zinc have a toxicologically inverse relationship. Zinc is an essential element and is reportedly antagonistic to some manifestations of cadmium toxicity. This review summarizes associations between blood, urine, and tissue cadmium concentrations with emphasis on cadmium exposure due to tobacco use and several disease states. Available data about zinc and cadmium/zinc ratios and tobacco-related diseases is summarized from studies reporting smoking status. Collectively, data suggest that blood, urine, and tissue cadmium and cadmium/zinc ratios are often significantly different between smokers and nonsmokers and they are also different in smokers for several diseases and cancers. Additional biomonitoring data such as blood or serum and urine zinc and cadmium levels and cadmium/zinc ratios in smokers may provide further insight into the development and progression of diseases of the lung, cardiovascular system, and possibly other organs. PMID:28961214

  2. Cadmium and Cadmium/Zinc Ratios and Tobacco-Related Morbidities.

    Science.gov (United States)

    Richter, Patricia; Faroon, Obaid; Pappas, R Steven

    2017-09-29

    Metals are one of five major categories of carcinogenic or toxic constituents in tobacco and tobacco smoke. Cadmium is highly volatile and a higher percentage of the total tobacco cadmium content is efficiently transferred to mainstream tobacco smoke than many other toxic metals in tobacco. Inhaled cadmium bioaccumulates in the lungs and is distributed beyond the lungs to other tissues, with a total body biological half-life of one to two decades. Chronic cadmium exposure through tobacco use elevates blood and urine cadmium concentrations. Cadmium is a carcinogen, and an inducer of proinflammatory immune responses. Elevated exposure to cadmium is associated with reduced pulmonary function, obstructive lung disease, bronchogenic carcinoma, cardiovascular diseases including myocardial infarction, peripheral arterial disease, prostate cancer, cervical cancer, pancreatic cancer, and various oral pathologies. Cadmium and zinc have a toxicologically inverse relationship. Zinc is an essential element and is reportedly antagonistic to some manifestations of cadmium toxicity. This review summarizes associations between blood, urine, and tissue cadmium concentrations with emphasis on cadmium exposure due to tobacco use and several disease states. Available data about zinc and cadmium/zinc ratios and tobacco-related diseases is summarized from studies reporting smoking status. Collectively, data suggest that blood, urine, and tissue cadmium and cadmium/zinc ratios are often significantly different between smokers and nonsmokers and they are also different in smokers for several diseases and cancers. Additional biomonitoring data such as blood or serum and urine zinc and cadmium levels and cadmium/zinc ratios in smokers may provide further insight into the development and progression of diseases of the lung, cardiovascular system, and possibly other organs.

  3. Cadmium and Cadmium/Zinc Ratios and Tobacco-Related Morbidities

    Directory of Open Access Journals (Sweden)

    Patricia Richter

    2017-09-01

    Full Text Available Metals are one of five major categories of carcinogenic or toxic constituents in tobacco and tobacco smoke. Cadmium is highly volatile and a higher percentage of the total tobacco cadmium content is efficiently transferred to mainstream tobacco smoke than many other toxic metals in tobacco. Inhaled cadmium bioaccumulates in the lungs and is distributed beyond the lungs to other tissues, with a total body biological half-life of one to two decades. Chronic cadmium exposure through tobacco use elevates blood and urine cadmium concentrations. Cadmium is a carcinogen, and an inducer of proinflammatory immune responses. Elevated exposure to cadmium is associated with reduced pulmonary function, obstructive lung disease, bronchogenic carcinoma, cardiovascular diseases including myocardial infarction, peripheral arterial disease, prostate cancer, cervical cancer, pancreatic cancer, and various oral pathologies. Cadmium and zinc have a toxicologically inverse relationship. Zinc is an essential element and is reportedly antagonistic to some manifestations of cadmium toxicity. This review summarizes associations between blood, urine, and tissue cadmium concentrations with emphasis on cadmium exposure due to tobacco use and several disease states. Available data about zinc and cadmium/zinc ratios and tobacco-related diseases is summarized from studies reporting smoking status. Collectively, data suggest that blood, urine, and tissue cadmium and cadmium/zinc ratios are often significantly different between smokers and nonsmokers and they are also different in smokers for several diseases and cancers. Additional biomonitoring data such as blood or serum and urine zinc and cadmium levels and cadmium/zinc ratios in smokers may provide further insight into the development and progression of diseases of the lung, cardiovascular system, and possibly other organs.

  4. Curcumin-induced histone acetylation inhibition improves stress-induced gastric ulcer disease in rats.

    Science.gov (United States)

    He, Ping; Zhou, Renmin; Hu, Guorui; Liu, Zhifeng; Jin, Yu; Yang, Guang; Li, Mei; Lin, Qian

    2015-03-01

    Curcumin is known to possess anti‑inflammatory properties. Despite the fact that curcumin is known to be a strong inhibitor of H+, K+‑ATPase activity, the mechanism underlying the curcumin‑induced inhibition of the transcription of the H+, K+‑ATPase α subunit in gastric mucosal parietal cells remains unclear. The present study investigated the possible mechanism by which curcumin inhibits stomach H+, K+‑ATPase activity during the acute phase of gastric ulcer disease. A rat model of stress‑induced gastric ulcers was produced, in which the anti‑ulcer effects of curcumin were examined. Curcumin‑induced inhibition of the H+, K+‑ATPase promoter via histone acetylation, was verified using a chromatin immunoprecipitation assay. The results showed that curcumin improved stress‑induced gastric ulcer disease in rats, as demonstrated by increased pH values and reduced gastric mucosal hemorrhage and ulcer index. These effects were accompanied by a significant reduction in the level of histone H3 acetylation at the site of the H+, K+‑ATPase promoter and in the expression of the gastric H+,K+‑ATPase α subunit gene and protein. In conclusion, curcumin downregulated the acetylation of histone H3 at the site of the H+, K+‑ATPase promoter gene, thereby inhibiting the transcription and expression of the H+, K+‑ATPase gene. Curcumin was shown to have a preventive and therapeutic effect in gastric ulcer disease.

  5. Impact of cadmium, cobalt and nickel on sequence-specific DNA binding of p63 and p73 in vitro and in cells

    Energy Technology Data Exchange (ETDEWEB)

    Adámik, Matej [Institute of Biophysics, Academy of Science of the Czech Republic, v.v.i., Královopolská 135, 612 65 Brno (Czech Republic); Bažantová, Pavla [Institute of Biophysics, Academy of Science of the Czech Republic, v.v.i., Královopolská 135, 612 65 Brno (Czech Republic); Department of Biology and Ecology, Faculty of Science, University of Ostrava, Chittussiho 10, 701 03 Ostrava (Czech Republic); Navrátilová, Lucie; Polášková, Alena [Institute of Biophysics, Academy of Science of the Czech Republic, v.v.i., Královopolská 135, 612 65 Brno (Czech Republic); Pečinka, Petr [Institute of Biophysics, Academy of Science of the Czech Republic, v.v.i., Královopolská 135, 612 65 Brno (Czech Republic); Department of Biology and Ecology, Faculty of Science, University of Ostrava, Chittussiho 10, 701 03 Ostrava (Czech Republic); Holaňová, Lucie [Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackého 1/3, 61242 Brno (Czech Republic); Tichý, Vlastimil [Institute of Biophysics, Academy of Science of the Czech Republic, v.v.i., Královopolská 135, 612 65 Brno (Czech Republic); Brázdová, Marie, E-mail: maruska@ibp.cz [Institute of Biophysics, Academy of Science of the Czech Republic, v.v.i., Královopolská 135, 612 65 Brno (Czech Republic); Department of Chemical Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences, Palackého 1/3, 61242 Brno (Czech Republic)

    2015-01-02

    Highlights: • DNA binding of p53 family core domains is inhibited by cadmium, cobalt and nickel. • Binding to DNA protects p53 family core domains from metal induced inhibition. • Cadmium, cobalt and nickel induced inhibition was reverted by EDTA in vitro. - Abstract: Site-specific DNA recognition and binding activity belong to common attributes of all three members of tumor suppressor p53 family proteins: p53, p63 and p73. It was previously shown that heavy metals can affect p53 conformation, sequence-specific binding and suppress p53 response to DNA damage. Here we report for the first time that cadmium, nickel and cobalt, which have already been shown to disturb various DNA repair mechanisms, can also influence p63 and p73 sequence-specific DNA binding activity and transactivation of p53 family target genes. Based on results of electrophoretic mobility shift assay and luciferase reporter assay, we conclude that cadmium inhibits sequence-specific binding of all three core domains to p53 consensus sequences and abolishes transactivation of several promoters (e.g. BAX and MDM2) by 50 μM concentrations. In the presence of specific DNA, all p53 family core domains were partially protected against loss of DNA binding activity due to cadmium treatment. Effective cadmium concentration to abolish DNA–protein interactions was about two times higher for p63 and p73 proteins than for p53. Furthermore, we detected partial reversibility of cadmium inhibition for all p53 family members by EDTA. DTT was able to reverse cadmium inhibition only for p53 and p73. Nickel and cobalt abolished DNA–p53 interaction at sub-millimolar concentrations while inhibition of p63 and p73 DNA binding was observed at millimolar concentrations. In summary, cadmium strongly inhibits p53, p63 and p73 DNA binding in vitro and in cells in comparison to nickel and cobalt. The role of cadmium inhibition of p53 tumor suppressor family in carcinogenesis is discussed.

  6. In Vitro Inhibition of Human Sperm Creatine Kinase by Nicotine,Cotinine and Cadmium, as a Mechanism in Smoker Men Infertility

    OpenAIRE

    Mohammad Ali Ghaffari; Mohammad Abromand; Behrooz Motlagh

    2009-01-01

    Background: Nicotine, cotinine and cadmium are harmful components of cigarettes that have aneffect on human reproductive function. Although the effects of cigarette smoke on male reproductivefunction is characterized in several articles its mechanism of action is still unknown.In the present study, we investigate the effect of nicotine, cotinine and cadmium on human spermcreatine kinase activity in vitro.Materials and Methods: Total creatine kinase activity is measured in sperm homogenates af...

  7. Fast cadmium inhibition of photosynthesis in cyanobacteria in vivo and in vitro studies using perturbed angular correlation of gamma-rays.

    Science.gov (United States)

    Sas, Klára Nárcisz; Kovács, László; Zsíros, Ottó; Gombos, Zoltán; Garab, Gyozo; Hemmingsen, Lars; Danielsen, Eva

    2006-09-01

    The effect of cadmium on the photosynthetic activity of Synechocystis PCC 6803 was monitored in this study. The oxygen evolving capacity of Synechocystis treated with 40 muM CdCl(2) was depressed to 10% of the maximum in 15 min, indicating that Cd(2+) penetrated rapidly into the cells and blocked the photosynthetic activity. However, neither photosystem II (PSII) nor photosystem I (PSI) activity showed a significant short-term decrease which would explain this fast decrease in the whole-chain electron transport. Thermoluminescence measurements have shown that the charge separation and stabilization in PSII remains essentially unchanged during the first few hours following the Cd(2+) treatment. The electron flow through PSI was monitored by following the redox changes of the P700 reaction centers of PSI. Alterations in the oxidation kinetics of P700 in the Cd(2+)-treated cells indicated that Cd(2+) treatment might affect the available electron acceptor pool of P700, including the CO(2) reduction and accumulation in the cells. Perturbed angular correlation of gamma-rays (PAC) using the radioactive (111m)Cd isotope was used to follow the Cd(2+) uptake at a molecular level. The most plausible interpretation of the PAC data is that Cd(2+) is taken up by one or more Zn proteins replacing Zn(2+) in Synechocystis PCC 6803. Using the radioactive (109)Cd isotope, a protein of approximately 30 kDa that binds Cd(2+) could be observed in sodium dodecyl sulfate polyacrylamide gel electrophoresis. The results indicate that Cd(2+) might inactivate different metal-containing enzymes, including carbonic anhydrase, by replacing the zinc ion, which would explain the rapid and almost full inhibition of the photosynthetic activity in cyanobacteria.

  8. Dose-response analysis of cadmium-induced tubular proteinuria. A study of urinary. beta. /sub 2/-microglobulin excretion among workers in a battery factory

    Energy Technology Data Exchange (ETDEWEB)

    Kjellstroem, T. (Karolinska Inst. and National Environment Protection Board, Stockholm); Evrin, P.E.; Rahnster, B.

    1977-04-01

    The study covered 240 male and female workers exposed to cadmium oxide and nickel hydroxide dust in a Swedish battery factory. The control group comprised 87 unexposed males. Air samples from the plant showed the present exposure level to be about 50 ..mu..g Cd/m/sup 3/ air. Cadmium-induced effects were studied by measuring urinary ..beta../sub 2/-microglobulin excretion. Urinary ..beta../sub 2/-microglobulin concentration followed a log-normal distribution in the reference group with a geometric mean of 84 ..mu..g/liter (adjusted to a specific gravity of 1.023). In the group of 185 persons continuously exposed to cadmium dust in the work environment, the prevalence of increased urinary ..beta../sub 2/-microglobulin excretion increased with employment time. The prevalence was 19% for the workers with 6-12 years of exposure to about 50 ..mu..g Cd/m/sup 3/ as compared to 3% for those in the reference group. Smokers had about three times higher prevalence than nonsmokers.

  9. In vivo study of cadmium-induced chromsomal changes in somatic and germinal tissue of C57BI/6J male mice

    Energy Technology Data Exchange (ETDEWEB)

    Felten, T.L.

    1978-08-01

    The objectives of this study were to determine if cadmium would induce chromosomal aberration, to determine if simultaneous aberration events occurred in somatic and germinal tissue, and to determine an estimated minimum exposure time required for significant chromosomal change. Bone marrow chromosome aberrations, specifically breaks and deletions, were found to increase after acute cadmium exposure both at MTD and normal exposure levels. Subacute exposure also resulted in increased occurrences of breaks, deletions, and despiralization. With longer in vivo exposure to cadmium, bone marrow cells continued to show increased numbers of breaks, as well as a physiological effect, despiralization, and more severe break-related aberrations; rearrangements and pulverization. In spermatocytes of the same animals, gaps, breaks, rearrangements, stickiness, and autosomal univalents were the principle aberrations. Correlation of bone marrow and spermatocyte aberrations indicated that in treated mice significant relationships existed for gaps, breaks, rearrangements, and stickiness in the tissues. An estimate of the minimum exposure time to produce chromosomal damage, based on the acute exposure experiment, would be 6 hours for bone marrow. This was confirmed by the exposure duration experiment. Spermatocytes also had chromosomal damage within 24 hours.

  10. Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin–cadmium induced diabetic nephrotoxic rats

    Energy Technology Data Exchange (ETDEWEB)

    Kandasamy, Neelamegam; Ashokkumar, Natarajan, E-mail: npashokkumar1@gmail.com

    2014-09-01

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)–cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ–Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ–Cd induced diabetic nephrotoxic rats. - Highlights: • Diabetic rats are more susceptible to cadmium nephrotoxicity. • Cadmium plays as a cumulative

  11. Arginase Inhibition Reverses Monocrotaline-Induced Pulmonary Hypertension

    Directory of Open Access Journals (Sweden)

    Christian Jung

    2017-07-01

    Full Text Available Pulmonary hypertension (PH is a heterogeneous disorder associated with a poor prognosis. Thus, the development of novel treatment strategies is of great interest. The enzyme arginase (Arg is emerging as important player in PH development. The aim of the current study was to determine the expression of ArgI and ArgII as well as the effects of Arg inhibition in a rat model of PH. PH was induced in 35 Sprague–Dawley rats by monocrotaline (MCT, 60 mg/kg as single-dose. There were three experimental groups: sham-treated controls (control group, n = 11, MCT-induced PH (MCT group, n = 11 and MCT-induced PH treated with the Arg inhibitor Nω-hydroxy-nor-l-arginine (nor-NOHA; MCT/NorNoha group, n = 13. ArgI and ArgII expression was determined by immunohistochemistry and Western blot. Right ventricular systolic pressure (RVPsys was measured and lung tissue remodeling was determined. Induction of PH resulted in an increase in RVPsys (81 ± 16 mmHg compared to the control group (41 ± 15 mmHg, p = 0.002 accompanied by a significant elevation of histological sum-score (8.2 ± 2.4 in the MCT compared to 1.6 ± 1.6 in the control group, p < 0.001. Both, ArgI and ArgII were relevantly expressed in lung tissue and there was a significant increase in the MCT compared to the control group (p < 0.01. Arg inhibition resulted in a significant reduction of RVPsys to 52 ± 19 mmHg (p = 0.006 and histological sum-score to 5.8 ± 1.4 compared to the MCT group (p = 0.022. PH leads to increased expression of Arg. Arg inhibition leads to reduction of RVPsys and diminished lung tissue remodeling and therefore represents a potential treatment strategy in PH.

  12. Salidroside inhibits endogenous hydrogen peroxide induced cytotoxicity of endothelial cells.

    Science.gov (United States)

    Zhao, Xingyu; Jin, Lianhai; Shen, Nan; Xu, Bin; Zhang, Wei; Zhu, Hongli; Luo, Zhengli

    2013-01-01

    Salidroside, a phenylpropanoid glycoside isolated from Rhodiola rosea L., shows potent antioxidant property. Herein, we investigated the protective effects of salidroside against hydrogen peroxide (H2O2)-induced oxidative damage in human endothelial cells (EVC-304). EVC-304 cells were incubated in the presence or absence of low steady states of H2O2 (3-4 µM) generated by glucose oxidase (GOX) with or without salidroside. 3(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) assays were performed, together with Hoechst 33258 staining and flow cytometric analysis using Annexin-V and propidium iodide (PI) label. The results indicated that salidroside pretreatment attenuated endogenous H2O2 induced apoptotic cell death in EVC-304 cells in a dose-dependent pattern. Furthermore, Western blot data revealed that salidroside inhibited activation of caspase-3, 9 and cleavage of poly(ADP-ribose) polymerase (PARP) induced by endogenous H2O2. It also decreased the expression of Bax and rescued the balance of pro- and anti-apoptotic proteins. All these results demonstrated that salidroside may present a potential therapy for oxidative stress in cardiovascular and cerebrovascular diseases.

  13. Soluble Moringa oleifera leaf extract reduces intracellular cadmium accumulation and oxidative stress in Saccharomyces cerevisiae.

    Science.gov (United States)

    Kerdsomboon, Kittikhun; Tatip, Supinda; Kosasih, Sattawat; Auesukaree, Choowong

    2016-05-01

    Moringa oleifera leaves are a well-known source of antioxidants and traditionally used for medicinal applications. In the present study, the protective action of soluble M. oleifera leaf extract (MOLE) against cadmium toxicity was investigated in the model eukaryote Saccharomyces cerevisiae. The results showed that this extract exhibited a protective effect against oxidative stress induced by cadmium and H2O2 through the reduction of intracellular reactive oxygen species. Interestingly, not only the co-exposure of soluble MOLE with cadmium but also pretreatment of this extract prior to cadmium exposure significantly reduced the cadmium uptake through an inhibition of Fet4p, a low-affinity iron(II) transporter. In addition, the supplementation of soluble MOLE significantly reduced intracellular iron accumulation in a Fet4p-independent manner. Our findings suggest the potential use of soluble extract from M. oleifera leaves as a dietary supplement for protection against cadmium accumulation and oxidative stress. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  14. Gingerol-induced hypoxia-inducible factor 1 alpha inhibits human prion peptide-mediated neurotoxicity.

    Science.gov (United States)

    Jeong, Jae-Kyo; Moon, Myung-Hee; Park, Yang-Gyu; Lee, Ju-Hee; Lee, You-Jin; Seol, Jae-Won; Park, Sang-Youel

    2013-08-01

    Prion diseases are a family member of neurodegenerative disorders caused by the accumulation of misfolded-prion proteins (scrapie form of PrP, PrP(Sc)). The accumulation of PrP(Sc) in the brain leads to neurotoxicity by the induction of mitochondrial-apoptotic pathways. Recent studies implicated gingerol in protection against neurodegeneration. However, the basis of the neuroprotection in prion disease remains unclear. Thus, we investigated the influence of gingerol on prion peptide-induced neuronal damage. Gingerol blocked PrP(106-126)-mediated neurotoxicity by protecting mitochondrial function. Moreover, the protective effect of gingerol against PrP(106-126)-induced mitochondrial damage was associated with hypoxia-inducible factor 1 alpha (HIF-1α) expression. Gingerol-induced HIF-1α expression inhibited the PrP(106-126)-induced mitochondrial dysfunction. On the other hand, inhibition of gingerol-induced HIF-1 α expression attenuated the gingerol-mediated neuroprotective effect. Here, we demonstrate for the first time that treatment with gingerol prevents prion peptide-mediated neuronal cell death and that the neuroprotection is induced by HIF-1α-mediated signals. This study suggests that treatment with gingerol may provide a novel therapeutic strategy for prion-mediated neurotoxicity. Copyright © 2012 John Wiley & Sons, Ltd.

  15. Effects of Arctium lappa on Cadmium-Induced Damage to the Testis and Epididymis of Adult Wistar Rats.

    Science.gov (United States)

    Predes, Fabricia de Souza; Diamante, M A S; Foglio, M A; Dolder, H

    2016-10-01

    The protective role of Arctium lappa (AL) on the testes of rats acutely exposed to cadmium (Cd) was tested. The rats were randomly divided into a control group (C-group) and three major experimental groups, which were further subdivided into minor groups (n = 6) according to the experimental period (7 or 56 days). The C-group was subdivided into C-7 and C-56 [receiving a single saline solution, intraperitoneal (i.p.), on the first day]; the AL-group, AL-7, and AL-56, received AL extract (300 mg/kg/daily); the Cd group, Cd-7 and Cd-56, received a single i.p. dose of CdCl2 (1.2 mg/kg body weight (BW)) on the first day; the CdAL group, CdAL-7 and CdAL-56, received the same Cd dose, followed by AL extract. Water or AL extract was administered daily by gavage. After either 7 or 56 days, the testis and accessory glands were removed after whole-body perfusion. Exposure to Cd and CdAL decreased the weight of the testis and epididymis, the gonadosomatic index, seminiferous tubular (ST) diameter, and ST volumetric proportion, and increased the volumetric proportion of interstitium after 56 days. In the epididymis caput, the tubular volumetric proportion decreased along with an increase of interstitial volumetric proportion and epithelium height after 56 days. The alterations observed were less severe only after 7 days. A progressive testicular damage resulted mainly in tubules lined only by Sertoli cells. The sperm number and cell debris decreased in the epididymis. We demonstrated that the testicular damage induced by single acute i.p. exposure to Cd occurred despite the daily oral intake of AL extract.

  16. Cadmium-induced anemia in growing pigs: protective effect of oral or parenteral iron

    Energy Technology Data Exchange (ETDEWEB)

    Pond, W.G.; Walker, E.F. Jr.; Kirtland, D.

    1973-01-01

    Forty-two weanling Yorkshire pigs were used in two experiments to determine the effect of oral or injected Fe on the anemia and growth depression induced by dietary Cd. In both experiments 154 ppm Cd (as CdCl/sub 2/) added to a corn-soybean meal diet significantly (P < .01) depressed hemoglobin; in experiment 2, daily weight gain and feed consumption were significantly (P < .01) depressed by Cd. The depression in hemoglobin induced by Cd was prevented by oral (400 ppm Fe as FeSO/sub 4/ 7H/sub 2/O) or intramuscular (800 mg Fe as iron dextrin) Fe (experiment 1) or by intramuscular (1000 mg Fe as iron dextrin) Fe (experiment 2). Daily weight gain of pigs fed the basal diet was not significantly different from that of pigs fed Cd when Fe was injected (experiment 2). Oral Fe was incorporated into the feed throughout the experiment; parenteral Fe was administered as a single intramuscular injection on day 1 of each experiment. The protective effect of Fe on Cd-induced anemia observed previously in the rat is apparently operative in the pig as well.

  17. Proteolytic pathways induced by herbicides that inhibit amino acid biosynthesis.

    Directory of Open Access Journals (Sweden)

    Amaia Zulet

    Full Text Available The herbicides glyphosate (Gly and imazamox (Imx inhibit the biosynthesis of aromatic and branched-chain amino acids, respectively. Although these herbicides inhibit different pathways, they have been reported to show several common physiological effects in their modes of action, such as increasing free amino acid contents and decreasing soluble protein contents. To investigate proteolytic activities upon treatment with Gly and Imx, pea plants grown in hydroponic culture were treated with Imx or Gly, and the proteolytic profile of the roots was evaluated through fluorogenic kinetic assays and activity-based protein profiling.Several common changes in proteolytic activity were detected following Gly and Imx treatment. Both herbicides induced the ubiquitin-26 S proteasome system and papain-like cysteine proteases. In contrast, the activities of vacuolar processing enzymes, cysteine proteases and metacaspase 9 were reduced following treatment with both herbicides. Moreover, the activities of several putative serine protease were similarly increased or decreased following treatment with both herbicides. In contrast, an increase in YVADase activity was observed under Imx treatment versus a decrease under Gly treatment.These results suggest that several proteolytic pathways are responsible for protein degradation upon herbicide treatment, although the specific role of each proteolytic activity remains to be determined.

  18. Irreversible inhibition of RANK expression as a possible mechanism for IL-3 inhibition of RANKL-induced osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Khapli, Shruti M.; Tomar, Geetanjali B.; Barhanpurkar, Amruta P.; Gupta, Navita; Yogesha, S.D.; Pote, Satish T. [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India); Wani, Mohan R., E-mail: mohanwani@nccs.res.in [National Center for Cell Science, University of Pune Campus, Pune 411 007 (India)

    2010-09-03

    Research highlights: {yields} IL-3 inhibits receptor activator of NF-{kappa}B ligand (RANKL)-induced osteoclastogenesis. {yields} IL-3 inhibits RANKL-induced JNK activation. {yields} IL-3 down-regulates expression of c-Fos and NFATc1 transcription factors. {yields} IL-3 down-regulates RANK expression posttranscriptionally and irreversibly. {yields} IL-3 inhibits in vivo RANK expression. -- Abstract: IL-3, a cytokine secreted by activated T lymphocytes, stimulates the proliferation, differentiation and survival of pluripotent hematopoietic stem cells. In this study, we investigated the mechanism of inhibitory action of IL-3 on osteoclast differentiation. We show here that IL-3 significantly inhibits receptor activator of NF-{kappa}B (RANK) ligand (RANKL)-induced activation of c-Jun N-terminal kinase (JNK). IL-3 down-regulates expression of c-Fos and nuclear factor of activated T cells (NFATc1) transcription factors. In addition, IL-3 down-regulates RANK expression posttranscriptionally in both purified osteoclast precursors and whole bone marrow cells. Furthermore, the inhibitory effect of IL-3 on RANK expression was irreversible. Interestingly, IL-3 inhibits in vivo RANK expression in mice. Thus, we provide the first evidence that IL-3 irreversibly inhibits RANK expression that results in inhibition of important signaling molecules induced by RANKL.

  19. Gastrokine 1 inhibits gastrin-induced cell proliferation.

    Science.gov (United States)

    Kim, Olga; Yoon, Jung Hwan; Choi, Won Suk; Ashktorab, Hassan; Smoot, Duane T; Nam, Suk Woo; Lee, Jung Young; Park, Won Sang

    2016-04-01

    Gastrokine 1 (GKN1) acts as a gastric tumor suppressor. Here, we investigated whether GKN1 contributes to the maintenance of gastric mucosal homeostasis by regulating gastrin-induced gastric epithelial cell growth. We assessed the effects of gastrin and GKN1 on cell proliferation in stable AGS(GKN1) and MKN1(GKN1) gastric cancer cell lines and HFE-145 nonneoplastic epithelial cells. Cell viability and proliferation were analyzed by MTT and BrdU incorporation assays, respectively. Cell cycle and expression of growth factor receptors were examined by flow cytometry and Western blot analyses. Gastrin treatment stimulated a significant time-dependent increase in cell viability and proliferation in AGS(mock) and MKN1(mock), but not in HFE-145, AGS(GKN1), and MKN1(GKN1), cells, which stably expressed GKN1. Additionally, gastrin markedly increased the S-phase cell population, whereas GKN1 significantly inhibited the effect of gastrin by regulating the expression of G1/S cell-cycle regulators. Furthermore, gastrin induced activation of the NF-kB and β-catenin signaling pathways and increased the expression of CCKBR, EGFR, and c-Met in AGS and MKN1 cells. However, GKN1 completely suppressed these effects of gastrin via downregulation of gastrin/CCKBR/growth factor receptor expression. Moreover, GKN1 reduced gastrin and CCKBR mRNA expression in AGS and MKN1 cells, and there was an inverse correlation between GKN1 and gastrin, as well as between GKN1 and CCKBR mRNA expression in noncancerous gastric mucosae. These data suggest that GKN1 may contribute to the maintenance of gastric epithelial homeostasis and inhibit gastric carcinogenesis by downregulating the gastrin-CCKBR signaling pathway.

  20. Calcium, zinc and vitamin E ameliorate cadmium-induced renal oxidative damage in albino Wistar rats

    Directory of Open Access Journals (Sweden)

    Pradeepkiran Jangampalli Adi

    2016-01-01

    Full Text Available This study was aimed to examine the protective effects of supplementation with calcium + zinc (Ca + Zn or vitamin E (Vit-E on Cd-induced renal oxidative damage. Young albino Wistar rats (180 ± 10 g (n = 6 control rats, Cd, Cd + Ca + Zn, and Cd + Vit-E experimental groups and the experimental period was 30 days. Rats were exposed to Cd (20 mg/kg body weight alone treated as Cd treated group and the absence or presence of Ca + Zn (2 mg/kg each or Vit-E (20 mg/kg body weight supplementation treated as two separate groups. The activities of the stress marker enzymes superoxide dismutase (SOD, catalase (CAT, glutathione reductase (GR, glutathione peroxidase (GPx, glutathione-S-transferase (GST and lipid peroxidase (LPx were determined in renal mitochondrial fractions of experimental rats. We observed quantitative changes in SOD isoenzymatic patterns by non-denaturing PAGE analysis, and quantified band densities. These results showed that Cd exposure leads to decreases in SOD, CAT, GR, and GPx activities and a concomitant increase in LPx and GST activities. Ca + Zn and Vit-E administration with Cd significantly reversed Cd-induced perturbations in oxidative stress marker enzymes. However, Vit-E showed more inhibitory activity against Cd than did Ca + Zn, and it protected against Cd-induced nephrotoxicity.

  1. The Protective Roles of Zinc and Magnesium in Cadmium-Induced Renal Toxicity in Male Wistar Rats

    Directory of Open Access Journals (Sweden)

    Nasim Babaknejad

    2014-12-01

    Full Text Available Background: Cadmium (Cd is a heavy metal that has widespread use. It enters the food chain in different ways, including soil and water. Cadmium can cause dysfunction of different body organs. Zinc (Zn and magnesium (Mg supplementation can have protective effects against cadmium toxicity due to their antagonistic and antioxidants properties. This study examines the influence of supplemental Zn and Mg on Cd renal toxicity. Methods: Young male Wistar rats were divided into six groups of five. The Cd group received 1 mg Cd/kg and the control group received 0.5 mg/kg normal saline (i.p.. The other four groups were administered 1 mg/kg Cd+0.5 mg/kg Zn, 1 mg/kg Cd+1.5 mg/kg Zn, 1 mg/kg Cd+ 0.5 mg/kg Mg, and 1 mg/kg Cd+ 1.5 mg/kg Mg (i.p. for 21 days. Then, serum sodium, potassium, urea, creatinine, and protein levels were measured. Results: The results indicated that creatinine and protein levels decreased while urea, sodium, and potassium levels increased as a result of Cd exposure. Co-administered Cd and Zn and Mg decreased urea and increased sodium serum level in comparison to the cadmium group. Treatment by Mg, contrary to co-administered Cd and Zn, reduced serum protein level compared to the cadmium group. Compared to the cadmium treated group, Zn and Mg treatment enhanced serum creatinine level and reduced serum potassium level. Conclusion: The findings seem to suggest that zinc and magnesium compounds, due to their antagonistic and antioxidant activities, can protect Cd renal toxic effects in a dose-dependent manner.

  2. Cadmium-induced accumulation of putrescine in oat and bean leaves

    Science.gov (United States)

    Weinstein, L. H.; Kaur-Sawhney, R.; Rajam, M. V.; Wettlaufer, S. H.; Galston, A. W.

    1986-01-01

    The effects of Cd2+ on putrescine (Put), spermidine (Spd), and spermine (Spm) titers were studied in oat and bean leaves. Treatment with Cd2+ for up to 16 hours in the light or dark resulted in a large increase in Put titer, but had little or no effect on Spd or Spm. The activity of arginine decarboxylase (ADC) followed the pattern of Put accumulation, and experiments with alpha-difluoromethylarginine established that ADC was the enzyme responsible for Put increase. Concentrations of Cd2+ as low as 10 micromolar increased Put titer in oat segments. In bean leaves, there was a Cd(2+)-induced accumulation of Put in the free and soluble conjugated fractions, but not in the insoluble fraction. This suggests a rapid exchange between Put that exists in the free form and Put found in acid soluble conjugate forms. It is concluded that Cd2+ can act like certain other stresses (K+ and Mg2+ deficiency, excess NH4+, low pH, salinity, osmotic stress, wilting) to induce substantial increases in Put in plant cells.

  3. CADMIUM AND DIAZINON-INDUCED CHANGES IN THE RAT TESTIS STRUCTURE AFTER A PERORAL ADMINISTRATION IN DRIKING WATER

    OpenAIRE

    Róbert Toman; Mária Adamkovičová; Peter Massányi; Michal Cabaj; Norbert Lukáč; Monika Martiniaková; Radoslav Omelka

    2012-01-01

    The present study was carried out to elucidate the effects of heavy metal cadmium (Cd) and a nonselective organophosphorus insecticide diazinon (DZN) administration on the testis structures in adult male rats in subchronic toxicity experiments. A total of 40 Wistar 4 weeks old rats were randomized into 4 groups of 10 animals each and dosed with cadmium (Cd) 30 mg/l (group A), diazinon (DZN) 40 mg/l (group B), and in combination of Cd and DZN (30 and 40 mg/l, respectively, group C) per os in d...

  4. [Effects of cadmium on testis function].

    Science.gov (United States)

    Martynowicz, Helena; Skoczyńska, Anna; Karczmarek-Wdowiak, Beata; Andrzejak, Ryszard

    2005-01-01

    The deterioration of male fertility, reported in numerous epidemiological studies over past decades, can be connected with growing exposure to environmental toxins. Heavy metals, especially cadmium, is widely spread and extremely toxic. The mechanisms of cadmium toxic effects vary and involve the damage of vascular endothelium, intracellular junctions, germ cells, Leydig and Sertoli cells. Cadmium can increase activity of reactive oxygen species and induce changes in activity of enzymatic systems and inflammatory reactions. The morphological changes caused by cadmium included the necrosis of seminiferous tubiles and interstitial edema. This metal can reduce testosterone synthesis at various levels and deteriorate spermatogenesis. Cadmium is also acknowledged carcinogen with confirmed mutagenic and genotoxic activity. Increasing environmental exposure to cadmium, currently existing occupational exposure and the prevalence of tobacco smoking results in constant increase in the number of diagnosed fertility impairments.

  5. Agaricus blazei Murill Polysaccharides Protect Against Cadmium-Induced Oxidative Stress and Inflammatory Damage in Chicken Spleens.

    Science.gov (United States)

    Xie, Wanqiu; Lv, Ai; Li, Ruyue; Tang, Zequn; Ma, Dexing; Huang, Xiaodan; Zhang, Ruili; Ge, Ming

    2017-10-14

    Agaricus blazei Murill polysaccharide (ABP) has exhibited antioxidant and immunoregulatory activity. The aim of this study was to investigate the effect of ABP on cadmium (Cd)-induced antioxidant functions and inflammatory damage in chicken spleens. In this study, groups of 7-day-old chickens were fed with normal saline (0.2 mL single/day), CdCl2 (140 mg/kg/day), ABP (30 mg/mL, 0.2 mL single/day), and Cd + ABP (140 mg/kg/day + 0.2 mL ABP). Spleens were separated on the 20th, 40th, and 60th day for each group. The Cd contents, expression of melanoma-associated differentiation gene 5 (MDA5) and its downstream signaling molecules (interferon promoter-stimulating factor 1 (IPS-1), transcription factors interferon regulatory factor 3 (IRF3), and nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB)), the content of cytokines (interleukin 1β (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and beta interferon (IFN-β)), protein levels of heat shock proteins (HSPs), levels of malondialdehyde (MDA), activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and histopathological changes of spleens were detected on the 20th, 40th, and 60th day. The results showed that ABP significantly reduced the accumulation of Cd in the chicken spleens and reduced the expression of MDA5, IPS-1, IRF-3, and NF-κB; their downstream inflammatory cytokines, IL-1β, IL-6, TNF-α, and IFN-β; and the protein levels of HSPs (HSP60, HSP70, and HSP90) in spleens. The activities of antioxidant enzymes (SOD and GSH-Px) significantly increased, and the level of MDA decreased in the ABP + Cd group. The results indicate that ABP has a protective effect on Cd-induced damage in chicken spleens.

  6. Galactose inhibits auxin-induced growth of Avena coleoptiles by two mechanisms

    Science.gov (United States)

    Cheung, S. P.; Cleland, R. E.

    1991-01-01

    Galactose inhibits auxin-induced growth of Avena coleoptiles by at least two mechanisms. First, it inhibits auxin-induced H(+)-excretion needed for the initiation of rapid elongation. Galactose cannot be doing so by directly interfering with the ATPase since fusicoccin-induced H(+)-excretion is not affected. Secondly, galactose inhibits long-term auxin-induced growth, even in an acidic (pH 4.5) solution. This may be due to an inhibition of cell wall synthesis. However, galactose does not reduce the capacity of walls to be loosened by H+, given exogenously or excreted in response to fusicoccin.

  7. Puromycin induces SUMO and ubiquitin redistribution upon proteasome inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Hotaru [Course for Biological Sciences, Faculty of Science, Kumamoto University, Kumamoto (Japan); Saitoh, Hisato, E-mail: hisa@kumamoto-u.ac.jp [Course for Biological Sciences, Faculty of Science, Kumamoto University, Kumamoto (Japan); Department of Biological Sciences, Graduate School of Science and Technology, Kumamoto University, Kumamoto (Japan)

    2016-07-29

    We have previously reported the co-localization of O-propargyl-puromycin (OP-Puro) with SUMO-2/3 and ubiquitin at promyelocytic leukemia-nuclear bodies (PML-NBs) in the presence of the proteasome inhibitor MG132, implying a role for the ubiquitin family in sequestering OP-puromycylated immature polypeptides to the nucleus during impaired proteasome activity. Here, we found that as expected puromycin induced SUMO-1/2/3 accumulation with ubiquitin at multiple nuclear foci in HeLa cells when co-exposed to MG132. Co-administration of puromycin and MG132 also facilitated redistribution of PML and the SUMO-targeted ubiquitin ligase RNF4 concurrently with SUMO-2/3. As removal of the drugs from the medium led to disappearance of the SUMO-2/3-ubiquitin nuclear foci, our findings indicated that nuclear assembly/disassembly of SUMO-2/3 and ubiquitin was pharmacologically manipulable, supporting our previous observation on OP-Puro, which predicted the ubiquitin family function in sequestrating aberrant proteins to the nucleus. -- Highlights: •Puromycin exhibits the O-propargyl-puromycin effect. •Puromycin induces SUMO redistribution upon proteasome inhibition. •Ubiquitin and RNF4 accumulate at PML-nuclear bodies with SUMO-2/3. •The ubiquitin family may function in nuclear sequestration of immature proteins.

  8. Cadmium-induced changes in antioxidative systems and differentiation in roots of contrasted Medicago truncatula lines.

    Science.gov (United States)

    Rahoui, Sondès; Martinez, Yves; Sakouhi, Lamia; Ben, Cécile; Rickauer, Martina; El Ferjani, Ezzeddine; Gentzbittel, Laurent; Chaoui, Abdelilah

    2017-01-01

    Defense pathways and stress responses induced under Cd stress were illustrated in roots of hydroponically grown Medicago truncatula seedlings. Actually, the ascorbate-glutathione and antioxidative system, secondary metabolism events including peroxidases, phenolic compounds, and lignification launching, and developmental modifications were described. Cd (100 μM) initially increased reactive oxygen species, enhanced antioxidative (total SOD, CAT, and PRX) and ascorbate-glutathione-related metabolism enzymes (APX and MDAR), except in A17 and TN1.11. In agreement with peroxidase enhancement, physiological measurement and in situ observation illustrated soluble phenolic compound accumulation under Cd treatment. However, lignification was restricted to recently created protoxylem elements established in the root tip area, usually constituting the elongation zone. Cell death was increased. In the absence of necrotic reactions, developmental changes including lignin deposition, increase in cellulose and pectin contents, intercellular meatus, and condensed and deformed hairs were noticed in Cd-treated roots.

  9. Ligand displacement-induced fluorescence switch of quantum dots for ultrasensitive detection of cadmium ions

    Energy Technology Data Exchange (ETDEWEB)

    Hu, Xianyun [State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China); Qiannan Medical College for Nationalities, Duyun 558000 (China); Zhu, Kao; Guo, Qingsheng; Liu, Yuqian; Ye, Mingfu [State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China); Sun, Qingjiang, E-mail: sunqj@seu.edu.cn [State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China)

    2014-02-17

    Graphical abstract: -- Highlights: •A simple CdTe QD–Phen sensor is constructed for detecting Cd{sup 2+}. •The sensor is operated with a ligand-displacement induced PL switch strategy. •The detection limit of 0.01 nM for Cd{sup 2+} is achieved. •This sensor features to discriminate Cd{sup 2+} versus Zn{sup 2+}, and succeeds in real water samples. -- Abstract: This paper reports the construction of a simple CdTe quantum dots (QDs)-based sensor with 1,10-phenanthroline (Phen) as ligand, and the demonstration of a novel ligand displacement-induced fluorescence switch strategy for sensitive and selective detection of Cd{sup 2+} in aqueous phase. The complexation of Phen at the surface quenches the green photoluminescence (PL) of QDs dominated by a photoinduced hole transfer (PHT) mechanism. In the presence of Cd{sup 2+}, the Phen ligands are readily detached from the surface of CdTe QDs, forming [Cd(Phen){sub 2}(H{sub 2}O){sub 2}]{sup 2+} in solution, and as a consequence the PL of CdTe QDs switches on. The detection limit for Cd{sup 2+} is defined as ∼0.01 nM, which is far below the maximum Cd{sup 2+} residue limit of drinking water allowed by the U.S. Environmental Protection Agency (EPA). Two consecutive linear ranges allow a wide determination of Cd{sup 2+} from 0.02 nM to 0.6 μM. Importantly, this CdTe QDs-based sensor features to distinctly discriminate between Cd{sup 2+} and Zn{sup 2+}, and succeeds in real water samples. This extremely simple strategy reported here represents an attempt for the development of fluorescent sensors for ultrasensitive chemo/biodetection.

  10. Cadmium Toxicity to Ringed Seals (Phoca hispida)

    DEFF Research Database (Denmark)

    Sonne, Christian; Dietz, R.; Riget, F. F.

    Cadmium concentrations in kidneys from ringed seals (Phoca hispida) from North West Greenland (Qaanaaq) are high. Concentrations range at level known to induce renal toxic effects (mainly tubulopathy) and demineralisation (osteopenia) of the skeletal system (Fanconi's Syndrome) in humans as well...... the absence of toxic effects of cadmium in ringed seal...

  11. Celastrol inhibits TGF-β1-induced epithelial–mesenchymal transition by inhibiting Snail and regulating E-cadherin expression

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Hyereen; Lee, Minjae [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Jang, Sung-Wuk, E-mail: swjang@amc.seoul.kr [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of)

    2013-08-09

    Highlights: •We investigated the effects of celastrol on TGF-β1-induced EMT in epithelial cells. •Celastrol regulates TGF-β1-induced morphological changes and E-cadherin expression. •Celastrol inhibits TGF-β1-induced Snail expression. •Celastrol strongly suppresses TGF-β1-induced invasion in MDCK and A549 cells. -- Abstract: The epithelial–mesenchymal transition (EMT) is a pivotal event in the invasive and metastatic potentials of cancer progression. Celastrol inhibits the proliferation of a variety of tumor cells including leukemia, glioma, prostate, and breast cancer; however, the possible role of celastrol in the EMT is unclear. We investigated the effect of celastrol on the EMT. Transforming growth factor-beta 1 (TGF-β1) induced EMT-like morphologic changes and upregulation of Snail expression. The downregulation of E-cadherin expression and upregulation of Snail in Madin–Darby Canine Kidney (MDCK) and A549 cell lines show that TGF-β1-mediated the EMT in epithelial cells; however, celastrol markedly inhibited TGF-β1-induced morphologic changes, Snail upregulation, and E-cadherin expression. Migration and invasion assays revealed that celastrol completely inhibited TGF-β1-mediated cellular migration in both cell lines. These findings indicate that celastrol downregulates Snail expression, thereby inhibiting TGF-β1-induced EMT in MDCK and A549 cells. Thus, our findings provide new evidence that celastrol suppresses lung cancer invasion and migration by inhibiting TGF-β1-induced EMT.

  12. Life history changes in the benthic cladoceran Chydorus piger induced by low concentrations of sediment-bound cadmium

    NARCIS (Netherlands)

    Dekker, T.; Krips, O.E.; Admiraal, W.

    2002-01-01

    The effect of sediment-bound cadmium on several life history parameters of the benthic cladoceran Chydorus piger, was tested in the laboratory. It was investigated whether a test with C. piger is an ecologically realistic alternative for the Daphnia test applied to sediments. Therefore, a culture of

  13. RSK4 inhibition results in bypass of stress-induced and oncogene-induced senescence.

    Science.gov (United States)

    López-Vicente, Laura; Pons, Berta; Coch, Laura; Teixidó, Cristina; Hernández-Losa, Javier; Armengol, Gemma; Ramon Y Cajal, Santiago

    2011-04-01

    p90 Ribosomal S6 kinase (RSK) 4 is a serine-threonine kinase that belongs to the p90RSK family. RSK4 has been proposed as a tumor suppressor gene, related with anti-invasive activity, inhibition of the RAS-mitogen-activated protein kinase (MAPK) pathway and induction of senescence. Despite the related findings, little is known about RSK4 effectors. In human tumors, RSK4 is downregulated even in some benign lesions, such as colon adenomas and breast papillomas, indicating that RSK4 inhibition could be an early event in cellular transformation. For cells to achieve immortality and transformation, it is believed that they must override senescence. In the present study, we found that when RSK4 is inhibited in vitro using short hairpin RNA technology, cells can bypass stress-induced senescence and oncogene-induced senescence: normal human fibroblasts grew following oxidative stress, induction of DNA damage and KRAS(V12) or BRAF(E600) overexpression. To investigate the RSK4 effectors, we used short hairpin RNA or inhibitor molecules against major senescence mediators. We found that RSK4-induced senescence is mediated through p21, but is independent of p16, p38MAPKs and induction of reactive oxygen species, delimiting RSK4 signaling. These data support the importance of RSK4 for regulating senescence and indicate that downregulation of this kinase could be an important element in facilitating cell transformation.

  14. Oxidative stress in duckweed (Lemna minor L.) caused by short-term cadmium exposure

    Energy Technology Data Exchange (ETDEWEB)

    Razinger, Jaka [Department for Environmental Technologies and Biomonitoring, Institute of Physical Biology, Veliko Mlacevo 59, SI-1290 Grosuplje (Slovenia)], E-mail: jaka@ifb.si; Dermastia, Marina [National Institute of Biology, Vecna pot 111, p.p. 141, SI-1001 Ljubljana (Slovenia); Biotechnical Faculty, Department of Biology, University of Ljubljana, Vecna pot 111, SI-1000 Ljubljana (Slovenia); Koce, Jasna Dolenc [Biotechnical Faculty, Department of Biology, University of Ljubljana, Vecna pot 111, SI-1000 Ljubljana (Slovenia); Zrimec, Alexis [Department for Environmental Technologies and Biomonitoring, Institute of Physical Biology, Veliko Mlacevo 59, SI-1290 Grosuplje (Slovenia)

    2008-06-15

    The mechanisms of plant defence against cadmium toxicity have been studied by short-term exposure of Lemna minor L. (common duckweed) to concentrations of CdCl{sub 2} ranging from 0 to 500 {mu}M. High accumulation of cadmium was observed (12,320 {+-} 2155 {mu}g g{sup -1} at 500 {mu}M CdCl{sub 2}), which caused a gradual decrease of plant growth, increased lipid peroxidation, and weakened the entire antioxidative defence. Total glutathione concentration decreased significantly; however, the concentration of oxidized glutathione remained stable. The responses of four antioxidant enzymes showed that catalase was the most inhibited after CdCl{sub 2} exposure, ascorbate peroxidase and guaiacol peroxidase moderately, and glutathione reductase least. The total antioxidative potential revealed an induced antioxidative network at 0.1 {mu}M CdCl{sub 2} (137 {+-} 13.2% of the control) and its reduction to only 47.4 {+-} 4.0% of the control at higher cadmium concentrations. The possible application of the examined biomarkers in ecotoxicological research is discussed. - The increase of total antioxidative potential at low cadmium concentration is one of the mechanisms that helps duckweed to cope with cadmium-induced oxidative stress.

  15. Intravitreal itraconazole inhibits laser-induced choroidal neovascularization in rats.

    Directory of Open Access Journals (Sweden)

    Jeong Hun Bae

    Full Text Available Choroidal neovascularization (CNV is a major cause of severe visual loss in patients with age-related macular degeneration (AMD. Recently, itraconazole has shown potent and dose-dependent inhibition of tumor-associated angiogenesis. We evaluated the anti-angiogenic effect of itraconazole in a rat model of laser-induced CNV. After laser photocoagulation in each eye to cause CNV, right eyes were administered intravitreal injections of itraconazole; left eyes received balanced salt solution (BSS as controls. On day 14 after laser induction, fluorescein angiography (FA was used to assess abnormal vascular leakage. Flattened retinal pigment epithelium (RPE-choroid tissue complex was stained with Alexa Fluor 594-conjugated isolectin B4 to measure the CNV area and volume. Vascular endothelial growth factor receptor 2 (VEGFR2 mRNA and protein expression was determined 1, 4, 7, and 14 days after intravitreal injection by quantitative RT-PCR or Western blot. VEGF levels were analyzed by enzyme-linked immunosorbent assay (ELISA. Intravitreal itraconazole significantly reduced leakage from CNV as assessed by FA and CNV area and volume on flat mounts compared with intravitreal BSS (p = 0.002 for CNV leakage, p<0.001 for CNV area and volume. Quantitative RT-PCR showed significantly lower expression of VEGFR2 mRNA in the RPE-choroid complexes of itraconazole-injected eyes than those of BSS-injected eyes on days 7 and 14 (p = 0.003 and p = 0.006. Western blots indicated that VEGFR2 was downregulated after itraconazole treatment. ELISA showed a significant difference in VEGF level between itraconazole-injected and BSS-injected eyes on days 7 and 14 (p = 0.04 and p = 0.001. Our study demonstrated that intravitreal itraconazole significantly inhibited the development of laser-induced CNV in rats. Itraconazole had anti-angiogenic activity along with the reduction of VEGFR2 and VEGF levels. Itraconazole may prove beneficial for treating CNV as an alternative or

  16. Expression of lysophosphatidic acid receptor 1 and relation with cell proliferation, apoptosis, and angiogenesis on preneoplastic changes induced by cadmium chloride in the rat ventral prostate.

    Directory of Open Access Journals (Sweden)

    Riánsares Arriazu

    Full Text Available BACKGROUND: Lysophosphatidic acid (LPA is a phospholipid growth factor involved in cell proliferation, differentiation, migration, inflammation, angiogenesis, wound healing, cancer invasion, and survival. This study was directed to evaluate the immunoexpression of LPA-1, cell proliferation, apoptosis, and angiogenesis markers in preneoplastic lesions induced with cadmium chloride in rat prostate. METHODS: The following parameters were calculated in ventral prostate of normal rats and rats that received Cd in drinking water during 24 months: percentages of cells immunoreactive to LPA-1 (LILPA1, PCNA (LIPCNA, MCM7 (LIMCM7, ubiquitin (LIUBI, apoptotic cells (LIAPO, and p53 (LIp53; volume fraction of Bcl-2 (VFBcl-2; and length of microvessels per unit of volume (LVMV/mm3. Data were analyzed using Student's t-test and Pearson correlation test. RESULTS: The LILPA1 in dysplastic lesions and normal epithelium of Cd-treated rats was significantly higher than those in the control group. Markers of proliferation were significantly increased in dysplastic lesions, whereas some apoptotic markers were significantly decreased. No significant differences between groups were found in VFBcl-2. Dysplastic lesions showed a significant increase of LIp53. The length of microvessels per unit of volume was elevated in dysplastic acini. Statistically significant correlations were found only between LILPA1 and LIUBI. CONCLUSIONS: Our results suggest that LPA-1 might be implicated in dysplastic lesions induced by cadmium chloride development. More studies are needed to confirm its potential contribution to the disease.

  17. Cadmium(Cd)-induced oxidative stress down-regulates the gene expression of DNA mismatch recognition proteins MutS homolog 2 (MSH2) and MSH6 in zebrafish (Danio rerio) embryos

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Todd, E-mail: toddhsu@mail.ntou.edu.tw [Institute of Bioscience and Biotechnology and Center of Excellence for Marine Bioenvironment and Biotechnology, National Taiwan Ocean University, Keelung 20224, Taiwan (China); Huang, Kuan-Ming; Tsai, Huei-Ting; Sung, Shih-Tsung; Ho, Tsung-Nan [Institute of Bioscience and Biotechnology and Center of Excellence for Marine Bioenvironment and Biotechnology, National Taiwan Ocean University, Keelung 20224, Taiwan (China)

    2013-01-15

    DNA mismatch repair (MMR) of simple base mismatches and small insertion-deletion loops in eukaryotes is initiated by the binding of the MutS homolog 2 (MSH2)-MSH6 heterodimer to mismatched DNA. Cadmium (Cd) is a genotoxic heavy metal that has been recognized as a human carcinogen. Oxidant stress and inhibition of DNA repair have been proposed as major factors underlying Cd genotoxicity. Our previous studies indicated the ability of Cd to disturb the gene expression of MSH6 in zebrafish (Danio rerio) embryos. This study was undertaken to explore if Cd-induced oxidative stress down-regulated MSH gene activities. Following the exposure of zebrafish embryos at 1 h post fertilization (hpf) to sublethal concentrations of Cd at 3-5 {mu}M for 4 or 9 h, a parallel down-regulation of MSH2, MSH6 and Cu/Zn superoxide dismutase (Cu/Zn-SOD) gene expression was detected by real-time RT-PCR and the expression levels were 40-50% of control after a 9-h exposure. Cd exposure also induced oxidative stress, yet no inhibition of catalase gene activity was observed. Whole mount in situ hybridization revealed a wide distribution of msh6 mRNA in the head regions of 10 hpf embryos and pretreatment of embryos with antioxidants butylhydroxytoluene (BHT), D-mannitol or N-acetylcysteine (NAC) at 1-10 {mu}M restored Cd-suppressed msh6 expression. QPCR confirmed the protective effects of antioxidants on Cd-suppressed msh2/msh6 mRNA production. Down-regulated MSH gene activities reaching about 50% of control were also induced in embryos exposed to paraquat, a reactive oxygen species (ROS)-generating herbicide, or hydrogen peroxide at 200 {mu}M. Hence, Cd at sublethal levels down-regulates msh2/msh6 expression primarily via ROS as signaling molecules. The transcriptional activation of human msh6 is known to be fully dependent on the specificity factor 1 (Sp1). Cd failed to inhibit the DNA binding activity of zebrafish Sp1 unless at lethal concentrations based on band shift assay, therefore

  18. Protective role of metallothionein during regeneration in Eisenia andrei exposed to cadmium.

    Science.gov (United States)

    Rorat, Agnieszka; Vandenbulcke, Franck; Gałuszka, Adrianna; Klimek, Beata; Plytycz, Barbara

    2017-12-01

    Lumbricid earthworms are often exposed to simultaneous action of various environmental stressors like soil contamination, temperature fluctuation or predators' attacks, which may induce extrusion of coelomocyte-containing coelomic fluid or loss of tail segments. If the injuries are not lethal, renewal of the immune-competent cells and soluble components of coelomic fluid and/or the regeneration of tail segments occurs. The aim of our investigations was to test the hypothesis that exposure of adult earthworms Eisenia andrei to cadmium-polluted soil at room temperature (RT) and/or low temperature (6°C) have adverse effects on restoration of experimentally depleted coelomocytes or on regeneration of amputated posterior segments. Intact control earthworms and their experimental counterparts subjected to electrostimulation-induced coelomocyte depletion or surgical amputation of posterior segments were maintained either in control soil or in soil spiked with cadmium chloride (500mg/kg air-dried soil) at RT or 6°C. Four weeks after the beginning of experiments, cadmium accumulation in earthworm bodies was significantly lower at 6°C than at room temperature. The numbers of restored cells and fluorophore contents were hardly affected by temperature or cadmium. However, cocoon production was reduced by cadmium and completely abolished at 6°C and regeneration of amputated posterior segments was inhibited in cold but was enhanced by cadmium exposure at RT. Independently on the temperature, the 4-week cadmium exposure of adult earthworms was connected with significantly upregulated expression of Cd-metallothionein (but not of catalase, lysenin and phytochelatin) in coelomocytes. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Inhibition of zymosan-induced alternative complement pathway activation by concanavalin A.

    OpenAIRE

    Smith, M C; Pensky, J; Naff, G B

    1982-01-01

    Zymosan, a polysaccharide composed primarily of glucan and mannan residues, activates the complement system through the alternative complement pathway. We showed that zymosan-induced complement activation is inhibited by zymosan-bound lectins with carbohydrate specificities for mannosyl and glycosyl residues. Lectins unable to bind mannosyl or glucosyl residues did not inhibit zymosan-induced complement activation.

  20. Induced sterility for coyote control: effect of cadmium chloride on potential fertility of the male canis familiaris.

    Science.gov (United States)

    Thompson, L H

    1976-01-01

    6 mature male dogs were treated with .025 gm cadmium chloride in defibrinated pig blood for 10 consecutive days; 4 control dogs received the carrier only. Semen was collected by means of an artificial vagina and digital stimulation and a microscopic examination was performed immediately to estimate percent of motile spermatozoa and motility score. Histological examination of testicular tissue using a hematoxylin-eosin stain was made at the end of the experiment. The data were evaluated by analysis of variance. The health of the animals was not altered by cadmium ingestion. The potential fertility was not influenced either permanently or temporarily, spermatogenesis was normal, and there was no evidence of testicular atrophy. Greater doses may be more effective but problematic because of the emetic response. Enteric encapsulation may provide a means for administering larger and effective quantities orally in wild populations.

  1. Is oxidative stress related to cadmium accumulation in the Mollusc Crassostrea angulata?

    Energy Technology Data Exchange (ETDEWEB)

    Macías-Mayorga, Dayanara, E-mail: dayanara.macias@uleam.edu.ec [Instituto de Ciencias Marinas de Andalucía (CSIC), Campus Río San Pedro, S/N, 11510 Puerto Real, Cádiz (Spain); Departamento Central De Investigación (DCI), Universidad Laica Eloy Alfaro de Manabí, Vía San Mateo, Manta (Ecuador); Laiz, Irene [Departamento de Física Aplicada, Facultad de Ciencias del Mar y Ambientales, Universidad de Cádiz, Campus Río San Pedro, S/N, 11510 Puerto Real, Cádiz (Spain); Moreno-Garrido, Ignacio; Blasco, Julián [Instituto de Ciencias Marinas de Andalucía (CSIC), Campus Río San Pedro, S/N, 11510 Puerto Real, Cádiz (Spain)

    2015-04-15

    Highlights: • The cadmium accumulation in C. angulata tended toward a stationary state. • Metallothionein-like protein (MTLP) is clearly induced by Cd accumulation. • The MTLP detoxification mechanism is affected at high Cd concentrations. • Cadmium toxicity causes GSH levels to decrease and inhibits antioxidant enzymes. - Abstract: The kinetics of cadmium (Cd) accumulation in the gills and digestive gland of Crassotrea angulata at three concentrations of cadmium (0.088 μM, 0.44 μM and 2.22 μM) was monitored for 28 days. The relationship between accumulation and toxicity was studied using metallothionein-like protein (MTLP) concentration and reduced glutathione levels (GSH) as biochemical endpoints. The activity of enzymes which form part of the antioxidant defense system, in particular glutathione reductase (GR), total glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), as enzymatic endpoints, was also assessed. A first order kinetic model demonstrated that the accumulation process does not take place linearly, as the Cd concentration in gills and digestive gland tended toward a stationary state. Metallothionein-like protein is clearly induced by Cd accumulation; however, at high Cd concentrations the detoxification mechanism of this protein is affected. High Cd concentrations (2.22 μM) lead to a decrease in GSH levels, and also inhibit antioxidant enzyme activities, demonstrating the adverse effect of this metal on the antioxidant balance system.

  2. Stress response to cadmium and manganese in Paracentrotus lividus developing embryos is mediated by nitric oxide

    Energy Technology Data Exchange (ETDEWEB)

    Migliaccio, Oriana; Castellano, Immacolata [Laboratory of Cellular and Developmental Biology, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples (Italy); Romano, Giovanna [Laboratory of Functional and Evolutionary Ecology, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples (Italy); Palumbo, Anna, E-mail: anna.palumbo@szn.it [Laboratory of Cellular and Developmental Biology, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Naples (Italy)

    2014-11-15

    Highlights: • NO is produced in sea urchin embryos in response to cadmium and manganese. • Cadmium and manganese affect the expression of specific genes. • NO levels regulate directly or indirectly the expression of some metal-induced genes. • NO is proposed as a sensor of different stress agents in sea urchin embryos. - Abstract: Increasing concentrations of contaminants, often resulting from anthropogenic activities, have been reported to occur in the marine environment and affect marine organisms. Among these, the metal ions cadmium and manganese have been shown to induce developmental delay and abnormalities, mainly reflecting skeleton elongation perturbation, in the sea urchin Paracentrotus lividus, an established model for toxicological studies. Here, we provide evidence that the physiological messenger nitric oxide (NO), formed by L-arginine oxidation by NO synthase (NOS), mediates the stress response induced by cadmium and manganese in sea urchins. When NO levels were lowered by inhibiting NOS, the proportion of abnormal plutei increased. Quantitative expression of a panel of 19 genes involved in stress response, skeletogenesis, detoxification and multidrug efflux processes was followed at different developmental stages and under different conditions: metals alone, metals in the presence of NOS inhibitor, NO donor and NOS inhibitor alone. These data allowed the identification of different classes of genes whose metal-induced transcriptional expression was directly or indirectly mediated by NO. These results open new perspectives on the role of NO as a sensor of different stress agents in sea urchin developing embryos.

  3. Oridonin attenuates Aβ1-42-induced neuroinflammation and inhibits NF-κB pathway.

    Directory of Open Access Journals (Sweden)

    Sulei Wang

    Full Text Available Neuroinflammation induced by beta-amyloid (Aβ plays a critical role in the pathogenesis of Alzheimer's disease (AD, and inhibiting Aβ-induced neuroinflammation serves as a potential strategy for the treatment of AD. Oridonin (Ori, a compound of Rabdosia rubescens, has been shown to exert anti-inflammatory effects. In this study, we demonstrated that Ori inhibited glial activation and decreased the release of inflammatory cytokines in the hippocampus of Aβ1-42-induced AD mice. In addition, Ori inhibited the NF-κB pathway and Aβ1-42-induced apoptosis. Furthermore, Ori could attenuate memory deficits in Aβ1-42-induced AD mice. In conclusion, our study demonstrated that Ori inhibited the neuroinflammation and attenuated memory deficits induced by Aβ1-42, suggesting that Ori might be a promising candidate for AD treatment.

  4. Minocycline inhibits alkali burn-induced corneal neovascularization in mice.

    Directory of Open Access Journals (Sweden)

    Ou Xiao

    Full Text Available The purpose of this study was to investigate the effects of minocycline on alkali burn-induced corneal neovascularization (CNV. A total of 105 mice treated with alkali burns were randomly divided into three groups to receive intraperitoneal injections of either phosphate buffered saline (PBS or minocycline twice a day (60 mg/kg or 30 mg/kg for 14 consecutive days. The area of CNV and corneal epithelial defects was measured on day 4, 7, 10, and14 after alkali burns. On day 14, a histopathological examination was performed to assess morphological change and the infiltration of polymorphonuclear neutrophils (PMNs. The mRNA expression levels of vascular endothelial growth factor (VEGF and its receptors (VEGFRs, basic fibroblast growth factor (bFGF, matrix metalloproteinases (MMPs, interleukin-1α, 1β, 6 (IL-1α, IL-1β, IL-6 were analyzed using real-time quantitative polymerase chain reaction. The expression of MMP-2 and MMP-9 proteins was determined by gelatin zymography. In addition, enzyme-linked immunosorbent assay was used to analyze the protein levels of VEGFR1, VEGFR2, IL-1β and IL-6. Minocycline at a dose of 60 mg/kg or 30 mg/kg significantly enhanced the recovery of the corneal epithelial defects more than PBS did. There were significant decreases of corneal neovascularization in the group of high-dosage minocycline compared with the control group at all checkpoints. On day 14, the infiltrated PMNs was reduced, and the mRNA expression of VEGFR1, VEGFR2, bFGF, IL-1β, IL-6, MMP-2, MMP-9, -13 as well as the protein expression of VEGFR2, MMP-2, -9, IL-1β, IL-6 in the corneas were down-regulated with the use of 60 mg/kg minocycline twice a day. Our results showed that the intraperitoneal injection of minocycline (60 mg/kg b.i.d. can significantly inhibit alkali burn-induced corneal neovascularization in mice, possibly by accelerating corneal wound healing and by reducing the production of angiogenic factors, inflammatory cytokines and MMPs.

  5. Shock releases bile acid inducing platelet inhibition and fibrinolysis.

    Science.gov (United States)

    Wiener, Gregory; Moore, Hunter B; Moore, Ernest E; Gonzalez, Eduardo; Diamond, Scott; Zhu, Shu; D'Alessandro, Angelo; Banerjee, Anirban

    2015-05-15

    Metabolites are underappreciated for their effect on coagulation. Taurocholic acid (TUCA), a bile acid, has been shown to regulate cellular activity and promote fibrin sealant degradation. We hypothesize that TUCA impairs whole blood clot formation and promotes fibrinolysis. TUCA was exogenously added to whole blood obtained from volunteers. A titration from 250 μM-750 μM was used due to biologic relevance. Whole blood mixtures were assayed using thrombelastography for clot strength (maximum amplitude [MA]) and fibrinolysis (LY30) quantification. Tranexamic acid was used to block plasmin-mediated fibrinolysis. Platelet microfluidics were performed. A proteomic analysis was completed on citrated plasma obtained from a shock and resuscitation rat model. Fibrinolysis increased when 750-μM TUCA was added to whole blood (median LY30 0.08-5.7, P = 0.010) and clot strength decreased (median MA of 53.3-43.8, P = 0.010). The addition of tranexamic acid, to a 750-μM TUCA titration, partially reversed the induced fibrinolysis (LY30: without 7.7 versus with 2.7) and the decrease in clot strength (MA: without 48.2 versus with 53.2), but did not reverse the effects to whole blood levels. Platelet function reduced by 50% in the presence of 100-μM TUCA. Rats had a median 52-fold increase in TUCA, after a shock state that stayed elevated after resuscitation. TUCA reduces clot strength and promotes fibrinolysis. The clot strength reduction is attributable to platelet inhibition. This metabolic effect on coagulation warrants further investigation, as localized areas of the body, with high levels of bile acid, may be at risk for postoperative bleeding. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Gingival tissue-produced inhibition of platelet aggregation and the loss of inhibition in streptozotocin-induced diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Kawamura, Keiichiroh; Tamai, Kazuharu; Shirakawa, Masaharu; Okamoto, Hiroshi; Dohi, Toshihiro; Tsujimoto, Akira

    1988-01-01

    Addition of medium incubated with normal rat gingival tissue to platelet-rich plasma inhibited ADP-induced platelet aggregation. The ability of rat gingiva to produce activity inhibiting platelet aggregation was enhanced by the addition of arachidonic acid. Diabetic rat gingiva failed to inhibit platelet aggregation but did produce the anti-platelet aggregating activity in the presence of arachidonic acid. Indomethacin blocked the production of anti-platelet aggregating activity. There was no difference in conversion of (1-/sup 14/C)arachidonic acid to prostaglandins by normal and diabetic rat gingiva. These results suggest that an arachidonic acid metabolite released from gingiva during incubation inhibits platelet aggregation, and the synthesis of the metabolite is impaired in diabetic rat gingiva. A decrease in availability of arachidonic acid may be a causal factor of the defect in diabetic rat gingiva.

  7. Cadmium induced changes in Solidago chilensis Meyen (Asteraceae) grown on organically fertilized soil with reference to mycorrhizae, metabolism, anatomy and ultrastructure.

    Science.gov (United States)

    Pereira, Lidiane Silva; de Araújo, Romária Pereira; de Oliveira, Priscila Souza; da Silva, Leandro Dias; Alves, Patricia Alves Casaes; Fernandes, Valéria Ferreira; Gross, Eduardo

    2018-04-15

    Solidago chilensis Meyen (Asteraceae) is a medicinal important plant with few studies on nutrition and metabolism and none information on cadmium phytotoxicity. The objective of this study was to investigate Cd induced responses on the growth and metabolism in S. chilensis and on arbuscular mycorrhiza (AM). The experiment was carried out in a greenhouse, consisting of a 5 × 4 factorial with five doses of manure (0, 3.5, 7, 14 and 21gdm-3) and four doses of cadmium (0, 25, 50 and 75mgdm-3) applied to a Dystrophic Ultisol. After 250 days of plant cultivation, biomass, nutrient content, photosynthetic rate, guaiacol peroxidase activity, mycorrhizal colonization, glomalin content, anatomical and ultrastucture were evaluated. Plants were significantly affected by interaction of manure and Cd doses with anatomical, ultrastructural, physiological and nutritional modifications. Manure applied into Cd contaminated soil significantly improved mycorrhizal colonization and glomalin production. The highest organic manure dose (21gdm-3) alleviated toxicity symptoms of Cd on S. chilensis. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. GR1-like gene expression in Lycium chinense was regulated by cadmium-induced endogenous jasmonic acids accumulation.

    Science.gov (United States)

    Ma, Zhigang; An, Ting; Zhu, Xuerui; Ji, Jing; Wang, Gang; Guan, Chunfeng; Jin, Chao; Yi, Lingling

    2017-06-27

    The G1-like gene from the Lycium chinense was cloned and transferred into N. tabacum. Evidence showed that endogenous JA accumulation was crucial to LcGR gene expression in cadmium-stressed L. chinense. Glutathione reductase (GR) plays a vital role in glutathione-ascorbate metabolism and is a key enzyme in maintaining the redox state in plants. Jasmonic acids (JA) are important hormones regulating protective responses against bacteria and mechanic damage in plants. At present, the relationship between the endogenous JA accumulation, the glutathione (GSH) content and GR gene expression in plants under cadmium (Cd) stress has not been elucidated. This study primarily aims to explore their interconnected relations. First, we isolated the GR1-like gene from Lycium chinense (LcGR). Real-time PCR showed that gene LcGR and allene oxide cyclase (LcAOC) (a JA synthesis gene) expression in L. chinense plants was significantly enhanced by CdCl2 and reduced by CdCl2 cotreatment with 12,13-epoxy-octadecenoic acid (EOA), a JA synthesis inhibitor. Meanwhile, the JA content in plants strongly increased under Cd stress and decreased under Cd + EOA treatment, which was in accordance with expression pattern of LcAOC. The function of gene LcGR was confirmed in vitro with E. coli expression system. The subcellular localization in chloroplasts of LcGR gene was proved in Nicotiana tabacum leaves with transient transfection system of Agrobacterium tumefaciens. Furthermore, the overexpression of gene LcGR in the transgenic tabacum led to great Cd-tolerance and higher GSH accumulation. Overall, the results showed that the endogenous JA accumulation in Cd-stressed plants affects the GR expression which is crucial to the GSH accumulation and GSH-dependent tolerance to cadmium in LcGR transformants.

  9. Di(2-ethylhexyl) phthalate inhibits antral follicle growth, induces atresia, and inhibits steroid hormone production in cultured mouse antral follicles

    Energy Technology Data Exchange (ETDEWEB)

    Hannon, Patrick R., E-mail: phannon2@illinois.edu; Brannick, Katherine E., E-mail: kbran@illinois.edu; Wang, Wei, E-mail: Wei.Wang2@covance.com; Gupta, Rupesh K., E-mail: drrupesh@yahoo.com; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2015-04-01

    Di(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental toxicant found in consumer products that causes ovarian toxicity. Antral follicles are the functional ovarian units and must undergo growth, survival from atresia, and proper regulation of steroidogenesis to ovulate and produce hormones. Previous studies have determined that DEHP inhibits antral follicle growth and decreases estradiol levels in vitro; however, the mechanism by which DEHP elicits these effects is unknown. The present study tested the hypothesis that DEHP directly alters regulators of the cell cycle, apoptosis, and steroidogenesis to inhibit antral follicle functionality. Antral follicles from adult CD-1 mice were cultured with vehicle control or DEHP (1–100 μg/ml) for 24–96 h to establish the temporal effects of DEHP on the follicle. Following 24–96 h of culture, antral follicles were subjected to gene expression analysis, and media were subjected to measurements of hormone levels. DEHP increased the mRNA levels of cyclin D2, cyclin dependent kinase 4, cyclin E1, cyclin A2, and cyclin B1 and decreased the levels of cyclin-dependent kinase inhibitor 1A prior to growth inhibition. Additionally, DEHP increased the mRNA levels of BCL2-associated agonist of cell death, BCL2-associated X protein, BCL2-related ovarian killer protein, B-cell leukemia/lymphoma 2, and Bcl2-like 10, leading to an increase in atresia. Further, DEHP decreased the levels of progesterone, androstenedione, and testosterone prior to the decrease in estradiol levels, with decreased mRNA levels of side-chain cleavage, 17α-hydroxylase-17,20-desmolase, 17β-hydroxysteroid dehydrogenase, and aromatase. Collectively, DEHP directly alters antral follicle functionality by inhibiting growth, inducing atresia, and inhibiting steroidogenesis. - Highlights: • DEHP inhibits antral follicle growth by dysregulating cell cycle regulators. • DEHP induces antral follicle atresia by dysregulating apoptosis regulators. • DEHP

  10. Cadmium-mediated disruption of cortisol biosynthesis involves suppression of corticosteroidogenic genes in rainbow trout

    Energy Technology Data Exchange (ETDEWEB)

    Sandhu, Navdeep [Department of Biology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada); Vijayan, Mathilakath M., E-mail: mvijayan@uwaterloo.ca [Department of Biology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1 (Canada)

    2011-05-15

    Cadmium is widely distributed in the aquatic environment and is toxic to fish even at sublethal concentrations. This metal is an endocrine disruptor, and one well established role in teleosts is the suppression of adrenocorticotrophic hormone (ACTH)-stimulated cortisol biosynthesis by the interrenal tissue. However the mechanism(s) leading to this steroid suppression is poorly understood. We tested the hypothesis that cadmium targets genes encoding proteins critical for corticosteroid biosynthesis, including melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc), in rainbow trout (Oncorhynchus mykiss). To test this, head kidney slices (containing the interrenal tissues) were incubated in vitro with cadmium chloride (0, 10, 100 and 1000 nM) for 4 h either in the presence or absence of ACTH (0.5 IU/mL). In the unstimulated head kidney slices, cadmium exposure did not affect basal cortisol secretion and the mRNA levels of MC2R and P450scc, while StAR gene expression was significantly reduced. Cadmium exposure significantly suppressed ACTH-stimulated cortisol production in a dose-related fashion. This cadmium-mediated suppression in corticosteroidogenesis corresponded with a significant reduction in MC2R, StAR and P450scc mRNA levels in trout head kidney slices. The inhibition of ACTH-stimulated cortisol production and suppression of genes involved in corticosteroidogenesis by cadmium were completely abolished in the presence of 8-Bromo-cAMP (a cAMP analog). Overall, cadmium disrupts the expression of genes critical for corticosteroid biosynthesis in rainbow trout head kidney slices. However, the rescue of cortisol production as well as StAR and P450scc gene expressions by cAMP analog suggests that cadmium impact occurs upstream of cAMP production. We propose that MC2R signaling, the primary step in ACTH-induced cortocosteroidogenesis, is a key target for cadmium-mediated disruption of

  11. Could cadmium be responsible for some of the neurological signs and symptoms of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

    Science.gov (United States)

    Pacini, Stefania; Fiore, Maria G; Magherini, Stefano; Morucci, Gabriele; Branca, Jacopo J V; Gulisano, Massimo; Ruggiero, Marco

    2012-09-01

    According to the World Health Organization, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a neurological disease characterized by widespread inflammation and multi-systemic neuropathology. Aetiology and pathogenesis are unknown, and several agents have been proposed as causative agents or as factors perpetuating the syndrome. Exposure to heavy metals, with particular reference to mercury and gold in dental amalgams, has been considered among the triggers of ME/CFS. Here we hypothesize that cadmium, a widespread occupational and environmental heavy metal pollutant, might be associated with some of the neurological findings described in ME/CFS. In fact, ME/CFS patients show a decrease of the volume of the gray matter in turn associated with objective reduction of physical activity. Cadmium induces neuronal death in cortical neurons through a combined mechanism of apoptosis and necrosis and it could then be hypothesized that cadmium-induced neuronal cell death is responsible for some of the effects of cadmium on the central nervous system, i.e. a decrease in attention level and memory in exposed humans as well as to a diminished ability for training and learning in rats, that are symptoms typical of ME/CFS. This hypothesis can be tested by measuring cadmium exposure in a cohort of ME/CFS patients compared with matched healthy controls, and by measuring gray matter volume in un-exposed healthy controls, exposed non-ME/CFS subjects, un-exposed ME/CFS patients and exposed ME/CFS patients. In addition, we hypothesize that cadmium exposure could be associated with reduced cerebral blood flow in ME/CFS patients because of the disruptive effects of cadmium on angiogenesis. In fact, cadmium inhibits angiogenesis and low global cerebral flow is associated with abnormal brain neuroimaging results and brain dysfunction in the form of reduced cognitive testing scores in ME/CFS patients. This hypothesis can be tested by measuring cerebral cortex blood flow in un

  12. Acute metal stress in Populus tremula x P. alba (717-1B4 genotype): leaf and cambial proteome changes induced by cadmium 2+.

    Science.gov (United States)

    Durand, Thomas C; Sergeant, Kjell; Planchon, Sébastien; Carpin, Sabine; Label, Philippe; Morabito, Domenico; Hausman, Jean-François; Renaut, Jenny

    2010-02-01

    The comprehension of metal homeostasis in plants requires the identification of molecular markers linked to stress tolerance. Proteomic changes in leaves and cambial zone of Populus tremula x P. alba (717-1B4 genotype) were analyzed after 61 days of exposure to cadmium (Cd) 360 mg/kg soil dry weight in pot-soil cultures. The treatment led to an acute Cd stress with a reduction of growth and photosynthesis. Cd stress induced changes in the display of 120 spots for leaf tissue and 153 spots for the cambial zone. It involved a reduced photosynthesis, resulting in a profound reorganisation of carbon and carbohydrate metabolisms in both tissues. Cambial cells underwent stress from the Cd actually present inside the tissue but also a deprivation of photosynthates caused by leaf stress. An important tissue specificity of the response was observed, according to the differences in cell structures and functions.

  13. Experimental investigation and theoretical calculation of {sup 3}He-particle induced nuclear reactions on cadmium up to 27 MeV

    Energy Technology Data Exchange (ETDEWEB)

    Ali, B.M. [Physics Department (Cyclotron Facility), Nuclear Research Centre, Atomic Energy Authority, Cairo 13759 (Egypt); Al-Abyad, M., E-mail: alabyad_m@yahoo.com [Physics Department (Cyclotron Facility), Nuclear Research Centre, Atomic Energy Authority, Cairo 13759 (Egypt); Seddik, U. [Physics Department (Cyclotron Facility), Nuclear Research Centre, Atomic Energy Authority, Cairo 13759 (Egypt); El-Kameesy, S.U. [Physics Department, Faculty of Science, Ain Shams University, Cairo (Egypt); Ditrói, F.; Takács, S.; Tárkányi, F. [Institute for Nuclear Research, Hungarian Academy of Sciences (ATOMKI), Debrecen H4026 (Hungary)

    2014-02-15

    Excitation functions of {sup 3}He-particle induced nuclear reactions on natural cadmium were measured using the standard stacked foil technique and high resolution gamma-ray spectroscopy. From their threshold energies up to 27 MeV, cross-sections for {sup nat}Cd({sup 3}He,xn){sup 117m,113,111,110}Sn, {sup nat}Cd({sup 3}He,xnp){sup 117m,g,116m,115m,114m,113m,111,110m,g,109,108,107}In, and {sup nat}Cd({sup 3}He,X){sup 115g,111m}Cd reactions were measured. The nuclear codes TALYS, and EMPIRE-3,1 were used to describe the formation of these products. The present data were compared to theoretical results and to the available experimental data. Integral yields for some important radioisotopes were determined.

  14. The Co-Induced Effects of Molybdenum and Cadmium on the Trace Elements and the mRNA Expression Levels of CP and MT in Duck Testicles.

    Science.gov (United States)

    Xia, Bing; Chen, Hua; Hu, Guoliang; Wang, Liqi; Cao, Huabin; Zhang, Caiying

    2016-02-01

    To investigate the chronic toxicity of molybdenum (Mo) and cadmium (Cd) on the trace elements and the mRNA expression levels of ceruloplasmin (CP) and metallothionein (MT) in duck testicles, 120 healthy 11-day-old male ducks were randomly divided into six groups with 20 ducks in each group. Ducks were treated with the diet containing different dosages of Mo or Cd. The source of Mo and Cd was hexaammonium molybdate ([(NH4)6Mo7O24·4H2O]) and cadmium sulfate (3CdSO4·8H2O), respectively, in this study. After being treated for 60 and 120 days, ten male birds in each group were randomly selected and euthanized and then testicles were aseptically collected for determining the mRNA expression levels of MT and CP, antioxidant indexes, and contents of trace elements in the testicle. In addition, testicle tissues at 120 days were subjected to histopathological analysis with the optical microscope. The results showed that co-exposure to Mo and Cd resulted in an increase in malondialdehyde (MDA) level while decrease in xanthine oxidase (XOD) and catalase (CAT) activities. The mRNA expression level of MT gene was upregulated while CP was decreased in combination groups. Contents of Mo, copper (Cu), iron (Fe), and zinc (Zn) decreased in combined groups while Cd increased in Cd and combined groups at 120 days. Furthermore, severe congestion, low sperm count, and malformation were observed in low dietary of Mo combined with Cd group and high dietary of Mo combined with Cd group. Our results suggested that Mo and Cd might aggravate testicular degeneration synergistically through altering the mRNA expression levels of MT and CP, increasing lipid peroxidation through inhibiting related enzyme activities and disturbing homeostasis of trace elements in testicles. Interaction of Mo and Cd may have a synergistic effect on the testicular toxicity.

  15. Glucocorticoid Induced Leucine Zipper inhibits apoptosis of cardiomyocytes by doxorubicin

    Energy Technology Data Exchange (ETDEWEB)

    Aguilar, David; Strom, Joshua; Chen, Qin M., E-mail: qchen@email.arizona.edu

    2014-04-01

    Doxorubicin (Dox) is an indispensable chemotherapeutic agent for the treatment of various forms of neoplasia such as lung, breast, ovarian, and bladder cancers. Cardiotoxicity is a major concern for patients receiving Dox therapy. Previous work from our laboratory indicated that glucocorticoids (GCs) alleviate Dox-induced apoptosis in cardiomyocytes. Here we have found Glucocorticoid-Induced Leucine Zipper (GILZ) to be a mediator of GC-induced cytoprotection. GILZ was found to be induced in cardiomyocytes by GC treatment. Knocking down of GILZ using siRNA resulted in cancelation of GC-induced cytoprotection against apoptosis by Dox treatment. Overexpressing GILZ by transfection was able to protect cells from apoptosis induced by Dox as measured by caspase activation, Annexin V binding and morphologic changes. Western blot analyses indicate that GILZ overexpression prevented cytochrome c release from mitochondria and cleavage of caspase-3. When bcl-2 family proteins were examined, we found that GILZ overexpression causes induction of the pro-survival protein Bcl-xL. Since siRNA against Bcl-xL reverses GC induced cytoprotection, Bcl-xL induction represents an important event in GILZ-induced cytoprotection. Our data suggest that GILZ functions as a cytoprotective gene in cardiomyocytes. - Highlights: • Corticosteroids act as a cytoprotective agent in cardiomyocytes • Corticosteroids induce GILZ expression in cardiomyocytes • Elevated GILZ results in resistance against apoptosis induced by doxorubicin • GILZ induces Bcl-xL protein without inducing Bcl-xL mRNA.

  16. Fluoxetine-induced inhibition of synaptosomal ( sup 3 H)5-HT release: Possible Ca sup 2+ -channel inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Stauderman, K.A. (Marion Merrell Dow Research Inst., Cincinnati, OH (United States)); Gandhi, V.C.; Jones, D.J. (Univ. of Texas Health Science Center, San Antonio, TX (United States))

    1992-01-01

    Fluoxetine, a selective 5-Ht uptake inhibitor, inhibited 15 mM K{sup +}-induced ({sup 3}H)5-HT release from rat spinal cord and cortical synaptosomes at concentrations > 0.5 uM. This effect reflected a property shared by another selective 5-HT uptake inhibitor paroxetine but not by less selective uptake inhibitors such as amitriptyline, desipramine, imipramine or nortriptyline. Inhibition of release by fluoxetine was inversely related to both the concentration of K{sup +} used to depolarize the synaptosomes and the concentration of external Ca{sup 2+}. Experiments aimed at determining a mechanism of action revealed that fluoxetine did not inhibit voltage-independent release of ({sup 3}H)5-HT release induced by the Ca{sup 2+}-ionophore A 23187 or Ca{sup 2+}-independent release induced by fenfluramine. Moreover the 5-HT autoreceptor antagonist methiothepin did not reverse the inhibitory actions of fluoxetine on K{sup +}-induced release. Further studies examined the effects of fluoxetine on voltage-dependent Ca{sup 2+} channels and Ca{sup 2+} entry.

  17. Chronic waterborne zinc and cadmium exposures induced different responses towards oxidative stress in the liver of zebrafish

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jia-Lang, E-mail: zhengjialang@aliyun.com [National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan 316022 (China); Yuan, Shuang-Shuang; Wu, Chang-Wen [National Engineering Research Center of Marine Facilities Aquaculture, Zhejiang Ocean University, Zhoushan 316022 (China); Li, Wei-Ye [Zhoushan fisheries research institute, Zhoushan 316022 (China)

    2016-08-15

    Highlights: • Zn and Cd induced some differences in oxidative damage in the liver of zebrafish. • Zn and Cd enhanced expression of Cu/Zn-SOD and CAT through Nrf2 pathway. • Zn and Cd did not affected protein levels of CAT. • Cd inhibited biological activities of Cu/Zn-SOD and CAT proteins. • Zn stimulated activity and protein levels of Cu/Zn-SOD. - Abstract: Based on the same toxic level of 0.6% LC{sub 50} for 96-h and the severe situation of water pollution, we compared effects of chronic Zn (180 μg L{sup −1}) and Cd exposures (30 μg L{sup −1}) on growth, survival, histology, ultrastructure, and oxidative stress in the liver of zebrafish for 5 weeks. Growth performance and survival rate remained relatively constant under Zn stress, but was reduced under Cd exposure. Cd exposure also induced severe pyknotic nuclei, evident ultrastructure damage, and considerable lipid inclusions in the hepatocytes. However, these phenomena were not pronounced under Zn exposure. The negative effects caused by Cd may be explained by an increase in hepatic oxidative damage, as reflected by the enhanced levels of lipid peroxidation (LPO) and protein carbonylation (PC). The reduced activity of Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and catalase (CAT) may result in the enhanced hepatic oxidative damage, though the mRNA and protein levels of both genes increased and remained unchanged respectively. On the contrary, Zn up-regulated the levels of mRNA, protein and activity of Cu/Zn-SOD, which may contribute to the decreased LPO levels. Nonetheless, the sharply up-regulated mRNA levels of CAT did not induce an increase in the protein and activity levels of CAT under Zn stress. Furthermore, transcription factor NF-E2-related factor 2 (Nrf2) expression parelleled with its target genes, suggesting that Nrf2 is required for the protracted induction of antioxidant genes. In conclusion, our data demonstrated that essential and non-essential metals induced some differences in

  18. Oxidative stress, endocrine disruption, and malformation of Bufo gargarizans embryo exposed to sub-lethal cadmium concentrations.

    Science.gov (United States)

    Wu, Chao; Zhang, Yuhui; Chai, Lihong; Wang, Hongyuan

    2017-01-01

    Thyroid hormone (TH) is critical for vertebrate postembryonic development as well as embryonic development. Chinese toad (Bufo gargarizans) embryos were exposed to different concentrations of cadmium (5, 50, 100, 200 and 500μg Cd L-1) for 7days. Malformations were monitored daily, and growth and development of embryos were measured at day 4 and 7, and type 2 and 3 iodothyronine deiodinase (Dio2 and Dio3), thyroid hormone receptors (TRα and TRβ) mRNA levels were also measured to assess disruption of TH synthesis. In addition, superoxide dismutase (SOD), glutathione peroxidase (GPx) and heat shock proteins (HSPs) mRNA expression were examined to evaluate the ability of scavenging ROS. Our results demonstrated a bimodal inhibitory effect of Cd on the embryo growth and development of Bufo gargarizans. Reduced mean stage, total length and weight were observed at 5, 50, 200 and 500, but not at 100μg Cd L-1. Embryos malformation occurred in all cadmium treatments. Morphological abnormalities of embryos are characterized by axial flexures, abdominal edema, stunted growth and fin flexure. Real-time PCR results show that exposure to cadmium down-regulated TRα and Dio3 mRNA expression and up-regulated Dio2 mRNA level. SOD and GPx mRNA expression was significantly up-regulated after cadmium exposure. We concluded that cadmium could change mRNA expression of TRα, Dio2 and Dio3 leading the inhibition of growth and development of B. gargarizans embryo, which suggests that cadmium might have the endocrine-disrupting effect in embryos. Moreover, the reduced ability of scavenging ROS induced by cadmium might be responsible for the teratogenic effects of cadmium. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Murine strain differences and the effects of zinc on cadmium concentrations in tissues after acute cadmium exposure

    Energy Technology Data Exchange (ETDEWEB)

    King, L.M. [ARS USDA, Germplasm and Gamete Physiology Lab., Beltsville, MD (United States); Anderson, M.B. [Dept. of Anatomy, Tulane Univ. School of Medicine, New Orleans, LA (United States); Sikka, S.C. [Dept. of Urology, Tulane Univ. School of Medicine, New Orleans, LA (United States); George, W.J. [Dept. of Pharmacology, Tulane Univ. School of Medicine, New Orleans, LA (United States)

    1998-10-01

    The role of strain differences in cadmium tissue distribution was studied using sensitive (129/J) and resistant (A/J) mice. These murine strains have previously been shown to differ in their susceptibility to cadmium-induced testicular toxicity. Cadmium concentration was measured in testis, epididymis, seminal vesicle, liver, and kidney at 24 h after cadmium chloride exposure (4, 10, and 20 {mu}mol/kg CdCl{sub 2}). The 129/J mice exhibited a significant increase in cadmium concentration in testis, epididymis, and seminal vesicle at all cadmium doses used, compared to A/J mice. However, cadmium concentrations in liver and kidney were not different between the strains, at any dose, indicating that cadmium uptake is similar in these organs at 24 h. These murine strains demonstrate similar hepatic and renal cadmium uptake but significantly different cadmium accumulation in the reproductive organs at 24 h. The mechanism of the protective effect of zinc on cadmium toxicity was studied by assessing the impact of zinc acetate (ZnAc) treatment on cadmium concentrations in 129/J mice after 24 h. Zinc pretreatment (250 {mu}mol/kg ZnAc), given 24 h prior to 20 {mu}mol/kg CdCl{sub 2} administration, significantly decreased the amount of cadmium in the testis, epididymis, and seminal vesicle of 129/J mice, and significantly increased the cadmium content of the liver after 24 h. Cadmium levels in the kidney were unaffected at this time. Zinc pretreatment also prevented the cadmium-induced decrease in testicular sperm concentration and epididymal sperm motility seen in 129/J mice. These findings suggest that the differences in the two murine strains may be attributed partly to the differential accumulation of cadmium in murine gonads. This may be caused by strain differences in the specificity of cadmium transport mechanisms. The protective role of zinc in cadmium-induced testicular toxicity in the sensitive strain may be due to an interference in the cadmium uptake by susceptible

  20. CADMIUM AND DIAZINON-INDUCED CHANGES IN THE RAT TESTIS STRUCTURE AFTER A PERORAL ADMINISTRATION IN DRIKING WATER

    Directory of Open Access Journals (Sweden)

    Róbert Toman

    2012-10-01

    Full Text Available The present study was carried out to elucidate the effects of heavy metal cadmium (Cd and a nonselective organophosphorus insecticide diazinon (DZN administration on the testis structures in adult male rats in subchronic toxicity experiments. A total of 40 Wistar 4 weeks old rats were randomized into 4 groups of 10 animals each and dosed with cadmium (Cd 30 mg/l (group A, diazinon (DZN 40 mg/l (group B, and in combination of Cd and DZN (30 and 40 mg/l, respectively, group C per os in drinking water for 90 days. Testicular histology using a light microscopy and morphometry using PC morphometric software M.I.S. Quick Photo were evaluated. The morphometric data supported histological observations at tubular and interstitial level. Reduced seminiferous epithelium (P<0.001 in Cd group showed desquamation of germ cells, cellular degeneration and necrosis. Increase in epithelial vacuoles and dilated blood vessels relative volume (P<0.001 were observed in all experimental groups. Cd and DZN and their combination exerted changes in the reproductive parameters which could be subsequently negatively related to male fertility. These data provide a novel insight into the reproductive toxicology of Cd-DZN in male rats. However, results did not indicate synergistic or additional effect of simultaneous administration of both toxicants.

  1. Cadmium action in synapses in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Minami, Akira; Takeda, Atsushi; Nishibaba, Daisuke; Tekefuta, Sachiyo; Oku, Naoto [Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka (Japan)

    2001-05-01

    Chronic exposure to cadmium causes central nervous system disorders, e.g., olfactory dysfunction. To clarify cadmium toxicity in synaptic neurotransmission in the brain, the movement and action of cadmium in the synapses was examined using in vivo microdialysis. One and 24 h after injection of {sup 109}CdCl{sub 2} into the amygdala of rats, {sup 109}Cd release into the extracellular space was facilitated by stimulation with high K{sup +}, suggesting that cadmium taken up in amygdalar neurons is released into the synaptic clefts in a calcium- and impulse-dependent manner. To examine the action of cadmium in the synapses, the amygdala was perfused with artificial cerebrospinal fluid containing 10-30 {mu}M CdCl{sub 2}. The release of excitatory neurotransmitters, i.e., glutamate and aspartate, into the extracellular space was decreased during perfusion with cadmium, while the release of inhibitory neurotransmitters, i.e., glycine and {gamma}-amino butyric acid (GABA), into the extracellular space was increased during the period. These results suggest that cadmium released from the amygdalar neuron terminals affects the degree and balance of excitation-inhibition in synaptic neurotransmission. (author)

  2. (+-Naloxone inhibits morphine-induced chemotaxis via prevention of heat shock protein 90 cleavage in microglia

    Directory of Open Access Journals (Sweden)

    Ru-Yin Tsai

    2015-05-01

    Conclusion: Based on the findings of the present study, we suggest that (+-naloxone inhibits morphine-induced microglia activation by regulating HDAC6-dependent α-tubulin deacetylation and HSP90 fragmentation.

  3. Inhibition of Estrogen-induced Growth of Breast Cancer by Targeting Mitochondrial Oxidants

    National Research Council Canada - National Science Library

    Roy, Deodutta; Felty, Quentin; Kunkle, Brian

    2008-01-01

    ...) Anchorage-independent cell growth, and (c) tumor spheroid formation using new 3D HuBiogel bioassay whether estrogen induced conversion of normal cells to transformed cells is inhibited by treatment with antioxidants, over expression of MnSOD...

  4. Lithium ions induce prestalk-associated gene expression and inhibit prespore gene expression in Dictyostelium discoideum

    NARCIS (Netherlands)

    Peters, Dorien J.M.; Lookeren Campagne, Michiel M. van; Haastert, Peter J.M. van; Spek, Wouter; Schaap, Pauline

    1989-01-01

    We investigated the effect of Li+ on two types of cyclic AMP-regulated gene expression and on basal and cyclic AMP-stimulated inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) levels. Li+ effectively inhibits cyclic AMP-induced prespore gene expression, half-maximal inhibition occurring at about 2mM-LiCl.

  5. Virus inhibition induced by polyvalent nanoparticles of different sizes

    Science.gov (United States)

    Vonnemann, Jonathan; Sieben, Christian; Wolff, Christopher; Ludwig, Kai; Böttcher, Christoph; Herrmann, Andreas; Haag, Rainer

    2014-01-01

    The development of antiviral agents is one of the major challenges in medical science. So far, small monovalent molecular drugs that inhibit the late steps in the viral replication cycle, i.e., virus budding, have not worked well which emphasizes the need for alternative approaches. Polyvalently presented viral receptors, however, show potential as good inhibitors of virus-cell binding, which is the first step in the viral infection cycle. By gradually increasing the size of ligand functionalized gold nanoparticles, up to virus-like dimensions, we are now able to quantify the polyvalent enhancement of virus-cell binding inhibition and to identify varying mechanisms of virus inhibition with different efficacies: by employing a new binding assay we found that surface area-normalized polysulfated gold nanoparticles of diameters equal to and larger than the virus diameter (>50 nm) more efficiently inhibit the binding of vesicular stomatitis virus (VSV) to cells than smaller particles. On a per particle basis, larger sized gold nanoparticles were surprisingly shown to inhibit the viral infection up to two orders of magnitude more efficiently than smaller particles, which suggests different mechanisms of virus inhibition. Based on complementary electron microscopic data, we noticed that larger gold nanoparticles act as efficient cross-linkers between virions, whereas smaller gold nanoparticles decorate the surface of individual virus particles. Our systematic study accentuates the need for the design of biodegradable, virus-sized inhibitors capitalizing on polyvalent binding.The development of antiviral agents is one of the major challenges in medical science. So far, small monovalent molecular drugs that inhibit the late steps in the viral replication cycle, i.e., virus budding, have not worked well which emphasizes the need for alternative approaches. Polyvalently presented viral receptors, however, show potential as good inhibitors of virus-cell binding, which is the

  6. Novel Cadmium Resistance Determinant in Listeria monocytogenes.

    Science.gov (United States)

    Parsons, Cameron; Lee, Sangmi; Jayeola, Victor; Kathariou, Sophia

    2017-03-01

    Listeria monocytogenes is a foodborne pathogen that can cause severe disease (listeriosis) in susceptible individuals. It is ubiquitous in the environment and often exhibits resistance to heavy metals. One of the determinants that enables Listeria to tolerate exposure to cadmium is the cadAC efflux system, with CadA being a P-type ATPase. Three different cadA genes (designated cadA1 to cadA3) were previously characterized in L. monocytogenes A novel putative cadmium resistance gene (cadA4) was recently identified through whole-genome sequencing, but experimental confirmation for its involvement in cadmium resistance is lacking. In this study, we characterized cadA4 in L. monocytogenes strain F8027, a cadmium-resistant strain of serotype 4b. By screening a mariner-based transposon library of this strain, we identified a mutant with reduced tolerance to cadmium and that harbored a single transposon insertion in cadA4 The tolerance to cadmium was restored by genetic complementation with the cadmium resistance cassette (cadA4C), and enhanced cadmium tolerance was conferred to two unrelated cadmium-sensitive strains via heterologous complementation with cadA4C Cadmium exposure induced cadA4 expression, even at noninhibitory levels. Virulence assessments in the Galleria mellonella model suggested that a functional cadA4 suppressed virulence, potentially promoting commensal colonization of the insect larvae. Biofilm assays suggested that cadA4 inactivation reduced biofilm formation. These data not only confirm cadA4 as a novel cadmium resistance determinant in L. monocytogenes but also provide evidence for roles in virulence and biofilm formation.IMPORTANCEListeria monocytogenes is an intracellular foodborne pathogen causing the disease listeriosis, which is responsible for numerous hospitalizations and deaths every year. Among the adaptations that enable the survival of Listeria in the environment are the abilities to persist in biofilms, grow in the cold, and tolerate

  7. Inhibition of cullin RING ligases by cycle inhibiting factor: evidence for interference with Nedd8-induced conformational control.

    Science.gov (United States)

    Boh, Boon Kim; Ng, Mei Ying; Leck, Yee Chin; Shaw, Barry; Long, Jed; Sun, Guang Wen; Gan, Yunn Hwen; Searle, Mark S; Layfield, Robert; Hagen, Thilo

    2011-10-21

    Cycle inhibiting factor (Cif) is produced by pathogenic intracellular bacteria and injected into the host cells via a type III secretion system. Cif is known to interfere with the eukaryotic cell cycle by inhibiting the function of cullin RING E3 ubiquitin ligases (CRLs). Cullin proteins form the scaffold protein of CRLs and are modified with the ubiquitin-like protein Nedd8, which exerts important conformational control required for CRL activity. Cif has recently been shown to catalyze the deamidation of Gln40 in Nedd8 to Glu. Here, we addressed how Nedd8 deamidation inhibits CRL activity. Our results indicate that Burkholderia pseudomallei Cif (also known as CHBP) inhibits the deconjugation of Nedd8 in vivo by inhibiting binding of the deneddylating COP9 signalosome (CSN) complex. We provide evidence that the reduced binding of CSN and the inhibition of CRL activity by Cif are due to interference with Nedd8-induced conformational control, which is dependent on the interaction between the Nedd8 hydrophobic patch and the cullin winged-helix B subdomain. Of note, mutation of Gln40 to Glu in ubiquitin, an additional target of Cif, inhibits the interaction between the hydrophobic surface of ubiquitin and the ubiquitin-binding protein p62/SQSTM1, showing conceptually that Cif activity can impair ubiquitin/ubiquitin-like protein non-covalent interactions. Our results also suggest that Cif may exert additional cellular effects by interfering with the association between ubiquitin and ubiquitin-binding proteins. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Mutagenic effect of cadmium on tetranucleotide repeats in human cells

    Energy Technology Data Exchange (ETDEWEB)

    Slebos, Robbert J.C. [Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States) and Department of Otolaryngology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States)]. E-mail: r.slebos@vanderbilt.edu; Li Ming [Department of Biostatistics, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States); Evjen, Amy N. [Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States); Coffa, Jordy [Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States); Shyr, Yu [Department of Biostatistics, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States); Yarbrough, Wendell G. [Department of Cancer Biology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States); Department of Otolaryngology, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232 (United States)

    2006-12-01

    Cadmium is a human carcinogen that affects cell proliferation, apoptosis and DNA repair processes that are all important to carcinogenesis. We previously demonstrated that cadmium inhibits DNA mismatch repair (MMR) in yeast cells and in human cell-free extracts (H.W. Jin, A.B. Clark, R.J.C. Slebos, H. Al-Refai, J.A. Taylor, T.A. Kunkel, M.A. Resnick, D.A. Gordenin, Cadmium is a mutagen that acts by inhibiting mismatch repair, Nat. Genet. 34 (3) (2003) 326-329), but cadmium also inhibits DNA excision repair. For this study, we selected a panel of three hypermutable tetranucleotide markers (MycL1, D7S1482 and DXS981) and studied their suitability as readout for the mutagenic effects of cadmium. We used a clonal derivative of the human fibrosarcoma cell line HT1080 to assess mutation levels in microsatellites after cadmium and/or N-methyl-N-nitro-N-nitrosoguanidine (MNNG) exposure to study effects of cadmium in the presence or absence of base damage. Mutations were measured in clonally expanded cells obtained by limiting dilution after exposure to zero dose, 0.5 {mu}M cadmium, 5 nM MNNG or a combination of 0.5 {mu}M cadmium and 5 nM MNNG. Exposure of HT1080-C1 to cadmium led to statistically significant increases in microsatellite mutations, either with or without concurrent exposure to MNNG. A majority of the observed mutant molecules involved 4-nucleotide shifts consistent with DNA slippage mutations that are normally repaired by MMR. These results provide evidence for the mutagenic effects of low, environmentally relevant levels of cadmium in intact human cells and suggest that inhibition of DNA repair is involved.

  9. Inhibition of Inducible Nitric Oxide Synthase, Cycleooxygenase-2 ...

    African Journals Online (AJOL)

    HP

    Purpose: To explore the antioxidant properties of the methanol extract of Pericarpium Zanthoxyli and its effect on inducible nitric oxide synthase (iNOS), cycleooxygenase-2 (COX-2) and lipopolysaccharides (LPS)-induced cell damage in macrophage cells. Methods: Anti-oxidant activities were tested by measuring free ...

  10. Eleutheroside E inhibits doxorubicin-induced inflammation and ...

    African Journals Online (AJOL)

    Purpose: To identify the effects of eleutheroside E (EE) on apoptosis and inflammation induced by doxorubicin (DOX) in H9c2 cells and to investigate the underlying mechanisms. Methods: The effect of EE on H9c2 cell viability was determined using Cell Counting Kit-8 (CCK8). EE effect on DOX-induced apoptosis and ...

  11. ACE inhibition attenuates radiation-induced cardiopulmonary damage

    NARCIS (Netherlands)

    van der Veen, Sonja J.; Ghobadi, Ghazaleh; de Boer, Rudolf A; Faber, Hette; Cannon, Megan V; Nagle, Peter W; Brandenburg, Sytze; Langendijk, Johannes A; van Luijk, Peter; Coppes, Robert P

    BACKGROUND AND PURPOSE: In thoracic irradiation, the maximum radiation dose is restricted by the risk of radiation-induced cardiopulmonary damage and dysfunction limiting tumor control. We showed that radiation-induced sub-clinical cardiac damage and lung damage in rats mutually interact and that

  12. Trolox induces inhibition of cell proliferation and apoptosis in human colon cancer cells

    OpenAIRE

    Li-Guang Yang; Xiang-An Tian; Xiao-Yan Li; Jian-Guo Huang; Nai-Qing Liu; Qin-Li Sun

    2015-01-01

    In the present study, the effect of trolox on human colon cancer cell lines was investigated. The results revealed that trolox treatment caused inhibition of cell growth in T84 and HCT-15 colon cancer cell lines in a dose-dependent manner. The inhibition was significant at 50 µM of trolox after 48 hours in both cell lines. Trolox treatment promoted expression of p38 and inhibited expression of survivin and Akt. It also induced cleavage of PARP and caspase-3 and ultimately induced apoptosis in...

  13. Rapid long-wave infrared laser-induced breakdown spectroscopy measurements using a mercury-cadmium-telluride linear array detection system.

    Science.gov (United States)

    Yang, Clayton S-C; Brown, Eiei; Kumi-Barimah, Eric; Hommerich, Uwe; Jin, Feng; Jia, Yingqing; Trivedi, Sudhir; D'souza, Arvind I; Decuir, Eric A; Wijewarnasuriya, Priyalal S; Samuels, Alan C

    2015-11-20

    In this work, we develop a mercury-cadmium-telluride linear array detection system that is capable of rapidly capturing (∼1-5  s) a broad spectrum of atomic and molecular laser-induced breakdown spectroscopy (LIBS) emissions in the long-wave infrared (LWIR) region (∼5.6-10  μm). Similar to the conventional UV-Vis LIBS, a broadband emission spectrum of condensed phase samples covering the whole 5.6-10 μm region can be acquired from just a single laser-induced microplasma or averaging a few single laser-induced microplasmas. Atomic and molecular signature emission spectra of solid inorganic and organic tablets and thin liquid films deposited on a rough asphalt surface are observed. This setup is capable of rapidly probing samples "as is" without the need of elaborate sample preparation and also offers the possibility of a simultaneous UV-Vis and LWIR LIBS measurement.

  14. Protective Effects of Dietary Spirulina platensis against Cadmium-Induced Oxidative Stress in Gills of Rainbow Trout

    Directory of Open Access Journals (Sweden)

    Hamid Evaz-Zadeh Samani

    2017-06-01

    Full Text Available Background: Contamination of feeds with cadmium leads to oxidative stress in vital tissues such as gills and affects the fish survival. Therefore, an increase in the capacity of the antioxidant defense system and detoxification system of fish may reduce adverse effects of pollutants. This study investigated the protective effects of microalga Spirulina platensis against oxidative stress in gills of cadmium-treated rainbow trout. Methods: This study was conducted at Fish Farm, Almas-Dime Village, Koohrang, Charmahal & Bakhtiari Province, Iran from April to July 2016. Rainbow trout were allocated into five groups of which one group received normal feed and served as control. Fish from group II received 0.2 mg CdCl2 per 1 kg feed. Groups III-V were fed with enriched diet with 2.5, 5 and 10 g S. platensis per 1 kg feed, respectively and simultaneously treated with 0.2 mg kg-1 CdCl2 for 21 d. Changes in biochemical parameters including alanine aminotransferase (ALT, aspartate aminotransferase (AST, alkaline phosphatase (ALP and lactate dehydrogenase (LDH, malondialdehyde (MDA as marker of lipid peroxidation and cellular total antioxidant capacity were evaluated. Results: Oral exposure to CdCl2 caused a significant increase in MDA levels and altered AST, ALT, ALP and LDH activities in gills (P<0.05. The cellular antioxidant capacity was significantly lowered in CdCl2-treated fish as compared to the control group (P<0.05. Oral administration of S. platensis significantly ameliorated these changes in certain biochemical parameters in gills of CdCl2-treated fish. Conclusion: The findings indicate that S. platensis has protective effects against toxic influence of CdCl2 on certain biochemical parameters in gills of fish.

  15. Application of Cold-Induced Aggregation Microextraction Based on Ionic Liquid for Determination of Trace Amount of Cadmium and Lead in Powder Milk Samples

    Directory of Open Access Journals (Sweden)

    Mostafa Delavar

    2014-06-01

    Full Text Available Background: cold-induced aggregation micro extraction based (CIAME based on ionic liquid was used as a rapid and simple method for determination trace amounts of cadmium and lead in milk powder by analysis with flame atomic absorption spectrometry (FAAS. Methods: Sample solution containing of Cd2+ and Pb2+ in dynamic range, phosphate buffer (pH = 9, 3 ml, diethyl dithiocarbamate (complexing agent, Triton X-100, NaPF6 ,[HMIM][PF6] (extraction solvent were transferred into conical bottom glass tube. Sample was kept in a thermostated bath and then ice bath; a cloudy solution was formed. Two phases separated by centrifugation. After removing of aqueous phase, IL-phase was dissolved in methanol and diluted was injected to the FAAS by microsampler introduction. Results: ILs, containing imidazoliumcation and hexafluoro phosphate anion, [HMIM][PF6](70mg, 200 mg NaPF6 ,0.01 mol.L-1 DDTC, 0.015% of Triton X-100 obtained, pH 9 and centrifuge time; 5 min (4000 rmp was chosen. Detection limit were obtained 0.12 µgL-1, 1.61µgL-1, RSD 0.95%, 2.2% and enrichment factor of 70, 67 for Cd and Pb, respectively. Conclusion: CIAME allows determination of cadmium and lead in real samples in a simple, rapid and safe method with only a small amount of ionic liquid was used. In comparison with the organic solvent extraction, CIAME is much safer and the determination of species in high ionic strength samples is possible.

  16. Cadmium sulfide membranes

    Science.gov (United States)

    Spanhel, Lubomir; Anderson, Marc A.

    1991-10-22

    A method is described for the creation of novel q-effect cadmium sulfide membranes. The membranes are made by first creating a dilute cadmium sulfide colloid in aqueous suspension and then removing the water and excess salts therefrom. The cadmium sulfide membrane thus produced is luminescent at room temperature and may have application in laser fabrication.

  17. Anti-Apoptotic and Anti-Oxidant Effects of Caffeic Acid Phenethyl Ester on Cadmium-Induced Testicular Toxicity in Rats.

    Science.gov (United States)

    Erboga, Mustafa; Kanter, Mehmet; Aktas, Cevat; Bozdemir Donmez, Yeliz; Fidanol Erboga, Zeynep; Aktas, Emel; Gurel, Ahmet

    2016-05-01

    Cadmium (Cd) is a serious environmental and occupational contaminant and may represent a serious health hazard to humans and other animals. Cd is reported to induce the generation of reactive oxygen species, and induces testicular damage in many species of animals. The goal of our study was to examine the anti-apoptotic and anti-oxidant effects of caffeic acid phenethyl ester (CAPE) on Cd-induced oxidative stress, apoptosis, and testicular injury in rats. A total of 40 male Wistar albino rats were divided into four groups: control, CAPE alone, Cd-treated, and Cd-treated with CAPE; each group consisted of 10 animals. To induce toxicity, Cd (1 mg/kg body weight) was dissolved in normal saline and subcutaneously injected into rats for 30 days. The rats in CAPE-treated group were given a daily dose of 10 μmol/kg body weight of CAPE by using intraperitoneal injection. This application was continued daily for a total of 30 days. To date, no examinations of the anti-apoptotic and anti-oxidant properties of CAPE on Cd-induced apoptosis, oxidative damage, and testicular injury in rat testes have been reported. CAPE-treated animals showed an improved histological appearance and serum testosterone levels in Cd-treated group. Our data indicate a significant reduction in the number of apoptotic cells in testis tissues of the Cd-treated group with CAPE treatment. Moreover, CAPE significantly suppressed lipid peroxidation, compensated deficits in the anti-oxidant defenses in testes tissue resulted from Cd administration. These findings suggest that the protective potential of CAPE in Cd toxicity might be due to its anti-oxidant and anti-apoptotic properties, which could be useful for achieving optimum effects in Cd-induced testicular injury.

  18. Modulation of the stress response during apoptosis and necrosis induction in cadmium-treated U-937 human promonocytic cells.

    Science.gov (United States)

    Galán, A; Troyano, A; Vilaboa, N E; Fernández, C; de Blas, E; Aller, P

    2001-02-05

    Treatment for 2 h with 200 microM cadmium chloride, followed by recovery, caused apoptosis and induced heat-shock protein 70 (HSP70) expression in U-937 promonocytic cells. However, pre-incubation with the GSH depleting agent L-buthionine-[S,R]-sulfoximine (BSO, 1 mM for 24 h) caused necrosis instead of apoptosis and failed to induce HSP70 expression. This failure was a consequence of necrosis instead of GSH depletion, since BSO allowed or even potentiated HSP70 induction when used in combination with heat shock (2 h at 42.5 degrees C) or with 50 microM cadmium, which caused apoptosis. The administration of N-acetyl-L-cysteine (NAC) at the beginning of recovery after BSO/200 microM cadmium treatment prevented the execution of necrosis and restored the execution of apoptosis, but did not restore HSP70 induction, indicating that the inhibition by BSO of HSP70 expression is an early regulated event. This contrasted with the capacity of NAC to prevent the alterations caused by BSO/200 microM cadmium in other proteins, namely the suppression of Bax expression and the increase in Bcl-2 and HSP-60 expression. Finally, it was observed that treatment with 200 microM cadmium rapidly increased the HSP70 mRNA level and stimulated heat-shock factor 1 (HSF1) trimerization and binding, and that these effects were prevented by pre-incubation with BSO. Taken together, these results indicate that the stress response is compatible with apoptosis but not with necrosis in cadmium-treated promonocytic cells. The suppression of the stress response is specifically due to the early inhibition of HSF1 activation.

  19. Clonal cell populations unresponsive to radiosensitization induced by telomerase inhibition

    Energy Technology Data Exchange (ETDEWEB)

    Ju, Yeun-Jin; Shin, Hyun-Jin; Park, Jeong-Eun; Juhn, Kyoung-Mi; Woo, Seon Rang; Kim, Hee-Young; Han, Young-Hoon; Hwang, Sang-Gu; Hong, Sung-Hee; Kang, Chang-Mo [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Yoo, Young-Do [Laboratory of Molecular Cell Biology, Graduate School of Medicine, Korea University College of Medicine, Korea University, Seoul 136-705 (Korea, Republic of); Park, Won-Bong [Division of Natural Science, Seoul Women' s University, Seoul 139-774 (Korea, Republic of); Cho, Myung-Haing [Laboratory of Toxicology, College of Veterinary Medicine, Seoul National University, Seoul (Korea, Republic of); Park, Gil Hong, E-mail: ghpark@korea.ac.kr [Department of Biochemistry, College of Medicine, Korea University, Seoul (Korea, Republic of); Lee, Kee-Ho, E-mail: khlee@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2010-11-12

    Research highlights: {yields} In our present manuscript, we have clearly showed an interesting but problematic obstacle of a radiosensitization strategy based on telomerase inhibition by showing that: Clonal population unresponsive to this radiosensitization occasionally arise. {yields} The telomere length of unsensitized clones was reduced, as was that of most sensitized clones. {yields} The unsensitized clones did not show chromosome end fusion which was noted in all sensitized clones. {yields} P53 status is not associated with the occurrence of unsensitized clone. {yields} Telomere end capping in unsensitized clone is operative even under telomerase deficiency. -- Abstract: A combination of a radiotherapeutic regimen with telomerase inhibition is valuable when tumor cells are to be sensitized to radiation. Here, we describe cell clones unresponsive to radiosensitization after telomere shortening. After extensive division of individual transformed clones of mTERC{sup -/-} cells, about 22% of clones were unresponsive to radiosensitization even though telomerase action was inhibited. The telomere lengths of unsensitized mTERC{sup -/-} clones were reduced, as were those of most sensitized clones. However, the unsensitized clones did not exhibit chromosomal end-to-end fusion to the extent noted in all sensitized clones. Thus, a defense mechanism preventing telomere erosion is operative even when telomeres become shorter under conditions of telomerase deficiency, and results in unresponsiveness to the radiosensitization generally mediated by telomere shortening.

  20. Hepatoprotective activity of Moringa oleifera against cadmium toxicity in rats

    Directory of Open Access Journals (Sweden)

    Reetu Toppo

    2015-04-01

    Full Text Available Aim: The present investigation has been conducted to evaluate the hepatoprotective activity of Moringa oleifera against cadmium-induced toxicity in rats. Materials and Methods: For this study, 18 Wistar albino rats were taken. Control group, Group I rats were given cadmium chloride @ 200 ppm per kg and Group II rats were treated with M. oleifera extract @ 500 mg/kg along with cadmium chloride @ 200 ppm per kg (daily oral for 28 days. On 29th day, animals were slaughtered and various parameters were determined. Serum biomarkers, oxidative stress parameters, histomorphological examination were carried out with estimation of cadmium concentration in liver tissues. Results: Oral administration of cadmium chloride @ 200 ppm/kg for 28 days resulted in a significant increase in aspartate aminotransferase (AST, alanine transaminase (ALT, alkaline phosphatase (ALP, significant (p≤0.01 increase of lipid peroxidation (LPO and decrease in superoxide dismutase (SOD, and increase in cadmium accumulation in liver. Treatment with M. oleifera @ 500 mg/kg significantly (p<0.01 decreased the elevated ALP, AST, ALT, LPO levels and increase in SOD levels, and as compared to cadmium chloride treated group. However, there was no significant difference in cadmium concentration in liver when compared with cadmium chloride treated group. Conclusion: The study conclude that supplementation of M. oleifera (500 mg/kg, daily oral for 28 days has shown protection against cadmium-induced hepatotoxicity.

  1. Aspirin Inhibits Platelet-Derived Sphingosine-1-Phosphate Induced Endothelial Cell Migration.

    Science.gov (United States)

    Polzin, Amin; Knoop, Betül; Böhm, Andreas; Dannenberg, Lisa; Zurek, Mark; Zeus, Tobias; Kelm, Malte; Levkau, Bodo; Rauch, Bernhard H

    2018-01-01

    Aspirin plays a crucial role in the prevention of cardiovascular diseases. We previously described that aspirin has effects beyond inhibition of platelet aggregation, as it inhibited thrombin-mediated release of sphingosine-1-phosphate (S1P) from human platelets. S1P is a bioactive lipid with important functions on inflammation and apoptosis. In endothelial cells (EC), S1P is a key regulator of cell migration. In this study, we aimed to analyze the effects of aspirin on platelet-induced EC migration. Human umbilical EC migration was measured by Boyden chamber assay. EC migration was induced by platelet supernatants of thrombin receptor-activating peptide-1 (AP1) stimulated platelets. To investigate the S1P receptor subtype that promotes EC migration, specific inhibitors of S1P receptor subtypes were applied. S1P induced EC migration in a concentration-dependent manner. EC migration induced by AP1-stimulated platelet supernatants was reduced by aspirin. S1P1 receptor inhibition almost completely abolished EC migration induced by activated platelets. The inhibition of S1P2 or S1P3 receptor had no effect. Aspirin inhibits EC migration induced by activated platelets that is in part due to S1P and mediated by the endothelial S1P1 receptor. The clinical significance of this novel mechanism of aspirin action has to be investigated in future studies. © 2017 S. Karger AG, Basel.

  2. BMPR2 inhibition induced apoptosis and autophagy via destabilization of XIAP in human chondrosarcoma cells

    Science.gov (United States)

    Jiao, G; Guo, W; Ren, T; Lu, Q; Sun, Y; Liang, W; Ren, C; Yang, K; Sun, K

    2014-01-01

    Bone morphogenetic proteins (BMPs) are multifunctional proteins, and their receptors (BMPRs) have crucial roles in the process of signaling. However, their function in cancer is somewhat inconsistent. It has been demonstrated that more prevalent expression of bone morphogenetic protein receptor 2 (BMPR2) has been detected in dedifferentiated chondrosarcomas than conventional chondrosarcomas. Here, we find that BMPR2 inhibition induces apoptosis and autophagy of chondrosarcoma. We found that BMPR2 expression was correlated with the clinicopathological features of chondrosarcomas, and could predict the treatment outcome. Knockdown of BMPR2 by small interfering RNA results in growth inhibition in chondrosarcoma cells. Silencing BMPR2 promoted G2/M cell cycle arrest, induced chondrosarcoma cell apoptosis through caspase-3-dependent pathway via repression of X-linked inhibitor of apoptosis protein (XIAP) and induced autophagy of chondrosarcoma cells via XIAP-Mdm2-p53 pathway. Inhibition of autophagy induced by BMPR2 small interfering RNA (siBMPR2) sensitized chondrosarcoma cells to siBMPR2-induced apoptotic cell death, suggesting that autophagy has a protective role for chondrosarcoma cells in context of siBMPR2-induced apoptotic cell death. In vivo tumorigenicity assay in mice indicated that inhibition of BMPR2 reduced tumor growth. Taken together, our results suggest that BMPR2 has a significant role in the tumorigenesis of chondrosarcoma, and could be an important prognostic marker for chondrosarcoma. BMPR2 inhibition could eventually provide a promising therapy for chondrosarcoma treatment. PMID:25501832

  3. BMPR2 inhibition induced apoptosis and autophagy via destabilization of XIAP in human chondrosarcoma cells.

    Science.gov (United States)

    Jiao, G; Guo, W; Ren, T; Lu, Q; Sun, Y; Liang, W; Ren, C; Yang, K; Sun, K

    2014-12-11

    Bone morphogenetic proteins (BMPs) are multifunctional proteins, and their receptors (BMPRs) have crucial roles in the process of signaling. However, their function in cancer is somewhat inconsistent. It has been demonstrated that more prevalent expression of bone morphogenetic protein receptor 2 (BMPR2) has been detected in dedifferentiated chondrosarcomas than conventional chondrosarcomas. Here, we find that BMPR2 inhibition induces apoptosis and autophagy of chondrosarcoma. We found that BMPR2 expression was correlated with the clinicopathological features of chondrosarcomas, and could predict the treatment outcome. Knockdown of BMPR2 by small interfering RNA results in growth inhibition in chondrosarcoma cells. Silencing BMPR2 promoted G2/M cell cycle arrest, induced chondrosarcoma cell apoptosis through caspase-3-dependent pathway via repression of X-linked inhibitor of apoptosis protein (XIAP) and induced autophagy of chondrosarcoma cells via XIAP-Mdm2-p53 pathway. Inhibition of autophagy induced by BMPR2 small interfering RNA (siBMPR2) sensitized chondrosarcoma cells to siBMPR2-induced apoptotic cell death, suggesting that autophagy has a protective role for chondrosarcoma cells in context of siBMPR2-induced apoptotic cell death. In vivo tumorigenicity assay in mice indicated that inhibition of BMPR2 reduced tumor growth. Taken together, our results suggest that BMPR2 has a significant role in the tumorigenesis of chondrosarcoma, and could be an important prognostic marker for chondrosarcoma. BMPR2 inhibition could eventually provide a promising therapy for chondrosarcoma treatment.

  4. The PDE4 inhibitor CHF-6001 and LAMAs inhibit bronchoconstriction-induced remodeling in lung slices.

    Science.gov (United States)

    Kistemaker, Loes E M; Oenema, Tjitske A; Baarsma, Hoeke A; Bos, I Sophie T; Schmidt, Martina; Facchinetti, Fabrizio; Civelli, Maurizio; Villetti, Gino; Gosens, Reinoud

    2017-09-01

    Combination therapy of PDE4 inhibitors and anticholinergics induces bronchoprotection in COPD. Mechanical forces that arise during bronchoconstriction may contribute to airway remodeling. Therefore, we investigated the impact of PDE4 inhibitors and anticholinergics on bronchoconstriction-induced remodeling. Because of the different mechanism of action of PDE4 inhibitors and anticholinergics, we hypothesized functional interactions of these two drug classes. Guinea pig precision-cut lung slices were preincubated with the PDE4 inhibitors CHF-6001 or roflumilast and/or the anticholinergics tiotropium or glycopyorrolate, followed by stimulation with methacholine (10 μM) or TGF-β1 (2 ng/ml) for 48 h. The inhibitory effects on airway smooth muscle remodeling, airway contraction, and TGF-β release were investigated. Methacholine-induced protein expression of smooth muscle-myosin was fully inhibited by CHF-6001 (0.3-100 nM), whereas roflumilast (1 µM) had smaller effects. Tiotropium and glycopyrrolate fully inhibited methacholine-induced airway remodeling (0.1-30 nM). The combination of CHF-6001 and tiotropium or glycopyrrolate, in concentrations partially effective by themselves, fully inhibited methacholine-induced remodeling in combination. CHF-6001 did not affect airway closure and had limited effects on TGF-β1-induced remodeling, but rather, it inhibited methacholine-induced TGF-β release. The PDE4 inhibitor CHF-6001, and to a lesser extent roflumilast, and the LAMAs tiotropium and glycopyrrolate inhibit bronchoconstriction-induced remodeling. The combination of CHF-6001 and anticholinergics was more effective than the individual compounds. This cooperativity might be explained by the distinct mechanisms of action inhibiting TGF-β release and bronchoconstriction. Copyright © 2017 the American Physiological Society.

  5. Gliclazide directly inhibits arginine-induced glucagon release

    DEFF Research Database (Denmark)

    Cejvan, Kenan; Coy, David H; Holst, Jens Juul

    2002-01-01

    of gliclazide or was secondary to the paracrine effect of released somatostatin. To eliminate the paracrine effects of somatostatin, we first perfused isolated rat pancreata with a medium supplemented with 23% of the standard calcium content. Second, we perifused isolated rat islets with a novel and highly...... specific antagonist of type 2 somatostatin receptor, DC-41-33 (2 micro mol/l), which fully antagonizes the suppressive somatostatin effect on rat A cells. Gliclazide (30 micro mol/l) inhibited glucagon release by 54% in the perfusion experiments, whereas the somatostatin response was nearly abolished...

  6. Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition

    Science.gov (United States)

    Park, Dohyun; Jeong, Heeyoon; Lee, Mi Nam; Koh, Ara; Kwon, Ohman; Yang, Yong Ryoul; Noh, Jungeun; Suh, Pann-Ghill; Park, Hwangseo; Ryu, Sung Ho

    2016-01-01

    Resveratrol (RSV) is a natural polyphenol that has a beneficial effect on health, and resveratrol-induced autophagy has been suggested to be a key process in mediating many beneficial effects of resveratrol, such as reduction of inflammation and induction of cancer cell death. Although various resveratrol targets have been suggested, the molecule that mediates resveratrol-induced autophagy remains unknown. Here, we demonstrate that resveratrol induces autophagy by directly inhibiting the mTOR-ULK1 pathway. We found that inhibition of mTOR activity and presence of ULK1 are required for autophagy induction by resveratrol. In line with this mTOR dependency, we found that resveratrol suppresses the viability of MCF7 cells but not of SW620 cells, which are mTOR inhibitor sensitive and insensitive cancer cells, respectively. We also found that resveratrol-induced cancer cell suppression occurred ULK1 dependently. For the mechanism of action of resveratrol on mTOR inhibition, we demonstrate that resveratrol directly inhibits mTOR. We found that resveratrol inhibits mTOR by docking onto the ATP-binding pocket of mTOR (i.e., it competes with ATP). We propose mTOR as a novel direct target of resveratrol, and inhibition of mTOR is necessary for autophagy induction. PMID:26902888

  7. Postreceptor signal transduction mechanisms involved in octreotide-induced inhibition of angiogenesis.

    Science.gov (United States)

    Patel, P C; Barrie, R; Hill, N; Landeck, S; Kurozawa, D; Woltering, E A

    1994-12-01

    Somatostatin analogues inhibit peptide release and cell growth through multiple postreceptor signal transduction mechanisms (PRSTM), including G proteins (GP), cyclic adenosine monophosphate (cAMP), calcium, protein kinase C (PKC), and tyrosine phosphatase (TP). Octreotide acetate (OA), a somatostatin analogue, has been shown to inhibit angiogenesis; however, the PRSTM involved are unknown. Fertilized chicken eggs were obtained and incubated. On day 3, embryos were removed and placed in plastic wrap hammocks. On day 7, disks containing OA, test substances that interfere with PRSTM, or combinations of OA plus a test substance were placed on the developing chorioallantoic membrane. Blood vessel growth under each disk was assessed at 24 hours. Data were evaluated by chi-squared analysis. OA's ability to inhibit angiogenesis is significantly diminished when combined with calcium, bradykinin (increases calcium), pertussis toxin (inhibits GP), or 3-isobutyl-1-methylxanthine (increases cAMP). In contrast, no significant decrease is noted in OA's ability to inhibit angiogenesis when combined with phorbol ester (activates PKC) or vanadate (inhibits TP). OA-induced inhibition of angiogenesis is GP, calcium, and cAMP dependent and is PKC and TP independent. Better understanding of the PRSTM involved with OA-induced inhibition of angiogenesis may lead to enhancement of OA's effect on angiogenesis.

  8. Polyphenols isolated from virgin coconut oil attenuate cadmium-induced dyslipidemia and oxidative stress due to their antioxidant properties and potential benefits on cardiovascular risk ratios in rats

    Directory of Open Access Journals (Sweden)

    Ademola Clement Famurewa

    2017-12-01

    Full Text Available Objective: Literature has confirmed the pathogenic role of cadmium (Cd and its exposure in the induction of dyslipidemia implicated in the development and increasing incidence of cardiovascular diseases. The current study explored whether polyphenolics isolated from virgin coconut oil (VCO prevent Cd-induced dyslipidemia and investigate the underlying mechanism of action, in rats. Materials and Methods: Rats were pretreated with VCO polyphenols (10, 20 and 50 mg/kg body weight; orally 2 weeks prior to concurrent Cd administration (5 mg/kg for 5 weeks. Subsequently, serum concentrations of lipid and lipoprotein cholesterol and cardiovascular risk ratios were determined. Hepatic activities of superoxide dismutase (SOD and catalase (CAT as well as reduced glutathione (GSH and malondialdehyde (MDA contents were analyzed. Results: Sub-chronic Cd administration significantly increased the serum levels of total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein cholesterol while markedly reduced high density lipoprotein cholesterol. Hepatic activities of SOD and CAT as well as GSH content were suppressed by Cd, whereas MDA level was obviously increased. The co-administration of VCO polyphenol with Cd remarkably restored lipid profile and cardiovascular risk ratios and stabilized antioxidant defense systems comparable to control group. Conclusion: This is the first study presenting that polyphenols isolated from VCO prevent Cd-induced lipid abnormalities and cardiovascular risk ratios by improving antioxidant defense systems.

  9. Polyphenols isolated from virgin coconut oil attenuate cadmium-induced dyslipidemia and oxidative stress due to their antioxidant properties and potential benefits on cardiovascular risk ratios in rats.

    Science.gov (United States)

    Famurewa, Ademola Clement; Ejezie, Fidelis Ebele

    2018-01-01

    Literature has confirmed the pathogenic role of cadmium (Cd) and its exposure in the induction of dyslipidemia implicated in the development and increasing incidence of cardiovascular diseases. The current study explored whether polyphenolics isolated from virgin coconut oil (VCO) prevent Cd-induced dyslipidemia and investigate the underlying mechanism of action, in rats. Rats were pretreated with VCO polyphenols (10, 20 and 50 mg/kg body weight; orally) 2 weeks prior to concurrent Cd administration (5 mg/kg) for 5 weeks. Subsequently, serum concentrations of lipid and lipoprotein cholesterol and cardiovascular risk ratios were determined. Hepatic activities of superoxide dismutase (SOD) and catalase (CAT) as well as reduced glutathione (GSH) and malondialdehyde (MDA) contents were analyzed. Sub-chronic Cd administration significantly increased the serum levels of total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein cholesterol while markedly reduced high density lipoprotein cholesterol. Hepatic activities of SOD and CAT as well as GSH content were suppressed by Cd, whereas MDA level was obviously increased. The co-administration of VCO polyphenol with Cd remarkably restored lipid profile and cardiovascular risk ratios and stabilized antioxidant defense systems comparable to control group. This is the first study presenting that polyphenols isolated from VCO prevent Cd-induced lipid abnormalities and cardiovascular risk ratios by improving antioxidant defense systems.

  10. Phenylbutyric acid inhibits epithelial-mesenchymal transition during bleomycin-induced lung fibrosis.

    Science.gov (United States)

    Zhao, Hui; Qin, Hou-Ying; Cao, Lin-Feng; Chen, Yuan-Hua; Tan, Zhu-Xia; Zhang, Cheng; Xu, De-Xiang

    2015-01-05

    A recent report showed that unfolded protein response (UPR) signaling was activated during bleomycin (BLM)-induced pulmonary fibrosis. Phenylbutyric acid (PBA) is an endoplasmic reticulum (ER) chemical chaperone that inhibits the UPR signaling. The present study investigated the effects of PBA on BLM-induced epithelial-mesenchymal transition (EMT) and pulmonary fibrosis. For induction of pulmonary fibrosis, all mice except controls were intratracheally injected with a single dose of BLM (3.0mg/kg). In PBA+BLM group, mice were intraperitoneally injected with PBA (150mg/kg) daily. Three weeks after BLM injection, EMT was measured and pulmonary fibrosis was evaluated. BLM-induced pulmonary UPR activation was inhibited by PBA. Moreover, BLM-induced pulmonary nuclear factor kappa B (NF-κB) p65 activation was blocked by PBA. In addition, BLM-induced up-regulation of pulmonary inflammatory cytokines was repressed by PBA. Further analysis showed that BLM-induced α-smooth muscle actin (α-SMA), a marker for EMT, was significantly attenuated by PBA. Moreover, BLM-induced pulmonary collagen (Col1α1 and Col1α2) was obviously inhibited by PBA. Importantly, BLM-induced pulmonary fibrosis, as determined using Sirius red staining, was obviously alleviated by PBA. Taken together, these results suggest that PBA alleviates ER stress-mediated EMT in the pathogenesis of BLM-induced pulmonary fibrosis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Phenylbutyrate inhibits homologous recombination induced by camptothecin and methyl methanesulfonate

    DEFF Research Database (Denmark)

    Kaiser, Gitte Schalck; Germann, Susanne Manuela; Westergaard, Tine

    2011-01-01

    . Treatment with PBA is accompanied by a dramatic reduction in histone H4 lysine 8 acetylation. Live cell imaging of homologous recombination proteins indicates that repair of CPT-induced DNA damage is redirected to a non-recombinogenic pathway in the presence of PBA without loss in cell viability...

  12. Selective macrophage inhibition abolishes warfarin-induced reduction of metastasis

    NARCIS (Netherlands)

    Maat, B.

    1980-01-01

    Warfarin administered to tumor-bearing mice reduces the number of spontaneous lung metastases. Both macrophage inhibitors silica and carrageenan abolish the warfarin-induced decrease in tumour metastasis, which strongly supports the concept that the antitumour effect of coumarin derivatives is

  13. Antiulcerogenic Effects of Kolaviron: Inhibition of Apoptosis induced ...

    African Journals Online (AJOL)

    The crude extracts of the seed of Garcinia kola (GK) and its constituent biflavonoid, Kolaviron (KV), have been shown to effectively protect the stomach of rats form ulceration induced by HCl/Ethanol mixture as well as indomethacin. However, the anti-ulcerogenic mechanisms are yet to be fully elucidated. Since apoptosis ...

  14. Plumbagin Inhibits Leptin-Induced Proliferation of Hepatic Stellate ...

    African Journals Online (AJOL)

    HP

    STAT3, JAK2, STAT3, p-. ERK1/2, ERK1/2 and MMP-1 were detected by Western blot assay. The content of type I collagen in the supernatant of HSCs was also measured after stimulation by leptin. Results: Leptin induced OB-Rb expression in ...

  15. Intermedin inhibits norepinephrine-induced contraction of rat seminal vesicle

    Directory of Open Access Journals (Sweden)

    P.F. Wong

    2014-09-01

    Conclusion: The results demonstrated that the inhibitory action of IMD on NE-induced seminal vesicle contraction was mediated via the ADM receptor(s and the nitric oxide production pathway, partially by the IMD receptor, but not by the CGRP receptor and the cAMP-PKA pathway.

  16. Chloroquinone Inhibits Cell Proliferation and Induces Apoptosis in ...

    African Journals Online (AJOL)

    Purpose: To demonstrate the role of chloroquinone (CQ) in inducing apoptosis in HONE-1 and HNE-1, nasopharyngeal carcinoma (NPC) cell lines. Methods: Water-soluble tetrazolium salt (WST)-1 assay was used for the determination of cell proliferation while an inverted microscope was employed for the analysis of ...

  17. Plumbagin Inhibits Leptin-Induced Proliferation of Hepatic Stellate ...

    African Journals Online (AJOL)

    Western blot assay revealed that plumbagin significantly decreased pJAK2 expression in leptin-treated HSCs (p < 0.01). Leptin induced expression of pSTAT3 significantly decreased after plumbagin treatment in HSC-LX2 (p < 0.01). p-ERK1/2 expression markedly decreased in plumbagin-treated HSCs (p < 0.01).

  18. Paclitaxel inhibits the hyper-activation of spleen cells by lipopolysaccharide and induces cell death.

    Science.gov (United States)

    Kim, Hyun-Ji; Joo, Hong-Gu

    2016-12-30

    Paclitaxel was isolated from the bark of the Pacific yew, Taxus brevifolia, and used as an anticancer agent. Paclitaxel prevents cancer cell division by inhibiting spindle fiber function, inducing cell death. A recent study demonstrated that paclitaxel binds to myeloid differentiation protein-2 of Toll-like receptor 4 and prevents the signal transduction of lipopolysaccharide (LPS). Paclitaxel converts immune cells hypo-responsive to LPS. In this study, we investigated whether paclitaxel can inhibit the phenotype and function of immune cells. To accomplish this, we used spleen cells, a major type of immune cell, LPS, a representative inflammatory agent and a mitogen for B lymphocytes. LPS profoundly increased the activation and cytokine production of spleen cells. However, paclitaxel significantly inhibited LPS-induced hyper-activation of spleen cells. Furthermore, we found that paclitaxel induced cell death of LPS-treated spleen cells. These results suggest that paclitaxel can inhibit the hyper-immune response of LPS in spleen cells via a variety of mechanisms. These findings suggest that paclitaxel can be used as a modulating agent for diseases induced by hyper-activation of B lymphocytes. Taken together, these results demonstrate that paclitaxel inhibits the function of spleen cells activated by LPS, and further induces cell death.

  19. Humic acid inhibits HBV-induced autophagosome formation and induces apoptosis in HBV-transfected Hep G2 cells.

    Science.gov (United States)

    Pant, Kishor; Yadav, Ajay K; Gupta, Parul; Rathore, Abhishek Singh; Nayak, Baibaswata; Venugopal, Senthil K

    2016-10-06

    Hepatitis B Virus (HBV) utilizes several mechanisms to survive in the host cells and one of the main pathways being autophagosome formation. Humic acid (HA), one of the major components of Mineral pitch, is an Ayurvedic medicinal food, commonly used by the people of the Himalayan regions of Nepal and India for various body ailments. We hypothesized that HA could induce cell death and inhibit HBV-induced autophagy in hepatic cells. Incubation of Hep G2.2.1.5 cells (HepG2 cells stably expressing HBV) with HA (100 μM) inhibited both cell proliferation and autophagosome formation significantly, while apoptosis induction was enhanced. Western blot results showed that HA incubation resulted in decreased levels of beclin-1, SIRT-1 and c-myc, while caspase-3 and β-catenin expression were up-regulated. Western blot results showed that HA significantly inhibited the expression of HBx (3-fold with 50 μM and 5-fold with 100 μM) compared to control cells. When HA was incubated with HBx-transfected Hep G2 cells, HBx-induced autophagosome formation and beclin-1 levels were decreased. These data showed that HA induced apoptosis and inhibited HBV-induced autophagosome formation and proliferation in hepatoma cells.

  20. Toxicological effects induced by cadmium in gills of Manila clam ruditapes philippinarum using NMR-based metabolomics

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Linbao; Liu, Xiaoli; You, Liping; Zhou, Di [Key Laboratory of Coastal Zone Environment Processes, CAS, Shandong Provincial Key Laboratory of Coastal Zone Environment Processes, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai (China); The Graduate School of Chinese Academy of Sciences, Beijing (China); Yu, Junbao; Zhao, Jianmin; Wu, Huifeng [Key Laboratory of Coastal Zone Environment Processes, CAS, Shandong Provincial Key Laboratory of Coastal Zone Environment Processes, Yantai Institute of Coastal Zone Research, Chinese Academy of Sciences, Yantai (China); Feng, Jianghua [Department of Electronic Science, Fujian Key Laboratory of Plasma and Magnetic Resonance, State Key Laboratory of Physical Chemistry of Solid Surfaces, Xiamen University, Xiamen (China)

    2011-11-15

    Cadmium (Cd) has become an important heavy metal contaminant in the sediment and seawater along the Bohai Sea and been of great ecological risk due to its toxic effects to marine organisms. In this work, the toxicological effects caused by environmentally relevant concentrations (10 and 40 {mu}g L{sup -1}) of Cd were studied in the gill tissues of Manila clam Ruditapes philippinarum after exposure for 24, 48, and 96 h. Both low (10 {mu}g L{sup -1}) and high (40 {mu}g L{sup -1}) doses of Cd caused the disturbances in energy metabolism and osmotic regulation and neurotoxicity based on the metabolic biomarkers such as succinate, alanine, branched chain amino acids, betaine, hypotaurine, and glutamate in clam gills after 24 h of exposure. However, the recovery of toxicological effects of Cd after exposure for 96 h was obviously observed in clam to Cd exposures. Overall, these results indicated that NMR-based metabolomics was applicable to elucidate the toxicological effects of heavy metal contaminants in the marine bioindicator. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  1. Cadmium induces cytotoxicity in human bronchial epithelial cells through upregulation of eIF5A1 and NF-kappaB

    Energy Technology Data Exchange (ETDEWEB)

    Chen, De-Ju; Xu, Yan-Ming; Du, Ji-Ying [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Huang, Dong-Yang [Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Lau, Andy T.Y., E-mail: andytylau@stu.edu.cn [Laboratory of Cancer Biology and Epigenetics, Shantou University Medical College, Shantou, Guangdong 515041 (China); Department of Cell Biology and Genetics, Shantou University Medical College, Shantou, Guangdong 515041 (China)

    2014-02-28

    Highlights: • Normal human bronchial epithelial cells (BEAS-2B) were dosed with cadmium (Cd). • A low level (2 μM) of Cd treatment for 36 h elicited negligible cytotoxicity. • High levels (20 or 30 μM) of Cd treatment for 36 h induced cell death. • High levels of Cd can upregulate the protein levels of eIF5A1 and NF-κB p65. • We suggest that eIF5A1 level is possibly modulated by NF-κB. - Abstract: Cadmium (Cd) and Cd compounds are widely-distributed in the environment and well-known carcinogens. Here, we report that in CdCl{sub 2}-exposed human bronchial epithelial cells (BEAS-2B), the level of p53 is dramatically decreased in a time- and dose-dependent manner, suggesting that the observed Cd-induced cytotoxicity is not likely due to the pro-apoptotic function of p53. Therefore, this prompted us to further study the responsive pro-apoptotic factors by proteomic approaches. Interestingly, we identified that high levels (20 or 30 μM) of Cd can significantly upregulate the protein levels of eukaryotic translation initiation factor 5A1 (eIF5A1) and redox-sensitive transcription factor NF-κB p65. Moreover, there is an enhanced NF-κB nuclear translocation as well as chromatin-binding in Cd-treated BEAS-2B cells. We also show that small interfering RNA-specific knockdown of eIF5A1 in Cd-exposed cells attenuated the Cd cytotoxicity, indicating the potential role of eIF5A1 in Cd cytotoxicity. As eIF5A1 is reported to be related with cell apoptosis but little is known about its transcriptional control, we hypothesize that NF-κB might likely modulate eIF5A1 gene expression. Notably, by bioinformatic analysis, several potential NF-κB binding sites on the upstream promoter region of eIF5A1 gene can be found. Subsequent chromatin immunoprecipitation assay revealed that indeed there is enhanced NF-κB binding on eIF5A1 promoter region of Cd-treated BEAS-2B cells. Taken together, our findings suggest for the first time a regulatory mechanism for the pro

  2. Eleutheroside E inhibits doxorubicin-induced inflammation and ...

    African Journals Online (AJOL)

    cytometry while IL-1β, IL-6, and TNF-α levels were determined by ELISA. The phosphorylation level of. NF-κB p65 was measured by Western blot. Results: Compared with control group, cell viability was notably elevated after treatment with 50-100. μM EE for 48 or 72 h. DOX induced higher rates of cell apoptosis in H9c2 ...

  3. Propofol inhibits desflurane-induced preconditioning in rabbits.

    Science.gov (United States)

    Smul, Thorsten M; Stumpner, Jan; Blomeyer, Christoph; Lotz, Christopher; Redel, Andreas; Lange, Markus; Roewer, Norbert; Kehl, Franz

    2011-04-01

    The authors tested the hypothesis that ischemic and desflurane-induced preconditioning are blocked by propofol. A prospective, randomized, vehicle-controlled study. A university research laboratory. New Zealand white rabbits (n = 52). Pentobarbital-anesthetized rabbits were subjected to 30 minutes of coronary artery occlusion followed by 3 hours of reperfusion. Rabbits received 0.0 (control) or 1.0 minimum alveolar concentration of desflurane (30 minutes' duration and a 30-minute memory period) or ischemic preconditioning (5 minutes of ischemia and a 30-minute memory period) in the absence or presence of propofol (10 mg/kg/h intravenously) or its vehicle (10% Intralipid emulsion; B Braun, Melsungen, Germany). The myocardial infarct size was measured with triphenyltetrazolium staining. Statistical analysis was performed with 1-way and 2-way analysis of variance when appropriate, followed by a post hoc Duncan test. Data are mean ± standard deviation. Myocardial infarct size was 56% ± 8% in control animals (n = 7). Desflurane significantly (p < 0.05) reduced the infarct size to 37% ± 6% (n = 7). Desflurane-induced preconditioning was blocked by propofol (65% ± 10%, n = 7) but not by its vehicle (45% ± 11%, n = 5). Propofol and its vehicle alone had no effect on the infarct size (62% ± 8% [n = 6] and 58% ± 3% [n=5], respectively). Ischemic preconditioning reduced infarct size in the absence or presence of propofol to 24% ± 7% (n = 7) and 29% ± 12% (n = 6). Desflurane-induced preconditioning markedly reduced infarct size and was blocked by propofol, whereas ischemic preconditioning was not blocked by propofol. The results suggest an important interference between propofol and anesthetic-induced preconditioning and might explain some contradictory findings in studies in humans. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Inhibition of the autophagy flux by gingerol enhances TRAIL-induced tumor cell death.

    Science.gov (United States)

    Nazim, Uddin Md; Jeong, Jae-Kyo; Seol, Jae-Won; Hur, Jin; Eo, Seong-Kug; Lee, John-Hwa; Park, Sang-Youel

    2015-05-01

    Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a primary anticancer agent and a member of the tumor necrosis factor family that selectively induces apoptosis in various tumor cells, but not in normal cells. Gingerol is a major ginger component with anti-inflammatory and anti‑tumorigenic activities. Autophagy flux is the complete process of autophagy, in which the autophagosomes are lysed by lysosomes. The role of autophagy in cell death or cell survival is controversial. A549 adenocarcinoma cells are TRAIL-resistant. In the present study, we showed that treatment with TRAIL slightly induced cell death, but gingerol treatment enhanced the TRAIL-induced cell death in human lung cancer cells. The combination of gingerol and TRAIL increased accumulation of microtubule-associated protein light chain 3-II and p62, confirming the inhibited autophagy flux. Collectively, our results suggest that gingerol sensitizes human lung cancer cells to TRAIL-induced apoptosis by inhibiting the autophagy flux.

  5. Rebaudioside A inhibits pentylenetetrazol-induced convulsions in rats

    Directory of Open Access Journals (Sweden)

    Yigit Uyanikgil

    2016-09-01

    Full Text Available The safety of patients with epilepsy consuming sweetening agents, which is becoming increasingly prevalent for various reasons, is a topic that should be emphasized as sensitively as it is for other diseases. Patients with epilepsy consume sweetening agents for different reasons such being diabetic or overweight. They can occasionally be exposed to sweetening agents unrestrainedly through consuming convenience food, primarily beverages. This study aimed to investigate the effects of rebaudioside A (Reb-A, which is a steviol glycoside produced from the herb Stevia rebaudiana (Bertoni, on epileptic seizures and convulsions induced by pentylenetetrazole (PTZ. Forty-eight male rats were used. Twenty-four rats were administered 35 mg/kg PTZ to trigger epileptiform activity; the remaining 24 rats were administered 70 mg/kg PTZ to trigger the convulsion model. The epileptiform activity was evaluated by spike percentage, whereas convulsion was evaluated by Racine's Convulsion Scale and the onset time of the first myoclonic jerk. Statistical analysis revealed a statistically significant decrease in the Racine's Convulsion Scale score and increase in the latency of first myoclonic jerk in a dose-dependent manner for the rat groups in which PTZ epilepsy had been induced and Reb-A had been administered. For the groups that were administered Reb-A, the spike decrease was apparent in a dose-dependent manner, based on the spike percentage calculation. These results indicated that Reb-A has positive effects on PTZ-induced convulsions.

  6. Interleukin-22 Inhibits Bleomycin-Induced Pulmonary Fibrosis

    Directory of Open Access Journals (Sweden)

    Minrui Liang

    2013-01-01

    Full Text Available Pulmonary fibrosis is a progressive and fatal fibrotic disease of the lungs with unclear etiology. Recent insight has suggested that early injury/inflammation of alveolar epithelial cells could lead to dysregulation of tissue repair driven by multiple cytokines. Although dysregulation of interleukin- (IL- 22 is involved in various pulmonary pathophysiological processes, the role of IL-22 in fibrotic lung diseases is still unclear and needs to be further addressed. Here we investigated the effect of IL-22 on alveolar epithelial cells in the bleomycin- (BLM- induced pulmonary fibrosis. BLM-treated mice showed significantly decreased level of IL-22 in the lung. IL-22 produced γδT cells were also decreased significantly both in the tissues of lungs and spleens. Administration of recombinant human IL-22 to alveolar epithelial cell line A549 cells ameliorated epithelial to mesenchymal transition (EMT and partially reversed the impaired cell viability induced by BLM. Furthermore, blockage of IL-22 deteriorated pulmonary fibrosis, with elevated EMT marker (α-smooth muscle actin (α-SMA and overactivated Smad2. Our results indicate that IL-22 may play a protective role in the development of BLM-induced pulmonary fibrosis and may suggest IL-22 as a novel immunotherapy tool in treating pulmonary fibrosis.

  7. Rosmarinic acid inhibits poly(I:C)-induced inflammatory reaction of epidermal keratinocytes.

    Science.gov (United States)

    Zhou, Ming-Wei; Jiang, Ri-Hua; Kim, Ki-Duck; Lee, Jin-Hyup; Kim, Chang-Deok; Yin, Wei-Tian; Lee, Jeung-Hoon

    2016-06-15

    Keratinocytes are the predominant cells in the epidermis, exerting their primary role of physical barrier through sophisticated differentiation process. In addition, keratinocytes contribute to the activation of innate immunity, providing the surveillant role against external pathogens. It has been known that chronic skin inflammatory disease such as psoriasis can be provoked by viral pathogens including double-stranded RNA. In this study, we demonstrated that rosmarinic acid (RA) has an inhibitory potential on inflammatory reaction induced by double-stranded RNA mimic poly(I:C) in epidermal keratinocytes. We cultured human epidermal keratinocytes and induced inflammatory reaction by poly(I:C) treatment. The effect of RA on inflammatory reaction of keratinocytes was determined by RT-PCR and Western blot. RA significantly inhibited poly(I:C)-induced expression of inflammatory cytokines including IL-1β, IL-6, IL-8, CCL20, and TNF-α, and downregulated NF-κB signaling pathway in human keratinocytes. In addition, RA significantly inhibited poly(I:C)-induced inflammasome activation, in terms of secretion of active form of IL-1β and caspase-1. Furthermore, RA markedly inhibited poly(I:C)-induced NLRP3 and ASC expression. These results indicate that RA can inhibit poly(I:C)-induced inflammatory reaction of keratinocytes, and suggest that it may be a potential candidate for the treatment of psoriasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Salidroside protects cortical neurons against glutamate-induced cytotoxicity by inhibiting autophagy.

    Science.gov (United States)

    Yin, Wei-Yong; Ye, Qiang; Huang, Huan-Jie; Xia, Nian-Ge; Chen, Yan-Yan; Zhang, Yi; Qu, Qiu-Min

    2016-08-01

    Recent evidence suggests that glutamate-induced cytotoxicity contributes to autophagic neuron death and is partially mediated by increased oxidative stress. Salidroside has been demonstrated to have neuroprotective effects in glutamate-induced neuronal damage. The precise mechanism of its regulatory role in neuronal autophagy is, however, poorly understood. This study aimed to probe the effects and mechanisms of salidroside in glutamate-induced autophagy activation in cultured rat cortical neurons. Cell viability assay, Western blotting, coimmunoprecipitation, and small interfering RNA were performed to analyze autophagy activities during glutamate-evoked oxidative injury. We found that salidroside protected neonatal neurons from glutamate-induced apoptotic cell death. Salidroside significantly attenuated the LC3-II/LC3-I ratio and expression of Beclin-1, but increased (SQSTM1)/p62 expression under glutamate exposure. Pretreatment with 3-methyladenine (3-MA), an autophagy inhibitor, decreased LC3-II/LC3-I ratio, attenuated glutamate-induced cell injury, and mimicked some of the protective effects of salidroside against glutamate-induced cell injury. Molecular analysis demonstrated that salidroside inhibited cortical neuron autophagy in response to glutamate exposure through p53 signaling by increasing the accumulation of cytoplasmic p53. Salidroside inhibited the glutamate-induced dissociation of the Bcl-2-Beclin-1 complex with minor affects on the PI3K/Akt/mTOR signaling pathways. These data demonstrate that the inhibition of autophagy could be responsible for the neuroprotective effects of salidroside on glutamate-induced neuronal injury.

  9. Zinc blocks SOS-induced antibiotic resistance via inhibition of RecA in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Bryan E Bunnell

    Full Text Available Zinc inhibits the virulence of diarrheagenic E. coli by inducing the envelope stress response and inhibiting the SOS response. The SOS response is triggered by damage to bacterial DNA. In Shiga-toxigenic E. coli, the SOS response strongly induces the production of Shiga toxins (Stx and of the bacteriophages that encode the Stx genes. In E. coli, induction of the SOS response is accompanied by a higher mutation rate, called the mutator response, caused by a shift to error-prone DNA polymerases when DNA damage is too severe to be repaired by canonical DNA polymerases. Since zinc inhibited the other aspects of the SOS response, we hypothesized that zinc would also inhibit the mutator response, also known as hypermutation. We explored various different experimental paradigms to induce hypermutation triggered by the SOS response, and found that hypermutation was induced not just by classical inducers such as mitomycin C and the quinolone antibiotics, but also by antiviral drugs such as zidovudine and anti-cancer drugs such as 5-fluorouracil, 6-mercaptopurine, and azacytidine. Zinc salts inhibited the SOS response and the hypermutator phenomenon in E. coli as well as in Klebsiella pneumoniae, and was more effective in inhibiting the SOS response than other metals. We then attempted to determine the mechanism by which zinc, applied externally in the medium, inhibits hypermutation. Our results show that zinc interferes with the actions of RecA, and protects LexA from RecA-mediated cleavage, an early step in initiation of the SOS response. The SOS response may play a role in the development of antibiotic resistance and the effect of zinc suggests ways to prevent it.

  10. Selenium Inhibits Homocysteine-Induced Endothelial Dysfunction and Apoptosis via Activation of AKT

    Directory of Open Access Journals (Sweden)

    Hui Ren

    2016-02-01

    Full Text Available Background/Aims: Endothelial cells are crucial in vascular homeostasis. Dysfunction of endothelial cells is involved in the development of cardiovascular diseases (CVD. High plasma homocysteine (Hcy correlates with CVD while selenium supplementation counteracts development of CVD. However, the underlying mechanism remained unclear. Here, we investigated the effects of selenium on homocysteine-induced endothelial dysfunction. Methods: An animal model of Hcy-induced endothelial dysfunction was established by intragastric administration of L-methionine. Plasma NO and von Willebrand factor (vWF were quantified using NO assay and ELISA kit respectively. Relaxation was measured in thoracic aortic ring assays. Cell viability and migration were detected by Cell Counting Kit-8 and Bio-Coat cell migration chambers respectively. Cellular apoptosis was determined by Annexin V-FITC apoptosis kit. Results: Selenium prevented homocysteine-induced endothelial injury and impairment of endothelium-dependent relaxation. Selenium reversed the impaired viability and migration of endothelial cells induced by homocysteine in a dose-dependent manner. Selenium inhibited the apoptosis of endothelial cells induced by homocysteine, through downregulating of Caspase-3 activity and expression of Caspase-3 and Bax, and by stimulating Bcl-2 expression. Selenium reversed the homocysteine-induced reduction of NO release, and increased the expression and phosphoylation of endothelial nitric oxide synthetase (eNOS in a dose-dependent manner. Moreover, selenium enhanced AKT phosphorylation, and selenium-induced phosphorylation and expression of eNOS were inhibited by AKT inhibition. NO production, cell viability and migration rescued by selenium were inhibited, while cell apoptosis was reversed by AKT inhibition. Conclusion: Selenium protected against homocysteine-induced dysfunction and apoptosis of endothelial cells through AKT pathway. The observations may provide novel

  11. Inhibition of protein phosphatase 2A induces serine/threonine phosphorylation, subcellular redistribution, and functional inhibition of STAT3

    DEFF Research Database (Denmark)

    Woetmann, A; Nielsen, M; Christensen, S T

    1999-01-01

    STAT3. We show that an inhibitor of protein phosphatases (PPs) PP1/PP2A, calyculin A, induces (i) phosphorylation of STAT3 on serine and threonine residues, (ii) inhibition of STAT3 tyrosine phosphorylation and DNA binding activity, and (iii) relocation of STAT3 from the nucleus to the cytoplasm......, whereas inhibitors of serine/threonine kinases, such as mitogen-activated protein kinase-1 extracellular-regulated kinase-kinase, mitogen-activated protein p38 kinase, and phosphatidylinositol 3-kinase, did not. In conclusion, we provide evidence that PP2A plays a crucial role in the regulation of STAT3....... Similar results were obtained with other PP2A inhibitors (okadaic acid, endothall thioanhydride) but not with inhibitors of PP1 (tautomycin) or PP2B (cyclosporine A). Pretreatment with the broad serine/threonine kinase inhibitor staurosporine partly blocked the calyculin A-induced STAT3 phosphorylation...

  12. Cadmium concentrations in the testes, sperm, and spermatids of mice subjected to long-term cadmium chloride exposure.

    Science.gov (United States)

    Bench, G; Corzett, M H; Martinelli, R; Balhorn, R

    1999-01-01

    Exposures to cadmium have been reported to reduce male fertility and there are several hypotheses that suggest how reduced male fertility may result from incorporation of cadmium into sperm chromatin. The purpose of this study was to determine whether mice subjected to long-term intraperitoneal cadmium exposure incorporated cadmium into their sperm chromatin. Male mice were exposed to 0.1 mg/kg body weight cadmium in the form of CdCl2 via intraperitoneal injection once per week for 4, 10, 26, and 52 weeks and then sacrificed. The cadmium contents of the liver, testes, pooled sperm, and pooled spermatids from dosed and control animals were determined by atomic absorption spectroscopy. Cadmium and zinc contents in individual sperm and spermatid heads were determined by particle-induced x-ray emission. Atomic absorption spectroscopy revealed that although cadmium accumulated in the liver and testes, cadmium was not detected in pooled sperm or spermatid samples down to minimum detectable limits of 0.02 microg/g dry weight. Particle-induced x-ray emission analyses did not show the presence of cadmium in any sperm or spermatid head down to minimum detectable limits of 15 microg/g dry weight. Particle-induced x-ray emission analyses also demonstrated that phosphorus, sulfur, and zinc concentrations in individual sperm and spermatid heads were not altered by exposure to CdCl2. Because cadmium was not incorporated into sperm chromatin at levels above 0.02 microg/g dry weight, the data cast doubt on hypotheses that suggest that reduced male fertility may result from incorporation of cadmium into sperm chromatin.

  13. hERG trafficking inhibition in drug-induced lethal cardiac arrhythmia.

    Science.gov (United States)

    Nogawa, Hisashi; Kawai, Tomoyuki

    2014-10-15

    Acquired long QT syndrome induced by non-cardiovascular drugs can cause lethal cardiac arrhythmia called torsades de points and is a significant problem in drug development. The prolongation of QT interval and cardiac action potential duration are mainly due to reduced physiological function of the rapidly activating voltage-dependent potassium channels encoded by human ether-a-go-go-related gene (hERG). Structurally diverse groups of drugs are known to directly inhibit hERG channel conductance. Therefore, the ability of acute hERG inhibition is routinely assessed at the preclinical stages in pharmaceutical testing. Recent findings indicated that chronic treatment with various drugs not only inhibits hERG channels but also decreases hERG channel expression in the plasma membrane of cardiomyocytes, which has become another concern in safety pharmacology. The mechanisms involve the disruption of hERG trafficking to the surface membrane or the acceleration of hERG protein degradation. From this perspective, we present a brief overview of mechanisms of drug-induced trafficking inhibition and pathological regulation. Understanding of drug-induced hERG trafficking inhibition may provide new strategies for predicting drug-induced QT prolongation and lethal cardiac arrhythmia in pharmaceutical drug development. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Sertraline inhibits formalin-induced nociception and cardiovascular responses

    Energy Technology Data Exchange (ETDEWEB)

    Santuzzi, C.H. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Futuro Neto, H.A. [Departamento de Morfologia, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil); Escola de Medicina da Empresa Brasileira de Ensino, Pesquisa e Extensão, Vitória, ES (Brazil); Escola Superior de Ciências da Saúde, Santa Casa de Misericórdia de Vitória, Vitória, ES (Brazil); Pires, J.G.P. [Escola de Medicina da Empresa Brasileira de Ensino, Pesquisa e Extensão, Vitória, ES (Brazil); Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Gonçalves, W.L.S. [Centro Universitário do Espírito Santo, Colatina, ES (Brazil); Tiradentes, R.V.; Gouvea, S.A.; Abreu, G.R. [Departamento de Ciências Fisiológicas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, ES (Brazil)

    2011-11-18

    The objective of the present study was to determine the antihyperalgesic effect of sertraline, measured indirectly by the changes of sciatic afferent nerve activity, and its effects on cardiorespiratory parameters, using the model of formalin-induced inflammatory nociception in anesthetized rats. Serum serotonin (5-HT) levels were measured in order to test their correlation with the analgesic effect. Male Wistar rats (250-300 g) were divided into 4 groups (N = 8 per group): sertraline-treated group (Sert + Saline (Sal) and Sert + Formalin (Form); 3 mg·kg{sup −1}·day{sup −1}, ip, for 7 days) and saline-treated group (Sal + Sal and Sal + Form). The rats were injected with 5% (50 µL) formalin or saline into the right hind paw. Sciatic nerve activity was recorded using a silver electrode connected to a NeuroLog apparatus, and cardiopulmonary parameters (mean arterial pressure, heart rate and respiratory frequency), assessed after arterial cannulation and tracheotomy, were monitored using a Data Acquisition System. Blood samples were collected from the animals and serum 5-HT levels were determined by ELISA. Formalin injection induced the following changes: sciatic afferent nerve activity (+50.8 ± 14.7%), mean arterial pressure (+1.4 ± 3 mmHg), heart rate (+13 ± 6.8 bpm), respiratory frequency (+4.6 ± 5 cpm) and serum 5-HT increased to 1162 ± 124.6 ng/mL. Treatment with sertraline significantly reduced all these parameters (respectively: +19.8 ± 6.9%, -3.3 ± 2 mmHg, -13.1 ± 10.8 bpm, -9.8 ± 5.7 cpm) and serum 5-HT level dropped to 634 ± 69 ng/mL (P < 0.05). These results suggest that sertraline plays an analgesic role in formalin-induced nociception probably through a serotonergic mechanism.

  15. Sertraline inhibits formalin-induced nociception and cardiovascular responses

    Directory of Open Access Journals (Sweden)

    C.H. Santuzzi

    2012-01-01

    Full Text Available The objective of the present study was to determine the antihyperalgesic effect of sertraline, measured indirectly by the changes of sciatic afferent nerve activity, and its effects on cardiorespiratory parameters, using the model of formalin-induced inflammatory nociception in anesthetized rats. Serum serotonin (5-HT levels were measured in order to test their correlation with the analgesic effect. Male Wistar rats (250-300 g were divided into 4 groups (N = 8/per group: sertraline-treated group (Sert + Saline (Sal and Sert + Formalin (Form; 3 mg·kg-1·day-1, ip, for 7 days and saline-treated group (Sal + Sal and Sal + Form. The rats were injected with 5% (50 µL formalin or saline into the right hind paw. Sciatic nerve activity was recorded using a silver electrode connected to a NeuroLog apparatus, and cardiopulmonary parameters (mean arterial pressure, heart rate and respiratory frequency, assessed after arterial cannulation and tracheotomy, were monitored using a Data Acquisition System. Blood samples were collected from the animals and serum 5-HT levels were determined by ELISA. Formalin injection induced the following changes: sciatic afferent nerve activity (+50.8 ± 14.7%, mean arterial pressure (+1.4 ± 3 mmHg, heart rate (+13 ± 6.8 bpm, respiratory frequency (+4.6 ± 5 cpm and serum 5-HT increased to 1162 ± 124.6 ng/mL. Treatment with sertraline significantly reduced all these parameters (respectively: +19.8 ± 6.9%, -3.3 ± 2 mmHg, -13.1 ± 10.8 bpm, -9.8 ± 5.7 cpm and serum 5-HT level dropped to 634 ± 69 ng/mL (P < 0.05. These results suggest that sertraline plays an analgesic role in formalin-induced nociception probably through a serotonergic mechanism.

  16. Inhibition of Delta-induced Notch signaling using fucose analogs.

    Science.gov (United States)

    Schneider, Michael; Kumar, Vivek; Nordstrøm, Lars Ulrik; Feng, Lei; Takeuchi, Hideyuki; Hao, Huilin; Luca, Vincent C; Garcia, K Christopher; Stanley, Pamela; Wu, Peng; Haltiwanger, Robert S

    2018-01-01

    Notch is a cell-surface receptor that controls cell-fate decisions and is regulated by O-glycans attached to epidermal growth factor-like (EGF) repeats in its extracellular domain. Protein O-fucosyltransferase 1 (Pofut1) modifies EGF repeats with O-fucose and is essential for Notch signaling. Constitutive activation of Notch signaling has been associated with a variety of human malignancies. Therefore, tools that inhibit Notch activity are being developed as cancer therapeutics. To this end, we screened L-fucose analogs for their effects on Notch signaling. Two analogs, 6-alkynyl and 6-alkenyl fucose, were substrates of Pofut1 and were incorporated directly into Notch EGF repeats in cells. Both analogs were potent inhibitors of binding to and activation of Notch1 by Notch ligands Dll1 and Dll4, but not by Jag1. Mutagenesis and modeling studies suggest that incorporation of the analogs into EGF8 of Notch1 markedly reduces the ability of Delta ligands to bind and activate Notch1.

  17. The Lemna minor growth inhibition test as basis to evaluate radiation or radionuclide-induced effects on freshwater plants

    Energy Technology Data Exchange (ETDEWEB)

    Horemans, N.; Van Hees, M.; Van Hoeck, A.; Vandenhove, H. [Belgian Nuclear Research Centre, SCK.CEN, Boeretang 200, 2400 Mol (Belgium)

    2014-07-01

    The setting of radiation protection criteria for wildlife is based on tiered Environmental Risk Assessments (ERA) methods. At various points in such a tiered ERA robust and transparent benchmark values are needed to indicate the levels of exposure that are considered safe to the environment. Although not ideal these benchmark values are today mainly based on laboratory-based experiments in which the toxic effects of radiation or radionuclides to one selected species exposed under standardised growth conditions is studied. As such an eco-toxicity test has been developed for the floating macrophyte Lemna minor that can be used to test the effect of different chemicals in freshwater. Here the use of this test to estimate effects of radiation or radionuclides and its relevance to the environment will be discussed. First single dose response curves are shown that were set up according to the guidelines for gamma, uranium and as a reference also cadmium. According to the guidelines growth inhibition can be calculated on different endpoints like frond number and frond area. The choice of this endpoint seems to be of major importance as dependent on the stressor significant shifts in the EC50 values, the concentration giving 50% effect, were observed. For gamma radiation a recovery experiment was set up in irradiated plants were allowed to grow again for 7 days in control conditions. It was shown that plant growth rate did not catch up with that of the non-irradiated group. On the contrary, plant cultures that showed a growth inhibition above 40% immediately after irradiation completely collapsed during the recovery period indicating no recovery from the gamma induced damage and resulting in a 3-fold lower EC50 value after 7 days recovery. The relevance of these data to the environment will be further discussed. Finally the influence of different cations on the uranium speciation and toxicity are studied. These experiments are the first steps to set up a biotic ligand

  18. Synergistic Interactions with PI3K Inhibition that Induce Apoptosis. | Office of Cancer Genomics

    Science.gov (United States)

    Activating mutations involving the PI3K pathway occur frequently in human cancers. However, PI3K inhibitors primarily induce cell cycle arrest, leaving a significant reservoir of tumor cells that may acquire or exhibit resistance. We searched for genes that are required for the survival of PI3K mutant cancer cells in the presence of PI3K inhibition by conducting a genome scale shRNA-based apoptosis screen in a PIK3CA mutant human breast cancer cell. We identified 5 genes (PIM2, ZAK, TACC1, ZFR, ZNF565) whose suppression induced cell death upon PI3K inhibition.

  19. Protective effect of zinc supplementation against cadmium-induced oxidative stress and the RANK/RANKL/OPG system imbalance in the bone tissue of rats

    Energy Technology Data Exchange (ETDEWEB)

    Brzóska, Malgorzata M., E-mail: Malgorzata.Brzoska@umb.edu.pl; Rogalska, Joanna

    2013-10-01

    It was investigated whether protective influence of zinc (Zn) against cadmium (Cd)-induced disorders in bone metabolism may be related to its antioxidative properties and impact on the receptor activator of nuclear factor (NF)-κΒ (RANK)/RANK ligand (RANKL)/osteoprotegerin (OPG) system. Numerous indices of oxidative/antioxidative status, and Cd and Zn were determined in the distal femur of the rats administered Zn (30 and 60 mg/l) or/and Cd (5 and 50 mg/l) for 6 months. Soluble RANKL (sRANKL) and OPG were measured in the bone and serum. Zn supplementation importantly protected from Cd-induced oxidative stress preventing protein, DNA, and lipid oxidation in the bone. Moreover, Zn protected from the Cd-induced increase in sRANKL concentration and the sRANKL/OPG ratio, and decrease in OPG concentration in the bone and serum. Numerous correlations were noted between indices of the oxidative/antioxidative bone status, concentrations of sRANKL and OPG in the bone and serum, as well as the bone concentrations of Zn and Cd, and previously reported by us in these animals (Brzóska et al., 2007) indices of bone turnover and bone mineral density. The results allow us to conclude that the ability of Zn to prevent from oxidative stress and the RANK/RANKL/OPG system imbalance may be implicated in the mechanisms of its protective impact against Cd-induced bone damage. This paper is the first report from an in vivo study providing evidence that beneficial Zn impact on the skeleton under exposure to Cd is related to the improvement of the bone tissue oxidative/antioxidative status and mediating the RANK/RANKL/OPG system. - Highlights: • Cd induces oxidative stress in the bone tissue. • Cd disturbs bone metabolism via disorder of the RANK/RANKL/OPG system balance. • Zn supplementation protects from Cd-induced oxidative stress in the bone tissue. • Zn protects from the RANK/RANKL/OPG system imbalance caused by Cd in the bone tissue. • Enhanced Zn intake protects from Cd-induced

  20. Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination

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    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China); Qiao, Juan, E-mail: qjuan@tsinghua.edu.cn [Department of Chemistry, Tsinghua University, Beijing 100084 (China); Lu, Yun, E-mail: luyun@tsinghua.edu.cn [Environmental Simulation and Pollution Control State Key Joint Laboratory, School of Environment, Tsinghua University, Beijing 100084 (China)

    2016-02-13

    Highlights: • Chlorination is effective to reduce the inflammation inducing capacity of LPS in lung. • LAL-detected endotoxin activity is not correlated to the potency of inflammation induction. • Alkyl chain of LPS was chlorinated in chlorination process. • LPS aggregate size decreases after chlorination. - Abstract: Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies.

  1. Heat-induced oxidative stress and inflammation involve in cadmium pollution history in the spleen of zebrafish.

    Science.gov (United States)

    Zhao, Shu-Jiang; Guo, Sai-Nan; Zhu, Qing-Ling; Yuan, Shuang-Shuang; Zheng, Jia-Lang

    2017-10-24

    Zebrafish were exposed to 0, 2.5 and 5 μg/L cadmium (Cd) for 10 weeks, and then each group was exposed to 26 °C(control) and 32 °C (high temperature) for 7 days. 22 indicators were compared between 26 °C and 32 °C in the spleen, including body weight, LPO and NO levels, activity levels of Cu/Zn-SOD, CAT and iNOS, MTs protein levels, and mRNA levels of Nrf2, Cu/Zn-SOD, CAT, HSF1, HSF2, HSP70, MTF-1, MTs, IL-6, IL-10, IL-1β, TNF-α, iNOS and NF-κB. Most indicators were not significantly affected by heat in fish from no Cd pollution. However, almost all of indicators were responsive to heat in fish pre-exposed to Cd. Several indicators were sensitive to heat in fish pre-exposed to 2.5 μg/L Cd such as iNOS activities, and mRNA levels of iNOS and IL-10. Most other indicators were sensitive to heat in fish pre-exposed to 5 μg/L. The mRNA levels of HSP70 and MTF-1 were up-regulated by heat in fish pre-exposed to 0, 2.5 and 5 μg/L Cd. However, the magnitude of increase was the greatest in fish pre-exposed to 5 μg/L Cd. These differences between control and high temperature would serve as biomarkers to distinguish healthy from Cd-polluted group. The findings imply that metal pollution history should be carefully considered when screening heat biomarkers in fish. Copyright © 2017. Published by Elsevier Ltd.

  2. Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin-cadmium induced diabetic nephrotoxic rats.

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    Kandasamy, Neelamegam; Ashokkumar, Natarajan

    2014-09-01

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)-cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ-Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ-Cd induced diabetic nephrotoxic rats. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Sinapic acid ameliorate cadmium-induced nephrotoxicity: In vivo possible involvement of oxidative stress, apoptosis, and inflammation via NF-κB downregulation.

    Science.gov (United States)

    Ansari, Mushtaq Ahmad; Raish, Mohammad; Ahmad, Ajaz; Alkharfy, Khalid M; Ahmad, Sheikh Fayaz; Attia, Sabry M; Alsaad, Abdulaziz M S; Bakheet, Saleh A

    2017-04-01

    Cadmium (CD), an environmental and industrial pollutant, generates reactive oxygen species (ROS) and NOS responsible for oxidative and nitrosative stress that can lead to nephrotoxic injury, including proximal tubule and glomerulus dysfunction. Sinapic acid (SA) has been found to possess potent antioxidant and anti-inflammatory effects in vitro and in vivo. We aimed to examine the nephroprotective, anti-oxidant, anti-inflammatory, and anti-apoptotic effects of SA against CD-induced nephrotoxicity and its underlying mechanism. Kidney functional markers (serum urea, uric acid, creatinine, LDH, and calcium) and histopathological examinations of the kidney were used to evaluate CD-induced nephrotoxicity. Oxidative stress markers (lipid peroxidation and total protein), renal nitrosative stress (nitric oxide), antioxidant enzymes (catalase and NP-SH), inflammation markers (NF-κB [p65], TNF-α, IL-6, and myeloperoxidase [MPO]), and apoptotic markers (caspase 3, Bax, and Bcl-2) were also assessed. SA (10 and 20mg/kg) pretreatment restored kidney function, upregulated antioxidant levels, and prevented the elevation of lipid peroxidation and nitric oxide levels, significantly reducing oxidative and nitrosative stress. CD upregulated renal cytokine levels (TNF-α, IL-6), nuclear NF-κB (p65) expression, NF-κB-DNA-binding activity, and MPO activity, which were significantly downregulated upon SA pretreatment. Furthermore, SA treatment prevented the upregulation of caspase 3 and Bax protein expression and upregulated Bcl-2 protein expression. SA pretreatment also alleviated the magnitude of histological injuries and reduced neutrophil infiltration in renal tubules. We conclude that the nephroprotective potential of SA in CD-induced nephrotoxicity might be due to its antioxidant, anti-inflammatory, and anti-apoptotic potential via downregulation of oxidative/nitrosative stress, inflammation, and apoptosis in the kidney. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Cadmium neurotoxicity to a freshwater planarian.

    Science.gov (United States)

    Wu, Jui-Pin; Lee, Hui-Ling; Li, Mei-Hui

    2014-11-01

    Although freshwater planarians are evolutionarily primitive, they are some of the simplest bilateral animals possessing integrated neural networks similar to those in vertebrates. We attempted to develop planarian Dugesia japonica as a model for investigating the neurotoxicity of environmental pollutants such as cadmium (Cd). This study was therefore designed to study the effects of Cd on the locomotor activity, neurobehavior, and neurological enzymes of D. japonica. After planarians were exposed to Cd at high concentrations, altered neurobehavior was observed that exhibited concentration-dependent patterns. Morphological alterations in Cd-treated planarians included irregular shape, body elongation, screw-like hyperkinesia, and bridge-like position. To study the direct effects of Cd on neurological enzymes, tissue homogenates of planarians were incubated in vitro with Cd before their activity was measured. Results showed that acetylcholinesterase (AChE), adenosine triphosphatase (ATPase), and monoamine oxidase A (MAO-A) activities were inhibited in a concentration-dependent manner. MAO-B activity was significantly induced by Cd at low concentrations and inhibited at high concentrations. Changes in the in vivo activity of AChE and ATPase were also found after planarians were treated with Cd at a sublethal concentration (5.56 μM). These observations indicate that neurotransmission systems in planarians are disturbed after Cd exposure.

  5. Citral inhibits lipopolysaccharide-induced acute lung injury by activating PPAR-γ.

    Science.gov (United States)

    Shen, Yongbin; Sun, Zhanfeng; Guo, Xiaotong

    2015-01-15

    Citral, a component of lemongrass oil, has been reported to have many pharmacological activities such as anti-bacterial and anti-inflammatory effects. However, the effects of citral on acute lung injury (ALI) and the molecular mechanisms have not been reported. The aim of this study was to detect the effects of citral on lipopolysaccharide (LPS)-induced acute lung injury and investigate the molecular mechanisms. LPS-induced acute lung injury model was used to detect the anti-inflammatory effect of citral in vivo. The alveolar macrophages were used to investigate the molecular mechanism of citral in vitro. The results showed that pretreatment with citral remarkably attenuated pulmonary edema, histological severities, TNF-α, IL-6 and IL-1β production in LPS-induced ALI in vivo. In vitro, citral inhibited LPS-induced TNF-α, IL-6 and IL-1β production in alveolar macrophages. LPS-induced NF-κB activation was also inhibited by citral. Furthermore, we found that citral activated PPAR-γ and the anti-inflammatory effects of citral can be reversed by PPAR-γ antagonist GW9662. In conclusion, this is the first to demonstrate that citral protects LPS-induced ALI in mice. The anti-inflammatory mechanism of citral is associated with activating PPAR-γ, thereby inhibiting LPS-induced inflammatory response. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. AG490 inhibits NFATc1 expression and STAT3 activation during RANKL induced osteoclastogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Chang-hong; Zhao, Jin-xia; Sun, Lin; Yao, Zhong-qiang; Deng, Xiao-li; Liu, Rui; Liu, Xiang-yuan, E-mail: liu-xiangyuan@263.net

    2013-06-14

    Highlights: •AG490 inhibits RANKL-induced osteoclastogenesis in RAW264.7 cells. •AG490 affects cell proliferation and cell cycle distribution. •AG490 reduces NFATc1 expression during RANKL-induced osteoclastogenesis. •AG490 disrupts the activation of RANKL-mediated JAK2/STAT3 signaling pathway. •STAT3 depletion partly mimics the effect of AG490 on RANKL-induced osteoclastogenesis. -- Abstract: Commonly, JAK/STAT relays cytokine signals for cell activation and proliferation, and recent studies have shown that the elevated expression of JAK/STAT is associated with the immune rejection of allografts and the inflammatory processes of autoimmune disease. However, the role which JAK2/STAT3 signaling plays in the receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis is unknown. In this study, we investigated the effects of AG490, specific JAK2 inhibitor, on osteoclast differentiation in vitro. AG490 significantly inhibited osteoclastogenesis in murine osteoclast precursor cell line RAW264.7 induced by RANKL. AG490 suppressed cell proliferation and delayed the G1 to S cell cycle transition. Furthermore, AG490 also suppressed the expression of nuclear factor of activated T cells (NFAT) c1 but not c-Fos in RAW264.7. Subsequently, we investigated various intracellular signaling components associated with osteoclastogenesis. AG490 had no effects on RANKL-induced activation of Akt, ERK1/2. Interestingly, AG490 partly inhibited RANKL-induced phosphorylation of Ser{sup 727} in STAT3. Additionally, down-regulation of STAT3 using siRNA resulted in suppression of TRAP, RANK and NFATc1 expression. In conclusion, we demonstrated that AG490 inhibited RANKL-induced osteoclastogenesis by suppressing NFATc1 production and cell proliferation via the STAT3 pathway. These results suggest that inhibition of JAK2 may be useful for the treatment of bone diseases characterized by excessive osteoclastogenesis.

  7. Xiao-Ban-Xia-Tang inhibits cisplatin-induced pica by down regulating obestatin in rats.

    Science.gov (United States)

    Qian, Qiuhai; Chen, Wenhui; Guo, Chunfang; Wu, Wenguang; Qian, Weibin; Li, Shuanglei

    2011-04-26

    Xiao-Ban-Xia-Tang (XBXT), a traditional Chinese herbal medicine, has been used in China for more than 2000 years, and proved to be effective in various cases of vomiting in the clinic. To investigate the inhibitive effect of XBXT on cisplatin-induced pica behaviour and its effective mechanism on obestatin, CCK and CGRP in the pica model of rat. The inhibitive effect of XBXT was investigated in the pica model of rats induced by cisplatin (3mg kg(-1), i.p.) in 72h observation, the expression of obestatin in the area postrema and ileum was measured by immunohistochemistry and PCR, and the levels of CCK and CGRP in blood were measured by Elisa. The weight of kaolin eaten in rats induced by cisplatin was significantly reduced by pretreatment with XBXT in a dose-dependent manner during the 0-24h and 24-72h periods (P<0.05). XBXT exhibited effective dose-dependent (P<0.05) inhibition on the increase of expression levels of obestatin in both the ileum and area postrema, and markedly suppressed the increase levels of CCK and CGRP in blood induced by cisplatin in a dose-dependent manner (P<0.05). XBXT has good activity against cisplatin-induced eating kaolin in rats possibly by inhibiting central or peripheral increase of obestatin, or the levels of CCK and CGRP in blood. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  8. Inhibition of neutrophil elastase-induced goblet cell metaplasia by tiotropium in mice.

    Science.gov (United States)

    Arai, N; Kondo, M; Izumo, T; Tamaoki, J; Nagai, A

    2010-05-01

    Airway occlusion by mucus in chronic obstructive disease (COPD) is associated with a poor prognosis. We hypothesised that tiotropium has the ability to inhibit neutrophil elastase (NE)-induced goblet cell metaplasia in mice and mucin production in vitro. On days 1, 4, and 7, tiotropium or vehicle was administered to C57BL/6 mice by inhalation and they were allowed to intranasally aspirate human NE. Bronchoalveolar lavage fluid (BALF) and lung sections were analysed on days 8, 11 and 14. The effect of late administration of tiotropium on the goblet cell metaplasia by NE aspiration was also assessed. NE-induced MUC5AC production by NCI-H292 cells was measured with ELISA. Repeated NE aspiration induced marked goblet cell metaplasia. The grading of goblet cell metaplasia, neutrophil count and eosinophil count in BALF, keratinocyte-derived chemokine level and leukotriene B(4) level in BALF, and M(3) receptor expression by immunohistochemistry, were lower in the tiotropium group than in the vehicle group. Late administration of tiotropium inhibited the established goblet cell metaplasia. Tiotropium inhibited NE-induced MUC5AC production. Tiotropium inhibited NE-induced goblet cell metaplasia and mucin production, probably mediated by suppression of inflammation and a direct action on epithelial cells. This result suggests that tiotropium may be useful for the treatment of mucus overproduction in COPD.

  9. Recombinant Rat CC10 Protein Inhibits PDGF-Induced Airway Smooth Muscle Cells Proliferation and Migration

    Directory of Open Access Journals (Sweden)

    Ying Wei

    2013-01-01

    Full Text Available Abnormal migration and proliferation of airway smooth muscle cells (ASMCs in the airway cause airway wall thickening, which is strongly related with the development of airway remodeling in asthma. Clara cell 10 kDa protein (CC10, which is secreted by the epithelial clara cells of the pulmonary airways, plays an important role in the regulation of immunological and inflammatory processes. Previous studies suggested that CC10 protein had great protective effects against inflammation in asthma. However, the effects of CC10 protein on ASMCs migration and proliferation in airway remodeling were poorly understood. In this study, we constructed the pET-22b-CC10 recombinant plasmid, induced expression and purified the recombinant rat CC10 protein from E. coli by Ni2+ affinity chromatography and ion exchange chromatography purification. We investigated the effect of recombinant rat CC10 protein on platelet-derived growth factor (PDGF-BB-induced ASMCs proliferation and migration. Our results demonstrated that the recombinant CC10 protein could inhibit PDGF-BB-induced cell viability, proliferation and migration. Western blot analysis showed that PDGF-BB-induced activation of cyclin D1 was inhibited by CC10. These findings implicated that CC10 could inhibit increased ASMCs proliferation, and migration induced by PDGF-BB, and this suppression effect might be associated with inhibition of cyclin D1 expression, which might offer hope for the future treatment of airway remodeling.

  10. Inhibiting the Ca2+ Influx Induced by Human CSF

    Directory of Open Access Journals (Sweden)

    Anna Drews

    2017-12-01

    Full Text Available One potential therapeutic strategy for Alzheimer’s disease (AD is to use antibodies that bind to small soluble protein aggregates to reduce their toxic effects. However, these therapies are rarely tested in human CSF before clinical trials because of the lack of sensitive methods that enable the measurement of aggregate-induced toxicity at low concentrations. We have developed highly sensitive single vesicle and single-cell-based assays that detect the Ca2+ influx caused by the CSF of individuals affected with AD and healthy controls, and we have found comparable effects for both types of samples. We also show that an extracellular chaperone clusterin; a nanobody specific to the amyloid-β peptide (Aβ; and bapineuzumab, a humanized monoclonal antibody raised against Aβ, could all reduce the Ca2+ influx caused by synthetic Aβ oligomers but are less effective in CSF. These assays could be used to characterize potential therapeutic agents in CSF before clinical trials.

  11. Preventative Effects of Caffeic Acid Phenyl Ester on Cadmium Intoxication Induced Hematological and Blood Coagulation Disturbances and Hepatorenal Damage in Rats

    Science.gov (United States)

    Ashour, Tariq Helal

    2014-01-01

    The preventative effect of caffeic acid phenyl ester (CAPE) against hematological, blood coagulation, and hepatorenal disturbances in cadmium (Cd) intoxication was investigated in rats. Male Wistar rats were randomly assigned into control group, Cd-group, and Cd + CAPE group. Cd intoxication was induced by intraperitoneal injection (i.p.) of CdCl2 (1 mg/kg/day) for 21 days, and CAPE was daily given (10 micromol/kg; i.p.) for also 21 days. The results showed that Cd intoxication impaired hepatorenal function and significantly prolonged prothrombin time and activated partial thromboplastin time and decreased fibrinogen level, red blood cells and platelets counts, hemoglobin concentration, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration. Interestingly, all these hematological, blood coagulation, and hepatorenal deteriorations of Cd toxicity were significantly prevented by CAPE. Additionally, CAPE significantly reversed the significant decreases in levels of total reduced glutathione and superoxide dismutase and increases in levels of thiobarbituric acid reactive substances that were observed in the sera and liver and kidney homogenates of Cd group. It is concluded that CAPE is a promising compound that can counteract the hematological and blood coagulation disturbances, oxidative stress, and hepatorenal damages in Cd intoxication. However, further studies are crucially needed to improve this treatment in patients. PMID:25006475

  12. Studies on the protective effect of the artichoke (Cynara scolymus) leaf extract against cadmium toxicity-induced oxidative stress, hepatorenal damage, and immunosuppressive and hematological disorders in rats.

    Science.gov (United States)

    El-Boshy, Mohamed; Ashshi, Ahmad; Gaith, Mazen; Qusty, Naeem; Bokhary, Thalat; AlTaweel, Nagwa; Abdelhady, Mohamed

    2017-05-01

    Our objective was to explore the protective effect of artichoke leaf extract (ALE) against cadmium (Cd) toxicity-induced oxidative organ damage in rats. Male albino Wistar rats were divided into four equal groups of eight animals each. The first group was assigned as a control. Groups 2-4 were orally administered with ALE (300 mg/kg bw), Cd (CdCl2, 100 mg/L drinking water), and ALE plus Cd, respectively, daily for 4 weeks. After treatment with Cd, the liver and kidney malondialdehyde (MDA) increased significantly compared with the control rats. The sera interleukin (IL)-1β, tumor necrosis factor (TNF-α), and IL-10, liver transaminase, urea, creatinine, and peripheral neutrophil count were significantly increased in Cd-exposed rats compared to the control group. The reduced glutathione (GSH), glutathione peroxidase (GPX), superoxide dismutase (SOD), and catalase (CAT) decreased in the liver and kidney in Cd-exposed group. In combination treatment, Cd and ALE significantly improved immune response, an antioxidant system, and hepatorenal function with a significant decline in MDA. In conclusion, ALE ameliorates the immunosuppressive and hepatorenal oxidative injury stimulated by Cd in rats. These results suggest that artichoke has shown promising effects against adverse effects of Cd toxicity.

  13. Montelukast inhibits pentylenetetrazol-induced seizures in rats.

    Science.gov (United States)

    Cevik, Betul; Solmaz, Volkan; Aksoy, Durdane; Erbas, Oytun

    2015-03-24

    Montelukast is an antiinflammatory drug with an antioxidant property. In this study, we aimed to reveal whether montelukast has a preventive effect against seizures and post-seizure oxidative stress in pentylenetetrazol (PTZ)-induced seizures in rats. Of the 48 male Sprague-Dawley rats used in the study, 24 were assigned to EEG recordings (group A) and 24 were assigned to behavioral studies (group B). In group A, the electrodes were implanted on dura over the left frontal cortex for EEG recording. After 10 days, in group A, i.p. saline, 25, 50, or 100 mg/kg montelukast+35 mg/kg PTZ was administered to the rats. EEG was recorded and spike percentage was evaluated. In group B, i.p. saline, 25, 50, or 100 mg/kg montelukast+70 mg/kg PTZ was administered to the rats. Racine's Convulsion Scale (RCS) and onset times of first myoclonic jerk (FMJ) was used to evaluate the seizures. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined in the brain tissue of animals. Animals treated with 50 or 100 mg/kg montelukast had significantly lower RCS and significantly increased FMJ onset time compared to the saline-treated animals. Moreover, groups given 25, 50, or 100 mg/kg montelukast had significantly lower MDA and higher SOD levels compared to the saline-treated group. The differences were more pronounced in the 100 mg/kg montelukast-pretreated group (pMontelukast showed anticonvulsant action and led to amelioration of oxidative stress markers in PTZ-induced seizures in rats.

  14. Synthetic RGDS peptide attenuates lipopolysaccharide-induced pulmonary inflammation by inhibiting integrin signaled MAP kinase pathways

    Directory of Open Access Journals (Sweden)

    Hah Jong

    2009-03-01

    Full Text Available Abstract Background Synthetic peptides containing the RGD sequence inhibit integrin-related functions in different cell systems. Here, we investigated the effects of synthetic Arg-Gly-Asp-Ser (RGDS peptide on key inflammatory responses to intratracheal (i.t. lipopolysaccharide (LPS treatment and on the integrin signaled mitogen-activated protein (MAP kinase pathway during the development of acute lung injury. Methods Saline or LPS (1.5 mg/kg was administered i.t. with or without a single dose of RGDS (1, 2.5, or 5 mg/kg, i.p., anti-αv or anti-β3 mAb (5 mg/kg, i.p.. Mice were sacrificed 4 or 24 h post-LPS. Results A pretreatment with RGDS inhibited LPS-induced increases in neutrophil and macrophage numbers, total protein levels and TNF-α and MIP-2 levels, and matrix metalloproteinase-9 activity in bronchoalveolar lavage (BAL fluid at 4 or 24 h post-LPS treatment. RGDS inhibited LPS-induced phosphorylation of focal adhesion kinase and MAP kinases, including ERK, JNK, and p38 MAP kinase, in lung tissue. Importantly, the inhibition of the inflammatory responses and the kinase pathways were still evident when this peptide was administered 2 h after LPS treatment. Similarly, a blocking antibody against integrin αv significantly inhibited LPS-induced inflammatory cell migration into the lung, protein accumulation and proinflammatory mediator production in BAL fluid, at 4 or 24 h post-LPS. Anti-β3 also inhibited all LPS-induced inflammatory responses, except the accumulation of BAL protein at 24 h post-LPS. Conclusion These results suggest that RGDS with high specificity for αvintegrins attenuates inflammatory cascade during LPS-induced development of acute lung injury.

  15. Celecoxib-induced cytotoxic effect is potentiated by inhibition of autophagy in human urothelial carcinoma cells.

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    Kuo-How Huang

    Full Text Available Celecoxib, a cyclooxygenase-2 (COX-2 inhibitor, can elicit anti-tumor effects in various malignancies. Here, we sought to clarify the role of autophagy in celecoxib-induced cytotoxicity in human urothelial carcinoma (UC cells. The results shows celecoxib induced cellular stress response such as endoplasmic reticulum (ER stress, phosopho-SAPK/JNK, and phosopho-c-Jun as well as autophagosome formation in UC cells. Inhibition of autophagy by 3-methyladenine (3-MA, bafilomycin A1 or ATG7 knockdown potentiated celecoxib-induced apoptosis. Up-regulation of autophagy by rapamycin or GFP-LC3B-transfection alleviated celecoxib-induced cytotoxicity in UC cells. Taken together, the inhibition of autophagy enhances therapeutic efficacy of celecoxib in UC cells, suggesting a novel therapeutic strategy against UC.

  16. Autotaxin is induced by TSA through HDAC3 and HDAC7 inhibition and antagonizes the TSA-induced cell apoptosis

    Science.gov (United States)

    2011-01-01

    Background Autotaxin (ATX) is a secreted glycoprotein with the lysophospholipase D (lysoPLD) activity to convert lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a bioactive lysophospholipid involved in diverse biological actions. ATX is highly expressed in some cancer cells and contributes to their tumorigenesis, invasion, and metastases, while in other cancer cells ATX is silenced or expressed at low level. The mechanism of ATX expression regulation in cancer cells remains largely unknown. Results In the present study, we demonstrated that trichostatin A (TSA), a well-known HDAC inhibitor (HDACi), significantly induced ATX expression in SW480 and several other cancer cells with low or undetectable endogenous ATX expression. ATX induction could be observed when HDAC3 and HDAC7 were down-regulated by their siRNAs. It was found that HDAC7 expression levels were low in the cancer cells with high endogenous ATX expression. Exogenous over-expression of HDAC7 inhibited ATX expression in these cells in a HDAC3-dependent manner. These data indicate that HDAC3 and HDAC7 collaboratively suppress ATX expression in cancer cells, and suggest that TSA induce ATX expression by inhibiting HDAC3 and HDAC7. The biological significance of this regulation mechanism was revealed by demonstrating that TSA-induced ATX protected cancer cells against TSA-induced apoptosis by producing LPA through its lysoPLD activity, which could be reversed by BrP-LPA and S32826, the inhibitors of the ATX-LPA axis. Conclusions We have demonstrated that ATX expression is repressed by HDAC3 and HDAC7 in cancer cells. During TSA treatment, ATX is induced due to the HDAC3 and HDAC7 inhibition and functionally antagonizes the TSA-induced apoptosis. These results reveal an internal HDACi-resistant mechanism in cancer cells, and suggest that the inhibition of ATX-LPA axis would be helpful to improve the efficacy of HDACi-based therapeutics against cancer. PMID:21314984

  17. Autotaxin is induced by TSA through HDAC3 and HDAC7 inhibition and antagonizes the TSA-induced cell apoptosis

    Directory of Open Access Journals (Sweden)

    Zhang Junjie

    2011-02-01

    Full Text Available Abstract Background Autotaxin (ATX is a secreted glycoprotein with the lysophospholipase D (lysoPLD activity to convert lysophosphatidylcholine (LPC into lysophosphatidic acid (LPA, a bioactive lysophospholipid involved in diverse biological actions. ATX is highly expressed in some cancer cells and contributes to their tumorigenesis, invasion, and metastases, while in other cancer cells ATX is silenced or expressed at low level. The mechanism of ATX expression regulation in cancer cells remains largely unknown. Results In the present study, we demonstrated that trichostatin A (TSA, a well-known HDAC inhibitor (HDACi, significantly induced ATX expression in SW480 and several other cancer cells with low or undetectable endogenous ATX expression. ATX induction could be observed when HDAC3 and HDAC7 were down-regulated by their siRNAs. It was found that HDAC7 expression levels were low in the cancer cells with high endogenous ATX expression. Exogenous over-expression of HDAC7 inhibited ATX expression in these cells in a HDAC3-dependent manner. These data indicate that HDAC3 and HDAC7 collaboratively suppress ATX expression in cancer cells, and suggest that TSA induce ATX expression by inhibiting HDAC3 and HDAC7. The biological significance of this regulation mechanism was revealed by demonstrating that TSA-induced ATX protected cancer cells against TSA-induced apoptosis by producing LPA through its lysoPLD activity, which could be reversed by BrP-LPA and S32826, the inhibitors of the ATX-LPA axis. Conclusions We have demonstrated that ATX expression is repressed by HDAC3 and HDAC7 in cancer cells. During TSA treatment, ATX is induced due to the HDAC3 and HDAC7 inhibition and functionally antagonizes the TSA-induced apoptosis. These results reveal an internal HDACi-resistant mechanism in cancer cells, and suggest that the inhibition of ATX-LPA axis would be helpful to improve the efficacy of HDACi-based therapeutics against cancer.

  18. Autotaxin is induced by TSA through HDAC3 and HDAC7 inhibition and antagonizes the TSA-induced cell apoptosis.

    Science.gov (United States)

    Li, Song; Wang, Baolu; Xu, Yan; Zhang, Junjie

    2011-02-12

    Autotaxin (ATX) is a secreted glycoprotein with the lysophospholipase D (lysoPLD) activity to convert lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), a bioactive lysophospholipid involved in diverse biological actions. ATX is highly expressed in some cancer cells and contributes to their tumorigenesis, invasion, and metastases, while in other cancer cells ATX is silenced or expressed at low level. The mechanism of ATX expression regulation in cancer cells remains largely unknown. In the present study, we demonstrated that trichostatin A (TSA), a well-known HDAC inhibitor (HDACi), significantly induced ATX expression in SW480 and several other cancer cells with low or undetectable endogenous ATX expression. ATX induction could be observed when HDAC3 and HDAC7 were down-regulated by their siRNAs. It was found that HDAC7 expression levels were low in the cancer cells with high endogenous ATX expression. Exogenous over-expression of HDAC7 inhibited ATX expression in these cells in a HDAC3-dependent manner. These data indicate that HDAC3 and HDAC7 collaboratively suppress ATX expression in cancer cells, and suggest that TSA induce ATX expression by inhibiting HDAC3 and HDAC7. The biological significance of this regulation mechanism was revealed by demonstrating that TSA-induced ATX protected cancer cells against TSA-induced apoptosis by producing LPA through its lysoPLD activity, which could be reversed by BrP-LPA and S32826, the inhibitors of the ATX-LPA axis. We have demonstrated that ATX expression is repressed by HDAC3 and HDAC7 in cancer cells. During TSA treatment, ATX is induced due to the HDAC3 and HDAC7 inhibition and functionally antagonizes the TSA-induced apoptosis. These results reveal an internal HDACi-resistant mechanism in cancer cells, and suggest that the inhibition of ATX-LPA axis would be helpful to improve the efficacy of HDACi-based therapeutics against cancer.

  19. Zinc-Nickel Codeposition in Sulfate Solution Combined Effect of Cadmium and Boric Acid

    Directory of Open Access Journals (Sweden)

    Y. Addi

    2011-01-01

    Full Text Available The combined effect of cadmium and boric acid on the electrodeposition of zinc-nickel from a sulfate has been investigated. The presence of cadmium ion decreases zinc in the deposit. In solution, cadmium inhibits the zinc ion deposition and suppresses it when deposition potential value is more negative than −1.2 V. Low concentration of CdSO4 reduces the anomalous nature of Zn-Ni deposit. Boric acid decreases current density and shifts potential discharge of nickel and hydrogen to more negative potential. The combination of boric acid and cadmium increases the percentage of nickel in the deposit. Boric acid and cadmium.

  20. Foliar modifications induced by inhibition of polar transport of auxin.

    Science.gov (United States)

    Ni, D A; Wang, L J; Xu, Z H; Xia, Z A

    1999-03-01

    The effects of auxin polar transport inhibitors, 9-hydroxy-fluorene-9-carboxylic acid (HFCA); 2, 3, 5-triiodobenzoic acid (TIBA) and trans-cinnamic acid (CA) on leaf pattern formation were investigated with shoots formed from cultured leaf explants of tobacco and cultured pedicel explants of Orychophragmus violaceus, and the seedlings of tobacco and Brassica chinensis. Although the effective concentration varies with the inhibitors used, all of the inhibitors induced the formation of trumpet-shaped and/or fused leaves. The frequency of trumpet-shaped leaf formation was related to the concentration of inhibitors in the medium. Histological observation of tobacco seedlings showed that there was only one main vascular bundle and several minor vascular bundles in normal leaves of the control, but there were several vascular bundles of more or less the same size in the trumpet-shaped leaves of treated ones. These results indicated that auxin polar transport played an important role on bilateral symmetry of leaf growth.

  1. Id1 induces apoptosis through inhibition of RORgammat expression

    Directory of Open Access Journals (Sweden)

    Sun Xiao-Hong

    2008-05-01

    Full Text Available Abstract Background Basic helix-loop-helix E proteins are transcription factors that play crucial roles in T cell development by controlling thymocyte proliferation, differentiation and survival. E protein functions can be repressed by their naturally occurring inhibitors, Id proteins (Id1-4. Transgenic expression of Id1 blocks T cell development and causes massive apoptosis of developing thymocytes. However, the underlying mechanisms are not entirely understood due to relatively little knowledge of the target genes regulated by E proteins. Results We designed a unique strategy to search for genes directly controlled by E proteins and found RORγt to be a top candidate. Using microarray analyses and reverse-transcriptase PCR assays, we showed that Id1 expression diminished RORγt mRNA levels in T cell lines and primary thymocytes while induction of E protein activity restored RORγt expression. E proteins were found to specifically bind to the promoter region of RORγt, suggesting their role in activating transcription of the gene. Functional significance of E protein-controlled RORγt expression was established based on the finding that RORγt rescued apoptosis caused by Id1 overexpression. Furthermore, expression of RORγt prevented Id1-induced p38 MAP kinase hyper-activation. Conclusion These results suggest that E protein-dependent RORγt gene expression aids the survival of developing thymocytes, which provides a possible explanation for the massive apoptosis found in Id1 transgenic mice.

  2. Inhibition of lipopolysaccharide induced acute inflammation in lung by chlorination.

    Science.gov (United States)

    Zhang, Jinshan; Xue, Jinling; Xu, Bi; Xie, Jiani; Qiao, Juan; Lu, Yun

    2016-02-13

    Lipopolysaccharide (LPS, also called endotoxin) is a pro-inflammatory constituent of gram negative bacteria and cyanobacteria, which causes a potential health risk in the process of routine urban application of reclaimed water, such as car wash, irrigation, scenic water refilling, etc. Previous studies indicated that the common disinfection treatment, chlorination, has little effect on endotoxin activity removal measured by Limulus amebocyte lysate (LAL) assay. However, in this study, significant decrease of acute inflammatory effects was observed in mouse lung, while LAL assay still presented a moderate increase of endotoxin activity. To explore the possible mechanisms, the nuclear magnetic resonance (NMR) results showed the chlorination happened in alkyl chain of LPS molecules, which could affect the interaction between LPS and LPS-binding protein. Also the size of LPS aggregates was found to drop significantly after treatment, which could be another results of chlorination caused polarity change. In conclusion, our observation demonstrated that chlorination is effective to reduce the LPS induced inflammation in lung, and it is recommended to use health effect-based methods to assess risk removal of water treatment technologies. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Blockade of store-operated calcium entry alleviates ethanol-induced hepatotoxicity via inhibiting apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Ruibing [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Lihui [Shandong Normal University, Jinan, Shandong Province 250012 (China); Luo, Zheng; Guo, Xiaolan [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China); Yan, Ming, E-mail: ymylh@163.com [Department of Hepatology and Gastroenterology, Qilu Hospital of Shandong University, Jinan, Shandong Province 250012 (China)

    2015-08-15

    Extracellular Ca{sup 2+} influx has been suggested to play a role in ethanol-induced hepatocyte apoptosis and necrosis. Previous studies indicated that store-operated Ca{sup 2+} entry (SOCE) was involved in liver injury induced by ethanol in HepG2 cells. However, the mechanisms underlying liver injury caused by SOCE remain unclear. We aimed to investigate the effects and mechanism of SOCE inhibition on liver injury induced by ethanol in BRL cells and Sprague–Dawley rats. Our data demonstrated that ethanol (0–400 mM) dose-dependently increased hepatocyte injury and 100 mM ethanol significantly upregulated the mRNA and protein expression of SOC for at least 72 h in BRL cells. Blockade of SOCE by pharmacological inhibitors and sh-RNA knockdown of STIM1 and Orai1 attenuated intracellular Ca{sup 2+} overload, restored the mitochondrial membrane potential (MMP), decreased cytochrome C release and inhibited ethanol-induced apoptosis. STIM1 and Orai1 expression was greater in ethanol-treated than control rats, and the SOCE inhibitor corosolic acid ameliorated the histopathological findings and alanine transaminase and aspartate transaminase activity as well as decreased cytochrome C release and inhibited alcohol-induced cell apoptosis. These findings suggest that SOCE blockade could alleviate alcohol-induced hepatotoxicity via inhibiting apoptosis. SOCE might be a useful therapeutic target in alcoholic liver diseases. - Highlights: • Blockade of SOCE alleviated overload of Ca{sup 2+} and hepatotoxicity after ethanol application. • Blockade of SOCE inhibited mitochondrial apoptosis after ethanol application. • SOCE might be a useful therapeutic target in alcoholic liver diseases.

  4. Inhibition of chlorine-induced lung injury by the type 4 phosphodiesterase inhibitor rolipram

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Weiyuan; Chen, Jing; Schlueter, Connie F. [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States); Rando, Roy J. [Department of Environmental Health Sciences, School of Public Health and Tropical Medicine, Tulane University Health Sciences Center, New Orleans, LA (United States); Pathak, Yashwant V. [College of Pharmacy, University of South Florida, Tampa, FL (United States); Hoyle, Gary W., E-mail: Gary.Hoyle@louisville.edu [Department of Environmental and Occupational Health Sciences, School of Public Health and Information Sciences, University of Louisville, Louisville, KY (United States)

    2012-09-01

    Chlorine is a highly toxic respiratory irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity, inflammation, and pulmonary edema. Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from acute lung injury. The type 4 phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for chlorine-induced lung injury. Rolipram inhibits degradation of the intracellular signaling molecule cyclic AMP. Potential beneficial effects of increased cyclic AMP levels include inhibition of pulmonary edema, inflammation, and airway hyperreactivity. Mice were exposed to chlorine (whole body exposure, 228–270 ppm for 1 h) and were treated with rolipram by intraperitoneal, intranasal, or intramuscular (either aqueous or nanoemulsion formulation) delivery starting 1 h after exposure. Rolipram administered intraperitoneally or intranasally inhibited chlorine-induced pulmonary edema. Minor or no effects were observed on lavage fluid IgM (indicative of plasma protein leakage), KC (Cxcl1, neutrophil chemoattractant), and neutrophils. All routes of administration inhibited chlorine-induced airway hyperreactivity assessed 1 day after exposure. The results of the study suggest that rolipram may be an effective rescue treatment for chlorine-induced lung injury and that both systemic and targeted administration to the respiratory tract were effective routes of delivery. -- Highlights: ► Chlorine causes lung injury when inhaled and is considered a chemical threat agent. ► Rolipram inhibited chlorine-induced pulmonary edema and airway hyperreactivity. ► Post-exposure rolipram treatments by both systemic and local delivery were effective. ► Rolipram shows promise as a rescue treatment for chlorine-induced lung injury.

  5. The tetrapeptide Arg-Leu-Tyr-Glu inhibits VEGF-induced angiogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Yi-Yong; Lee, Dong-Keon [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); So, Ju-Hoon; Kim, Cheol-Hee [Department of Biology, Chungnam National University, Daejeon, 305-764 (Korea, Republic of); Jeoung, Dooil [Department of Biochemistry, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Lee, Hansoo [Department of Life Sciences, College of Natural Sciences, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Choe, Jongseon [Department of Immunology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Won, Moo-Ho [Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Ha, Kwon-Soo [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of); Kwon, Young-Guen [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-752 (Korea, Republic of); Kim, Young-Myeong, E-mail: ymkim@kangwon.ac.kr [Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, Gangwon-do, 200-702 (Korea, Republic of)

    2015-08-07

    Kringle 5, derived from plasminogen, is highly capable of inhibiting angiogenesis. Here, we have designed and synthesized 10 tetrapeptides, based on the amino acid properties of the core tetrapeptide Lys-Leu-Tyr-Asp (KLYD) originating from anti-angiogenic kringle 5 of human plasminogen. Of these, Arg-Leu-Tyr-Glu (RLYE) effectively inhibited vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation, migration and tube formation, with an IC{sub 50} of 0.06–0.08 nM, which was about ten-fold lower than that of the control peptide KLYD (0.79 nM), as well as suppressed developmental angiogenesis in a zebrafish model. Furthermore, this peptide effectively inhibited the cellular events that precede angiogenesis, such as ERK and eNOS phosphorylation and nitric oxide production, in endothelial cells stimulated with VEGF. Collectively, these data demonstrate that RLYE is a potent anti-angiogenic peptide that targets the VEGF signaling pathway. - Highlights: • The tetrapeptide RLYE inhibited VEGF-induced angiogenesis in vitro. • RLYE also suppressed neovascularization in a zebrafish model. • Its effect was correlated with inhibition of VEGF-induced ERK and eNOS activation. • RLYE may be used as a therapeutic drug for angiogenesis-related diseases.

  6. Leflunomide/teriflunomide inhibit Epstein-Barr virus (EBV)- induced lymphoproliferative disease and lytic viral replication.

    Science.gov (United States)

    Bilger, Andrea; Plowshay, Julie; Ma, Shidong; Nawandar, Dhananjay; Barlow, Elizabeth A; Romero-Masters, James C; Bristol, Jillian A; Li, Zhe; Tsai, Ming-Han; Delecluse, Henri-Jacques; Kenney, Shannon C

    2017-07-04

    EBV infection causes mononucleosis and is associated with specific subsets of B cell lymphomas. Immunosuppressed patients such as organ transplant recipients are particularly susceptible to EBV-induced lymphoproliferative disease (LPD), which can be fatal. Leflunomide (a drug used to treat rheumatoid arthritis) and its active metabolite teriflunomide (used to treat multiple sclerosis) inhibit de novo pyrimidine synthesis by targeting the cellular dihydroorotate dehydrogenase, thereby decreasing T cell proliferation. Leflunomide also inhibits the replication of cytomegalovirus and BK virus via both "on target" and "off target" mechanisms and is increasingly used to treat these viruses in organ transplant recipients. However, whether leflunomide/teriflunomide block EBV replication or inhibit EBV-mediated B cell transformation is currently unknown. We show that teriflunomide inhibits cellular proliferation, and promotes apoptosis, in EBV-transformed B cells in vitro at a clinically relevant dose. In addition, teriflunomide prevents the development of EBV-induced lymphomas in both a humanized mouse model and a xenograft model. Furthermore, teriflunomide inhibits lytic EBV infection in vitro both by preventing the initial steps of lytic viral reactivation, and by blocking lytic viral DNA replication. Leflunomide/teriflunomide might therefore be clinically useful for preventing EBV-induced LPD in patients who have high EBV loads yet require continued immunosuppression.

  7. Carbon Monoxide Attenuates Dextran Sulfate Sodium-Induced Colitis via Inhibition of GSK-3β Signaling

    Directory of Open Access Journals (Sweden)

    Md. Jamal Uddin

    2013-01-01

    Full Text Available Endogenous carbon monoxide (CO is produced by heme oxygenase-1 (HO-1 which mediates the degradation of heme into CO, iron, and biliverdin. Also, CO ameliorates the human inflammatory bowel diseases and ulcerative colitis. However, the mechanism for the effect of CO on the inflammatory bowel disease has not yet been known. In this study, we showed that CO significantly increases survival percentage, body weight, colon length as well as histologic parameters in DSS-treated mice. In addition, CO inhalation significantly decreased DSS induced pro-inflammatory cytokines by inhibition of GSK-3β in mice model. To support the in vivo observation, TNF-α, iNOS and IL-10 after CO and LiCl treatment were measured in mesenteric lymph node cells (MLNs and bone marrow-derived macrophages (BMMs from DSS treated mice. In addition, we determined that CO potentially inhibited GSK-3β activation and decreased TNF-α and iNOS expression by inhibition of NF-κB activation in LPS-stimulated U937 and MLN cells pretreated with CO. Together, our findings indicate that CO attenuates DSS-induced colitis via inhibition of GSK-3β signaling in vitro and in vivo. Importantly, this is the first report that investigated the molecular mechanisms mediated the novel effects of CO via inhibition GSK-3β in DSS-induced colitis model.

  8. Epigallocatechin gallate (EGCG) attenuates infrasound-induced neuronal impairment by inhibiting microglia-mediated inflammation.

    Science.gov (United States)

    Cai, Jing; Jing, Da; Shi, Ming; Liu, Yang; Lin, Tian; Xie, Zhen; Zhu, Yi; Zhao, Haibo; Shi, Xiaodan; Du, Fang; Zhao, Gang

    2014-07-01

    Infrasound, a kind of common environmental noise and a major contributor of vibroacoustic disease, can induce the central nervous system (CNS) damage. However, no relevant anti-infrasound drugs have been reported yet. Our recent studies have shown that infrasound resulted in excessive microglial activation rapidly and sequential inflammation, revealing a potential role of microglia in infrasound-induced CNS damage. Epigallocatechin gallate (EGCG), a major bioactive component in green tea, has the capacity of protecting against various neurodegenerative diseases via an anti-inflammatory mechanism. However, it is still unknown to date whether EGCG acts on infrasound-induced microglial activation and neuronal damage. We showed that, after 1-, 2- or 5-day exposure of rats to 16 Hz, 130 dB infrasound (2 h/day), EGCG significantly inhibited infrasound-induced microglial activation in rat hippocampal region, evidenced by reduced expressions of Iba-1 (a marker for microglia) and proinflammatory cytokines (IL-1β, IL-6, IL-18 and TNF-α). Moreover, infrasound-induced neuronal apoptosis in rat hippocampi was significantly suppressed by EGCG. EGCG also inhibited infrasound-induced activation of primary microglia in vitro and decreased the levels of proinflammatory cytokines in the supernatants of microglial culture, which were toxic to cultured neurons. Furthermore, EGCG attenuated infrasound-induced increases in nuclear NF-κB p65 and phosphorylated IκBα, and ameliorated infrasound-induced decrease in IκB in microglia. Therefore, our study provides the first evidence that EGCG acts against infrasound-induced neuronal impairment by inhibiting microglia-mediated inflammation through a potential NF-κB pathway-related mechanism, suggesting that EGCG can be used as a promising drug for the treatment of infrasound-induced CNS damage. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. IL-33 attenuates anoxia/reoxygenation-induced cardiomyocyte apoptosis by inhibition of PKCβ/JNK pathway.

    Directory of Open Access Journals (Sweden)

    Tao Rui

    Full Text Available Interleukin-33 (IL-33 is a new member of the IL-1 cytokine family. The objectives of present study are to assess whether IL-33 can protect cardiomyocytes from anoxia/reoxygenation (A/R-induced injury and the mechanism involved in the protection.Cardiomyocytes derived from either wild type or JNK1(-/- mice were challenged with an A/R with or without IL-33. Myocyte apoptosis was assessed by measuring caspase 3 activity, fragmented DNA and TUNEL staining. In addition, cardiomyocyte oxidative stress was assessed by measuring DHR123 oxidation; PKCβII and JNK phosphorylation were assessed with Western blot.Challenge of cardiomyocytes with an A/R resulted in cardiomyocyte oxidative stress, PKCβII and JNK phosphorylation, and myocyte apoptosis. Treatment of the cardiomyocytes with IL-33 attenuated the A/R-induced myocyte oxidative stress, prevented PKCβII and JNK phosphorylation and attenuated the A/R-induced myocyte apoptosis. The protective effect of the IL-33 did not show in cardiac myocytes with siRNA specific to PKCβII or myocytes deficient in JNK1. Inhibition of PKCβII prevented the A/R-induced JNK phosphorylation, but inhibition of JNK1 showed no effect on A/R-induced PKCβII phosphorylation.Our results indicate that IL-33 prevents the A/R-induced myocyte apoptosis through inhibition of PKCβ/JNK pathway.

  10. Lansoprazole induces apoptosis of breast cancer cells through inhibition of intracellular proton extrusion

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Shangrong; Wang, Yifan; Li, Shu Jie, E-mail: shujieli@nankai.edu.cn

    2014-06-13

    Highlights: • Lansoprazole (LPZ) induces cell apoptosis in breast cancer cells. • LPZ markedly inhibits intracellular proton extrusion. • LPZ induces an increase in intracellular ATP level, lysosomal alkalinization and ROS accumulation. - Abstract: The increased glycolysis and proton secretion in tumors is proposed to contribute to the proliferation and invasion of cancer cells during the process of tumorigenesis and metastasis. Here, treatment of human breast cancer cells with proton pump inhibitor (PPI) lansoprazole (LPZ) induces cell apoptosis in a dose-dependent manner. In the implantation of the MDA-MB-231 xenografts in nude mice, administration of LPZ significantly inhibits tumorigenesis and induces large-scale apopotosis of tumor cells. LPZ markedly inhibits intracellular proton extrusion, induces an increase in intracellular ATP level, lysosomal alkalinization and accumulation of reactive oxygen species (ROS) in breast cancer cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and diphenyleneiodonium (DPI), a specific pharmacological inhibitor of NADPH oxidases (NOX), significantly abolish LPZ-induced ROS accumulation in breast cancer cells. Our results suggested that LPZ may be used as a new therapeutic drug for breast tumor.

  11. Perivascular delivery of Notch 1 siRNA inhibits injury-induced arterial remodeling.

    Directory of Open Access Journals (Sweden)

    Eileen M Redmond

    Full Text Available To determine the efficacy of perivascular delivery of Notch 1 siRNA in preventing injury-induced arterial remodeling.Carotid artery ligation was performed to induce arterial remodeling. After 14 days, morphometric analysis confirmed increased vSMC growth and subsequent media thickening and neointimal formation. Laser capture microdissection, quantitative qRT-PCR and immunoblot analysis of medial tissue revealed a significant increase in Notch1 receptor and notch target gene, Hrt 1 and 2 expression in the injured vessels. Perivascular delivery of Notch 1 siRNA by pluronic gel inhibited the injury-induced increase in Notch 1 receptor and target gene expression when compared to scrambled siRNA controls while concomitantly reducing media thickening and neointimal formation to pre-injury, sham-operated levels. Selective Notch 1 knockdown also reversed the injury-induced inhibition of pro-apoptotic Bax expression while decreasing injury-induced anti-apoptotic Bcl-XL expression to sham-operated control levels. In parallel experiments, proliferative cyclin levels, as measured by PCNA expression, were reversed to sham-operated control levels following selective Notch 1 knockdown.These results suggest that injury-induced arterial remodeling can be successfully inhibited by localized perivascular delivery of Notch 1 siRNA.

  12. Lumican Inhibits SNAIL-Induced Melanoma Cell Migration Specifically by Blocking MMP-14 Activity.

    Directory of Open Access Journals (Sweden)

    Marta Stasiak

    Full Text Available Lumican, a small leucine rich proteoglycan, inhibits MMP-14 activity and melanoma cell migration in vitro and in vivo. Snail triggers epithelial-mesenchymal transitions endowing epithelial cells with migratory and invasive properties during tumor progression. The aim of this work was to investigate lumican effects on MMP-14 activity and migration of Snail overexpressing B16F1 (Snail-B16F1 melanoma cells and HT-29 colon adenocarcinoma cells. Lumican inhibits the Snail induced MMP-14 activity in B16F1 but not in HT-29 cells. In Snail-B16F1 cells, lumican inhibits migration, growth, and melanoma primary tumor development. A lumican-based strategy targeting Snail-induced MMP-14 activity might be useful for melanoma treatment.

  13. Effective inhibition by beta-carotene of cellular DNA breaking induced by peroxynitrous acid.

    Science.gov (United States)

    Hiramoto, K; Tomiyama, S; Kikugawa, K

    1999-01-01

    Peroxynitrous acid synthesized by reaction of hydrogen peroxide and nitrite and generated from 3-morpholinosydononimine (SIN-1) induced cellular DNA breaking of human promyelocytic leukemia HL-60 cells in phosphate buffer (pH 7.5) as assessed by alkaline single cell gel electrophoresis (comet) assay and quantification of comet types. Ascorbate and Trolox inhibited cellular DNA breaking induced by peroxynitrous acid, but the concentrations of these antioxidants required for effective inhibition was about 50-fold higher than that of peroxynitrous acid. beta-Carotene protected DNA breaking by peroxynitrous acid in 20% tetrahydrofuran-phosphate buffer (pH 7.5) much more effectively than ascorbate and Trolox. The concentrations of beta-carotene required for effective inhibition was lower than the concentration of peroxynitrous acid.

  14. Antimicrobial and inhibition on heat-induced protein denaturation of constituents isolated from Polygonatum verticillatum rhizomes.

    Science.gov (United States)

    Khan, Haroon; Saeed, Muhammad; Rauf, Abdur; Khan, Muhammad Atif; Muhammad, Naveed

    2015-01-01

    This study was designed to assess the susceptibility of various microorganisms and inhibition on heat-induced protein denaturation against diosgenin and santonin, isolated from Polygonatum verticillatum rhizomes. Both diosgenin and santonin showed significant zone of inhibition when studied against various Gram-positive (Bacillus subtilis, Bacillus cereus, Staphylococcus aureus and Staphylococcus epidermidis) and Gram-negative bacteria (Escherichia coli and Salmonella typhi). In antifungal assay, only santonin exhibited profound sensitivity against various fungi (Aspergillus flavus, Aspergillus niger, Trichoderma harzianum and Fusarium oxysporum) used in the test. Both diosgenin and santonin also exhibited marked attenuation on heat-induced protein denaturation in a concentration-dependent manner with EC50 values of 375 and 310 μg/mL, respectively. In conclusion, both the isolated compounds have antimicrobial potential supported by strong inhibition on protein denaturation and thus support the antimicrobial uses of plant in traditional system of treatment.

  15. Inhibition of autophagy induced by TSA sensitizes colon cancer cell to radiation.

    Science.gov (United States)

    He, Gang; Wang, Yan; Pang, Xueli; Zhang, Bo

    2014-02-01

    Radiotherapy is one of the main treatments for clinical cancer therapy. However, its application was limited due to lack of radiosensitivity in some cancers. Trichostatin A (TSA) is a classic histone deacetylases inhibitor (HDACi) that specifically inhibits the biochemical functions of HDAC and is demonstrated to be an active anticancer drug. However, whether it could sensitize colon cancer to radiation is not clear. Our results showed that TSA enhanced the radiosensitivity of colon cancer cells as determined by CCK-8 and clonogenic survival assay. Moreover, apoptotic cell death induced by radiation was enhanced by TSA treatment. Additionally, TSA also induced autophagic response in colon cancer cells, while autophagy inhibition led to cell apoptosis and enhanced the radiosensitivity of colon cancer cells. Our data suggested that inhibition of cytoprotective autophagy sensitizes cancer cell to radiation, which might be further investigated for clinical cancer radiotherapy.

  16. Inhibition of Lipopolysaccharide-Induced iNOS, COX- 2, and TNF ...

    African Journals Online (AJOL)

    Inhibition of Lipopolysaccharide-Induced iNOS, COX- 2, and TNF-α Expression by Aqueous Extract of Orixa Japonica in RAW 264.7 Cells via Suppression of NF- kB Activity. C-H Kang, YH Choi, I-W Choi, J-D Lee, G-Y Kim ...

  17. An RNA Aptamer Inhibits a Mutation-Induced Inactivating Misfolding of a Serpin

    DEFF Research Database (Denmark)

    Madsen, Jeppe B; Andersen, Lisbeth M; Dupont, Daniel M

    2016-01-01

    ) or extracellularly (type-II serpinopathies). We have isolated a 2'-fluoropyrimidine-modified RNA aptamer, which inhibits a mutation-induced inactivating misfolding of the serpin α1-antichymotrypsin. It is the first agent able to stabilize a type-II mutation of a serpin without interfering with the inhibitory...

  18. Inhibition of Chlorine-Induced Lung Injury by the Type 4 Phosphodiesterase Inhibitor Rolipram

    Science.gov (United States)

    Chang, Weiyuan; Chen, Jing; Schlueter, Connie F.; Rando, Roy J.; Pathak, Yashwant V.; Hoyle, Gary W.

    2012-01-01

    Chlorine is a highly toxic respiratory irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity, inflammation, and pulmonary edema. Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from acute lung injury. The type 4 phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for chlorine-induced lung injury. Rolipram inhibits degradation of the intracellular signaling molecule cyclic AMP. Potential beneficial effects of increased cyclic AMP levels include inhibition of pulmonary edema, inflammation, and airway hyperreactivity. Mice were exposed to chlorine (whole body exposure, 228–270 ppm for 1 h) and were treated with rolipram by intraperitoneal, intranasal, or intramuscular (either aqueous or nanoemulsion formulation) delivery starting 1 h after exposure. Rolipram administered intraperitoneally or intranasally inhibited chlorine-induced pulmonary edema. Minor or no effects were observed on lavage fluid IgM (indicative of plasma protein leakage), KC (Cxcl1, neutrophil chemoattractant), and neutrophils. All routes of administration inhibited chlorine-induced airway hyperreactivity assessed 1 day after exposure. The results of the study suggest that rolipram may be an effective rescue treatment for chlorine-induced lung injury and that both systemic and targeted administration to the respiratory tract were effective routes of delivery. PMID:22763362

  19. Implication of unfolded protein response in resveratrol-induced inhibition of K562 cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Bao-Qin; Gao, Yan-Yan; Niu, Xiao-Fang [Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001 (China); Xie, Ji-Sheng [Youjiang Medical College for Nationalities, Guangxi 533000 (China); Meng, Xin; Guan, Yifu [Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001 (China); Wang, Hua-Qin, E-mail: wanghq_doctor@hotmail.com [Department of Biochemistry and Molecular Biology, China Medical University, Shenyang 110001 (China)

    2010-01-01

    Resveratrol (RES), a natural plant polyphenol, is an effective inducer of cell cycle arrest and apoptosis in a variety of carcinoma cell types. In addition, RES has been reported to inhibit tumorigenesis in several animal models suggesting that it functions as a chemopreventive and anti-tumor agent in vivo. The chemopreventive and chemotherapeutic properties associated with resveratrol offer promise for the design of new chemotherapeutic agents. However, the mechanisms by which RES mediates its effects are not yet fully understood. In this study, we showed that RES caused cell cycle arrest and proliferation inhibition via induction of unfolded protein response (UPR) in human leukemia K562 cell line. Treatment of K562 cells with RES induced a number of signature UPR markers, including transcriptional induction of GRP78 and CHOP, phosphorylation of eukaryotic initiation factor 2{alpha} (eIF2{alpha}), ER stress-specific XBP-1 splicing, suggesting the induction of UPR by RES. RES inhibited proliferation of K562 in a concentration-dependent manner. Flow cytometric analyses revealed that K562 cells were arrested in G1 phase upon RES treatment. Salubrinal, an eIF2{alpha} inhibitor, or overexpression of dominant negative mutants of PERK or eIF2{alpha}, effectively restored RES-induced cell cycle arrest, underscoring the important role of PERK/eIF2{alpha} branch of UPR in RES-induced inhibition of cell proliferation.

  20. Inhibition of Pim1 kinase, new therapeutic approach in virus-induced asthma exacerbations

    NARCIS (Netherlands)

    Vries, de Maaike; Bedke, Nicole; Smithers, Natalie P.; Loxham, Matthew; Howarth, Peter H.; Nawijn, Martijn C.; Davies, Donna E.

    Therapeutic options to treat virus-induced asthma exacerbations are limited and urgently needed. Therefore, we tested Pim1 kinase as potential therapeutic target in human rhinovirus (HRV) infections. We hypothesised that inhibition of Pim1 kinase reduces HRV replication by augmenting the

  1. Calpain inhibition prevents amyloid-beta-induced neurodegeneration and associated behavioral dysfunction in rats

    NARCIS (Netherlands)

    Granic, Ivica; Nyakas, Csaba; Luiten, Paul G. M.; Eisel, Ulrich L. M.; Halmy, Laszlo G.; Gross, Gerhard; Schoemaker, Hans; Moeller, Achim; Nimmrich, Volker

    2010-01-01

    Amyloid-beta (A beta) is toxic to neurons and such toxicity is - at least in part - mediated via the NMDA receptor. Calpain, a calcium dependent cystein protease, is part of the NMDA receptor-induced neurodegeneration pathway, and we previously reported that inhibition of calpain prevents

  2. Decreased growth-induced water potential: A primary cause of growth inhibition at low water potentials

    Energy Technology Data Exchange (ETDEWEB)

    Nonami, Hiroshi [Ehime Univ., Matsuyama (Japan); Wu, Yajun; Boyer, J.S. [Univ. of Delaware, Lewes, DE (United States)

    1997-06-01

    Cell enlargement depends on a growth-induced difference in water potential to move water into the cells. Water deficits decrease this potential difference and inhibit growth. To investigate whether the decrease causes the growth inhibition, pressure was applied to the roots of soybean seedlings and the growth and potential difference were monitored in the stems. In water-limited plants, the inhibited stem growth increased when the roots were pressurized and it reverted to the previous rate when the pressure was released. The pressure around the roots was perceived as an increased turgor in the stem in small cells next to the xylem, but not in outlying cortical cells. This local effect implied that water transport was impeded by the small cells. The diffusivity for water was much less in the small cells than in the outlying cells. The small cells thus were a barrier that caused the growth-induced potential difference to be large during rapid growth, but to reverse locally during the early part of a water deficit. Such a barrier may be a frequent property of meristems. Because stem growth responded to the pressure-induced recovery of the potential difference across this barrier, we conclude that a decrease in the growth-induced potential difference was a primary cause of the inhibition.

  3. Bactericidal synergistic effect due to chloramphenicol-induced inhibition of staphyloccal penicillinase.

    Science.gov (United States)

    Michel, J; Jacobs, J; Sacks, T

    1977-01-01

    A synergistic bactericidal effect of chloramphenicol and penicillin-G was observed with 17 out of 20 beta-lactamase producing strains of Staphylococcus aureus. The synergism was due to chloramphenicol-induced inhibition of beta-lactamase production. With seven of the strains the synergistic effect was operative only with subinhibitory concentrations of chloramphenicol, while higher concentrations produced antagonism.

  4. Effect of magnesium on vascular reactivity in NOS inhibition-induced hypertension.

    Science.gov (United States)

    Basralı, Filiz; Nasırcılar Ülker, Seher; Koçer, Günnur; Ülker Karadamar, Pınar; Özyurt, Dilek; Cengiz, Melike; Şentürk, Ümit Kemal

    2015-06-01

    This study investigated the effect of magnesium on the vascular reactivity of conduit and resistance arteries in a nitric oxide synthase inhibition-induced hypertension model. The aorta and third-order branches of the mesenteric artery were dissected from normotensive control and hypertensive rats, and their constriction and dilation responses in physiological saline solution containing normal (1.2 mM) or high (4.8 mM) magnesium concentrations were examined. The responses of the vessels were evaluated using potassium chloride (KCl) and phenylephrine (Phe), acetylcholine (ACh) and sodium nitroprusside. The Phe-induced constriction response of the aortic rings increased, whereas the ACh-induced dilation response decreased, in the hypertensive group compared to controls, in the presence of a normal magnesium concentration. High magnesium did not alter these responses in either group. Both the KCl- and Phe-induced constriction responses of the mesenteric arteries increased, and the ACh-induced dilation response decreased in the hypertensive group compared to controls, in the presence of a normal magnesium concentration. High magnesium significantly decreased the KCl and Phe-induced constriction and increased the ACh-induced dilation response of the mesenteric arteries in the hypertensive group, while it did not alter these responses in controls. This study suggests that high magnesium improves vascular reactivity of resistance-, but not conduit-type arteries in the nitric oxide synthase inhibition-induced hypertension model.

  5. G9a Inhibition Induces Autophagic Cell Death via AMPK/mTOR Pathway in Bladder Transitional Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Feng Li

    Full Text Available G9a has been reported to highly express in bladder transitional cell carcinoma (TCC and G9a inhibition significantly attenuates cell proliferation, but the underlying mechanism is not fully understood. The present study aimed at examining the potential role of autophagy in the anti-proliferation effect of G9a inhibition on TCC T24 and UMUC-3 cell lines in vitro. We found that both pharmaceutical and genetical G9a inhibition significantly attenuated cell proliferation by MTT assay, Brdu incorporation assay and colony formation assay. G9a inhibition induced autophagy like morphology as determined by transmission electron microscope and LC-3 fluorescence assay. In addition, autophagy flux was induced by G9a inhibition in TCC cells, as determined by p62 turnover assay and LC-3 turnover assay. The autophagy induced positively contributed to the inhibition of cell proliferation because the growth attenuation capacity of G9a inhibition was reversed by autophagy inhibitors 3-MA. Mechanically, AMPK/mTOR pathway was identified to be involved in the regulation of G9a inhibition induced autophagy. Intensively activating mTOR by Rheb overexpression attenuated autophagy and autophagic cell death induced by G9a inhibition. In addition, pre-inhibiting AMPK by Compound C attenuated autophagy together with the anti-proliferation effect induced by G9a inhibition while pre-activating AMPK by AICAR enhanced them. In conclusion, our results indicate that G9a inhibition induces autophagy through activating AMPK/mTOR pathway and the autophagy induced positively contributes to the inhibition of cell proliferation in TCC cells. These findings shed some light on the functional role of G9a in cell metabolism and suggest that G9a might be a therapeutic target in bladder TCC in the future.

  6. Inhalation of ambroxol inhibits cigarette smoke-induced acute lung injury in a mouse model by inhibiting the Erk pathway.

    Science.gov (United States)

    Ge, Ling-tian; Liu, Ya-nan; Lin, Xi-xi; Shen, Hui-juan; Jia, Yong-liang; Dong, Xin-wei; Sun, Yun; Xie, Qiang-min

    2016-04-01

    Oral and injection administration of ambroxol has been clinically used to treat airway disease. However, little is known about its potentials in inhalation therapy. In present studies, we tested the effects of ambroxol by inhalation with intravenous administration, and explored the underlying working mechanism. The mice received 10 cigarettes exposure every day for 4 days. Inhaled solution of ambroxol was aerosolized 20 min before the exposure of cigarette smoke (CS). The effect of ambroxol on the expression of mucoprotein 5 AC (MUC5AC) and proinflammatory cytokines in NCI-H292 cells stimulated with cigarette smoke extract (CSE). Four days of daily inhalation of ambroxol at 3.75 or 7.5mg/ml for 20 min suppressed the accumulation of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) and lung tissues, and inhibited increases in the mRNA and protein levels of tumor necrosis factor (TNF)-α, CCL-2 and KC, but not interleukin (IL)-1β in the CS-exposed mice. Moreover, ambroxol at 3.75 or 7.5mg/ml facilitated airway mucosa cilia clearance, reduced glycosaminoglycans level in BALF and MUC5AC mRNA levels in lung tissues. The effects of ambroxol by inhalation at 7.5mg/ml was comparable to that of ambroxol at 20mg/kg i.v. and dexamethasone at 0.5mg/kg i.p. Using cultured lung epithelial cells, we demonstrated that pretreatment with ambroxol at 2 or 20 μM inhibited the CSE-induced up-regulation of MUC5AC, TNF-α, IL-1β mRNA levels, which was through inhibiting Erk signaling pathway. Our results demonstrate the beneficial effects of ambroxol as an inhalation replace systemic administration for COPD therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Pharmacological BACE1 and BACE2 inhibition induces hair depigmentation by inhibiting PMEL17 processing in mice.

    Science.gov (United States)

    Shimshek, Derya R; Jacobson, Laura H; Kolly, Carine; Zamurovic, Natasa; Balavenkatraman, Kamal Kumar; Morawiec, Laurent; Kreutzer, Robert; Schelle, Juliane; Jucker, Mathias; Bertschi, Barbara; Theil, Diethilde; Heier, Annabelle; Bigot, Karine; Beltz, Karen; Machauer, Rainer; Brzak, Irena; Perrot, Ludovic; Neumann, Ulf

    2016-02-25

    Melanocytes of the hair follicle produce melanin and are essential in determining the differences in hair color. Pigment cell-specific MELanocyte Protein (PMEL17) plays a crucial role in melanogenesis. One of the critical steps is the amyloid-like functional oligomerization of PMEL17. Beta Site APP Cleaving Enzyme-2 (BACE2) and γ-secretase have been shown to be key players in generating the proteolytic fragments of PMEL17. The β-secretase (BACE1) is responsible for the generation of amyloid-β (Aβ) fragments in the brain and is therefore proposed as a therapeutic target for Alzheimer's disease (AD). Currently BACE1 inhibitors, most of which lack selectivity over BACE2, have demonstrated efficacious reduction of amyloid-β peptides in animals and the CSF of humans. BACE2 knock-out mice have a deficiency in PMEL17 proteolytic processing leading to impaired melanin storage and hair depigmentation. Here, we confirm BACE2-mediated inhibition of PMEL17 proteolytic processing in vitro in mouse and human melanocytes. Furthermore, we show that wildtype as well as bace2(+/-) and bace2(-/-) mice treated with a potent dual BACE1/BACE2 inhibitor NB-360 display dose-dependent appearance of irreversibly depigmented hair. Retinal pigmented epithelium showed no morphological changes. Our data demonstrates that BACE2 as well as additional BACE1 inhibition affects melanosome maturation and induces hair depigmentation in mice.

  8. Caffeine-Induced Suppression of GABAergic Inhibition and Calcium-Independent Metaplasticity

    Directory of Open Access Journals (Sweden)

    Masako Isokawa

    2016-01-01

    Full Text Available GABAergic inhibition plays a critical role in the regulation of neuron excitability; thus, it is subject to modulations by many factors. Recent evidence suggests the elevation of intracellular calcium ([Ca2+]i and calcium-dependent signaling molecules underlie the modulations. Caffeine induces a release of calcium from intracellular stores. We tested whether caffeine modulated GABAergic transmission by increasing [Ca2+]i. A brief local puff-application of caffeine to hippocampal CA1 pyramidal cells transiently suppressed GABAergic inhibitory postsynaptic currents (IPSCs by 73.2 ± 6.98%. Time course of suppression and the subsequent recovery of IPSCs resembled DSI (depolarization-induced suppression of inhibition, mediated by endogenous cannabinoids that require a [Ca2+]i rise. However, unlike DSI, caffeine-induced suppression of IPSCs (CSI persisted in the absence of a [Ca2+]i rise. Intracellular applications of BAPTA and ryanodine (which blocks caffeine-induced calcium release from intracellular stores failed to prevent the generation of CSI. Surprisingly, ruthenium red, an inhibitor of multiple calcium permeable/release channels including those of stores, induced metaplasticity by amplifying the magnitude of CSI independently of calcium. This metaplasticity was accompanied with the generation of a large inward current. Although ionic basis of this inward current is undetermined, the present result demonstrates that caffeine has a robust Ca2+-independent inhibitory action on GABAergic inhibition and causes metaplasticity by opening plasma membrane channels.

  9. Changes in peroxidases associated with radiation-induced sprout inhibition in garlic (Allium sativum L. )

    Energy Technology Data Exchange (ETDEWEB)

    Croci, C.A.; Curvetto, N.R.; Orioli, G.A. (Universidad Nacional del Sur, Bahia Blanca (Argentina)); Arguello, J.A. (Universidad Nacional de Cordoba (Argentina). Dept. de Biologia Aplicada)

    1991-02-01

    The effects of an acute dose of {gamma}-rays (10 Gy) to post-dormant garlic cloves on inner sprout growth and changes in peroxidases and soluble proteins were evaluated up to 100 days of storage in darkness at 19+-1{sup 0}C and 42+-2% relative humidity. Radiation-induced inhibition of sprout growth became evident after 25 days of treatment and was synchronous with a marked increase in peroxidase activity. Thin-layer isoelectric focusing revealed that radiation induced an increase in the number of anodic peroxidase isoenzymes at 100 days, suggesting modifications in the vascularization process. Neither the soluble protein content nor the protein pattern were affected by irradiation. These results are discussed in terms of a possible mediating effect of peroxidase on radiation-induced sprout inhibition in garlic. (author).

  10. Irisolidone attenuates ethanol-induced gastric injury in mice by inhibiting the infiltration of neutrophils.

    Science.gov (United States)

    Kang, Geum-Dan; Lee, Sang-Yoon; Jang, Se-Eun; Han, Myung Joo; Kim, Dong-Hyun

    2017-02-01

    This study was designed to determine whether irisolidone and its glycoside kakkalide, which are the major constituents of the flower of Pueraria lobata (Kudzu) can attenuate ethanol-induced gastritic injury in mice. Irisolidone and kakkalide inhibited IL-8 secretion and NF-κB activation in lipopolysaccharide-stimulated KATO III cells. Therefore, we investigated their protective effects against ethanol-induced gastric injury in mice. Pretreatment with kakkalide or irisolidone decreased the area of hemorrhagic ulcerative lesions caused by ethanol and suppressed stomach myeloperoxidase activity, CXCL4 secretion, and NF-κB activation. The ameliorating effect of irisolidone was more potent than that of kakkalide. Irisolidone may attenuate ethanol-induced gastritis by inhibiting the infiltration of immune cells, particularly neutrophils, through the regulation of CXCL-4 or IL-8 secretion. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Inhibition of telomerase causes vulnerability to endoplasmic reticulum stress-induced neuronal cell death.

    Science.gov (United States)

    Hosoi, Toru; Nakatsu, Kanako; Shimamoto, Akira; Tahara, Hidetoshi; Ozawa, Koichiro

    2016-08-26

    Endoplasmic reticulum (ER) stress is implicated in several diseases, such as cancer and neurodegenerative diseases. In the present study, we investigated the possible involvement of telomerase in ER stress-induced cell death. ER stress-induced cell death was ameliorated in telomerase reverse transcriptase (TERT) over-expressing MCF7 cells (MCF7-TERT cell). Telomerase specific inhibitor, BIBR1532, reversed the inhibitory effect of TERT on ER stress-induced cell death in MCF7-TERT cells. These findings suggest that BIBR1532 may specifically inhibit telomerase activity, thereby inducing cell death in ER stress-exposed cells. TERT was expressed in the SH-SY5Y neuroblastoma cell line. To analyze the possible involvement of telomerase in ER stress-induced neuronal cell death, we treated SH-SY5Y neuroblastoma cells with BIBR1532 and analyzed ER stress-induced cell death. We found that BIBR1532 significantly enhanced the ER stress-induced neuronal cell death. These findings suggest that inhibition of telomerase activity may enhance vulnerability to neuronal cell death caused by ER stress. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Inhibition of Cariogenic Plaque Formation on Root Surface with Polydopamine-Induced-Polyethylene Glycol Coating

    Directory of Open Access Journals (Sweden)

    May Lei Mei

    2016-05-01

    Full Text Available Root caries prevention has been a challenge for clinicians due to its special anatomical location, which favors the accumulation of dental plaque. Researchers are looking for anti-biofouling material to inhibit bacterial growth on exposed root surfaces. This study aimed to develop polydopamine-induced-polyethylene glycol (PEG and to study its anti-biofouling effect against a multi-species cariogenic biofilm on the root dentine surface. Hydroxyapatite disks and human dentine blocks were divided into four groups for experiments. They received polydopamine-induced-PEG, PEG, polydopamine, or water application. Contact angle, quartz crystal microbalance, and Fourier transform infrared spectroscopy were used to study the wetting property, surface affinity, and an infrared spectrum; the results indicated that PEG was induced by polydopamine onto a hydroxyapatite disk. Salivary mucin absorption on hydroxyapatite disks with polydopamine-induced-PEG was confirmed using spectrophotometry. The growth of a multi-species cariogenic biofilm on dentine blocks with polydopamine-induced-PEG was assessed and monitored by colony-forming units, confocal laser scanning microscopy, and scanning electron microscopy. The results showed that dentine with polydopamine-induced-PEG had fewer bacteria than other groups. In conclusion, a novel polydopamine-induced-PEG coating was developed. Its anti-biofouling effect inhibited salivary mucin absorption and cariogenic biofilm formation on dentine surface and thus may be used for the prevention of root dentine caries.

  13. Inhibition of Cariogenic Plaque Formation on Root Surface with Polydopamine-Induced-Polyethylene Glycol Coating.

    Science.gov (United States)

    Mei, May Lei; Li, Quan-Li; Chu, Chun Hung

    2016-05-25

    Root caries prevention has been a challenge for clinicians due to its special anatomical location, which favors the accumulation of dental plaque. Researchers are looking for anti-biofouling material to inhibit bacterial growth on exposed root surfaces. This study aimed to develop polydopamine-induced-polyethylene glycol (PEG) and to study its anti-biofouling effect against a multi-species cariogenic biofilm on the root dentine surface. Hydroxyapatite disks and human dentine blocks were divided into four groups for experiments. They received polydopamine-induced-PEG, PEG, polydopamine, or water application. Contact angle, quartz crystal microbalance, and Fourier transform infrared spectroscopy were used to study the wetting property, surface affinity, and an infrared spectrum; the results indicated that PEG was induced by polydopamine onto a hydroxyapatite disk. Salivary mucin absorption on hydroxyapatite disks with polydopamine-induced-PEG was confirmed using spectrophotometry. The growth of a multi-species cariogenic biofilm on dentine blocks with polydopamine-induced-PEG was assessed and monitored by colony-forming units, confocal laser scanning microscopy, and scanning electron microscopy. The results showed that dentine with polydopamine-induced-PEG had fewer bacteria than other groups. In conclusion, a novel polydopamine-induced-PEG coating was developed. Its anti-biofouling effect inhibited salivary mucin absorption and cariogenic biofilm formation on dentine surface and thus may be used for the prevention of root dentine caries.

  14. Catalase inhibits ionizing radiation-induced apoptosis in hematopoietic stem and progenitor cells.

    Science.gov (United States)

    Xiao, Xia; Luo, Hongmei; Vanek, Kenneth N; LaRue, Amanda C; Schulte, Bradley A; Wang, Gavin Y

    2015-06-01

    Hematologic toxicity is a major cause of mortality in radiation emergency scenarios and a primary side effect concern in patients undergoing chemo-radiotherapy. Therefore, there is a critical need for the development of novel and more effective approaches to manage this side effect. Catalase is a potent antioxidant enzyme that coverts hydrogen peroxide into hydrogen and water. In this study, we evaluated the efficacy of catalase as a protectant against ionizing radiation (IR)-induced toxicity in hematopoietic stem and progenitor cells (HSPCs). The results revealed that catalase treatment markedly inhibits IR-induced apoptosis in murine hematopoietic stem cells and hematopoietic progenitor cells. Subsequent colony-forming cell and cobble-stone area-forming cell assays showed that catalase-treated HSPCs can not only survive irradiation-induced apoptosis but also have higher clonogenic capacity, compared with vehicle-treated cells. Moreover, transplantation of catalase-treated irradiated HSPCs results in high levels of multi-lineage and long-term engraftments, whereas vehicle-treated irradiated HSPCs exhibit very limited hematopoiesis reconstituting capacity. Mechanistically, catalase treatment attenuates IR-induced DNA double-strand breaks and inhibits reactive oxygen species. Unexpectedly, we found that the radioprotective effect of catalase is associated with activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway and pharmacological inhibition of STAT3 abolishes the protective activity of catalase, suggesting that catalase may protect HSPCs against IR-induced toxicity via promoting STAT3 activation. Collectively, these results demonstrate a previously unrecognized mechanism by which catalase inhibits IR-induced DNA damage and apoptosis in HSPCs.

  15. Targeted inhibition of RAGE in substantia nigra of rats blocks 6-OHDA-induced dopaminergic denervation.

    Science.gov (United States)

    Gasparotto, Juciano; Ribeiro, Camila Tiefensee; Bortolin, Rafael Calixto; Somensi, Nauana; Rabelo, Thallita Kelly; Kunzler, Alice; Souza, Natália Cabral; Pasquali, Matheus Augusto de Bittencourt; Moreira, José Claudio Fonseca; Gelain, Daniel Pens

    2017-08-18

    The receptor for advanced glycation endproducts (RAGE) is a pattern-recognition receptor associated with inflammation in most cell types. RAGE up-regulates the expression of proinflammatory mediators and its own expression via activation of NF-kB. Recent works have proposed a role for RAGE in Parkinson's disease (PD). In this study, we used the multimodal blocker of RAGE FPS-ZM1, which has become available recently, to selectively inhibit RAGE in the substantia nigra (SN) of rats intracranially injected with 6-hydroxydopamine (6-OHDA). FPS-ZM1 (40 μg per rat), injected concomitantly with 6-OHDA (10 μg per rat) into the SN, inhibited the increase in RAGE, activation of ERK1/2, Src and nuclear translocation of NF-kB p65 subunit in the SN. RAGE inhibition blocked glial fibrillary acidic protein and Iba-1 upregulation as well as associated astrocyte and microglia activation. Circulating cytokines in serum and CSF were also decreased by FPS-ZM1 injection. The loss of tyrosine hydroxylase and NeuN-positive neurons was significantly inhibited by RAGE blocking. Finally, FPS-ZM1 attenuated locomotory and exploratory deficits induced by 6-OHDA. Our results demonstrate that RAGE is an essential component in the neuroinflammation and dopaminergic denervation induced by 6-OHDA in the SN. Selective inhibition of RAGE may offer perspectives for therapeutic approaches.

  16. Thiol-reducing agents prevent sulforaphane-induced growth inhibition in ovarian cancer cells.

    Science.gov (United States)

    Kim, Seung Cheol; Choi, Boyun; Kwon, Youngjoo

    2017-01-01

    The inhibitory potential of sulforaphane against cancer has been suggested for different types of cancer, including ovarian cancer. We examined whether this effect is mediated by mitogen-activated protein kinase (MAPK) and reactive oxygen species (ROS), important signaling molecules related to cell survival and proliferation, in ovarian cancer cells. Sulforaphane at a concentration of 10 μM effectively inhibited the growth of cancer cells. Use of specific inhibitors revealed that activation of MAPK pathways by sulforaphane is unlikely to mediate sulforaphane-induced growth inhibition. Sulforaphane did not generate significant levels of intracellular ROS. Pretreatment with thiol reducers, but not ROS scavengers, prevented sulforaphane-induced growth inhibition. Furthermore, diamide, a thiol-oxidizing agent, enhanced both growth inhibition and cell death induced by sulforaphane, suggesting that the effect of sulforaphane on cell growth may be related to oxidation of protein thiols or change in cellular redox status. Our data indicate that supplementation with thiol-reducing agents should be avoided when sulforaphane is used to treat cancer.

  17. Coumestan inhibits radical-induced oxidation of DNA: is hydroxyl a necessary functional group?

    Science.gov (United States)

    Xi, Gao-Lei; Liu, Zai-Qun

    2014-06-18

    Coumestan is a natural tetracycle with a C═C bond shared by a coumarin moiety and a benzofuran moiety. In addition to the function of the hydroxyl group on the antioxidant activity of coumestan, it is worth exploring the influence of the oxygen-abundant scaffold on the antioxidant activity as well. In this work, seven coumestans containing electron-withdrawing and electron-donating groups were synthesized to evaluate the abilities to trap 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cationic radical (ABTS(•+)), 2,2'-diphenyl-1-picrylhydrazyl radical (DPPH), and galvinoxyl radical, respectively, and to inhibit the oxidations of DNA mediated by (•)OH, Cu(2+)/glutathione (GSH), and 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH), respectively. It was found that all of the coumestans used herein can quench the aforementioned radicals and can inhibit (•)OH-, Cu(2+)/GSH-, and AAPH-induced oxidations of DNA. In particular, substituent-free coumestan exhibits higher ability to quench DPPH and to inhibit AAPH-induced oxidation of DNA than Trolox. In addition, nonsubstituted coumestan shows a similar ability to inhibit (•)OH- and Cu(2+)/GSH-induced oxidations of DNA relative to that of Trolox. The antioxidant effectiveness of the coumestan can be attributed to the lactone in the coumarin moiety and, therefore, a hydroxyl group may not be a necessary functional group for coumestan to be an antioxidant.

  18. Inhibition of soluble epoxide hydrolase limits niacin-induced vasodilation in mice

    Science.gov (United States)

    Inceoglu, A. B.; Clifton, H.L.; Yang, J.; Hegedus, C.; Hammock, B. D.; Schaefer, S.

    2012-01-01

    Background The use of niacin in the treatment of dyslipidemias is limited by the common side effect of cutaneous vasodilation, commonly termed flushing. Flushing is thought to be due to release of the vasodilatory prostanoids PGD2 and PGE2 from arachidonic acid metabolism through the cyclooxygenase (COX) pathway. Arachidonic acid is also metabolized by the cytochrome P450 system which is regulated, in part, by the enzyme soluble epoxide hydrolase (sEH). Methods: These experiments used an established murine model in which ear tissue perfusion was measured by laser Doppler to test the hypothesis that inhibition of sEH would limit niacin-induced flushing. Results: Niacin-induced flushing was reduced from 506 ± 126 to 213 ± 39 % in sEH knockout animals. Pharmacologic treatment with 3 structurally distinct sEH inhibitors similarly reduced flushing in a dose dependent manner, with maximal reduction to 143±15% of baseline flow using a concentration of 1 mg/kg TPAU (1-trifluoromethoxyphenyl-3-(1-acetylpiperidin-4-yl) urea). Systemically administered PGD2 caused ear vasodilation which was not changed by either pharmacologic sEH inhibition or by sEH gene deletion. Conclusions: Inhibition of sEH markedly reduces niacin-induced flushing in this model without an apparent effect on the response to PGD2. sEH inhibition may be a new therapeutic approach to limit flushing in humans. PMID:22526297

  19. Featured Article: Cardioprotective effects of lysyl oxidase inhibition against volume overload-induced extracellular matrix remodeling

    Science.gov (United States)

    El Hajj, Elia C; El Hajj, Milad C; Ninh, Van K

    2015-01-01

    A hallmark of heart failure (HF) is adverse extracellular matrix (ECM) remodeling, which is regulated by the collagen cross-linking enzyme, lysyl oxidase (LOX). In this study, we evaluate the efficacy of LOX inhibition to prevent adverse left ventricular (LV) remodeling and dysfunction using an experimental model of HF. Sprague–Dawley rats were subjected to surgically induced volume overload (VO) by creation of aortocaval fistula (ACF). A LOX inhibitor, beta-aminopropionitrile (BAPN; 100 mg/kg/day), was administered to rats with ACF or sham surgery at eight weeks postsurgery. Echocardiography was used to assess progressive alterations in cardiac ventricular structure and function. Left ventricular (LV) catheterization was used to assess alterations in contractility, stiffness, LV pressure and volume, and other indices of cardiac function. The LV ECM alterations were assessed by: (a) histological staining of collagen, (b) protein expression of collagen types I and III, (c) hydroxyproline assay, and (d) cross-linking assay. LOX inhibition attenuated VO-induced increases in cardiac stress, and attenuated increases in interstitial myocardial collagen, total collagen, and protein levels of collagens I and III. Both echocardiography and catheterization measurements indicated improved cardiac function post-VO in BAPN treated rats vs. untreated. Inhibition of LOX attenuated VO-induced decreases in LV stiffness and cardiac function. Overall, our data indicate that LOX inhibition was cardioprotective in the volume overloaded heart. PMID:26582054

  20. Inhibition of autophagy promotes metastasis and glycolysis by inducing ROS in gastric cancer cells.

    Science.gov (United States)

    Qin, Wenjie; Li, Chao; Zheng, Wen; Guo, Qingqu; Zhang, Yuefeng; Kang, Muxing; Zhang, Bo; Yang, Bin; Li, Baozhong; Yang, Haijun; Wu, Yulian

    2015-11-24

    Autophagy defect has been shown to be correlated with malignant phenotype and poor prognosis of human cancers, however, the detailed mechanisms remain obscure. In this study, we investigated the biological changes induced by autophagy inhibition in gastric cancer. We showed that inhibition of autophagy in gastric cancer cells promotes epithelial-mesenchymal transition (EMT) and metastasis, alters metabolic phenotype from mitochondrial oxidative phosphorylation to aerobic glycolysis and converts cell phenotype toward malignant, which maybe further contribute to chemoresistance and poor prognosis of gastric cancer. We also identified that the EMT and metabolism alterations induced by autophagy inhibition were dependent on ROS-NF-κB-HIF-1α pathway. More importantly, scavenging of ROS by the antioxidant N-acetylcysteine (NAC) attenuated activation of NF-κB and HIF-1α in autophagy-deficient gastric cancer cells, and autophagy inhibition induced metastasis and glycolysis were also diminished by NAC in vivo. Taken together, our findings suggested that autophagy defect promotes metastasis and glycolysis of gastric cancer, and antioxidants could be used to improve disease outcome for gastric cancer patients with autophagy defect.

  1. Antibiotic drug tigecycline inhibited cell proliferation and induced autophagy in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Chunling; Yang, Liqun; Jiang, Xiaolan [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Xu, Chuan [Division of Scientific Research and Training, General Hospital of PLA Chengdu Military Area Command, Chengdu, Sichuan 610083 (China); Wang, Mei; Wang, Qinrui [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Zhou, Zhansong, E-mail: zhouzhans@sina.com [Institute of Urinary Surgery, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Xiang, Zhonghuai [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China); Cui, Hongjuan, E-mail: hcui@swu.edu.cn [State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing 400716 (China)

    2014-03-28

    Highlights: • Tigecycline inhibited cell growth and proliferation in human gastric cancer cells. • Tigecycline induced autophagy not apoptosis in human gastric cancer cells. • AMPK/mTOR/p70S6K pathway was activated after tigecycline treatment. • Tigecycline inhibited tumor growth in xenograft model of human gastric cancer cells. - Abstract: Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activat