Partial IGF-1 deficiency induces brain oxidative damage and edema, which are ameliorated by replacement therapy.

Science.gov (United States)

Puche, Juan E; Muñoz, Úrsula; García-Magariño, Mariano; Sádaba, María C; Castilla-Cortázar, Inma

2016-01-01

Insulin-like growth factor 1 (IGF-1) induces multiple cytoprotective effects on every tissue, including the brain. Since the mechanisms by which IGF-1 produces neuroprotection are not fully understood, the aim of this work was to delve into the underlying mechanisms. IGF-1 deficient mice (Hz) were compared with wild type (WT) and Hz mice treated with low doses of IGF-1 (2 µg/100 g body weight/day) for 10 days (Hz + IGF). Gene expression, quantitative PCR, histology, and magnetic resonance imaging were performed in the three groups. IGF-1 deficiency induced increased oxidative damage determined by markers of lipid peroxidation and hypoxia, as well as gene expression of heat shock proteins, antioxidant enzymes, and molecules involved in inflammation, apoptosis, and mitochondrial protection. These changes correlated with edema and learning impairment in Hz mice. IGF-1 therapy improved all these alterations. In conclusion, IGF-1 deficiency is responsible for increased brain oxidative damage, edema, and impaired learning and memory capabilities which are rescued by IGF-1 replacement therapy. © 2016 International Union of Biochemistry and Molecular Biology.

Sildenafil Attenuates Inflammation and Oxidative Stress in Pelvic Ganglia Neurons after Bilateral Cavernosal Nerve Damage

Directory of Open Access Journals (Sweden)

Leah A. Garcia

2014-09-01

Full Text Available Erectile dysfunction is a common complication for patients undergoing surgeries for prostate, bladder, and colorectal cancers, due to damage of the nerves associated with the major pelvic ganglia (MPG. Functional re-innervation of target organs depends on the capacity of the neurons to survive and switch towards a regenerative phenotype. PDE5 inhibitors (PDE5i have been successfully used in promoting the recovery of erectile function after cavernosal nerve damage (BCNR by up-regulating the expression of neurotrophic factors in MPG. However, little is known about the effects of PDE5i on markers of neuronal damage and oxidative stress after BCNR. This study aimed to investigate the changes in gene and protein expression profiles of inflammatory, anti-inflammatory cytokines and oxidative stress related-pathways in MPG neurons after BCNR and subsequent treatment with sildenafil. Our results showed that BCNR in Fisher-344 rats promoted up-regulation of cytokines (interleukin- 1 (IL-1 β, IL-6, IL-10, transforming growth factor β 1 (TGFβ1, and oxidative stress factors (Nicotinamide adenine dinucleotide phosphate (NADPH oxidase, Myeloperoxidase (MPO, inducible nitric oxide synthase (iNOS, TNF receptor superfamily member 5 (CD40 that were normalized by sildenafil treatment given in the drinking water. In summary, PDE5i can attenuate the production of damaging factors and can up-regulate the expression of beneficial factors in the MPG that may ameliorate neuropathic pain, promote neuroprotection, and favor nerve regeneration.

Role of phenolics from Spondias pinnata bark in amelioration of iron overload induced hepatic damage in Swiss albino mice.

Science.gov (United States)

Chaudhuri, Dipankar; Ghate, Nikhil Baban; Panja, Sourav; Mandal, Nripendranath

2016-07-26

Crude Spondias pinnata bark extract was previously assessed for its antioxidant, anticancer and iron chelating potentials. The isolated compounds gallic acid (GA) and methyl gallate (MG) were evaluated for their curative potential against iron overload-induced liver fibrosis and hepatocellular damage. In vitro iron chelation property and in vivo ameliorating potential from iron overload induced liver toxicity of GA and MG was assessed by different biochemical assays and histopathological studies. MG and GA demonstrated excellent reducing power activities but iron chelation potential of MG is better than GA. Oral MG treatment in mice displayed excellent efficacy (better than GA) to significantly restore the levels of liver antioxidants, serum markers and cellular reactive oxygen species in a dose-dependent fashion. Apart from these, MG exceptionally prevented lipid peroxidation and protein oxidation whereas GA demonstrated better activity to reduce collagen content, thereby strengthening its position as an efficient drug against hepatic damage/fibrosis, which was further supported by histopathological studies. Alongside, MG efficiently eliminated the cause of liver damage, i.e., excess iron, by chelating free iron and reducing the ferritin-bound iron. The present study confirmed the curative effect of GA and MG against iron overload hepatic damage via their potent antioxidant and iron-chelating potential.

Zinc Supplementation against Eimeria acervulina-Induced Oxidative Damage in Broiler Chickens

Directory of Open Access Journals (Sweden)

Nedyalka V. Georgieva

2011-01-01

Full Text Available This study was undertaken to determine the dietary supplements of Zn containing diet on the antioxidant status in chickens experimentally infected with Eimeria acervulina. The antioxidant status was monitored via determination of MDA concentrations and erythrocyte SOD and CAT activities, as well as vitamin E, vitamin C, Cu, and Zn in liver, muscle, and serum. The results showed increased MDA (<.05, CAT (<.001, and decreased SOD (<.001 in the infected birds. Significant changes in Cu and Zn concentrations and dramatically reduction of vitamin C and E concentrations in the infected chickens were found. The observed deviations in the studied enzymes and nonenzymatic parameters evidence the occurrence of oxidative stress following the infection and impaired antioxidant status of chickens, infected with Eimeria acervulina. Our results proved the ameliorating role of CuZn(OH3Cl (0.170 g per kg food against Eimeria acervulina-induced oxidative damage in infected chickens.

Effects of ozone oxidative preconditioning on radiation-induced organ damage in rats

International Nuclear Information System (INIS)

Gultekin, Fatma Ayca; Bakkal, Bekir Hakan; Guven, Berrak; Tasdoven, Ilhan; Bektas, Sibel; Can, Murat; Comert, Mustafa

2013-01-01

Because radiation-induced cellular damage is attributed primarily to harmful effects of free radicals, molecules with direct free radical scavenging properties are particularly promising as radioprotectors. It has been demonstrated that controlled ozone administration may promote an adaptation to oxidative stress, preventing the damage induced by reactive oxygen species. Thus, we hypothesized that ozone would ameliorate oxidative damage caused by total body irradiation (TBI) with a single dose of 6 Gy in rat liver and ileum tissues. Rats were randomly divided into groups as follows: control group; saline-treated and irradiated (IR) groups; and ozone oxidative preconditioning (OOP) and IR groups. Animals were exposed to TBI after a 5-day intraperitoneal pretreatment with either saline or ozone (1 mg/kg/day). They were decapitated at either 6 h or 72 h after TBI. Plasma, liver and ileum samples were obtained. Serum AST, ALT and TNF-α levels were elevated in the IR groups compared with the control group and were decreased after treatment with OOP. TBI resulted in a significant increase in the levels of MDA in the liver and ileal tissues and a decrease of SOD activities. The results demonstrated that the levels of MDA liver and ileal tissues in irradiated rats that were pretreated with ozone were significantly decreased, while SOD activities were significantly increased. OOP reversed all histopathological alterations induced by irradiation. In conclusion, data obtained from this study indicated that ozone could increase the endogenous antioxidant defense mechanism in rats and there by protect the animals from radiation-induced organ toxicity. (author)

Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver

Directory of Open Access Journals (Sweden)

Zeba Farooqui

Full Text Available Cisplatin (CP is a potent anti-cancer drug widely used against solid tumors. However, it exhibits pronounced adverse effects including hepatotoxicity. Several strategies were attempted to prevent CP hepatotoxicity but were not found suitable for therapeutic application. Nigella sativa has been shown to prevent/reduce the progression of certain type of cardiovascular, kidney and liver diseases. Present study investigates whether N. sativa oil (NSO can prevent CP induced hepatotoxic effects. Rats were divided into four groups viz. control, CP, NSO and CPNSO. Animals in CPNSO and NSO group were administered NSO (2 ml/kg bwt, orally with or without single hepatotoxic dose of CP (6 mg/kg bwt, i.p. respectively. CP hepatotoxicity was recorded by increased serum ALT and AST activities. CP treatment caused oxidant/antioxidant imbalances as reflected by increased lipid peroxidation and decreased enzymatic and non-enzymatic antioxidants. Furthermore, the activities of various carbohydrate metabolism and membrane enzymes were altered by CP treatment. In contrast, NSO administration to CP treated rats, markedly ameliorated the CP elicited deleterious alterations in liver. Histopathological observations showed extensive liver damage in CP treated animals while greatly reduced tissue injury in CPNSO group. In conclusion, NSO appears to protect CP induced hepatotoxicity by improving energy metabolism and strengthening antioxidant defense mechanism. Keywords: Cisplatin, Nigella sativa oil, Carbohydrate metabolism, Antioxidant

Oxidative DNA damage & repair: An introduction.

Science.gov (United States)

Cadet, Jean; Davies, Kelvin J A

2017-06-01

This introductory article should be viewed as a prologue to the Free Radical Biology & Medicine Special Issue devoted to the important topic of Oxidatively Damaged DNA and its Repair. This special issue is dedicated to Professor Tomas Lindahl, co-winner of the 2015 Nobel Prize in Chemistry for his seminal discoveries in the area repair of oxidatively damaged DNA. In the past several years it has become abundantly clear that DNA oxidation is a major consequence of life in an oxygen-rich environment. Concomitantly, survival in the presence of oxygen, with the constant threat of deleterious DNA mutations and deletions, has largely been made possible through the evolution of a vast array of DNA repair enzymes. The articles in this Oxidatively Damaged DNA & Repair special issue detail the reactions by which intracellular DNA is oxidatively damaged, and the enzymatic reactions and pathways by which living organisms survive such assaults by repair processes. Copyright © 2017 Elsevier Inc. All rights reserved.

Coagulin-L ameliorates TLR4 induced oxidative damage and immune response by regulating mitochondria and NOX-derived ROS

Energy Technology Data Exchange (ETDEWEB)

Reddy, Sukka Santosh [Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Chauhan, Parul [Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Maurya, Preeti [Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Academy of Scientific and Innovative Research, New Delhi 110025 (India); Saini, Deepika [Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Yadav, Prem Prakash, E-mail: pp_yadav@cdri.res.in [Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226031 (India); Barthwal, Manoj Kumar, E-mail: manojbarthwal@cdri.res.in [Pharmacology Division, CSIR-Central Drug Research Institute, Lucknow 226031 (India)

2016-10-15

Withanolides possess diverse biological and pharmacological activity but their immunomodulatory function is less realized. Hence, coagulin-L, a withanolide isolated from Withania coagulans Dunal has been studied for such an effect in human and murine cells, and mice model. Coagulin-L (1, 3, 10 μM) exhibited immunomodulatory effect by suppressing TLR4 induced immune mediators such as cytokines (GMCSF, IFNα, IFNγ, IL-1α, IL-1Rα, IL-1β, IL-2, IL-2R, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12 (p40/p70), IL-13, IL-15, IL-17), chemokines (IL-8/CXCL8, MIG/CXCL9, IP-10/CXCL10, KC, MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4, RANTES/CCL5, eotaxin/CCL11), growth factors (FGF-basic, VEGF), nitric oxide and intracellular superoxide. Mechanistically, coagulin-L abrogated LPS induced total and mitochondrial ROS generation, NOX2, NOX4 mRNA expression, IRAK and MAPK (p38, JNK, ERK) activation. Coagulin-L also attenuated IκBα degradation, which prevented NFκB downstream iNOS expression and pro-inflammatory cytokine release. Furthermore, coagulin-L (10, 25, 50 mg/kg, p.o.), undermined the LPS (10 mg/kg, i.p.) induced endotoxemia response in mice as evinced from diminished cytokine release, nitric oxide, aortic p38 MAPK activation and endothelial tissue impairment besides suppressing NOX2 and NOX4 expression in liver and aorta. Moreover, coagulin-L also alleviated the ROS mediated oxidative damage which was assessed through protein carbonyl, lipid hydroperoxide, 8-isoprostane and 8-hydroxy-2-deoxyguanosine quantification. To extend, coagulin-L also suppressed carrageenan-induced paw edema and thioglycollate-induced peritonitis in mice. Therefore, coagulin-L can be of therapeutic importance in pathological conditions induced by oxidative damage. - Highlights: • Coagulin-L demonstrates immunomodulatory effects in vivo and in vitro by modulating ROS. • Coagulin-L modulates TH1/TH2/TH17 immunokines. • Coagulin-L exerts immunomodulatory effect by regulating TLR4-IRAK- ROS

Oxidative DNA damage and oxidative stress in lead-exposed workers.

Science.gov (United States)

Dobrakowski, M; Pawlas, N; Kasperczyk, A; Kozłowska, A; Olewińska, E; Machoń-Grecka, A; Kasperczyk, S

2017-07-01

There are many discrepancies among the results of studies on the genotoxicity of lead. The aim of the study was to explore lead-induced DNA damage, including oxidative damage, in relation to oxidative stress intensity parameters and the antioxidant defense system in human leukocytes. The study population consisted of 100 male workers exposed to lead. According to the blood lead (PbB) levels, they were divided into the following three subgroups: a group with PbB of 20-35 μg/dL (low exposure to lead (LE) group), a group with a PbB of 35-50 µg/dL (medium exposure to lead (ME) group), and a group with a PbB of >50 μg/dL (high exposure to lead (HE) group). The control group consisted of 42 healthy males environmentally exposed to lead (PbB lead exposure induces DNA damage, including oxidative damage, in human leukocytes. The increase in DNA damage was accompanied by an elevated intensity of oxidative stress.

Anti-inflammatory and ameliorative effects of gallic acid on fluoxetine-induced oxidative stress and liver damage in rats.

Science.gov (United States)

Karimi-Khouzani, Omid; Heidarian, Esfandiar; Amini, Sayed Asadollah

2017-08-01

Fluoxetine-induced liver damage is a cause of chronic liver disease. In the present study the hepatoprotective effects of gallic acid against fluoxetine-induced liver damage were examined. Forty-eight male rats were divided into six groups as follow: group 1, the control group; group 2, rats receiving fluoxetine (24mg/kg bw daily, po) without treatment; group 3, rats receiving 24mg/kg bw fluoxetine, treated with 50mg/kg bw silymarin and groups 4, 5, and 6 in which gallic acid (50, 100, and 200mg/kg bw, po, respectively) was prescribed after the consumption of fluoxetine. The histopathological changes of hepatic tissues were checked out. Fluoxetine caused a significant increase in the levels of serum glutamate oxaloacetate transaminase (GOT), serum glutamate pyruvate transaminase (GPT), lipid profiles, urea, fasting blood sugar (FBS), creatinine (Cr), protein carbonyl (PC) content, malondialdehyde (MDA), and liver TNF-α as an inflammatory element. Also, the obtained results of group 2 revealed a significant decline in ferric reducing ability of plasma (FRAP), liver catalase (CAT), superoxide dismutase (SOD), and vitamin C levels. The treatment with gallic acid showed significant ameliorations in abnormalities of fluoxetine-induced liver injury as represented by the improvement of hepatic CAT, SOD activities, vitamin C levels, serum biochemical parameters, and histopathological changes, in addition to the recovery of antioxidant defense system status. Gallic acid has inhibitory effects on fluoxetine-induced liver damage. The effect of gallic acid is derived from free radical scavenging properties and the anti-inflammatory effect related to TNF-α. Copyright © 2017. Published by Elsevier Urban & Partner Sp. z o.o.

Diminution of Oxidative Damage to Human Erythrocytes and Lymphocytes by Creatine: Possible Role of Creatine in Blood.

Directory of Open Access Journals (Sweden)

Neha Qasim

Full Text Available Creatine (Cr is naturally produced in the body and stored in muscles where it is involved in energy generation. It is widely used, especially by athletes, as a staple supplement for improving physical performance. Recent reports have shown that Cr displays antioxidant activity which could explain its beneficial cellular effects. We have evaluated the ability of Cr to protect human erythrocytes and lymphocytes against oxidative damage. Erythrocytes were challenged with model oxidants, 2, 2'-azobis(2-amidinopropane dihydrochloride (AAPH and hydrogen peroxide (H2O2 in the presence and absence of Cr. Incubation of erythrocytes with oxidant alone increased hemolysis, methemoglobin levels, lipid peroxidation and protein carbonyl content. This was accompanied by decrease in glutathione levels. Antioxidant enzymes and antioxidant power of the cell were compromised while the activity of membrane bound enzyme was lowered. This suggests induction of oxidative stress in erythrocytes by AAPH and H2O2. However, Cr protected the erythrocytes by ameliorating the AAPH and H2O2 induced changes in these parameters. This protective effect was confirmed by electron microscopic analysis which showed that oxidant-induced cell damage was attenuated by Cr. No cellular alterations were induced by Cr alone even at 20 mM, the highest concentration used. Creatinine, a by-product of Cr metabolism, was also shown to exert protective effects, although it was slightly less effective than Cr. Human lymphocytes were similarly treated with H2O2 in absence and presence of different concentrations of Cr. Lymphocytes incubated with oxidant alone had alterations in various biochemical and antioxidant parameters including decrease in cell viability and induction of DNA damage. The presence of Cr attenuated all these H2O2-induced changes in lymphocytes. Thus, Cr can function as a blood antioxidant, protecting cells from oxidative damage, genotoxicity and can potentially increase their

Ginger extract protects rat's kidneys against oxidative damage after chronic ethanol administration.

Science.gov (United States)

Shirpoor, Aireza; Rezaei, Farzaneh; Fard, Amin Abdollahzade; Afshari, Ali Taghizadeh; Gharalari, Farzaneh Hosseini; Rasmi, Yousef

2016-12-01

Chronic alcohol ingestion is associated with pronounced detrimental effects on the renal system. In the current study, the protective effect of ginger extract on ethanol-induced damage was evaluated through determining 8-OHdG, cystatin C, glomerular filtration rate, and pathological changes such as cell proliferation and fibrosis in rats' kidneys. Male wistar rats were randomly divided into three groups and were treated as follows: (1) control, (2) ethanol and (3) ginger extract treated ethanolic (GETE) groups. After a six weeks period of treatment, the results revealed proliferation of glomerular and tubular cells, fibrosis in glomerular and peritubular and a significant rise in the level of 8-OHdG, cystatin C, plasma urea and creatinine. Moreover, compared to the control group, the ethanol group showed a significant decrease in the urine creatinine and creatinine clearance. In addition, significant amelioration of changes in the structure of kidneys, along with restoration of the biochemical alterations were found in the ginger extract treated ethanolic group, compared to the ethanol group. These findings indicate that ethanol induces kidneys abnormality by oxidative DNA damage and oxidative stress, and that these effects can be alleviated using ginger as an antioxidant and anti-inflammatory agent. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Melatonin and vitamin C exacerbate Cannabis sativa-induced testicular damage when administered separately but ameliorate it when combined in rats.

Science.gov (United States)

Alagbonsi, Isiaka A; Olayaki, Luqman A; Salman, Toyin M

2016-05-01

The mechanisms involved in the spermatotoxic effect of Cannabis sativa are inconclusive. The involvement of oxidative stress in male factor infertility has been well documented, and the antioxidative potential of melatonin and vitamin C in many oxidative stress conditions has been well reported. This study sought to investigate whether melatonin and vitamin C will ameliorate C. sativa-induced spermatotoxicity or not. Fifty-five (55) male albino rats (250-300 g) were randomly divided in a blinded fashion into five oral treatment groups as follows: group I (control, n=5) received 1 mL/kg of 10% ethanol for 30 days; groups IIa, IIb, and IIc (n=5 each) received 2 mg/kg C. sativa for 20, 30, and 40 days, respectively; groups IIIa, IIIb, and IIIc (n=5 each) received a combination of 2 mg/kg C. sativa and 4 mg/kg melatonin for 20, 30, and 40 days, respectively; groups IVa, IVb, and IVc (n=5 each) received a combination of 2 mg/kg C. sativa and 1.25 g/kg vitamin C for 20, 30, and 40 days, respectively; group V (n=5) received a combination of 2 mg/kg C. sativa, 4 mg/kg melatonin, and 1.25 g/kg vitamin C for 30 days. Cannabis treatments reduced the Johnsen score, sperm count, motility, morphology, paired testicular/body weight ratio, and total antioxidant capacity, but increased lactate dehydrogenase activity. In addition, supplementation of cannabis-treated rats with either melatonin or vitamin C exacerbates the effect of cannabis on those parameters, whereas combination of melatonin and vitamin C reversed the trend to the level comparable to control. This study further showed the gonadotoxic effect of C. sativa, which could be mediated by oxidative stress. It also showed that melatonin and vitamin C exacerbate C. sativa-induced testicular damage when administered separately but ameliorate it when combined in rats.

Amelioration of streptozotocin‑induced pancreatic β cell damage by morin: Involvement of the AMPK‑FOXO3‑catalase signaling pathway.

Science.gov (United States)

Wang, Ning; Zhang, Jiahui; Qin, Mengting; Yi, Wenjing; Yu, Shuang; Chen, Yi; Guan, Jing; Zhang, Rui

2018-03-01

Pancreatic β cells are sensitive to oxidative stress, which is one of the predominant causes of cell damage and the emergence of diabetes. The identification of effective therapeutic strategies to protect pancreatic cells from oxidative stress has increased interest in the screening of antioxidants from natural products. The present study aimed to investigate the protective effects of morin against streptozotocin (STZ)‑induced cell damage in a rat insulinoma cell line (RINm5F pancreatic β cells) and to identify the underlying mechanisms. The results indicated that morin inhibited the increase in intracellular reactive oxygen species, attenuated the activity of poly (ADP‑ribose) polymerase, restored intracellular nicotinamide adenine dinucleotide levels and reduced the apoptotic cell death of STZ‑treated pancreatic β cells. Treatment with morin significantly upregulated catalase in pancreatic β cells, and ameliorated the STZ‑induced loss of catalase at the genetic, protein and enzymatic level. In further experiments, morin induced the phosphorylation of 5' adenosine monophosphate‑activated protein kinase (AMPK), which subsequently promoted the translocation of forkhead box O3 (FOXO3) to the nucleus. Specific small interfering RNAs (siRNAs) against AMPK and FOXO3 suppressed morin‑induced catalase expression. Furthermore, catalase‑specific siRNA abolished the protective effects of morin against STZ‑stimulated cell death. Taken together, these results indicated that morin protected RINm5F cells from STZ‑induced cell damage by triggering the phosphorylation of AMPK, thus resulting in subsequent activation of FOXO3 and induction of catalase.

Exogenous nitric oxide improves salt tolerance during establishment of Jatropha curcas seedlings by ameliorating oxidative damage and toxic ion accumulation.

Science.gov (United States)

Gadelha, Cibelle Gomes; Miranda, Rafael de Souza; Alencar, Nara Lídia M; Costa, José Hélio; Prisco, José Tarquinio; Gomes-Filho, Enéas

2017-05-01

Jatropha curcas is an oilseed species that is considered an excellent alternative energy source for fossil-based fuels for growing in arid and semiarid regions, where salinity is becoming a stringent problem to crop production. Our working hypothesis was that nitric oxide (NO) priming enhances salt tolerance of J. curcas during early seedling development. Under NaCl stress, seedlings arising from NO-treated seeds showed lower accumulation of Na + and Cl - than those salinized seedlings only, which was consistent with a better growth for all analyzed time points. Also, although salinity promoted a significant increase in hydrogen peroxide (H 2 O 2 ) content and membrane damage, the harmful effects were less aggressive in NO-primed seedlings. The lower oxidative damage in NO-primed stressed seedlings was attributed to operation of a powerful antioxidant system, including greater glutathione (GSH) and ascorbate (AsA) contents as well as catalase (CAT) and glutathione reductase (GR) enzyme activities in both endosperm and embryo axis. Priming with NO also was found to rapidly up-regulate the JcCAT1, JcCAT2, JcGR1 and JcGR2 gene expression in embryo axis, suggesting that NO-induced salt responses include functional and transcriptional regulations. Thus, NO almost completely abolished the deleterious salinity effects on reserve mobilization and seedling growth. In conclusion, NO priming improves salt tolerance of J. curcas during seedling establishment by inducing an effective antioxidant system and limiting toxic ion and reactive oxygen species (ROS) accumulation. Copyright © 2017 Elsevier GmbH. All rights reserved.

Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53

Energy Technology Data Exchange (ETDEWEB)

Khan, Rehan; Khan, Abdul Quaiyoom; Qamar, Wajhul; Lateef, Abdul; Tahir, Mir; Rehman, Muneeb U; Ali, Farrah; Sultana, Sarwat, E-mail: sarwat786@rediffmail.com

2012-02-01

Cisplatin, an antineoplastic drug, is widely used as a foremost therapy against numerous forms of cancer but it has pronounced adverse effects viz., nephrotoxicity, ototoxicity etc. CDDP-induced emesis and diarrhea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants possesses multiple biological activities, such as antioxidant, anti-inflammatory and anti-cancer effects. In the present study, we investigated the protective effect of chrysin against CDDP-induced colon toxicity. The plausible mechanism of CDDP-induced colon toxicity and damage includes oxidative stress, activation of p38MAPK and p53, and colonic epithelial cell apoptosis via upregulating the expression of Bak and cleaved caspase-3. Chrysin was administered to Wistar rats once daily for 14 consecutive days at the doses of 25 and 50 mg/kg body weight orally in corn oil. On day 14, a single intraperitoneal injection of cisplatin was given at the dose of 7.5 mg/kg body weight and animals were euthanized after 24 h of cisplatin injection. Chrysin ameliorated CDDP-induced lipid peroxidation, xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6 phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin also attenuated goblet cell disintegration, expression of phospho-p38MAPK and p53, and apoptotic tissue damage which were induced by CDDP. Histological findings further supported the protective effects of chrysin against CDDP-induced colonic damage. The results of the present study suggest that the protective effect of chrysin against CDDP-induced colon toxicity was related with attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic tissue damage. Highlights: ► Cisplatin-induced colon toxicity is associated with oxidative stress and

Chrysin protects against cisplatin-induced colon. toxicity via amelioration of oxidative stress and apoptosis: Probable role of p38MAPK and p53

International Nuclear Information System (INIS)

Khan, Rehan; Khan, Abdul Quaiyoom; Qamar, Wajhul; Lateef, Abdul; Tahir, Mir; Rehman, Muneeb U; Ali, Farrah; Sultana, Sarwat

2012-01-01

Cisplatin, an antineoplastic drug, is widely used as a foremost therapy against numerous forms of cancer but it has pronounced adverse effects viz., nephrotoxicity, ototoxicity etc. CDDP-induced emesis and diarrhea are also marked toxicities that may be due to intestinal injury. Chrysin (5,7-dihydroxyflavone), a natural flavone commonly found in many plants possesses multiple biological activities, such as antioxidant, anti-inflammatory and anti-cancer effects. In the present study, we investigated the protective effect of chrysin against CDDP-induced colon toxicity. The plausible mechanism of CDDP-induced colon toxicity and damage includes oxidative stress, activation of p38MAPK and p53, and colonic epithelial cell apoptosis via upregulating the expression of Bak and cleaved caspase-3. Chrysin was administered to Wistar rats once daily for 14 consecutive days at the doses of 25 and 50 mg/kg body weight orally in corn oil. On day 14, a single intraperitoneal injection of cisplatin was given at the dose of 7.5 mg/kg body weight and animals were euthanized after 24 h of cisplatin injection. Chrysin ameliorated CDDP-induced lipid peroxidation, xanthine oxidase activity, glutathione depletion, decrease in antioxidant (catalase, glutathione reductase, glutathione peroxidase and glucose-6 phosphate dehydrogenase) and phase-II detoxifying (glutathione-S-transferase and quinone reductase) enzyme activities. Chrysin also attenuated goblet cell disintegration, expression of phospho-p38MAPK and p53, and apoptotic tissue damage which were induced by CDDP. Histological findings further supported the protective effects of chrysin against CDDP-induced colonic damage. The results of the present study suggest that the protective effect of chrysin against CDDP-induced colon toxicity was related with attenuation of oxidative stress, activation of p38MAPK and p53, and apoptotic tissue damage. Highlights: ► Cisplatin-induced colon toxicity is associated with oxidative stress and

Protective Effects of an Ancient Chinese Kidney-Tonifying Formula against H2O2-Induced Oxidative Damage to MES23.5 Cells.

Science.gov (United States)

Xu, Yihui; Lin, Wei; Ye, Shuifen; Wang, Huajin; Wang, Tingting; Su, Youyan; Wu, Liangning; Wang, Yuanwang; Xu, Qian; Xu, Chuanshan; Cai, Jing

2017-01-01

Oxidative damage plays a critical role in the etiology of neurodegenerative disorders including Parkinson's disease (PD). In our study, an ancient Chinese kidney-tonifying formula, which consists of Cistanche , Epimedii, and Polygonatum cirrhifolium , was investigated to protect MES23.5 dopaminergic neurons against hydrogen peroxide- (H 2 O 2 -) induced oxidative damage. The damage effects of H 2 O 2 on MES23.5 cells and the protective effects of KTF against oxidative stress were evaluated using MTT assay, transmission electron microscopy (TEM), immunocytochemistry (ICC), enzyme-linked immunosorbent assay (ELISA), and immunoblotting. The results showed that cell viability was dramatically decreased after a 12 h exposure to 150  μ M H 2 O 2 . TEM observation found that the H 2 O 2 -treated MES23.5 cells presented cellular organelle damage. However, when cells were incubated with KTF (3.125, 6.25, and 12.5  μ g/ml) for 24 h after H 2 O 2 exposure, a significant protective effect against H 2 O 2 -induced damage was observed in MES23.5 cells. Using ICC, we found that KTF inhibited the reduction of the tyrosine hydroxylase (TH) induced by H 2 O 2 , upregulated the mRNA and protein expression of HO-1, CAT, and GPx-1, and downregulated the expression of caspase 3. These results indicated that KTF may provide neuron protection against H 2 O 2 -induced cell damage through ameliorating oxidative stress, and our findings provide a new potential strategy for the prevention and treatment of Parkinson's disease.

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

Directory of Open Access Journals (Sweden)

Pradeepkiran Jangampalli Adi

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. Keywords: Cadmium (Cd, Oxidative stress, Lipid peroxidation, Nephrotoxicity, PAGE analysis

Quercitrin protects skin from UVB-induced oxidative damage

Energy Technology Data Exchange (ETDEWEB)

Yin, Yuanqin [Cancer Institute, The First Affiliated Hospital, China Medical University, Shenyang (China); Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Yao, Hua [Department of Stomatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang (China); Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J. [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Luo, Jia [Department of Internal Medicine, University of Kentucky, 800 Rose Street, Lexington, KY (United States); Gao, Ning [Department of Pharmacognos, College of Pharmacy, 3rd Military Medical University, Chongqing (China); Shi, Xianglin [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States); Zhang, Zhuo, E-mail: zhuo.zhang@uky.edu [Graduate Center for Toxicology, University of Kentucky, 1095 VA Drive, Lexington, KY (United States)

2013-06-01

Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries.

Quercitrin protects skin from UVB-induced oxidative damage

International Nuclear Information System (INIS)

Yin, Yuanqin; Li, Wenqi; Son, Young-Ok; Sun, Lijuan; Lu, Jian; Kim, Donghern; Wang, Xin; Yao, Hua; Wang, Lei; Pratheeshkumar, Poyil; Hitron, Andrew J.; Luo, Jia; Gao, Ning; Shi, Xianglin; Zhang, Zhuo

2013-01-01

Exposure of the skin to ultraviolet B (UVB) radiation causes oxidative damage to skin, resulting in sunburn, photoaging, and skin cancer. It is generally believed that the skin damage induced by UV irradiation is a consequence of generation of reactive oxygen species (ROS). Recently, there is an increased interest in the use of natural products as chemopreventive agents for non-melanoma skin cancer (NMSC) due to their antioxidants and anti-inflammatory properties. Quercitrin, glycosylated form of quercetin, is the most common flavonoid in nature with antioxidant properties. The present study investigated the possible beneficial effects of quercitrin to inhibit UVB irradiation-induced oxidative damage in vitro and in vivo. Our results showed that quercitrin decreased ROS generation induced by UVB irradiation in JB6 cells. Quercitrin restored catalase expression and GSH/GSSG ratio reduced by UVB exposure, two major antioxidant enzymes, leading to reductions of oxidative DNA damage and apoptosis and protection of the skin from inflammation caused by UVB exposure. The present study demonstrated that quercitrin functions as an antioxidant against UVB irradiation-induced oxidative damage to skin. - Highlights: • Oxidative stress plays a key role in UV-induced cell and tissue injuries. • Quercitrin decreases ROS generation and restores antioxidants irradiated by UVB. • Quercitrin reduces UVB-irradiated oxidative DNA damage, apoptosis, and inflammation. • Quercitrin functions as an antioxidant against UVB-induced skin injuries

Weight Loss and Melatonin Reduce Obesity-Induced Oxidative Damage in Rat Testis

Directory of Open Access Journals (Sweden)

Dogan Atilgan

2013-01-01

Full Text Available Aim. We aimed to evaluate the antioxidant effects of weight loss and melatonin on the obesity-induced oxidative damage in rat testes. Materials and Methods. 28 male Wistar albino rats were randomly divided into 4 groups, each consisting of 7 rats: control group (Group 1, obesity group (Group 2, obesity + MLT group (Group 3, and weight loss group (Group 4. Rats were weighed at the beginning and at the end of the study. Bilateral orchiectomy was performed and 5 cc blood samples were obtained from all of the rats. Superoxide dismutase (SOD, malondialdehyde (MDA, and protein carbonyl (PC levels were analysed in the testicular tissues and serum. Spermatogenesis was evaluated with the Johnsen scoring system. Results. The testicular tissue and serum levels of MDA, PC, and SOD activity were increased in the obesity group in comparison to the sham operated group (P<0.05. Weight loss and melatonin treatment ameliorated MDA, PC, and SOD levels in testicular tissue and serum significantly (P<0.05. There was no significant difference between groups in terms of mean Johnsen score (P=0.727. Conclusion. Experimentally created obesity caused oxidative stress and both melatonin and weight loss reduced oxidative stress parameters in rat testes.

Ameliorative Effects of Hydroalcoholic Extract of Lavandula officinalis L. on Methotrexate-Induced Oxidative Stress in Rats

Directory of Open Access Journals (Sweden)

Mojtaba Kalantar, Saeed Shirali, Amin Hasanvand , Masoud Valizadeh , Ramin Tavakoli , Marzieh Asadi , Mehdi Goudarzi

2017-03-01

Full Text Available Background: Methotrexate as a chemotherapy drug can causes chronic liver damage and oxidative stress. The aim of this study was to evaluate the protective effect of hydroalcoholic extract of Lavandula officinalis on methotrexate-induced oxidative stress in rats. Methods: In this experimental study, thirty five Wistar male rats weighting 200-250 g were randomly divided into 5 groups (n = 7 in each group. Negative control group (normal saline 5ml/kg; positive control group received normal salin orally for 10 days, and a single dose of methotrexate (MTX, 20mg/kg, i.p. was administrated on the 9th day. Groups 3-5 received respectively 100, 200 and 400 mg/kg of Lavandula officinalis extract (LOE orally for 10 days, and a single dose of MTX was injected on the 9th day. 24 h after the last injection, animals were sacrificed. Blood samples were collected to determine serum AST, ALT and ALP levels. Malondialdehyde (MDA, glutathione (GSH levels and catalase (CAT, superoxide dismutase (SOD and glutathione peroxidase (GPx activity were assayed in liver tissue. A portion of liver was maintained in 10% formalin for Hematoxylin and Eosin (H&E staining and histological examination. Results: The result obtained from current study was showed a significant increase in the levels of AST, ALT, ALP, MDA and decrease of GSH, CAT and SOD by MTX administration. Pre-treatment with LOE showed reduction in the levels of AST, ALT, ALP, MDA and increase of GSH, CAT and SOD in all doses but the most significant alteration was observed in doses of 200 and 400 mg/kg (P<0.05. Histological results showed that methotrexate could lead to liver damage. Also the hepatoprotective effect of the LOE was confirmed by the histological examination of the liver. Conclusion: Our results indicate that hydroalcoholic extract of Lavandula officinalis have produced amelioration in biochemical and oxidative stress parameters against MTX -induced oxidative stress.

Possible role of licorice roots (glycyrrhiza glabra) as a natural radioprotector against oxidative damage in rats

International Nuclear Information System (INIS)

Darwish, M. M.; Hussien, E. M.; Haggag, A. M.

2007-01-01

This study was conducted to investigate the possible role of Licorice against damages induced by gamma rays. Adult female albino rats (130-140 g) were divided into four groups. Group 1: control animals, group 2: rats whole body exposed to gamma radiations (6.5 Gy), group 3: animals received Licorice in drinking water for four weeks (100 mg/ kg body wt/ day), and group 4: received Licorice two weeks before and two weeks after irradiation. Blood and liver samples were obtained two weeks post-irradiation. Total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C) and low density lipoprotein-cholesterol (LDL-C), glucose, sodium (Na + ) and potassium (K + ) levels were determined in serum. Per oxidative hepatic damage was studied by assessing; thiobarbituric acid reactive substances (TBARs) and reduced glutathione (GSH) contents, as well as, superoxide dismutase (SOD) and catalase (CAT) activities in liver tissue. The data obtained revealed a significant increase in serum glucose, K + , TC, TG and LDL-C and liver TABRs. While, significant decreases were recorded for serum Na + and HDL-C levels, liver GSH content, SOD and CAT activities. On the other hand, Licorice treated irradiation rats showed a significant amelioration in the changes produced by gamma radiation with variable degree. Thus, it could be concluded that Licorice might provide protection against radiation-induced disturbances in metabolic activities and oxidative damage in liver tissues

Internalization of Staphylococcus aureus in Lymphocytes Induces Oxidative Stress and DNA Fragmentation: Possible Ameliorative Role of Nanoconjugated Vancomycin

Directory of Open Access Journals (Sweden)

Subhankari Prasad Chakraborty

2011-01-01

Full Text Available Staphylococcus aureus is the most frequently isolated pathogen causing bloodstream infections, skin and soft tissue infections and pneumonia. Lymphocyte is an important immune cell. The aim of the present paper was to test the ameliorative role of nanoconjugated vancomycin against Vancomycin-sensitive Staphylococcus aureus (VSSA and vancomycin-resistant Staphylococcus aureus (VRSA infection-induced oxidative stress in lymphocytes. VSSA and VRSA infections were developed in Swiss mice by intraperitoneal injection of 5×106 CFU/mL bacterial solutions. Nanoconjugated vancomycin was adminstrated to VSSA- and VRSA-infected mice at its effective dose for 10 days. Vancomycin was adminstrated to VSSA- and VRSA-infected mice at a similar dose, respectively, for 10 days. Vancomycin and nanoconjugated vancomycin were adminstrated to normal mice at their effective doses for 10 days. The result of this study reveals that in vivo VSSA and VRSA infection significantly increases the level of lipid peroxidation, protein oxidation, oxidized glutathione level, nitrite generation, nitrite release, and DNA damage and decreases the level of reduced glutathione, antioxidant enzyme status, and glutathione-dependent enzymes as compared to control group, which were increased or decreased significantly near to normal in nanoconjugated vancomycin-treated group. These findings suggest the potential use and beneficial role of nanoconjugated vancomycin against VSSA and VRSA infection-induced oxidative stress in lymphocytes.

Aging and oxidatively damaged nuclear DNA in animal organs

DEFF Research Database (Denmark)

Møller, Peter; Løhr, Mille; Folkmann, Janne K

2010-01-01

Oxidative stress is considered to contribute to aging and is associated with the generation of oxidatively damaged DNA, including 8-oxo-7,8-dihydroguanine. We have identified 69 studies that have measured the level of oxidatively damaged DNA in organs of animals at various ages. In general, organs...... with limited cell proliferation, i.e., liver, kidney, brain, heart, pancreas, and muscle, tended to show accumulation of DNA damage with age, whereas organs with highly proliferating cells, such as intestine, spleen, and testis, showed more equivocal or no effect of age. A restricted analysis of studies...... evidence for aging-associated accumulation of oxidatively damaged DNA in organs with limited cell proliferation....

Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats

Energy Technology Data Exchange (ETDEWEB)

Wang, Tingting; Zhao, Ling; Liu, Mengyu; Xie, Fei; Ma, Xuemei, E-mail: xmma@bjut.edu.cn; Zhao, Pengxiang; Liu, Yunqi; Li, Jiala; Wang, Minglian; Yang, Zhaona; Zhang, Yutong

2014-10-01

Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75 mg/kg body weight (1/20 LD{sub 50}) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity. - Highlights: • Hydrogen molecules protect rats from CPF-induced damage of hippocampal neurons. • The increased GFAP expression induced by CPF can also be ameliorated by hydrogen. • Hydrogen molecules attenuated the increase in CPF-induced oxidative stress. • Hydrogen molecules attenuated AChE inhibition in vivo

Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats

International Nuclear Information System (INIS)

Wang, Tingting; Zhao, Ling; Liu, Mengyu; Xie, Fei; Ma, Xuemei; Zhao, Pengxiang; Liu, Yunqi; Li, Jiala; Wang, Minglian; Yang, Zhaona; Zhang, Yutong

2014-01-01

Chronic exposure to low-levels of organophosphate (OP) compounds, such as chlorpyrifos (CPF), induces oxidative stress and could be related to neurological disorders. Hydrogen has been identified as a novel antioxidant which could selectively scavenge hydroxyl radicals. We explore whether intake of hydrogen-rich water (HRW) can protect Wistar rats from CPF-induced neurotoxicity. Rats were gavaged daily with 6.75 mg/kg body weight (1/20 LD 50 ) of CPF and given HRW by oral intake. Nissl staining and electron microscopy results indicated that HRW intake had protective effects on the CPF-induced damage of hippocampal neurons and neuronal mitochondria. Immunostaining results showed that the increased glial fibrillary acidic protein (GFAP) expression in astrocytes induced by CPF exposure can be ameliorated by HRW intake. Moreover, HRW intake also attenuated CPF-induced oxidative stress as evidenced by enhanced level of MDA, accompanied by an increase in GSH level and SOD and CAT activity. Acetylcholinesterase (AChE) activity tests showed significant decrease in brain AChE activity after CPF exposure, and this effect can be ameliorated by HRW intake. An in vitro study demonstrated that AChE activity was more intense in HRW than in normal water with or without chlorpyrifos-oxon (CPO), the metabolically-activated form of CPF. These observations suggest that HRW intake can protect rats from CPF-induced neurotoxicity, and the protective effects of hydrogen may be mediated by regulating the oxidant and antioxidant status of rats. Furthermore, this work defines a novel mechanism of biological activity of hydrogen by directly increasing the AChE activity. - Highlights: • Hydrogen molecules protect rats from CPF-induced damage of hippocampal neurons. • The increased GFAP expression induced by CPF can also be ameliorated by hydrogen. • Hydrogen molecules attenuated the increase in CPF-induced oxidative stress. • Hydrogen molecules attenuated AChE inhibition in vivo and in

Viewing oxidative stress through the lens of oxidative signalling rather than damage.

Science.gov (United States)

Foyer, Christine H; Ruban, Alexander V; Noctor, Graham

2017-03-07

Concepts of the roles of reactive oxygen species (ROS) in plants and animals have shifted in recent years from focusing on oxidative damage effects to the current view of ROS as universal signalling metabolites. Rather than having two opposing activities, i.e. damage and signalling, the emerging concept is that all types of oxidative modification/damage are involved in signalling, not least in the induction of repair processes. Examining the multifaceted roles of ROS as crucial cellular signals, we highlight as an example the loss of photosystem II function called photoinhibition, where photoprotection has classically been conflated with oxidative damage. © 2017 The Author(s). This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution Licence 4.0 (CC BY).

Ionizing radiation, antioxidant response and oxidative damage: A meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Einor, D., E-mail: daniel@einor.com [Department of Biological Sciences, University of South Carolina, Columbia, SC 29208 (United States); Bonisoli-Alquati, A., E-mail: andreabonisoli@gmail.com [Department of Biological Sciences, University of South Carolina, Columbia, SC 29208 (United States); School of Renewable Natural Resources, Louisiana State University AgCenter, Baton Rouge, LA 70803 (United States); Costantini, D., E-mail: davidcostantini@libero.it [Department of Biology, University of Antwerp, Wilrijk, B-2610, Antwerp (Belgium); Mousseau, T.A., E-mail: mousseau@sc.edu [Department of Biological Sciences, University of South Carolina, Columbia, SC 29208 (United States); Faculty of Bioscience and Biotechnology, Chubu University, Kasugai (Japan); Møller, A.P., E-mail: anders.moller@u-psud.fr [Laboratoire d' Ecologie, Systématique et Evolution, CNRS UMR 8079, Université Paris-Sud, Bâtiment 362, F-91405 Orsay Cedex (France)

2016-04-01

One mechanism proposed as a link between exposure to ionizing radiation and detrimental effects on organisms is oxidative damage. To test this hypothesis, we surveyed the scientific literature on the effects of chronic low-dose ionizing radiation (LDIR) on antioxidant responses and oxidative damage. We found 40 publications and 212 effect sizes for antioxidant responses and 288 effect sizes for effects of oxidative damage. We performed a meta-analysis of signed and unsigned effect sizes. We found large unsigned effects for both categories (0.918 for oxidative damage; 0.973 for antioxidant response). Mean signed effect size weighted by sample size was 0.276 for oxidative damage and − 0.350 for antioxidant defenses, with significant heterogeneity among effects for both categories, implying that ionizing radiation caused small to intermediate increases in oxidative damage and small to intermediate decreases in antioxidant defenses. Our estimates are robust, as shown by very high fail-safe numbers. Species, biological matrix (tissue, blood, sperm) and age predicted the magnitude of effects for oxidative damage as well as antioxidant response. Meta-regression models showed that effect sizes for oxidative damage varied among species and age classes, while effect sizes for antioxidant responses varied among species and biological matrices. Our results are consistent with the description of mechanisms underlying pathological effects of chronic exposure to LDIR. Our results also highlight the importance of resistance to oxidative stress as one possible mechanism associated with variation in species responses to LDIR-contaminated areas. - Highlights: • There is interest in variation in metabolic effects of chronic low-dose ionizing radiation • A random effect meta-analysis of effect sizes of radioactive contamination was performed • We found significant effects of radiation on oxidative damage and antioxidant response • We found significant heterogeneity among

Ionizing radiation, antioxidant response and oxidative damage: A meta-analysis.

Science.gov (United States)

Einor, D; Bonisoli-Alquati, A; Costantini, D; Mousseau, T A; Møller, A P

2016-04-01

One mechanism proposed as a link between exposure to ionizing radiation and detrimental effects on organisms is oxidative damage. To test this hypothesis, we surveyed the scientific literature on the effects of chronic low-dose ionizing radiation (LDIR) on antioxidant responses and oxidative damage. We found 40 publications and 212 effect sizes for antioxidant responses and 288 effect sizes for effects of oxidative damage. We performed a meta-analysis of signed and unsigned effect sizes. We found large unsigned effects for both categories (0.918 for oxidative damage; 0.973 for antioxidant response). Mean signed effect size weighted by sample size was 0.276 for oxidative damage and -0.350 for antioxidant defenses, with significant heterogeneity among effects for both categories, implying that ionizing radiation caused small to intermediate increases in oxidative damage and small to intermediate decreases in antioxidant defenses. Our estimates are robust, as shown by very high fail-safe numbers. Species, biological matrix (tissue, blood, sperm) and age predicted the magnitude of effects for oxidative damage as well as antioxidant response. Meta-regression models showed that effect sizes for oxidative damage varied among species and age classes, while effect sizes for antioxidant responses varied among species and biological matrices. Our results are consistent with the description of mechanisms underlying pathological effects of chronic exposure to LDIR. Our results also highlight the importance of resistance to oxidative stress as one possible mechanism associated with variation in species responses to LDIR-contaminated areas. Copyright © 2016 Elsevier B.V. All rights reserved.

Iron-Mediated Lysosomal Membrane Permeabilization in Ethanol-Induced Hepatic Oxidative Damage and Apoptosis: Protective Effects of Quercetin

Directory of Open Access Journals (Sweden)

Yanyan Li

2016-01-01

Full Text Available Iron, in its free ferrous states, can catalyze Fenton reaction to produce OH∙, which is recognized as a crucial role in the pathogenesis of alcoholic liver diseases (ALD. As a result of continuous decomposition of iron-containing compounds, lysosomes contain a pool of redox-active iron. To investigate the important role of intralysosomal iron in alcoholic liver injury and the potential protection of quercetin, male C57BL/6J mice fed by Lieber De Carli diets containing ethanol (30% of total calories were cotreated by quercetin or deferoxamine (DFO for 15 weeks and ethanol-incubated mice primary hepatocytes were pretreated with FeCl3, DFO, and bafilomycin A1 at their optimal concentrations and exposure times. Chronic ethanol consumption caused an evident increase in lysosomal redox-active iron accompanying sustained oxidative damage. Iron-mediated ROS could trigger lysosomal membrane permeabilization (LMP and subsequent mitochondria apoptosis. The hepatotoxicity was attenuated by reducing lysosomal iron while being exacerbated by escalating lysosomal iron. Quercetin substantially alleviated the alcoholic liver oxidative damage and apoptosis by decreasing lysosome iron and ameliorating iron-mediated LMP, which provided a new prospective of the use of quercetin against ALD.

Edaravone ameliorates compression-induced damage in rat nucleus pulposus cells.

Science.gov (United States)

Lin, Hui; Ma, Xuan; Wang, Bai-Chuan; Zhao, Lei; Liu, Jian-Xiang; Pu, Fei-Fei; Hu, Yi-Qiang; Hu, Hong-Zhi; Shao, Zeng-Wu

2017-11-15

Edaravone is a strong free radical scavenger most used for treating acute ischemic stroke. In this study we investigated the protective effects and underlying mechanisms of edaravone on compression-induced damage in rat nucleus pulposus (NP) cells. Cell viability was determined using MTT assay methods. NP cell apoptosis was measured by Hoechst 33,258 staining and Annexin V/PI double staining. Intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and intracellular calcium ([Ca 2+ ] i ) were determined by fluorescent probes DCFH-DA, JC-1 and Fluo-3/AM, respectively. Apoptosis-related proteins (cleaved caspase-3, cytosolic cytochrome c, Bax and Bcl-2) and extracellular matrix proteins (aggrecan and collagen II) were analyzed by western blot. Edaravone attenuated the compression-induced decrease in viability of NP cells in a dose-dependent manner. 33,258 and Annexin V/PI double staining showed that edaravone protected NP cells from compression-induced apoptosis. Further studies confirmed that edaravone protected NP cells against compression-induced mitochondrial pathway of apoptosis by inhibiting overproduction of ROS, collapse of MMP and overload of [Ca 2+ ] i . In addition, edaravone promoted the expression of aggrecan and collagen II in compression-treated NP cells. These results strongly indicate that edaravone ameliorates compression-induced damage in rat nucleus pulposus cells. Edaravone could be a potential new drug for treatment of IDD. Copyright © 2017 Elsevier Inc. All rights reserved.

Propofol ameliorates doxorubicin-induced oxidative stress and cellular apoptosis in rat cardiomyocytes

Energy Technology Data Exchange (ETDEWEB)

Lai, H.C. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Yeh, Y.C. [Graduate Institute of Natural Healing Sciences, Nanhua University, Chiayi, Taiwan (China); Wang, L.C. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Ting, C.T.; Lee, W.L. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Lee, H.W. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Wang, K.Y. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine, Chung-Shan Medical University, Taichung, Taiwan (China); Wu, A. [College of Biological Science, University of California, Davis (United States); Su, C.S. [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China); Liu, T.J., E-mail: trliu@vghtc.gov.tw [Cardiovascular Center and Department of Anesthesiology, Taichung Veterans General Hospital, Taichung, Taiwan (China); Department of Medicine and Cardiovascular Research Center, National Yang-Ming University School of Medicine, Taipei, Taiwan (China)

2011-12-15

Background: Propofol is an anesthetic with pluripotent cytoprotective properties against various extrinsic insults. This study was designed to examine whether this agent could also ameliorate the infamous toxicity of doxorubicin, a widely-used chemotherapeutic agent against a variety of cancer diseases, on myocardial cells. Methods: Cultured neonatal rat cardiomyocytes were administrated with vehicle, doxorubicin (1 {mu}M), propofol (1 {mu}M), or propofol plus doxorubicin (given 1 h post propofol). After 24 h, cells were harvested and specific analyses regarding oxidative/nitrative stress and cellular apoptosis were conducted. Results: Trypan blue exclusion and MTT assays disclosed that viability of cardiomyocytes was significantly reduced by doxorubicin. Contents of reactive oxygen and nitrogen species were increased and antioxidant enzymes SOD1, SOD2, and GPx were decreased in these doxorubicin-treated cells. Mitochondrial dehydrogenase activity and membrane potential were also depressed, along with activation of key effectors downstream of mitochondrion-dependent apoptotic signaling. Besides, abundance of p53 was elevated and cleavage of PKC-{delta} was induced in these myocardial cells. In contrast, all of the above oxidative, nitrative and pro-apoptotic events could be suppressed by propofol pretreatment. Conclusions: Propofol could extensively counteract oxidative/nitrative and multiple apoptotic effects of doxorubicin in the heart; hence, this anesthetic may serve as an adjuvant agent to assuage the untoward cardiac effects of doxorubicin in clinical application. -- Highlights: Black-Right-Pointing-Pointer We evaluate how propofol prevents doxorubicin-induced toxicity in cardiomyocytes. Black-Right-Pointing-Pointer Propofol reduces doxorubicin-imposed nitrative and oxidative stress. Black-Right-Pointing-Pointer Propofol suppresses mitochondrion-, p53- and PKC-related apoptotic signaling. Black-Right-Pointing-Pointer Propofol ameliorates apoptosis and

Ameliorative effects of oleanolic acid on fluoride induced metabolic and oxidative dysfunctions in rat brain: Experimental and biochemical studies.

Science.gov (United States)

Sarkar, Chaitali; Pal, Sudipta; Das, Niranjan; Dinda, Biswanath

2014-04-01

Beneficial effects of oleanolic acid on fluoride-induced oxidative stress and certain metabolic dysfunctions were studied in four regions of rat brain. Male Wistar rats were treated with sodium fluoride at a dose of 20 mg/kg b.w./day (orally) for 30 days. Results indicate marked reduction in acidic, basic and neutral protein contents due to fluoride toxicity in cerebrum, cerebellum, pons and medulla. DNA, RNA contents significantly decreased in those regions after fluoride exposure. Activities of proteolytic enzymes (such as cathepsin, trypsin and pronase) were inhibited by fluoride, whereas transaminase enzyme (GOT and GPT) activities increased significantly in brain tissue. Fluoride appreciably elevated brain malondialdehyde level, free amino acid nitrogen, NO content and free OH radical generation. Additionally, fluoride perturbed GSH content and markedly reduced SOD, GPx, GR and CAT activities in brain tissues. Oral supplementation of oleanolic acid (a plant triterpenoid), at a dose of 5mg/kgb.w./day for last 14 days of fluoride treatment appreciably ameliorated fluoride-induced alteration of brain metabolic functions. Appreciable counteractive effects of oleanolic acid against fluoride-induced changes in protein and nucleic acid contents, proteolytic enzyme activities and other oxidative stress parameters indicate that oleanolic acid has potential antioxidative effects against fluoride-induced oxidative brain damage. Copyright © 2014 Elsevier Ltd. All rights reserved.

Diphenylmethyl selenocyanate attenuates malachite green induced oxidative injury through antioxidation & inhibition of DNA damage in mice

Science.gov (United States)

Das, Jayanta Kumar; Sarkar, Sibani; Hossain, Sk Ugir; Chakraborty, Pramita; Das, Rajat Kumar; Bhattacharya, Sudin

2013-01-01

Background & objectives: Malachite green (MG), an environmentally hazardous material, is used as a non permitted food colouring agent, especially in India. Selenium (Se) is an essential nutritional trace element required for animals and humans to guard against oxidative stress induced by xenobiotic compounds of diverse nature. In the present study, the role of the selenium compound diphenylmethyl selenocyanate (DMSE) was assessed on the oxidative stress (OS) induced by a food colouring agent, malachite green (MG) in vivo in mice. Methods: Swiss albino mice (Mus musculus) were intraperitoneally injected with MG at a standardized dose of 100 μg/ mouse for 30 days. DMSE was given orally at an optimum dose of 3 mg/kg b.w. in pre (15 days) and concomitant treatment schedule throughout the experimental period. The parameters viz. ALT, AST, LPO, GSH, GST, SOD, CAT, GPx, TrxR, CA, MN, MI and DNA damage have been evaluated. Results: The DMSE showed its potential to protect against MG induced hepatotoxicity by controlling the serum alanine aminotransferase and aspartate amino transferase (ALT and AST) levels and also ameliorated oxidative stress by modulating hepatic lipid peroxidation and different detoxifying and antioxidative enzymes such as glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), and also the selenoenzymes such as glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) and reduced glutathione level which in turn reduced DNA damage. Interpretation & conclusions: The organo-selenium compound DMSE showed significant protection against MG induced heptotoxicity and DNA damage in murine model. Better protection was observed in pretreatment group than in the concomitant group. Further studies need to be done to understand the mechanism of action. PMID:23852297

Satureja bachtiarica ameliorate beta-amyloid induced memory impairment, oxidative stress and cholinergic deficit in animal model of Alzheimer's disease.

Science.gov (United States)

Soodi, Maliheh; Saeidnia, Soodabeh; Sharifzadeh, Mohammad; Hajimehdipoor, Homa; Dashti, Abolfazl; Sepand, Mohammad Reza; Moradi, Shahla

2016-04-01

Extracellular deposition of Beta-amyloid peptide (Aβ) is the main finding in the pathophysiology of Alzheimer's disease (AD), which damages cholinergic neurons through oxidative stress and reduces the cholinergic neurotransmission. Satureja bachtiarica is a medicinal plant from the Lamiaceae family which was widely used in Iranian traditional medicine. The aim of the present study was to investigate possible protective effects of S. bachtiarica methanolic extract on Aβ induced spatial memory impairment in Morris Water Maze (MWM), oxidative stress and cholinergic neuron degeneration. Pre- aggregated Aβ was injected into the hippocampus of each rat bilaterally (10 μg/rat) and MWM task was performed 14 days later to evaluate learning and memory function. Methanolic extract of S.bachtiarica (10, 50 and 100 mg/Kg) was injected intraperitoneally for 19 consecutive days, after Aβ injection. After the probe test the brain tissue were collected and lipid peroxidation, Acetylcholinesterase (AChE) activity and Cholin Acetyl Transferees (ChAT) immunorectivity were measured in the hippocampus. Intrahipocampal injection of Aβ impaired learning and memory in MWM in training days and probe trail. Methanolic extract of S. bachtiarica (50 and 100 mg/Kg) could attenuate Aβ-induced memory deficit. ChAT immunostaining revealed that cholinergic neurons were loss in Aβ- injected group and S. bachtiarica (100 mg/Kg) could ameliorate Aβ- induced ChAT reduction in the hippocampus. Also S. bachtiarica could ameliorate Aβ-induced lipid peroxidation and AChE activity increase in the hippocampus. In conclusion our study represent that S.bachtiarica methanolic extract can improve Aβ-induced memory impairment and cholinergic loss then we recommended this extract as a candidate for further investigation in treatment of AD.

Plumbagin, a vitamin K3 analogue ameliorate malaria pathogenesis by inhibiting oxidative stress and inflammation.

Science.gov (United States)

Gupta, Amit Chand; Mohanty, Shilpa; Saxena, Archana; Maurya, Anil Kumar; Bawankule, Dnyaneshwar U

2018-03-22

Plumbagin, a vitamin K3 analogue is the major active constituent in several plants including root of Plumbago indica Linn. This compound has been shown to exhibit a wide spectrum of pharmacological activities. The present investigation was to evaluate the ameliorative effects of plumbagin (PL) against severe malaria pathogenesis due to involvement of oxidative stress and inflammatory response in Plasmodium berghei infected malaria in mice. Malaria pathogenesis was induced by intra-peritoneal injection of P. berghei infected red blood cells into the Swiss albino mice. PL was administered orally at doses of 3, 10 and 30 mg/kg/day following Peter's 4 day suppression test. Oral administration of PL showed significant reduction of parasitaemia and increase in mean survival time. PL treatment is also attributed to significant increase in the blood glucose and haemoglobin level when compared with vehicle-treated infected mice. Significant inhibition in level of oxidative stress and pro-inflammation related markers were observed in PL treated group. The trend of inhibition in oxidative stress markers level after oral treatment of PL was MPO > LPO > ROS in organ injury in P. berghei infected mice. This study showed that plumbagin is able to ameliorate malaria pathogenesis by augmenting anti-oxidative and anti-inflammatory mechanism apart from its effect on reducing parasitaemia and increasing mean survival time of malaria-induced mice.

Pomegranate Alleviates Oxidative Damage and Neurotransmitter Alterations in Rats Brain Exposed to Aluminum Chloride and/or Gamma Radiation

International Nuclear Information System (INIS)

Said, U.Z.; EL-Tahawey, N.A.; Elassal, A.A.; Elsayed, E.M.; Shousha, W.Gh.

2013-01-01

Aluminum and gamma radiation, both are potent neurotoxins and have been implicated in many human neuro degenerative diseases. The present study was designed to investigate the role of pomegranate in alleviating oxidative damage and alteration of neurotransmitters in the brain of rats exposed to aluminum chloride (AlCl 3 ), and/or gamma radiation (IR). The results revealed that rats whole body exposed to γ- rays, (1 Gy/week up to 4 Gy), and/or administered aluminum chloride (35 mg/kg body weight), via gavages for 4 weeks, resulted in brain tissue damage, featuring by significant increase of the level of thiobarbituric acid reactive substances (TBARS), and advanced oxidation protein products (AOPP), associated with significant decrease of superoxide dismutase (SOD) and catalase (CAT) activities, as well as glutathione (GSH) content indicating occurrence of oxidative stress. A significant decrease of serotonin (5-HT) level associated with a significant increase of 5-hydroxyindole acetic acid (5-HIAA), in addition to a significant decrease in dopamine (DA), norepinephrine (NE) and epinephrine (EPI) contents recorded at the 1st, 7th and 14th day post-irradiation, indicating alterations in the metabolism of brain monoamines. On the other hand, the results exhibited that, supplementation of rats with pomegranate, via gavages, at a dose of 3 ml /kg body weight/ day, for 4 weeks along with AlCl 3 with or without radiation has significantly ameliorated the changes occurred in the mentioned parameters and the values returned close to the normal ones. It could be concluded that pomegranate, by its antioxidant constituents might antagonize brain oxidative damage and minimize the severity of aluminum (Al), and/or radiation-induced neurotransmitters disorders

Measurement of oxidative damage to DNA in nanomaterial exposed cells and animals

DEFF Research Database (Denmark)

Møller, Peter; Jensen, Ditte Marie; Christophersen, Daniel Vest

2015-01-01

-reactivity with other molecules in cells. This review provides an overview of efforts to reliably detect oxidatively damaged DNA and a critical assessment of the published studies on DNA damage levels. Animal studies with high baseline levels of oxidatively damaged DNA are more likely to show positive associations...... of oxidatively damaged DNA in lung tissue. Oral exposure to nanosized carbon black, TiO2 , carbon nanotubes and ZnO is associated with elevated levels of oxidatively damaged DNA in tissues. These observations are supported by cell culture studies showing concentration-dependent associations between ENM exposure...... and oxidatively damaged DNA measured by the comet assay. Cell culture studies show relatively high variation in the ability of ENMs to oxidatively damage DNA; hence, it is currently impossible to group ENMs according to their DNA damaging potential. Environ. Mol. Mutagen., 2014. © 2014 Wiley Periodicals, Inc....

Honey Supplementation in Spontaneously Hypertensive Rats Elicits Antihypertensive Effect via Amelioration of Renal Oxidative Stress

Directory of Open Access Journals (Sweden)

Omotayo O. Erejuwa

2012-01-01

Full Text Available Oxidative stress is implicated in the pathogenesis and/or maintenance of elevated blood pressure in hypertension. This study investigated the effect of honey on elevated systolic blood pressure (SBP in spontaneously hypertensive rats (SHR. It also evaluated the effect of honey on the amelioration of oxidative stress in the kidney of SHR as a possible mechanism of its antihypertensive effect. SHR and Wistar Kyoto (WKY rats were randomly divided into 2 groups and administered distilled water or honey by oral gavage once daily for 12 weeks. The control SHR had significantly higher SBP and renal malondialdehyde (MDA levels than did control WKY. The mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2 and glutathione S-transferase (GST were significantly downregulated while total antioxidant status (TAS and activities of GST and catalase (CAT were higher in the kidney of control SHR. Honey supplementation significantly reduced SBP and MDA levels in SHR. Honey significantly reduced the activities of GST and CAT while it moderately but insignificantly upregulated the Nrf2 mRNA expression level in the kidney of SHR. These results indicate that Nrf2 expression is impaired in the kidney of SHR. Honey supplementation considerably reduces elevated SBP via amelioration of oxidative stress in the kidney of SHR.

Preterm newborns show slower repair of oxidative damage and paternal smoking associated DNA damage.

Science.gov (United States)

Vande Loock, Kim; Ciardelli, Roberta; Decordier, Ilse; Plas, Gina; Haumont, Dominique; Kirsch-Volders, Micheline

2012-09-01

Newborns have to cope with hypoxia during delivery and a sudden increase in oxygen at birth. Oxygen will partly be released as reactive oxygen species having the potential to cause damage to DNA and proteins. In utero, increase of most (non)-enzymatic antioxidants occurs during last weeks of gestation, making preterm neonates probably more sensitive to oxidative stress. Moreover, it has been hypothesized that oxidative stress might be the common etiological factor for certain neonatal diseases in preterm infants. The aim of this study was to assess background DNA damage; in vitro H(2)O(2) induced oxidative DNA damage and repair capacity (residual DNA damage) in peripheral blood mononucleated cells from 25 preterm newborns and their mothers. In addition, demographic data were taken into account and repair capacity of preterm was compared with full-term newborns. Multivariate linear regression analysis revealed that preterm infants from smoking fathers have higher background DNA damage levels than those from non-smoking fathers, emphasizing the risk of paternal smoking behaviour for the progeny. Significantly higher residual DNA damage found after 15-min repair in preterm children compared to their mothers and higher residual DNA damage after 2 h compared to full-term newborns suggest a slower DNA repair capacity in preterm children. In comparison with preterm infants born by caesarean delivery, preterm infants born by vaginal delivery do repair more slowly the in vitro induced oxidative DNA damage. Final impact of passive smoking and of the slower DNA repair activity of preterm infants need to be confirmed in a larger study population combining transgenerational genetic and/or epigenetic effects, antioxidant levels, genotypes, repair enzyme efficiency/levels and infant morbidity.

Inflammation, oxidative DNA damage, and carcinogenesis

International Nuclear Information System (INIS)

Lewis, J.G.; Adams, D.O.

1987-01-01

Inflammation has long been associated with carcinogenesis, especially in the promotion phase. The mechanism of action of the potent inflammatory agent and skin promoter 12-tetradecanoyl phorbol-13-acetate (TPA) is unknown. It is though that TPA selectively enhances the growth of initiated cells, and during this process, initiated cells progress to the preneoplastic state and eventually to the malignant phenotype. The authors and others have proposed that TPA may work, in part, by inciting inflammation and stimulating inflammatory cells to release powerful oxidants which then induce DNA damage in epidermal cells. Macrophages cocultured with target cells and TPA induce oxidized thymine bases in the target cells. This process is inhibited by both catalase and inhibitors of lipoxygenases, suggesting the involvement of both H 2 O 2 and oxidized lipid products. In vivo studies demonstrated that SENCAR mice, which are sensitive to promotion by TPA, have a more intense inflammatory reaction in skin that C57LB/6 mice, which are resistant to promotion by TPA. In addition, macrophages from SENCAR mice release more H 2 O 2 and metabolites of AA, and induce more oxidative DNA damage in cocultured cells than macrophages from C57LB/6 mice. These data support the hypothesis that inflammation and the release of genotoxic oxidants may be one mechanism whereby initiated cells receive further genetic insults. They also further complicate risk assessment by suggesting that some environmental agents may work indirectly by subverting host systems to induce damage rather than maintaining homeostasis

Protection of naturally occurring antioxidants against oxidative damages to protein

International Nuclear Information System (INIS)

Zhu Hongping; Zhang Zhaoxia; Hao Shumei; Wang Wenfeng; Yao Side

2006-01-01

One of the most compelling theories explaining age-related deterioration is the free radical theory of aging. It has been shown that reactive oxygen species are involved in oxidative damages to biomolecules and this is related to a number of diseases. Proteins, the second most abundant components of cells (next to water by weight), are now increasingly recognized as major biological targets of oxidative damages. Convincing evidences have indicated that damages to protein have been implicated in Alzheimer's disease, Parkinson's disease, cancer, and aging. Antioxidant has been the subject of great attention because they are known to lower the risk of cardiovascular and other diseases. Hydroxycinnamic acid derivatives (HCAs) are antioxidants abundant in tea, red wine, fruits, beverages and various medicinal plants. Results showed that they exhibit remarkable activity for scavenging oxidizing radicals and triplet states. The protective effects of four kinds of HCAs on oxidative damages to lysozyme were investigated in our lab. Protein damages induced by two different paradigms: riboflavin-sensitized photooxidation and hydroxyl ( . OH)-mediated oxidation, were investigated using polyacrylamide gel electrophoresis. HCAs were found to inhibit the cross-linking of protein induced by riboflavin-mediated photooxidation. HCAs also exhibited protection effect on lysozyme damage induced by γ-ray irradiation. The rate constants for quenching triplet state of riboflavin by lysozyme and HCAs were obtained using laser flash photolysis. The protective mechanism was proposed based on the dynamic study. HCAs were found to protect protein against oxidation by scavenging oxidizing species and repairing the damaged protein. (authors)

Gymnaster koraiensis and its major components, 3,5-di-O-caffeoylquinic acid and gymnasterkoreayne B, reduce oxidative damage induced by tert-butyl hydroperoxide or acetaminophen in HepG2 cells

Directory of Open Access Journals (Sweden)

Eun Hye Jho

2013-10-01

Full Text Available We investigated the protective effects of Gymnaster koraiensisagainst oxidative stress-induced hepatic cell damage. We usedtwo different cytotoxicity models, i.e., the administration oftert-butyl hydroperoxide (t-BHP and acetaminophen, in HepG2cells to evaluate the protective effects of G. koraiensis. The ethylacetate (EA fraction of G. koraiensis and its major compound,3,5-di-O-caffeoylquinic acid (DCQA, exerted protective effectsin the t-BHP-induced liver cytotoxicity model. The EA fractionand DCQA ameliorated t-BHP-induced reductions in GSHlevels and exhibited free radical scavenging activity. The EAfraction and DCQA also significantly reduced t-BHP-inducedDNA damage in HepG2 cells. Furthermore, the hexane fractionof G. koraiensis and its major compound, gymnasterkoreayne B(GKB, exerted strong hepatoprotection in the acetaminopheninducedcytotoxicity model. CYP 3A4 enzyme activity wasstrongly inhibited by the extract, hexane fraction, and GKB. Thehexane fraction and GKB ameliorated acetaminophen-inducedreductions in GSH levels and protected against cell death. [BMBReports 2013; 46(10: 513-518

Prophylactic effects of pomegranate (Punica granatum) juice on sodium fluoride induced oxidative damage in liver and erythrocytes of rats.

Science.gov (United States)

Bouasla, Asma; Bouasla, Ihcène; Boumendjel, Amel; Abdennour, Cherif; El Feki, Abdelfattah; Messarah, Mahfoud

2016-07-01

The objective of this study was to investigate the protective effects of pomegranate (Punica granatum) juice (PGJ) on oxidative damages in liver tissue and erythrocytes of rats intoxicated by sodium fluoride (NaF). Rats were randomly divided into two groups: group I received standard diet and group II received orally 1 mL of PGJ. After 5 weeks of pretreatment, each group was divided again into two subgroups and treated for another 3 weeks as follows: group I was subdivided into a control group and a group that was treated with 100 ppm of NaF (in drinking water); group II was subdivided into one group that was treated daily with both 100 ppm NaF and PGJ (1 mL orally) and one that received daily 1 mL of pomegranate juice. Exposure to NaF decreased hematological parameters, changed the total protein, albumin, bilirubin levels, and increased the activities of hepatic marker enzymes. We also noted an increase in lipid peroxidation contents, accompanied by a decrease of reduced glutathione levels. Antioxidant enzyme activities in both tissues were modified in the NaF group compared with the control group. However, the administration of PGJ juice caused an amelioration of the previous parameters. Our results indicated the potential effects of NaF to induce oxidative damage in tissues and the ability of PGJ to attenuate NaF-induced oxidative injury.

Lycopene ameliorates atrazine-induced oxidative damage in adrenal cortex of male rats by activation of the Nrf2/HO-1 pathway.

Science.gov (United States)

Abass, Marwa Ahmed; Elkhateeb, Shereen Ahmed; Abd El-Baset, Samia Adel; Kattaia, Asmaa Alhosiny; Mohamed, Eman Mosallam; Atteia, Hebatallah Husseini

2016-08-01

Atrazine (ATZ) is one of the most commonly used herbicides contaminating plants, soil and water resources. Several strategies have been used to counteract ATZ toxicity. Here, we tested the hypothesis that lycopene could ameliorate ATZ-induced toxicity in the adrenal cortex. For this purpose, 35 adult male albino rats were randomized into five equal groups: untreated control, vehicle control (received 0.5 mL corn oil/day), lycopene (treated with lycopene dissolved in 0.5 mL corn oil, 10 mg/kg b.w./day), ATZ (received ATZ dissolved in 0.5 mL corn oil 300 mg/kg b.w./day), and ATZ + lycopene (treated with ATZ and lycopene at the same previously mentioned doses). All treatments were given by oral gavage for 4 weeks. We found that ATZ exposure significantly increased relative adrenal weight, plasma ACTH levels, and adrenal oxidative stress as manifested by elevated malondialdehyde levels, decreased reduced glutathione content and depressed antioxidant enzyme activities in adrenal cortex tissues with respect to control groups. Furthermore, the transcription of adrenal cortex nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), nuclear factor kappa B, and caspase-3 genes was increased significantly compared with the control groups. This was accompanied with DNA fragmentation and structural and ultrastructural changes in zona glomerulosa and zona fasiculata of the adrenal cortex. Notably, all these changes were partially ameliorated in rats treated concomitantly with ATZ and lycopene. Our results showed that lycopene exerts protective effects against ATZ-induced toxicity in rat adrenal cortex. These effects may be attributed to the antioxidative property of lycopene and its ability to activate the Nrf2/HO-1 pathway.

Hawkmoths use nectar sugar to reduce oxidative damage from flight.

Science.gov (United States)

Levin, E; Lopez-Martinez, G; Fane, B; Davidowitz, G

2017-02-17

Nectar-feeding animals have among the highest recorded metabolic rates. High aerobic performance is linked to oxidative damage in muscles. Antioxidants in nectar are scarce to nonexistent. We propose that nectarivores use nectar sugar to mitigate the oxidative damage caused by the muscular demands of flight. We found that sugar-fed moths had lower oxidative damage to their flight muscle membranes than unfed moths. Using respirometry coupled with δ 13 C analyses, we showed that moths generate antioxidant potential by shunting nectar glucose to the pentose phosphate pathway (PPP), resulting in a reduction in oxidative damage to the flight muscles. We suggest that nectar feeding, the use of PPP, and intense exercise are causally linked and have allowed the evolution of powerful fliers that feed on nectar. Copyright © 2017, American Association for the Advancement of Science.

OXIDATIVE STRESS AND VASCULAR DAMAGE IN HYPOXIA PROCESSES. MALONDIALDEHYDE (MDA AS BIOMARKER FOR OXIDATIVE DAMAGE

Directory of Open Access Journals (Sweden)

Muñiz P

2014-05-01

Full Text Available Changes in the levels oxidative stress biomarkers are related with different diseases such as ischemia/reperfusion, cardiovascular, renal, aging, etc. One of these biomarkers is the malondialdehyde (MDA generated as resulted of the process of lipid peroxidation. This biomarker is increased under conditions of the oxidative stress. Their levels, have been frequently used to measure plasma oxidative damage to lipids by their atherogenic potential. Its half-life high and their reactivity allows it to act both inside and outside of cells and interaction with proteins and DNA involve their role in different pathophysiological processes. This paper presents an analysis of the use of MDA as a biomarker of oxidative stress and its implications associated pathologies such as cardiovascular diseases ago.

Increased oxidative DNA damage in mononuclear leukocytes in vitiligo

Energy Technology Data Exchange (ETDEWEB)

Giovannelli, Lisa [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy)]. E-mail: lisag@pharm.unifi.it; Bellandi, Serena [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Pitozzi, Vanessa [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Fabbri, Paolo [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Dolara, Piero [Department of Preclinical and Clinical Pharmacology, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy); Moretti, Silvia [Department of Dermatological Sciences, University of Florence, Viale Pieraccini 6, 50139 Florence (Italy)

2004-11-22

Vitiligo is an acquired pigmentary disorder of the skin of unknown aetiology. The autocytotoxic hypothesis suggests that melanocyte impairment could be related to increased oxidative stress. Evidences have been reported that in vitiligo oxidative stress might also be present systemically. We used the comet assay (single cell alkaline gel electrophoresis) to evaluate DNA strand breaks and DNA base oxidation, measured as formamidopyrimidine DNA glycosylase (FPG)-sensitive sites, in peripheral blood cells from patients with active vitiligo and healthy controls. The basal level of oxidative DNA damage in mononuclear leukocytes was increased in vitiligo compared to normal subjects, whereas DNA strand breaks (SBs) were not changed. This alteration was not accompanied by a different capability to respond to in vitro oxidative challenge. No differences in the basal levels of DNA damage in polymorphonuclear leukocytes were found between patients and healthy subjects. Thus, this study supports the hypothesis that in vitiligo a systemic oxidative stress exists, and demonstrates for the first time the presence of oxidative alterations at the nuclear level. The increase in oxidative DNA damage shown in the mononuclear component of peripheral blood leukocytes from vitiligo patients was not particularly severe. However, these findings support an adjuvant role of antioxidant treatment in vitiligo.

Increased oxidative DNA damage in mononuclear leukocytes in vitiligo

International Nuclear Information System (INIS)

Giovannelli, Lisa; Bellandi, Serena; Pitozzi, Vanessa; Fabbri, Paolo; Dolara, Piero; Moretti, Silvia

2004-01-01

Vitiligo is an acquired pigmentary disorder of the skin of unknown aetiology. The autocytotoxic hypothesis suggests that melanocyte impairment could be related to increased oxidative stress. Evidences have been reported that in vitiligo oxidative stress might also be present systemically. We used the comet assay (single cell alkaline gel electrophoresis) to evaluate DNA strand breaks and DNA base oxidation, measured as formamidopyrimidine DNA glycosylase (FPG)-sensitive sites, in peripheral blood cells from patients with active vitiligo and healthy controls. The basal level of oxidative DNA damage in mononuclear leukocytes was increased in vitiligo compared to normal subjects, whereas DNA strand breaks (SBs) were not changed. This alteration was not accompanied by a different capability to respond to in vitro oxidative challenge. No differences in the basal levels of DNA damage in polymorphonuclear leukocytes were found between patients and healthy subjects. Thus, this study supports the hypothesis that in vitiligo a systemic oxidative stress exists, and demonstrates for the first time the presence of oxidative alterations at the nuclear level. The increase in oxidative DNA damage shown in the mononuclear component of peripheral blood leukocytes from vitiligo patients was not particularly severe. However, these findings support an adjuvant role of antioxidant treatment in vitiligo

Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

Energy Technology Data Exchange (ETDEWEB)

Zhang, Ying [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China); Li, Jianguo, E-mail: 2010lijianguo@sina.cn [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China)

2012-11-16

Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

Sweet potato Ipomoea Batatas Modulates Radiation-induced Oxidative damage in Liver and kidney of Male Albino Rats

International Nuclear Information System (INIS)

Darwish, M. M.; Farag, M. F. S.; Osman, N. N.

2010-01-01

Sweet potato Ipomoea Batatas, one of the major vegetable crops consumed worldwide, is rich in phytochemicals, which displayed antioxidant activities. This work aims at assessing the radio-protective properties of sweet potato tubers on liver and kidney tissues. Male albino rats were whole body exposed to 0.5 Gy day after day for a period of 20 days. Animal received orally prepared aqueous extract of sweet potato tubers (100 mg kg/body weight), one week before irradiation and during the period of radiation exposure. The results demonstrated that irradiation of rats induced a significant increase in lipid peroxides level measured as thiobarbituric acid reactive substances (TBARS) concomitant with a significant decrease in superoxide dismutase (SOD), and catalase (CAT) activity and glutathione (GSH) content in liver and kidney tissues. Administration of a freshly prepared aqueous extract of sweet potato tubers to rats, one week pre-irradiation and during the period of radiation exposure has significantly of ameliorated the oxidative stress in both tissues. The significant amelioration in oxidative stress was substantiated by improvement of liver and kidney enzymes Treatment of rats with sweet potato has significantly reduced the increase in serum alanine amino transferase (ALT), aspartate amino transferase (AST) and lactate dehydrogenase (LDH) activity, serum creatinine and urea levels. Furthermore, hyperglycemia and alteration in lipid profile manifested by a significant increase in triglycerides (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C), and a significant decrease in high density lipoprotein cholesterol (HDL-C), were improved in sweet potato-treated irradiated rats compared to those only irradiated. According to the results obtained in the present study, it could be concluded that sweet potato through its antioxidant activities could protect cellular membrane from radiation induced oxidative damage in animals and preserve the

Lymphocyte DNA damage and oxidative stress in patients with iron deficiency anemia.

Science.gov (United States)

Aslan, Mehmet; Horoz, Mehmet; Kocyigit, Abdurrahim; Ozgonül, Saadet; Celik, Hakim; Celik, Metin; Erel, Ozcan

2006-10-10

Oxidant stress has been shown to play an important role in the pathogenesis of iron deficiency anemia. The aim of this study was to investigate the association between lymphocyte DNA damage, total antioxidant capacity and the degree of anemia in patients with iron deficiency anemia. Twenty-two female with iron deficiency anemia and 22 healthy females were enrolled in the study. Peripheral DNA damage was assessed using alkaline comet assay and plasma total antioxidant capacity was determined using an automated measurement method. Lymphocyte DNA damage of patients with iron deficiency anemia was significantly higher than controls (ptotal antioxidant capacity was significantly lower (ptotal antioxidant capacity and hemoglobin levels (r=0.706, ptotal antioxidant capacity and hemoglobin levels were negatively correlated with DNA damage (r=-0.330, p<0.05 and r=-0.323, p<0.05, respectively). In conclusion, both oxidative stress and DNA damage are increased in IDA patients. Increased oxidative stress seems as an important factor that inducing DNA damage in those IDA patients. The relationships of oxidative stress and DNA damage with the severity of anemia suggest that both oxidative stress and DNA damage may, in part, have a role in the pathogenesis of IDA.

Jinlida reduces insulin resistance and ameliorates liver oxidative stress in high-fat fed rats.

Science.gov (United States)

Liu, Yixuan; Song, An; Zang, Shasha; Wang, Chao; Song, Guangyao; Li, Xiaoling; Zhu, Yajun; Yu, Xian; Li, Ling; Wang, Yun; Duan, Liyuan

2015-03-13

Jinlida (JLD) is a compound preparation formulated on the basis of traditional Chinese medicine and is officially approved for the treatment of type 2 diabetes (T2DM) in China. We aimed to elucidate the mechanism of JLD treatment, in comparison to metformin treatment, on ameliorating insulin sensitivity in insulin resistant rats and to reveal its anti-oxidant properties. Rats were fed with standard or high-fat diet for 6 weeks. After 6 weeks, the high-fat fed rats were subdivided into five groups and orally fed with JLD or metformin for 8 weeks. Fasting blood glucose (FBG), fasting blood insulin, blood lipid and antioxidant enzymes were measured. Intraperitoneal glucose tolerance test (IPGTT) and hyperinsulinemic euglycemic clamp technique were carried out to measure insulin sensitivity. Gene expression of the major signaling pathway molecules that regulate glucose uptake, including insulin receptor (INSR), insulin receptor substrate-1 (IRS-1), phosphoinositide-3-kinase (PI3K), protein kinase beta (AKT), and glucose transporter type 2 (GLUT2), were assessed by quantitative RT-PCR. The totle and phosphorylation expression of IRS-1, AKT, JNK and p38MAPK were determined by Western blot. Treatment with JLD effectively ameliorated the high-fat induced hyperglycemia, hyperinsulinemia and hyperlipidemia. Similar to metformin, the high insulin resistance in high-fat fed rats was significantly decreased by JLD treatment. JLD displayed anti-oxidant effects, coupled with up-regulation of the insulin signaling pathway. The attenuation of hepatic oxidative stress by JLD treatment was associated with reduced phosphorylation protein levels of JNK and p38MAPK. Treatment with JLD could moderate glucose and lipid metabolism as well as reduce hepatic oxidative stress, most likely through the JNK and p38MAPK pathways. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Thyroid hormone-induced oxidative damage on lipids, glutathione and DNA in the mouse heart.

Science.gov (United States)

Gredilla, R; Barja, G; López-Torres, M

2001-10-01

Oxygen radicals of mitochondrial origin are involved in oxidative damage. In order to analyze the possible relationship between metabolic rate, oxidative stress and oxidative damage, OF1 female mice were rendered hyper- and hypothyroid by chronic administration of 0.0012% L-thyroxine (T4) and 0.05% 6-n-propyl-2-thiouracil (PTU), respectively, in their drinking water for 5 weeks. Hyperthyroidism significantly increased the sensitivity to lipid peroxidation in the heart, although the endogenous levels of lipid peroxidation were not altered. Thyroid hormone-induced oxidative stress also resulted in higher levels of GSSG and GSSG/GSH ratio. Oxidative damage to mitochondrial DNA was greater than that to genomic DNA. Hyperthyroidism decreased oxidative damage to genomic DNA. Hypothyroidism did not modify oxidative damage in the lipid fraction but significantly decreased GSSG and GSSG/GSH ratio and oxidative damage to mitochondrial DNA. These results indicate that thyroid hormones modulate oxidative damage to lipids and DNA, and cellular redox potential in the mouse heart. A higher oxidative stress in the hyperthyroid group is presumably neutralized in the case of nuclear DNA by an increase in repair activity, thus protecting this key molecule. Treatment with PTU, a thyroid hormone inhibitor, reduced oxidative damage in the different cell compartments.

The Inhibition Effect of Cell DNA Oxidative Damage and LDL Oxidation by Bovine Colostrums

Directory of Open Access Journals (Sweden)

Chih-Wei Chen

2016-10-01

Full Text Available In the present study, we investigated the effect of bovine colostrums on inhibition of DNA oxidative damage and low density lipoprotein (LDL oxidation in vitro. Results showed that whey and skimmed milk exhibited not only higher inhibitory activities of oxidative damage of deoxyribose but also an inhibitory effect on the breakdown of supercoiled DNA into open circular DNA and linear DNA. The quantities of 8-OH-2′-dG formed under whey, caseins and skimmed milk treatment were 0.24, 0.24 and 1.24 μg/mL, respectively. The quantity of malondialdehyde formed through LDL oxidation induced by copprous ion was significantly decreased as colostrums protein solutions were added, in which whey and caseins led to a more significant decrease than skimmed milk. The formation of conjugated dienes could be inhibited by treatment with colostrums protein solutions. Whey exhibited the longest lag time of conjugated dienes formation among the colostrums proteins. The lag time of the whey was 2.33 times that of the control. From the results of foregoing, the bovine colostrums protein has potential value in the inhibition of DNA oxidation damage and LDL oxidation.

Aging-associated oxidized albumin promotes cellular senescence and endothelial damage

Directory of Open Access Journals (Sweden)

Luna C

2016-02-01

Full Text Available Carlos Luna,1,* Matilde Alique,2,* Estefanía Navalmoral,2 Maria-Victoria Noci,3 Lourdes Bohorquez-Magro,2 Julia Carracedo,1 Rafael Ramírez2 1Nephrology Unit, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC, Reina Sofía University Hospital, Córdoba, Spain; 2Department of Systems Biology, Physiology Unit, Universidad de Alcalá, Madrid, Spain; 3Anesthesia Unit, Reina sofía University Hospital, Córdoba, Spain*These authors contributed equally to this work Abstract: Increased levels of oxidized proteins with aging have been considered a cardiovascular risk factor. However, it is unclear whether oxidized albumin, which is the most abundant serum protein, induces endothelial damage. The results of this study indicated that with aging processes, the levels of oxidized proteins as well as endothelial microparticles release increased, a novel marker of endothelial damage. Among these, oxidized albumin seems to play a principal role. Through in vitro studies, endothelial cells cultured with oxidized albumin exhibited an increment of endothelial damage markers such as adhesion molecules and apoptosis levels. In addition, albumin oxidation increased the amount of endothelial microparticles that were released. Moreover, endothelial cells with increased oxidative stress undergo senescence. In addition, endothelial cells cultured with oxidized albumin shown a reduction in endothelial cell migration measured by wound healing. As a result, we provide the first evidence that oxidized albumin induces endothelial injury which then contributes to the increase of cardiovascular disease in the elderly subjects.Keywords: elderly, oxidative stress, microparticles, vascular damage

Oxidative DNA damage during sleep periods among nightshift workers.

Science.gov (United States)

Bhatti, Parveen; Mirick, Dana K; Randolph, Timothy W; Gong, Jicheng; Buchanan, Diana Taibi; Zhang, Junfeng Jim; Davis, Scott

2016-08-01

Oxidative DNA damage may be increased among nightshift workers because of suppression of melatonin, a cellular antioxidant, and/or inflammation related to sleep disruption. However, oxidative DNA damage has received limited attention in previous studies of nightshift work. From two previous cross-sectional studies, urine samples collected during a night sleep period for 217 dayshift workers and during day and night sleep (on their first day off) periods for 223 nightshift workers were assayed for 8-hydroxydeoxyguanosine (8-OH-dG), a marker of oxidative DNA damage, using high-performance liquid chromatography with electrochemical detection. Urinary measures of 6-sulfatoxymelatonin (aMT6s), a marker of circulating melatonin levels, and actigraphy-based sleep quality data were also available. Nightshift workers during their day sleep periods excreted 83% (p=0.2) and 77% (p=0.03) of the 8-OH-dG that dayshift workers and they themselves, respectively, excreted during their night sleep periods. Among nightshift workers, higher aMT6s levels were associated with higher urinary 8-OH-dG levels, and an inverse U-shaped trend was observed between 8-OH-dG levels and sleep efficiency and sleep duration. Reduced excretion of 8-OH-dG among nightshift workers during day sleep may reflect reduced functioning of DNA repair machinery, which could potentially lead to increased cellular levels of oxidative DNA damage. Melatonin disruption among nightshift workers may be responsible for the observed effect, as melatonin is known to enhance repair of oxidative DNA damage. Quality of sleep may similarly impact DNA repair. Cellular levels of DNA damage will need to be evaluated in future studies to help interpret these findings. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Hepatocyte growth factor gene-modified adipose-derived mesenchymal stem cells ameliorate radiation induced liver damage in a rat model.

Directory of Open Access Journals (Sweden)

Jiamin Zhang

Full Text Available Liver damage caused by radiotherapy is associated with a high mortality rate, but no established treatment exists. Adipose-derived mesenchymal stem cells (ADSCs are capable of migration to injured tissue sites, where they aid in the repair of the damage. Hepatocyte growth factor (HGF is critical for damage repair due to its anti-apoptotic, anti-fibrotic and cell regeneration-promoting effects. This study was performed to investigate the therapeutic effects of HGF-overexpressing ADSCs on radiation-induced liver damage (RILD. ADSCs were infected with a lentivirus encoding HGF and HGF-shRNA. Sprague-Dawley (SD rats received 60Gy of irradiation to induce liver injury and were immediately given either saline, ADSCs, ADSCs + HGF or ADSCs + shHGF. Two days after irradiation, a significant reduction in apoptosis was observed in the HGF-overexpressing ADSC group compared with the RILD group, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL staining. Scanning electron microscopy showed chromatin condensation after irradiation, which was ameliorated in the group that received ADSCs and was reversed in the group that received HGF-overexpressing ADSCs. HGF-overexpressing ADSCs ameliorated radiation- induced liver fibrosis through down regulation of α-SMA and fibronectin. Hepatocyte regeneration was significantly improved in rats treated with ADSCs compared with rats from the RILD group, as assessed by Ki-67 immunohistochemistry. Rats that received HGF-overexpressing ADSCs showed an even greater level of hepatocyte regeneration. HGF-overexpressing ADSCs completely blocked the radiation-induced increase in the enzymes ALT and AST. The effect of mitigating RILD was compromised in the ADSC + shHGF group compared with the ADSC group. Altogether, these results suggest that HGF-overexpressing ADSCs can significantly improve RILD in a rat model, which may serve as a valuable therapeutic alternative.

Oxidatively generated DNA/RNA damage in psychological stress states

DEFF Research Database (Denmark)

Jørgensen, Anders

2013-01-01

age-related somatic disorders. The overall aim of the PhD project was to investigate the relation between psychopathology, psychological stress, stress hormone secretion and oxidatively generated DNA and RNA damage, as measured by the urinary excretion of markers of whole-body DNA/RNA oxidation (8...... between the 24 h urinary cortisol excretion and the excretion of 8-oxodG/8-oxoGuo, determined in the same samples. Collectively, the studies could not confirm an association between psychological stress and oxidative stress on nucleic acids. Systemic oxidatively generated DNA/RNA damage was increased......Both non-pathological psychological stress states and mental disorders are associated with molecular, cellular and epidemiological signs of accelerated aging. Oxidative stress on nucleic acids is a critical component of cellular and organismal aging, and a suggested pathogenic mechanism in several...

Oxidative damage of DNA in subjects occupationally exposed to lead.

Science.gov (United States)

Pawlas, Natalia; Olewińska, Elżbieta; Markiewicz-Górka, Iwona; Kozłowska, Agnieszka; Januszewska, Lidia; Lundh, Thomas; Januszewska, Ewa; Pawlas, Krystyna

2017-09-01

Exposure to lead (Pb) in environmental and occupational settings continues to be a serious public health problem and may pose an elevated risk of genetic damage. The aim of this study was to assess the level of oxidative stress and DNA damage in subjects occupationally exposed to lead. We studied a population of 78 male workers exposed to lead in a lead and zinc smelter and battery recycling plant and 38 men from a control group. Blood lead levels were detected by graphite furnace atomic absorption spectrophotometry and plasma lead levels by inductively coupled plasma-mass spectrometry. The following assays were performed to assess the DNA damage and oxidative stress: comet assay, determination of 8-hydroxy-2'-deoxyguanosine (8-OHdG), lipid peroxidation and total antioxidant status (TAS). The mean concentration of lead in the blood of the exposed group was 392 ± 103 μg/L and was significantly higher than in the control group (30.3 ± 29.4 μg/L, p lead exposure [lead in blood, lead in plasma, zinc protoporphyrin (ZPP)] and urine concentration of 8-OHdG. The level of oxidative damage of DNA was positively correlated with the level of lipid peroxidation (TBARS) and negatively with total anti-oxidative status (TAS). Our study suggests that occupational exposure causes an increase in oxidative damage to DNA, even in subjects with relatively short length of service (average length of about 10 years). 8-OHdG concentration in the urine proved to be a sensitive and non-invasive marker of lead induced genotoxic damage.

Ameliorative effects of low dose/low dose-rate irradiation on reactive oxygen species-related diseases model mice

International Nuclear Information System (INIS)

Nomura, Takaharu

2008-01-01

β-cells against superoxide generated by glycation reaction evoked by high glucose environment. Continuous irradiation at 0.63 mGy/hr from 28 days of age elongates life span, and recovers splenic inflammatory response in Klotho-mice bearing ageing syndrome. The radiation increases anti-oxidants in liver, implicating the prevention of ageing through the suppression of cellular oxidative damages. Our results suggest that low dose/low dose-rate radiation effectively ameliorates diseases related to reactive oxygen species, and elongates life span of animals, at least in part through the stimulation of protective responses against oxidative stress. These findings are important not only for clinical use of low dose/low dose-rate radiation for human diseases, but also for non-cancerous risk estimation at dose and dose rate range argued in legal restrictions. (author)

Lipids and Oxidative Stress Associated with Ethanol-Induced Neurological Damage

Directory of Open Access Journals (Sweden)

José A. Hernández

2016-01-01

Full Text Available The excessive intake of alcohol is a serious public health problem, especially given the severe damage provoked by chronic or prenatal exposure to alcohol that affects many physiological processes, such as memory, motor function, and cognitive abilities. This damage is related to the ethanol oxidation in the brain. The metabolism of ethanol to acetaldehyde and then to acetate is associated with the production of reactive oxygen species that accentuate the oxidative state of cells. This metabolism of ethanol can induce the oxidation of the fatty acids in phospholipids, and the bioactive aldehydes produced are known to be associated with neurotoxicity and neurodegeneration. As such, here we will review the role of lipids in the neuronal damage induced by ethanol-related oxidative stress and the role that lipids play in the related compensatory or defense mechanisms.

Ameliorating effects of goby fish protein hydrolysates on high-fat-high-fructose diet-induced hyperglycemia, oxidative stress and deterioration of kidney function in rats.

Science.gov (United States)

Nasri, Rim; Abdelhedi, Ola; Jemil, Ines; Daoued, Ines; Hamden, Khaled; Kallel, Choumous; Elfeki, Abdelfattah; Lamri-Senhadji, Myriem; Boualga, Ahmed; Nasri, Moncef; Karra-Châabouni, Maha

2015-12-05

This study investigated the therapeutic potential of undigested goby fish (Zosterisessor ophiocephalus) muscle proteins (UGP) and their hydrolysates on high-fat-high-fructose diet (HFFD)-fed rats. HFFD induced hyperglycemia, manifested by a significant increase in the levels of glucose and glycogen as well as α-amylase activity when compared to normal rats. The administration of GPHs to HFFD-fed rats significantly decreased α-amylase activity and the contents of blood glucose and hepatic glycogen. By contrast, the UGP increased the glucose metabolic disorders in HFFD-fed rats. Furthermore, HFFD-fed rats showed oxidative stress, as evidenced by decreased antioxidant enzyme activities and glutathione (GSH) levels and increased concentration of the lipid peroxidation product malondialdehyde in liver and kidney. Interestingly, the daily gavage of UGP and GPHs improved the redox status in liver and kidney of HFFD-rats by ameliorating or reversing the above-mentioned changes. Moreover, GPHs exhibited a renal protective role by reversing the HFFD-induced decease of uric acid and increase of creatinine levels in serum and preventing some HFFD-induced changes in kidney architecture. The results demonstrate that GPHs contain bioactive peptides that possess significant hypoglycemic and antioxidant properties, and ameliorate renal damage in rats fed hypercaloric diet. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cardioprotective effect of amlodipine in oxidative stress induced by experimental myocardial infarction in rats

Directory of Open Access Journals (Sweden)

Sudhira Begum

2007-12-01

Full Text Available The present study investigated whether the administration of amlodipine ameliorates oxidative stress induced by experimental myocardial infarction in rats. Adrenaline was administered and myocardial damage was evaluated biochemically [significantly increased serum aspertate aminotransferase (AST, lactate dehydrogenase (LDH and malondialdehyde (MDA levels of myocardial tissue] and histologically (morphological changes of myocardium. Amlodipine was administered as pretreatment for 14 days in adrenaline treated rats. Statistically significant amelioration in all the biochemical parameters supported by significantly improved myocardial morphology was observed in amlodipine pretreatment. It was concluded that amlodipine afforded cardioprotection by reducing oxidative stress induced in experimental myocardial infarction of catecholamine assault.

Evaluation of ameliorative potential of supranutritional selenium on enrofloxacin-induced testicular toxicity.

Science.gov (United States)

Rungsung, Soya; Khan, Adil Mehraj; Sood, Naresh Kumar; Rampal, Satyavan; Singh Saini, Simrat Pal

2016-05-25

The study was designed to assess the ameliorative potential of selenium (Se) on enrofloxacin-induced testicular toxicity in rats. There was a significant decrease in body weight and non-significant decrease in mean testicular weight of enrofloxacin treated rats. In enrofloxacin treated rats, total sperm count and viability decreased where as sperm abnormalities increased. Testicular histopathology revealed dose dependent dysregulation of spermatogenesis and presence of necrotic debris in seminiferous tubules which was marginally improved with Se. Enrofloxacin also produced a dose dependent decrease in testosterone level. The activity of testicular antioxidant enzymes decreased where as lipid peroxidation increased in a dose-dependent manner. Se supplementation partially restored oxidative stress and sperm damage and did not affect the plasma concentrations of enrofloxacin or ciprofloxacain. The results indicate that enrofloxacin produces a dose-dependent testicular toxicity in rats that is moderately ameliorated with supranutritional Se. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats

Energy Technology Data Exchange (ETDEWEB)

Chen, Haw-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Huang, Chin-Shiu [Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China); Li, Chien-Chun [School of Nutrition, Chung Shan Medical University, Taichung, Taiwan (China); Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Ai-Hsuan; Huang, Yu-Ju [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Wang, Tsu-Shing [Department of Biomedical Science, Chung Shan Medical University, Taichung, Taiwan (China); Yao, Hsien-Tsung [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Lii, Chong-Kuei [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China)

2014-10-01

Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1 μM which peaked at 30 min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50 mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (p < 0.05). Immunoblot analysis and EMSA revealed that andrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl{sub 4}) at day 6. Andrographolide pretreatment suppressed CCl{sub 4}-induced plasma aminotransferase activity and hepatic lipid peroxidation (p < 0.05). These results suggest that andrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues. - Highlights: • The bioavailability of andrographolide is 1.19% in rats. • Plasma concentration reaches 1 μM after giving 50 mg/kg andrographolide. • Andrographolide up-regulates Nrf2-dependent antioxidant genes. • Andrographolide increases antioxidant defense

Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats

International Nuclear Information System (INIS)

Chen, Haw-Wen; Huang, Chin-Shiu; Li, Chien-Chun; Lin, Ai-Hsuan; Huang, Yu-Ju; Wang, Tsu-Shing; Yao, Hsien-Tsung; Lii, Chong-Kuei

2014-01-01

Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1 μM which peaked at 30 min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50 mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (p < 0.05). Immunoblot analysis and EMSA revealed that andrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl 4 ) at day 6. Andrographolide pretreatment suppressed CCl 4 -induced plasma aminotransferase activity and hepatic lipid peroxidation (p < 0.05). These results suggest that andrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues. - Highlights: • The bioavailability of andrographolide is 1.19% in rats. • Plasma concentration reaches 1 μM after giving 50 mg/kg andrographolide. • Andrographolide up-regulates Nrf2-dependent antioxidant genes. • Andrographolide increases antioxidant defense in

Analysis of the relationships between oxidative stress, DNA damage and sperm vitality in a patient population: development of diagnostic criteria.

Science.gov (United States)

Aitken, R John; De Iuliis, Geoffry N; Finnie, Jane M; Hedges, Andrew; McLachlan, Robert I

2010-10-01

DNA damage in human spermatozoa is known to be associated with a variety of adverse clinical outcomes affecting both reproductive efficiency and the health and wellbeing of the offspring. However, the origin of this damage, its biochemical nature and strategies for its amelioration, still await resolution. Using novel methods to simultaneously assess DNA fragmentation (modified TUNEL assay), DNA-base adduct formation (8-hydroxy-2'-deoxyguanosine [8OHdG]) and cell vitality, spermatozoa from a cohort of 50 assisted conception patients were examined and compared with a group of donors. Receiver operating characteristic (ROC) curve analysis was then used to examine the frequency distribution of the data and to determine optimized thresholds for identifying patients exhibiting abnormally high levels of DNA damage. 8OHdG formation and DNA fragmentation were highly correlated with each other and frequently associated with cell death. Percoll centrifugation improved sperm quality but, unexpectedly, increased 8OHdG formation in live cells, as did sperm fractionation using Puresperm gradients. ROC analysis indicated that the frequency distribution of 8OHdG and DNA fragmentation data were significantly different between patients and donors (P live cells. However, the development of novel methods and optimized thresholds for diagnosing oxidative DNA damage in human spermatozoa should assist in the clinical management of this pathology.

Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

Energy Technology Data Exchange (ETDEWEB)

Zheng, Juanjuan; Zhang, Yu [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Xu, Wentao, E-mail: xuwentaoboy@sina.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Luo, YunBo [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Hao, Junran [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Shen, Xiao Li [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Yang, Xuan [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); Li, Xiaohong [The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China); Huang, Kunlun, E-mail: hkl009@163.com [Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083 (China); The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083 (China)

2013-04-15

Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ{sub m}). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by

Zinc protects HepG2 cells against the oxidative damage and DNA damage induced by ochratoxin A

International Nuclear Information System (INIS)

Zheng, Juanjuan; Zhang, Yu; Xu, Wentao; Luo, YunBo; Hao, Junran; Shen, Xiao Li; Yang, Xuan; Li, Xiaohong; Huang, Kunlun

2013-01-01

Oxidative stress and DNA damage are the most studied mechanisms by which ochratoxin A (OTA) induces its toxic effects, which include nephrotoxicity, hepatotoxicity, immunotoxicity and genotoxicity. Zinc, which is an essential trace element, is considered a potential antioxidant. The aim of this paper was to investigate whether zinc supplement could inhibit OTA-induced oxidative damage and DNA damage in HepG2 cells and the mechanism of inhibition. The results indicated that that exposure of OTA decreased the intracellular zinc concentration; zinc supplement significantly reduced the OTA-induced production of reactive oxygen species (ROS) and decrease in superoxide dismutase (SOD) activity but did not affect the OTA-induced decrease in the mitochondrial membrane potential (Δψ m ). Meanwhile, the addition of the zinc chelator N,N,N′,N′-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) strongly aggravated the OTA-induced oxidative damage. This study also demonstrated that zinc helped to maintain the integrity of DNA through the reduction of OTA-induced DNA strand breaks, 8-hydroxy-2′-deoxyguanosine (8-OHdG) formation and DNA hypomethylation. OTA increased the mRNA expression of metallothionein1-A (MT1A), metallothionein2-A (MT2A) and Cu/Zn superoxide dismutase (SOD1). Zinc supplement further enhanced the mRNA expression of MT1A and MT2A, but it had no effect on the mRNA expression of SOD1 and catalase (CAT). Zinc was for the first time proven to reduce the cytotoxicity of OTA through inhibiting the oxidative damage and DNA damage, and regulating the expression of zinc-associated genes. Thus, the addition of zinc can potentially be used to reduce the OTA toxicity of contaminated feeds. - Highlights: ► OTA decreased the intracellular zinc concentration. ► OTA induced the formation of 8-OHdG in HepG2 cells. ► It was testified for the first time that OTA induced DNA hypomethylation. ► Zinc protects against the oxidative damage and DNA damage induced by OTA in

Copper-mediated oxidative degradation of catecholamines and oxidative damage of protein

Energy Technology Data Exchange (ETDEWEB)

Goncalves, P.R.; Harria, M.I.N.; Felix, J.M.; Hoffmann, M.E. [Universidade Estadual de Campinas, SP (Brazil). Inst. de Biologia

1997-12-31

Full text. Degradative oxidation of catecholamines has been a matter of large interest in recent years due to the evidences associating their autoxidation with the etiology of neurotoxic and cardiotoxic processes. In this work we present data on the degradative oxidation of catecholamines of physiological importance: isoproterenol (IP), epinephrine (EP), norepinephrine (NEP), deoxyepinephrine (DEP) and dopamine (DA). The degradative oxidation of the catecholamines was followed by measurement of spectral changes and oxygen consumption by neutral aqueous solutions. The data show that Cu{sup 2+} strongly accelerated the rate of catecholamine oxidation, following the decreasing order; EP>DEP>IP>NEP>DA. The production of superoxide anion radical during catecholamine oxidation was very slow, even in the presence of Cu{sup 2+}. The ability of IP to induce damages on bovine serum albumin (BSA) was determined by measuring the formation of carbonyl-groups in the protein, detected by reduction with tritiated Na BH{sub 4}. The incubation of BSA with IP (50-500{mu}M), in the presence of 100{mu}M Cu{sup 2+} leaded to an increased and dose dependent {sup 3} H-incorporation by the oxidized protein. The production of oxidative damage by IP/Cu{sup 2+} was accompanied by marked BSA fragmentation, detected by SDS-polyacrylamide gel dependent (25-400{mu}M IP) des appearance of the original BSA band and appearance of smaller fragments spread in the gel, when incubation has been done in the presence of 100{mu}M Cu{sup 2+}. These results suggest that copper-catalysed oxidative degradation of proteins induced by catecholamines might be critically involved in the toxic action of these molecules

Characterization of oxidative guanine damage and repair in mammalian telomeres.

Directory of Open Access Journals (Sweden)

Zhilong Wang

2010-05-01

Full Text Available 8-oxo-7,8-dihydroguanine (8-oxoG and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG are among the most common oxidative DNA lesions and are substrates for 8-oxoguanine DNA glycosylase (OGG1-initiated DNA base excision repair (BER. Mammalian telomeres consist of triple guanine repeats and are subject to oxidative guanine damage. Here, we investigated the impact of oxidative guanine damage and its repair by OGG1 on telomere integrity in mice. The mouse cells were analyzed for telomere integrity by telomere quantitative fluorescence in situ hybridization (telomere-FISH, by chromosome orientation-FISH (CO-FISH, and by indirect immunofluorescence in combination with telomere-FISH and for oxidative base lesions by Fpg-incision/Southern blot assay. In comparison to the wild type, telomere lengthening was observed in Ogg1 null (Ogg1(-/- mouse tissues and primary embryonic fibroblasts (MEFs cultivated in hypoxia condition (3% oxygen, whereas telomere shortening was detected in Ogg1(-/- mouse hematopoietic cells and primary MEFs cultivated in normoxia condition (20% oxygen or in the presence of an oxidant. In addition, telomere length abnormalities were accompanied by altered telomere sister chromatid exchanges, increased telomere single- and double-strand breaks, and preferential telomere lagging- or G-strand losses in Ogg1(-/- mouse cells. Oxidative guanine lesions were increased in telomeres in Ogg1(-/- mice with aging and primary MEFs cultivated in 20% oxygen. Furthermore, oxidative guanine lesions persisted at high level in Ogg1(-/- MEFs after acute exposure to hydrogen peroxide, while they rapidly returned to basal level in wild-type MEFs. These findings indicate that oxidative guanine damage can arise in telomeres where it affects length homeostasis, recombination, DNA replication, and DNA breakage repair. Our studies demonstrate that BER pathway is required in repairing oxidative guanine damage in telomeres and maintaining telomere integrity

Experimental study of oxidative DNA damage

DEFF Research Database (Denmark)

Loft, Steffen; Deng, Xin-Sheng; Tuo, Jingsheng

1998-01-01

Animal experiments allow the study of oxidative DNA damage in target organs and the elucidation of dose-response relationships of carcinogenic and other harmful chemicals and conditions as well as the study of interactions of several factors. So far the effects of more than 50 different chemical ...

Oxidative DNA damage causes mitochondrial genomic instability in Saccharomyces cerevisiae.

Science.gov (United States)

Doudican, Nicole A; Song, Binwei; Shadel, Gerald S; Doetsch, Paul W

2005-06-01

Mitochondria contain their own genome, the integrity of which is required for normal cellular energy metabolism. Reactive oxygen species (ROS) produced by normal mitochondrial respiration can damage cellular macromolecules, including mitochondrial DNA (mtDNA), and have been implicated in degenerative diseases, cancer, and aging. We developed strategies to elevate mitochondrial oxidative stress by exposure to antimycin and H(2)O(2) or utilizing mutants lacking mitochondrial superoxide dismutase (sod2Delta). Experiments were conducted with strains compromised in mitochondrial base excision repair (ntg1Delta) and oxidative damage resistance (pif1Delta) in order to delineate the relationship between these pathways. We observed enhanced ROS production, resulting in a direct increase in oxidative mtDNA damage and mutagenesis. Repair-deficient mutants exposed to oxidative stress conditions exhibited profound genomic instability. Elimination of Ntg1p and Pif1p resulted in a synergistic corruption of respiratory competency upon exposure to antimycin and H(2)O(2). Mitochondrial genomic integrity was substantially compromised in ntg1Delta pif1Delta sod2Delta strains, since these cells exhibit a total loss of mtDNA. A stable respiration-defective strain, possessing a normal complement of mtDNA damage resistance pathways, exhibited a complete loss of mtDNA upon exposure to antimycin and H(2)O(2). This loss was preventable by Sod2p overexpression. These results provide direct evidence that oxidative mtDNA damage can be a major contributor to mitochondrial genomic instability and demonstrate cooperation of Ntg1p and Pif1p to resist the introduction of lesions into the mitochondrial genome.

Maresin 1 Ameliorates Lung Ischemia/Reperfusion Injury by Suppressing Oxidative Stress via Activation of the Nrf-2-Mediated HO-1 Signaling Pathway

Directory of Open Access Journals (Sweden)

Quanchao Sun

2017-01-01

Full Text Available Lung ischemia/reperfusion (I/R injury occurs in various clinical conditions and heavily damaged lung function. Oxidative stress reaction and antioxidant enzymes play a pivotal role in the etiopathogenesis of lung I/R injury. In the current study, we investigated the impact of Maresin 1 on lung I/R injury and explored the possible mechanism involved in this process. MaR 1 ameliorated I/R-induced lung injury score, wet/dry weight ratio, myeloperoxidase, tumor necrosis factor, bronchoalveolar lavage fluid (BALF leukocyte count, BALF neutrophil ratio, and pulmonary permeability index levels in lung tissue. MaR 1 significantly reduced ROS, methane dicarboxylic aldehyde, and 15-F2t-isoprostane generation and restored antioxidative enzyme (superoxide dismutase, glutathione peroxidase, and catalase activities. Administration of MaR 1 improved the expression of nuclear Nrf-2 and cytosolic HO-1 in I/R-treated lung tissue. Furthermore, we also found that the protective effects of MaR 1 on lung tissue injury and oxidative stress were reversed by HO-1 activity inhibitor, Znpp-IX. Nrf-2 transcription factor inhibitor, brusatol, significantly decreased MaR 1-induced nuclear Nrf-2 and cytosolic HO-1 expression. In conclusion, these results indicate that MaR 1 protects against lung I/R injury through suppressing oxidative stress. The mechanism is partially explained by activation of the Nrf-2-mediated HO-1 signaling pathway.

Ameliorative Effects of Acacia Honey against Sodium Arsenite-Induced Oxidative Stress in Some Viscera of Male Wistar Albino Rats

OpenAIRE

Muhammad Aliyu; Sani Ibrahim; Hajiya M. Inuwa; Abdullahi B. Sallau; Olagunju Abbas; Idowu A. Aimola; Nathan Habila; Ndidi S. Uche

2013-01-01

Cancer is a leading cause of death worldwide and its development is frequently associated with oxidative stress-induced by carcinogens such as arsenicals. Most foods are basically health-promoting or disease-preventing and a typical example of such type is honey. This study was undertaken to investigate the ameliorative effects of Acacia honey on sodium arsenite-induced oxidative stress in the heart, lung and kidney tissues of male Wistar rats. Male Wistar albino rats divided into four groups...

D-Saccharic acid 1,4-lactone protects diabetic rat kidney by ameliorating hyperglycemia-mediated oxidative stress and renal inflammatory cytokines via NF-κB and PKC signaling

Energy Technology Data Exchange (ETDEWEB)

Bhattacharya, Semantee [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Manna, Prasenjit [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India); Gachhui, Ratan [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India)

2013-02-15

Increasing evidence suggests that oxidative stress is involved in the pathogenesis of diabetic nephropathy (DN) and this can be attenuated by antioxidants. D-Saccharic acid 1,4-lactone (DSL) is known for its detoxifying and antioxidant properties. Our early investigation showed that DSL can ameliorate alloxan (ALX) induced diabetes mellitus and oxidative stress in rats by inhibiting pancreatic β-cell apoptosis. In the present study we, therefore, investigated the protective role of DSL against renal injury in ALX induced diabetic rats. ALX exposure (at a dose of 120 mg/kg body weight, i. p., once) elevated the blood glucose level, serum markers related to renal injury, the production of reactive oxygen species (ROS), and disturbed the intra-cellular antioxidant machineries. Oral administration of DSL (80 mg/kg body weight) restored all these alterations close to normal. In addition, DSL could also normalize the aldose reductase activity which was found to increase in the diabetic rats. Investigating the mechanism of its protective activity, we observed the activation of different isoforms of PKC along with the accumulation of matrix proteins like collagen and fibronectin. The diabetic rats also showed nuclear translocation of NF-κB and increase in the concentration of inflammatory cytokines in the renal tissue. The activation of mitochondria dependent apoptotic pathway was observed in the diabetic rat kidneys. However, treatment of diabetic rats with DSL counteracted all these changes. These findings, for the first time, demonstrated that DSL could ameliorate renal dysfunction in diabetic rats by suppressing the oxidative stress related signalling pathways. - Highlights: ► Sustained hyperglycemia and oxidative stress lead to diabetic renal injury. ► D-saccharic acid 1,4-lactone prevents renal damage in alloxan-induced diabetes. ► It restores intra-cellular antioxidant machineries and kidney apoptosis. ► DSL reduces hyperglycemia-mediated oxidative stress

Oxidative damage and antioxidant defense in thymus of malnourished lactating rats.

Science.gov (United States)

Gavia-García, Graciela; González-Martínez, Haydeé; Miliar-García, Ángel; Bonilla-González, Edmundo; Rosas-Trejo, María de Los Ángeles; Königsberg, Mina; Nájera-Medina, Oralia; Luna-López, Armando; González-Torres, María Cristina

2015-01-01

Malnutrition has been associated with oxidative damage by altered antioxidant protection mechanisms. Specifically, the aim of this study was to evaluate oxidative damage (DNA and lipid) and antioxidant status (superoxide dismutase [SOD], glutathione peroxidase [GPx], and catalase [CAT] mRNA, and protein expression) in thymus from malnourished rat pups. Malnutrition was induced during the lactation period by the food competition method. Oxidative DNA damage was determined quantifying 8-oxo-7, 8-dihydro-2'-deoxyguanosine adduct by high-performance liquid chromatography. Lipid peroxidation was assessed by the formation of thiobarbituric acid-reactive substances. Levels of gene and protein expression of SOD, GPx, and CAT were evaluated by real-time polymerase chain reaction and Western blot, respectively. Antioxidant enzyme activities were measured spectrophotometrically. Oxidative DNA damage and lipid peroxidation significantly increased in second-degree (MN-2) and third-degree malnourished (MN-3) rats compared with well-nourished rats. Higher amounts of oxidative damage, lower mRNA expression, and lower relative concentrations of protein, as well as decreased antioxidant activity of SOD, GPx, and CAT were associated with the MN-2 and MN-3 groups. The results of this study demonstrated that higher body-weight deficits were related to alterations in antioxidant protection, which contribute to increased levels of damage in the thymus. To our knowledge, this study demonstrated for the first time that early in life, malnutrition leads to increased DNA and lipid oxidative damage, attributable to damaged antioxidant mechanisms including transcriptional and enzymatic activity alterations. These findings may contribute to the elucidation of the causes of previously reported thymus dysfunction, and might explain partially why children and adults who have overcome child undernourishment experience immunologic deficiencies. Copyright © 2015 Elsevier Inc. All rights reserved.

Detection of DNA damage by using hairpin molecular beacon probes and graphene oxide.

Science.gov (United States)

Zhou, Jie; Lu, Qian; Tong, Ying; Wei, Wei; Liu, Songqin

2012-09-15

A hairpin molecular beacon tagged with carboxyfluorescein in combination with graphene oxide as a quencher reagent was used to detect the DNA damage by chemical reagents. The fluorescence of molecular beacon was quenched sharply by graphene oxide; while in the presence of its complementary DNA the quenching efficiency decreased because their hybridization prevented the strong adsorbability of molecular beacon on graphene oxide. If the complementary DNA was damaged by a chemical reagent and could not form intact duplex structure with molecular beacon, more molecular beacon would adsorb on graphene oxide increasing the quenching efficiency. Thus, damaged DNA could be detected based on different quenching efficiencies afforded by damaged and intact complementary DNA. The damage effects of chlorpyrifos-methyl and three metabolites of styrene such as mandelieaeids, phenylglyoxylieaeids and epoxystyrene on DNA were studied as models. The method for detection of DNA damage was reliable, rapid and simple compared to the biological methods. Copyright © 2012 Elsevier B.V. All rights reserved.

Oxidative Damage and Cellular Defense Mechanisms in Sea Urchin Models of Aging

Science.gov (United States)

Du, Colin; Anderson, Arielle; Lortie, Mae; Parsons, Rachel; Bodnar, Andrea

2013-01-01

The free radical or oxidative stress theory of aging proposes that the accumulation of oxidative cellular damage is a major contributor to the aging process and a key determinant of species longevity. This study investigates the oxidative stress theory in a novel model for aging research, the sea urchin. Sea urchins present a unique model for the study of aging due to the existence of species with tremendously different natural life spans including some species with extraordinary longevity and negligible senescence. Cellular oxidative damage, antioxidant capacity and proteasome enzyme activities were measured in the tissues of three sea urchin species: short-lived Lytechinus variegatus, long-lived Strongylocentrotus franciscanus and Strongylocentrotus purpuratus which has an intermediate lifespan. Levels of protein carbonyls and 4-hydroxynonenal (HNE) measured in tissues (muscle, nerve, esophagus, gonad, coelomocytes, ampullae) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) measured in cell-free coelomic fluid showed no general increase with age. The fluorescent age-pigment lipofuscin measured in muscle, nerve and esophagus, increased with age however it appeared to be predominantly extracellular. Antioxidant mechanisms (total antioxidant capacity, superoxide dismutase) and proteasome enzyme activities were maintained with age. In some instances, levels of oxidative damage were lower and antioxidant activity higher in cells or tissues of the long-lived species compared to the short-lived species, however further studies are required to determine the relationship between oxidative damage and longevity in these animals. Consistent with the predictions of the oxidative stress theory of aging, the results suggest that negligible senescence is accompanied by a lack of accumulation of cellular oxidative damage with age and maintenance of antioxidant capacity and proteasome enzyme activities may be important mechanisms to mitigate damage. PMID:23707327

Therapeutic Hypothermia Reduces Oxidative Damage and Alters Antioxidant Defenses after Cardiac Arrest

Science.gov (United States)

Hackenhaar, Fernanda S.; Medeiros, Tássia M.; Heemann, Fernanda M.; Behling, Camile S.; Putti, Jordana S.; Mahl, Camila D.; Verona, Cleber; da Silva, Ana Carolina A.; Guerra, Maria C.; Gonçalves, Carlos A. S.; Oliveira, Vanessa M.; Riveiro, Diego F. M.; Vieira, Silvia R. R.

2017-01-01

After cardiac arrest, organ damage consequent to ischemia-reperfusion has been attributed to oxidative stress. Mild therapeutic hypothermia has been applied to reduce this damage, and it may reduce oxidative damage as well. This study aimed to compare oxidative damage and antioxidant defenses in patients treated with controlled normothermia versus mild therapeutic hypothermia during postcardiac arrest syndrome. The sample consisted of 31 patients under controlled normothermia (36°C) and 11 patients treated with 24 h mild therapeutic hypothermia (33°C), victims of in- or out-of-hospital cardiac arrest. Parameters were assessed at 6, 12, 36, and 72 h after cardiac arrest in the central venous blood samples. Hypothermic and normothermic patients had similar S100B levels, a biomarker of brain injury. Xanthine oxidase activity is similar between hypothermic and normothermic patients; however, it decreases posthypothermia treatment. Xanthine oxidase activity is positively correlated with lactate and S100B and inversely correlated with pH, calcium, and sodium levels. Hypothermia reduces malondialdehyde and protein carbonyl levels, markers of oxidative damage. Concomitantly, hypothermia increases the activity of erythrocyte antioxidant enzymes superoxide dismutase, glutathione peroxidase, and glutathione S-transferase while decreasing the activity of serum paraoxonase-1. These findings suggest that mild therapeutic hypothermia reduces oxidative damage and alters antioxidant defenses in postcardiac arrest patients. PMID:28553435

Transgenic Mouse Model for Reducing Oxidative Damage in Bone

Science.gov (United States)

Schreurs, Ann-Sofie; Torres, S.; Truong, T.; Moyer, E. L.; Kumar, A.; Tahimic, Candice C. G.; Alwood, J. S.; Limoli, C. L.; Globus, R. K.

2016-01-01

Bone loss can occur due to many challenges such age, radiation, microgravity, and Reactive Oxygen Species (ROS) play a critical role in bone resorption by osteoclasts (Bartell et al. 2014). We hypothesize that suppression of excess ROS in skeletal cells, both osteoblasts and osteoclasts, regulates skeletal growth and remodeling. To test our hypothesis, we used transgenic mCAT mice which overexpress the human anti-oxidant catalase gene targeted to the mitochondria, the main site for endogenous ROS production. mCAT mice have a longer life-span than wildtype controls and have been used to study various age-related disorders. To stimulate remodeling, 16 week old mCAT mice or wildtype mice were exposed to treatment (hindlimb-unloading and total body-irradiation) or sham treatment conditions (control). Tissues were harvested 2 weeks later for skeletal analysis (microcomputed tomography), biochemical analysis (gene expression and oxidative damage measurements), and ex vivo bone marrow derived cell culture (osteoblastogenesis and osteoclastogenesis). mCAT mice expressed the transgene and displayed elevated catalase activity in skeletal tissue and marrow-derived osteoblasts and osteoclasts grown ex vivo. In addition, when challenged with treatment, bone tissues from wildtype mice showed elevated levels of malondialdehyde (MDA), indicating oxidative damage) whereas mCAT mice did not. Correlation analysis revealed that increased catalase activity significantly correlated with decreased MDA levels and that increased oxidative damage correlated with decreased percent bone volume (BVTV). In addition, ex-vivo cultured osteoblast colony growth correlated with catalase activity in the osteoblasts. Thus, we showed that these transgenic mice can be used as a model to study the relationship between markers of oxidative damage and skeletal properties. mCAT mice displayed reduced BVTV and trabecular number relative to wildtype mice, as well as increased structural model index in the

Bilirubin and its oxidation products damage brain white matter

Science.gov (United States)

Lakovic, Katarina; Ai, Jinglu; D'Abbondanza, Josephine; Tariq, Asma; Sabri, Mohammed; Alarfaj, Abdullah K; Vasdev, Punarjot; Macdonald, Robert Loch

2014-01-01

Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke. PMID:25160671

NDE for Characterizing Oxidation Damage in Reinforced Carbon-Carbon

Science.gov (United States)

Roth, Don J.; Rauser, Richard W.; Jacobson, nathan S.; Wincheski, Russell A.; Walker, James L.; Cosgriff, Laura A.

2009-01-01

In this study, coated reinforced carbon-carbon (RCC) samples of similar structure and composition as that from the NASA space shuttle orbiter s thermal protection system were fabricated with slots in their coating simulating craze cracks. These specimens were used to study oxidation damage detection and characterization using NDE methods. These specimens were heat treated in air at 1143 and 1200 C to create cavities in the carbon substrate underneath the coating as oxygen reacted with the carbon and resulted in its consumption. The cavities varied in diameter from approximately 1 to 3 mm. Single-sided NDE methods were used since they might be practical for on-wing inspection, while x-ray micro-computed tomography (CT) was used to measure cavity sizes in order to validate oxidation models under development for carbon-carbon materials. An RCC sample having a naturally-cracked coating and subsequent oxidation damage was also studied with x-ray micro-CT. This effort is a follow-on study to one that characterized NDE methods for assessing oxidation damage in an RCC sample with drilled holes in the coating. The results of that study are briefly reviewed in this article as well. Additionally, a short discussion on the future role of simulation to aid in these studies is provided.

Interactions between Biliverdin, Oxidative Damage, and Spleen Morphology after Simulated Aggressive Encounters in Veiled Chameleons.

Directory of Open Access Journals (Sweden)

Michael W Butler

Full Text Available Stressors frequently increase oxidative damage--unless organisms simultaneously mount effective antioxidant responses. One putative mitigative mechanism is the use of biliverdin, an antioxidant produced in the spleen during erythrocyte degradation. We hypothesized that both wild and captive-bred male veiled chameleons (Chamaeleo calyptratus, which are highly aggressive to conspecifics, would respond to agonistic displays with increased levels of oxidative damage, but that increased levels of biliverdin would limit this increase. We found that even just visual exposure to a potential combatant resulted in decreased body mass during the subsequent 48-hour period, but that hematocrit, biliverdin concentration in the bile, relative spleen size, and oxidative damage in plasma, liver, and spleen were unaffected. Contrary to our predictions, we found that individuals with smaller spleens exhibited greater decreases in hematocrit and higher bile biliverdin concentrations, suggesting a revision to the idea of spleen-dependent erythrocyte processing. Interestingly, individuals with larger spleens had reduced oxidative damage in both the liver and spleen, demonstrating the spleen's importance in modulating oxidative damage. We also uncovered differences in spleen size and oxidative damage between wild and captive-bred chameleons, highlighting environmentally dependent differences in oxidative physiology. Lastly, we found no relationship between oxidative damage and biliverdin concentration, calling into question biliverdin's antioxidant role in this species.

Natural plant polyphenols for alleviating oxidative damage in man ...

African Journals Online (AJOL)

cumulative effects of oxidative damage over human life span. Current research reveals ... aging, cardiovascular and neurodegenerative diseases [3,4]. .... natural antioxidants and mortality from age- .... health and longevity in normal cells by calorie restriction [63]. ..... H(2)O(2)-induced oxidative stress and senescence via.

Chemoprotective Effect of Taurine on Potassium Bromate-Induced DNA Damage, DNA-Protein Cross-Linking and Oxidative Stress in Rat Intestine

Science.gov (United States)

Ahmad, Mir Kaisar; Khan, Aijaz Ahmed; Ali, Shaikh Nisar; Mahmood, Riaz

2015-01-01

Potassium bromate (KBrO3) is widely used as a food additive and is a major water disinfection by-product. It induces multiple organ toxicity in humans and experimental animals and is a probable human carcinogen. The present study reports the protective effect of dietary antioxidant taurine on KBrO3-induced damage to the rat intestine. Animals were randomly divided into four groups: control, KBrO3 alone, taurine alone and taurine+ KBrO3. Administration of KBrO3 alone led to decrease in the activities of intestinal brush border membrane enzymes while those of antioxidant defence and carbohydrate metabolism were also severely altered. There was increase in DNA damage and DNA-protein cross-linking. Treatment with taurine, prior to administration of KBrO3, resulted in significant attenuation in all these parameters but the administration of taurine alone had no effect. Histological studies supported these biochemical results showing extensive intestinal damage in KBrO3-treated animals and greatly reduced tissue injury in the taurine+ KBrO3 group. These results show that taurine ameliorates bromate induced tissue toxicity and oxidative damage by improving the antioxidant defence, tissue integrity and energy metabolism. Taurine can, therefore, be potentially used as a therapeutic/protective agent against toxicity of KBrO3 and related compounds. PMID:25748174

Endogenous melatonin and oxidatively damaged guanine in DNA

DEFF Research Database (Denmark)

Davanipour, Zoreh; Poulsen, Henrik E; Weimann, Allan

2009-01-01

overnight guanine DNA damage. 8-oxodG and 8-oxoGua were measured using a high-performance liquid chromatography-electrospray ionization tandem mass spectrometry assay. The mother, father, and oldest sampled daughter were used for these analyses. Comparisons between the mothers, fathers, and daughters were...... attack and increase the rate of repair of that damage. This paper reports the results of a study relating the level of overnight melatonin production to the overnight excretion of the two primary urinary metabolites of the repair of oxidatively damaged guanine in DNA. METHODS: Mother...

Is reproduction costly? No increase of oxidative damage in breeding bank voles.

Science.gov (United States)

Ołdakowski, Łukasz; Piotrowska, Zaneta; Chrzaácik, Katarzyna M; Sadowska, Edyta T; Koteja, Paweł; Taylor, Jan R E

2012-06-01

According to life-history theory, investment in reproduction is associated with costs, which should appear as decreased survival to the next reproduction or lower future reproductive success. It has been suggested that oxidative stress may be the proximate mechanism of these trade-offs. Despite numerous studies of the defense against reactive oxygen species (ROS) during reproduction, very little is known about the damage caused by ROS to the tissues of wild breeding animals. We measured oxidative damage to lipids and proteins in breeding bank vole (Myodes glareolus) females after rearing one and two litters, and in non-breeding females. We used bank voles from lines selected for high maximum aerobic metabolic rates (which also had high resting metabolic rates and food intake) and non-selected control lines. The oxidative damage was determined in heart, kidneys and skeletal muscles by measuring the concentration of thiobarbituric acid-reactive substances, as markers of lipid peroxidation, and carbonyl groups in proteins, as markers of protein oxidation. Surprisingly, we found that the oxidative damage to lipids in kidneys and muscles was actually lower in breeding than in non-breeding voles, and it did not differ between animals from the selected and control lines. Thus, contrary to our predictions, females that bred suffered lower levels of oxidative stress than those that did not reproduce. Elevated production of antioxidant enzymes and the protective role of sex hormones may explain the results. The results of the present study do not support the hypothesis that oxidative damage to tissues is the proximate mechanism of reproduction costs.

Oxidative stress, activity behaviour and body mass in captive parrots

OpenAIRE

Larcombe, S. D.; Tregaskes, C. A.; Coffey, J.; Stevenson, A. E.; Alexander, L. G.; Arnold, K. E.

2015-01-01

Many parrot species are kept in captivity for conservation, but often show poor reproduction, health and survival. These traits are known to be influenced by oxidative stress, the imbalance between the production of reactive oxygen species (ROS) and ability of antioxidant defences to ameliorate ROS damage. In humans, oxidative stress is linked with obesity, lack of exercise and poor nutrition, all of which are common in captive animals. Here, we tested whether small parrots (budgerigars, Melo...

Biomarkers of oxidative stress and DNA damage in agricultural workers: A pilot study

International Nuclear Information System (INIS)

Muniz, Juan F.; McCauley, Linda; Scherer, J.; Lasarev, M.; Koshy, M.; Kow, Y.W.; Nazar-Stewart, Valle; Kisby, G.E.

2008-01-01

Oxidative stress and DNA damage have been proposed as mechanisms linking pesticide exposure to health effects such as cancer and neurological diseases. A study of pesticide applicators and farmworkers was conducted to examine the relationship between organophosphate pesticide exposure and biomarkers of oxidative stress and DNA damage. Urine samples were analyzed for OP metabolites and 8-hydroxy-2'-deoxyguanosine (8-OH-dG). Lymphocytes were analyzed for oxidative DNA repair activity and DNA damage (Comet assay), and serum was analyzed for lipid peroxides (i.e., malondialdehyde, MDA). Cellular damage in agricultural workers was validated using lymphocyte cell cultures. Urinary OP metabolites were significantly higher in farmworkers and applicators (p < 0.001) when compared to controls. 8-OH-dG levels were 8.5 times and 2.3 times higher in farmworkers or applicators (respectively) than in controls. Serum MDA levels were 4.9 times and 24 times higher in farmworkers or applicators (respectively) than in controls. DNA damage (Comet assay) and oxidative DNA repair were significantly greater in lymphocytes from applicators and farmworkers when compared with controls. Markers of oxidative stress (i.e., increased reactive oxygen species and reduced glutathione levels) and DNA damage were also observed in lymphocyte cell cultures treated with an OP. The findings from these in vivo and in vitro studies indicate that organophosphate pesticides induce oxidative stress and DNA damage in agricultural workers. These biomarkers may be useful for increasing our understanding of the link between pesticides and a number of health effects

Early bichemical markers of effects: Enzyme induction, oncogene activation and markers of oxidative damage

DEFF Research Database (Denmark)

Poulsen, Henrik E.; Loft, Steffen

1995-01-01

Early bichemical marker, enzyme induction, oncogene activation, oxidative damage, low-density lipoprotein......Early bichemical marker, enzyme induction, oncogene activation, oxidative damage, low-density lipoprotein...

Curcumin ameliorates gastrointestinal dysfunction and oxidative damage in diabetic rats

Directory of Open Access Journals (Sweden)

Nitin Indarchandji Kochar

2014-05-01

Full Text Available Diabetes is known to be associated with gastrointestinal complications characterized by nausea, vomiting, early satiety, bloating, and abdominal discomfort or pain commonly occurring in the advanced stages of the disease. Curcumin is the lipid-soluble antioxidant obtained from the rhizomes of Curcuma longa Linn, also known as turmeric. Curcumin targets multiple chemotherapeutic and oxidative stress pathways and has demonstrated safety and tolerability in humans, supporting its potential as a therapeutic agent; however, literature lacks conclusive evidence supporting its use as a therapeutic agent for the treatment of diabetes induced gastrointestinal complications. Hence, Curcumin was given in different doses to SD rats after 4 weeks of diabetic GI complication induction. At the end of 4 weeks, significant GI dysfunction characterized by weight loss, delayed gastric emptying and intestinal transit associated with reduction in antioxidant enzyme levels and increased lipid peroxidation was observed.  Upon treatment with Curcumin for further 4 weeks, reversal of GI dysfunction evidenced by restoration of body weight, GI emptying, intestinal transit, and restoration of antioxidant enzyme level and lipid peroxidation proves the beneficial role of Curcumin in diabetes induced GI complications due to its antioxidant potential.     

Caryocar brasiliense camb protects against genomic and oxidative damage in urethane-induced lung carcinogenesis

Directory of Open Access Journals (Sweden)

N.B.R. Colombo

2015-01-01

Full Text Available The antioxidant effects of Caryocar brasiliense Camb, commonly known as the pequi fruit, have not been evaluated to determine their protective effects against oxidative damage in lung carcinogenesis. In the present study, we evaluated the role of pequi fruit against urethane-induced DNA damage and oxidative stress in forty 8-12 week old male BALB/C mice. An in vivo comet assay was performed to assess DNA damage in lung tissues and changes in lipid peroxidation and redox cycle antioxidants were monitored for oxidative stress. Prior supplementation with pequi oil or its extract (15 µL, 60 days significantly reduced urethane-induced oxidative stress. A protective effect against DNA damage was associated with the modulation of lipid peroxidation and low protein and gene expression of nitric oxide synthase. These findings suggest that the intake of pequi fruit might protect against in vivo genotoxicity and oxidative stress.

Ganoderma atrum polysaccharide ameliorates anoxia/reoxygenation-mediated oxidative stress and apoptosis in human umbilical vein endothelial cells.

Science.gov (United States)

Zhang, Yan-Song; Li, Wen-Juan; Zhang, Xian-Yi; Yan, Yu-Xin; Nie, Shao-Ping; Gong, De-Ming; Tang, Xiao-Fang; He, Ming; Xie, Ming-Yong

2017-05-01

Ganoderma atrum polysaccharide (PSG-1), a main polysaccharide from Ganoderma atrum, possesses potent antioxidant capacity and cardiovascular benefits. The aim of this study was to investigate the role of PSG-1 in oxidative stress and apoptosis in human umbilical vein endothelial cells (HUVECs) under anoxia/reoxygenation (A/R) injury conditions. The results showed that exposure of HUVECs to A/R triggered cell death and apoptosis. Administration of PSG-1 significantly inhibited A/R-induced cell death and apoptosis in HUVECs. PSG-1-reduced A/R injury was mediated via mitochondrial apoptotic pathway, as evidenced by elevation of mitochondrial Bcl-2 protein and mitochondrial membrane potential, and attenuation of Bax translocation, cytochrome c release and caspases activation. Furthermore, PSG-1 enhanced the activities of superoxide dismutase, catalase and glutathione peroxidase and glutathione content, and concomitantly attenuated reactive oxygen species generation, lipid peroxidation and glutathione disulfide content. The antioxidant, N-acetyl-l-cysteine, significantly ameliorated all of these endothelial injuries caused by A/R, suggesting that antioxidant activities might play a key role in PSG-1-induced endothelial protection. Taken together, these findings suggested that PSG-1 could be as a promising adjuvant against endothelial dysfunction through ameliorating oxidative stress and apoptosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Bee products prevent agrichemical-induced oxidative damage in fish.

Directory of Open Access Journals (Sweden)

Daiane Ferreira

Full Text Available In southern South America and other parts of the world, aquaculture is an activity that complements agriculture. Small amounts of agrichemicals can reach aquaculture ponds, which results in numerous problems caused by oxidative stress in non-target organisms. Substances that can prevent or reverse agrichemical-induced oxidative damage may be used to combat these effects. This study includes four experiments. In each experiment, 96 mixed-sex, 6-month-old Rhamdia quelen (118±15 g were distributed into eight experimental groups: a control group that was not exposed to contaminated water, three groups that were exposed to various concentrations of bee products, three groups that were exposed to various concentrations of bee products plus tebuconazole (TEB; Folicur 200 CE™ and a group that was exposed to 0.88 mg L(-1 of TEB alone (corresponding to 16.6% of the 96-h LC50. We show that waterborne bee products, including royal jelly (RJ, honey (H, bee pollen (BP and propolis (P, reversed the oxidative damage caused by exposure to TEB. These effects were likely caused by the high polyphenol contents of these bee-derived compounds. The most likely mechanism of action for the protective effects of bee products against tissue oxidation and the resultant damage is that the enzymatic activities of superoxide dismutase (SOD, catalase (CAT and glutathione-S-transferase (GST are increased.

Bee products prevent agrichemical-induced oxidative damage in fish.

Science.gov (United States)

Ferreira, Daiane; Rocha, Helio Carlos; Kreutz, Luiz Carlos; Loro, Vania Lucia; Marqueze, Alessandra; Koakoski, Gessi; da Rosa, João Gabriel Santos; Gusso, Darlan; Oliveira, Thiago Acosta; de Abreu, Murilo Sander; Barcellos, Leonardo José Gil

2013-01-01

In southern South America and other parts of the world, aquaculture is an activity that complements agriculture. Small amounts of agrichemicals can reach aquaculture ponds, which results in numerous problems caused by oxidative stress in non-target organisms. Substances that can prevent or reverse agrichemical-induced oxidative damage may be used to combat these effects. This study includes four experiments. In each experiment, 96 mixed-sex, 6-month-old Rhamdia quelen (118±15 g) were distributed into eight experimental groups: a control group that was not exposed to contaminated water, three groups that were exposed to various concentrations of bee products, three groups that were exposed to various concentrations of bee products plus tebuconazole (TEB; Folicur 200 CE™) and a group that was exposed to 0.88 mg L(-1) of TEB alone (corresponding to 16.6% of the 96-h LC50). We show that waterborne bee products, including royal jelly (RJ), honey (H), bee pollen (BP) and propolis (P), reversed the oxidative damage caused by exposure to TEB. These effects were likely caused by the high polyphenol contents of these bee-derived compounds. The most likely mechanism of action for the protective effects of bee products against tissue oxidation and the resultant damage is that the enzymatic activities of superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) are increased.

Lipoic acid in combination with a chelator ameliorates lead-induced peroxidative damages in rat kidney

Energy Technology Data Exchange (ETDEWEB)

Sivaprasad, R.; Nagaraj, M.; Varalakshmi, P. [Department of Medical Biochemistry, University of Madras (Taramani), Chennai 600 113 (India)

2002-08-01

The deleterious effect of lead has been attributed to lead-induced oxidative stress with the consequence of lipid peroxidation. The present study was designed to investigate the combined effect of DL-{alpha}-lipoic acid (LA) and meso-2,3-dimercaptosuccinic acid (DMSA) on lead-induced peroxidative damages in rat kidney. The increase in peroxidated lipids in lead-poisoned rats was accompanied by alterations in antioxidant defence systems. Lead acetate (Pb, 0.2%) was administered in drinking water for 5 weeks to induce lead toxicity. LA (25 mg/kg body weight per day i.p) and DMSA (20 mg/kg body weight per day i.p) were administered individually and also in combination during the sixth week. Nephrotoxic damage was evident from decreases in the activities of {gamma}-glutamyl transferase and N-acetyl {beta}-D-glucosaminidase, which were reversed upon combined treatment with LA and DMSA. Rats subjected to lead intoxication showed a decline in the thiol capacity of the cell, accompanied by high malondialdehyde levels along with lowered activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione metabolizing enzymes (glutathione reductase, glucose-6-phosphate dehydrogenase, glutathione-S-transferase). Supplementation with LA as a sole agent showed considerable changes over oxidative stress parameters. The study has highlighted the combined effect of both drugs as being more effective in reversing oxidative damage by bringing about an improvement in the reductive status of the cell. (orig.)

Piracetam ameliorated oxygen and glucose deprivation-induced injury in rat cortical neurons via inhibition of oxidative stress, excitatory amino acids release and P53/Bax.

Science.gov (United States)

He, Zhi; Hu, Min; Zha, Yun-hong; Li, Zi-cheng; Zhao, Bo; Yu, Ling-ling; Yu, Min; Qian, Ying

2014-05-01

Our previous work has demonstrated that piracetam inhibited the decrease in amino acid content induced by chronic hypoperfusion, ameliorated the dysfunction of learning and memory in a hypoperfusion rat model, down-regulated P53, and BAX protein, facilitated the synaptic plasticity, and may be helpful in the treatment of vascular dementia. To explore the precise mechanism, the present study further evaluated effects of piracetam on Oxygen and glucose deprivation (OGD)-induced neuronal damage in rat primary cortical cells. The addition of piracetam to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and lactate dehydrogenase release experiments. Piracetam also lowered the levels of malondialdehyde, nitrogen monoxidum, and xanthine oxidase which was increased in the OGD cells, and enhanced the activities of superoxide dismutase and glutathione peroxidase, which were decreased in the OGD cells. We also demonstrated that piracetam could decrease glutamate and aspartate release when cortical cells were subjected to OGD. Furthermore, Western blot study demonstrated that piracetam attenuated the increased expression of P53 and BAX protein in OGD cells. These observations demonstrated that piracetam reduced OGD-induced neuronal damage by inhibiting the oxidative stress and decreasing excitatory amino acids release and lowering P53/Bax protein expression in OGD cells.

Tempol, a superoxide dismutase mimetic agent, ameliorates cisplatin-induced nephrotoxicity through alleviation of mitochondrial dysfunction in mice.

Directory of Open Access Journals (Sweden)

Lamiaa A Ahmed

Full Text Available Mitochondrial dysfunction is a crucial mechanism by which cisplatin, a potent chemotherapeutic agent, causes nephrotoxicity where mitochondrial electron transport complexes are shifted mostly toward imbalanced reactive oxygen species versus energy production. In the present study, the protective role of tempol, a membrane-permeable superoxide dismutase mimetic agent, was evaluated on mitochondrial dysfunction and the subsequent damage induced by cisplatin nephrotoxicity in mice.Nephrotoxicity was assessed 72 h after a single i.p. injection of cisplatin (25 mg/kg with or without oral administration of tempol (100 mg/kg/day. Serum creatinine and urea as well as glucosuria and proteinuria were evaluated. Both kidneys were isolated for estimation of oxidative stress markers, adenosine triphosphate (ATP content and caspase-3 activity. Moreover, mitochondrial oxidative phosphorylation capacity, complexes I-IV activities and mitochondrial nitric oxide synthase (mNOS protein expression were measured along with histological examinations of renal tubular damage and mitochondrial ultrastructural changes. Tempol was effective against cisplatin-induced elevation of serum creatinine and urea as well as glucosuria and proteinuria. Moreover, pretreatment with tempol notably inhibited cisplatin-induced oxidative stress and disruption of mitochondrial function by restoring mitochondrial oxidative phosphorylation, complexes I and III activities, mNOS protein expression and ATP content. Tempol also provided significant protection against apoptosis, tubular damage and mitochondrial ultrastructural changes. Interestingly, tempol did not interfere with the cytotoxic effect of cisplatin against the growth of solid Ehrlich carcinoma.This study highlights the potential role of tempol in inhibiting cisplatin-induced nephrotoxicity without affecting its antitumor activity via amelioration of oxidative stress and mitochondrial dysfunction.

Oxidative stress and inflammation generated DNA damage by exposure to air pollution particles

DEFF Research Database (Denmark)

Møller, Peter; Danielsen, Pernille Høgh; Karottki, Dorina Gabriela

2014-01-01

at different locations (spatial variability), times (temporal variability) or particle size fraction across different experimental systems of acellular conditions, cultured cells, animals and humans. Nevertheless, there is substantial variation in the genotoxic, inflammation and oxidative stress potential......Generation of oxidatively damaged DNA by particulate matter (PM) is hypothesized to occur via production of reactive oxygen species (ROS) and inflammation. We investigated this hypothesis by comparing ROS production, inflammation and oxidatively damaged DNA in different experimental systems...... investigating air pollution particles. There is substantial evidence indicating that exposure to air pollution particles was associated with elevated levels of oxidatively damaged nucleobases in circulating blood cells and urine from humans, which is supported by observations of elevated levels of genotoxicity...

Age-dependent oxidative stress-induced DNA damage in Down's lymphocytes

International Nuclear Information System (INIS)

Zana, Marianna; Szecsenyi, Anita; Czibula, Agnes; Bjelik, Annamaria; Juhasz, Anna; Rimanoczy, Agnes; Szabo, Krisztina; Vetro, Agnes; Szucs, Peter; Varkonyi, Agnes; Pakaski, Magdolna; Boda, Krisztina; Rasko, Istvan; Janka, Zoltan; Kalman, Janos

2006-01-01

The aim of the present study was to investigate the oxidative status of lymphocytes from children (n = 7) and adults (n = 18) with Down's syndrome (DS). The basal oxidative condition, the vulnerability to in vitro hydrogen peroxide exposure, and the repair capacity were measured by means of the damage-specific alkaline comet assay. Significantly and age-independently elevated numbers of single strand breaks and oxidized bases (pyrimidines and purines) were found in the nuclear DNA of the lymphocytes in the DS group in the basal condition. These results may support the role of an increased level of endogenous oxidative stress in DS and are similar to those previously demonstrated in Alzheimer's disease. In the in vitro oxidative stress-induced state, a markedly higher extent of DNA damage was observed in DS children as compared with age- and gender-matched healthy controls, suggesting that young trisomic lymphocytes are more sensitive to oxidative stress than normal ones. However, the repair ability itself was not found to be deteriorated in either DS children or DS adults

Peroxiredoxin 1 Protects Telomeres from Oxidative Damage and Preserves Telomeric DNA for Extension by Telomerase

Directory of Open Access Journals (Sweden)

Eric Aeby

2016-12-01

Full Text Available Oxidative damage of telomeres can promote cancer, cardiac failure, and muscular dystrophy. Specific mechanisms protecting telomeres from oxidative damage have not been described. We analyzed telomeric chromatin composition during the cell cycle and show that the antioxidant enzyme peroxiredoxin 1 (PRDX1 is enriched at telomeres during S phase. Deletion of the PRDX1 gene leads to damage of telomeric DNA upon oxidative stress, revealing a protective function of PRDX1 against oxidative damage at telomeres. We also show that the oxidized nucleotide 8-oxo-2′deoxyguanosine-5′-triphosphate (8oxodGTP causes premature chain termination when incorporated by telomerase and that some DNA substrates terminating in 8oxoG prevent extension by telomerase. Thus, PRDX1 safeguards telomeres from oxygen radicals to counteract telomere damage and preserve telomeric DNA for elongation by telomerase.

Dunnione ameliorates cisplatin-induced small intestinal damage by modulating NAD{sup +} metabolism

Energy Technology Data Exchange (ETDEWEB)

Pandit, Arpana; Kim, Hyung-Jin; Oh, Gi-Su; Shen, AiHua; Lee, Su-Bin; Khadka, Dipendra; Lee, SeungHoon [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Shim, Hyeok; Yang, Sei-Hoon; Cho, Eun-Young [Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwon, Kang-Beom [Department of Oriental Medical Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwak, Tae Hwan [PAEAN Biotechnology, 160 Techno-2 Street, Yuseong-gu, Daejeon 305-500 (Korea, Republic of); Choe, Seong-Kyu; Park, Raekil [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); So, Hong-Seob, E-mail: jeanso@wku.ac.kr [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of)

2015-11-27

Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD{sup +}) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD{sup +} in the small intestine after cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD{sup +} levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD{sup +} levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage. - Highlights: • NAD{sup +} acts as a cofactor for numerous enzymes including Sirtuins and PARP. • Up-regulation of SIRT1 could attenuate the cisplatin-induced intestinal damage. • Modulation of the cellular NAD{sup +} could be a promising therapeutic approach.

Photoexcited riboflavin induces oxidative damage to human serum albumin

Science.gov (United States)

Hirakawa, Kazutaka; Yoshioka, Takuto

2015-08-01

Photoexcited riboflavin induced damage of human serum albumin (HSA), a water soluble protein, resulting in the diminishment of fluorescence from the tryptophan residue. Because riboflavin hardly photosensitized singlet oxygen generation and sodium azide, a singlet oxygen quencher, did not inhibit protein damage, electron transfer-mediated oxidation of HSA was speculated. Fluorescence lifetime of riboflavin was not affected by HSA, suggesting that the excited triplet state of riboflavin is responsible for protein damage through electron transfer. In addition, the preventive effect of xanthone derivatives, triplet quenchers, on photosensitized protein damage could be evaluated using this photosensitized reaction system of riboflavin and HSA.

Genetic and environmental influences on oxidative damage assessed in elderly Danish twins

DEFF Research Database (Denmark)

Broedbaek, Kasper; Ribel-Madsen, Rasmus; Henriksen, Trine

2011-01-01

Previous studies have shown an association between oxidative stress and various diseases in humans including cancer, cardiovascular disease, diabetes, and chronic respiratory disease. To what extents this damage is determined by genetic and environmental factors is unknown. In a classical twin...... of oxidative stress were closely correlated (r=0.60-0.84). In conclusion, we demonstrated in a large population of elderly Danish twins that "whole-body" oxidative damage to nucleic acids and lipids is predominantly determined by potentially modifiable nongenetic factors....

Portulaca oleracea Linn seed extract ameliorates hydrogen ...

African Journals Online (AJOL)

Portulaca oleracea Linn seed extract ameliorates hydrogen ... induced cell death by inhibiting oxidative stress and ROS generation. Keywords: ... culture medium; therefore the stock solutions of ... acetic acid (1 %) and ethanol (50 %) to extract.

Oxidative damage and neurodegeneration in manganese-induced neurotoxicity

International Nuclear Information System (INIS)

Milatovic, Dejan; Zaja-Milatovic, Snjezana; Gupta, Ramesh C.; Yu, Yingchun; Aschner, Michael

2009-01-01

Exposure to excessive manganese (Mn) levels results in neurotoxicity to the extrapyramidal system and the development of Parkinson's disease (PD)-like movement disorder, referred to as manganism. Although the mechanisms by which Mn induces neuronal damage are not well defined, its neurotoxicity appears to be regulated by a number of factors, including oxidative injury, mitochondrial dysfunction and neuroinflammation. To investigate the mechanisms underlying Mn neurotoxicity, we studied the effects of Mn on reactive oxygen species (ROS) formation, changes in high-energy phosphates (HEP), neuroinflammation mediators and associated neuronal dysfunctions both in vitro and in vivo. Primary cortical neuronal cultures showed concentration-dependent alterations in biomarkers of oxidative damage, F 2 -isoprostanes (F 2 -IsoPs) and mitochondrial dysfunction (ATP), as early as 2 h following Mn exposure. Treatment of neurons with 500 μM Mn also resulted in time-dependent increases in the levels of the inflammatory biomarker, prostaglandin E 2 (PGE 2 ). In vivo analyses corroborated these findings, establishing that either a single or three (100 mg/kg, s.c.) Mn injections (days 1, 4 and 7) induced significant increases in F 2 -IsoPs and PGE 2 in adult mouse brain 24 h following the last injection. Quantitative morphometric analyses of Golgi-impregnated striatal sections from mice exposed to single or three Mn injections revealed progressive spine degeneration and dendritic damage of medium spiny neurons (MSNs). These findings suggest that oxidative stress, mitochondrial dysfunction and neuroinflammation are underlying mechanisms in Mn-induced neurodegeneration.

The basic chemistry of exercise-induced DNA oxidation: oxidative damage, redox signalling and their interplay

Directory of Open Access Journals (Sweden)

James Nathan Cobley

2015-06-01

Full Text Available Acute exercise increases reactive oxygen and nitrogen species generation. This phenomenon is associated with two major outcomes: (1 redox signalling and (2 macromolecule damage. Mechanistic knowledge of how exercise-induced redox signalling and macromolecule damage are interlinked is limited. This review focuses on the interplay between exercise-induced redox signalling and DNA damage, using hydroxyl radical (·OH and hydrogen peroxide (H2O2 as exemplars. It is postulated that the biological fate of H2O2 links the two processes and thus represents a bifurcation point between redox signalling and damage. Indeed, H2O2 can participate in two electron signalling reactions but its diffusion and chemical properties permit DNA oxidation following reaction with transition metals and ·OH generation. It is also considered that the sensing of DNA oxidation by repair proteins constitutes a non-canonical redox signalling mechanism. Further layers of interaction are provided by the redox regulation of DNA repair proteins and their capacity to modulate intracellular H2O2 levels. Overall, exercise-induced redox signalling and DNA damage may be interlinked to a greater extent than was previously thought but this requires further investigation.

Shape-dependent bactericidal activity of copper oxide nanoparticle mediated by DNA and membrane damage

International Nuclear Information System (INIS)

Laha, Dipranjan; Pramanik, Arindam; Laskar, Aparna; Jana, Madhurya; Pramanik, Panchanan; Karmakar, Parimal

2014-01-01

Highlights: • Spherical and sheet shaped copper oxide nanoparticles were synthesized. • Physical characterizations of these nanoparticles were done by TEM, DLS, XRD, FTIR. • They showed shape dependent antibacterial activity on different bacterial strain. • They induced both membrane damage and ROS mediated DNA damage in bacteria. - Abstract: In this work, we synthesized spherical and sheet shaped copper oxide nanoparticles and their physical characterizations were done by the X-ray diffraction, fourier transform infrared spectroscopy, transmission electron microscopy and dynamic light scattering. The antibacterial activity of these nanoparticles was determined on both gram positive and gram negative bacterial. Spherical shaped copper oxide nanoparticles showed more antibacterial property on gram positive bacteria where as sheet shaped copper oxide nanoparticles are more active on gram negative bacteria. We also demonstrated that copper oxide nanoparticles produced reactive oxygen species in both gram negative and gram positive bacteria. Furthermore, they induced membrane damage as determined by atomic force microscopy and scanning electron microscopy. Thus production of and membrane damage are major mechanisms of the bactericidal activity of these copper oxide nanoparticles. Finally it was concluded that antibacterial activity of nanoparticles depend on physicochemical properties of copper oxide nanoparticles and bacterial strain

Shape-dependent bactericidal activity of copper oxide nanoparticle mediated by DNA and membrane damage

Energy Technology Data Exchange (ETDEWEB)

Laha, Dipranjan; Pramanik, Arindam [Department of Life Science and Biotechnology, Jadavpur University, 188, Raja S C Mallick Road, Kolkata 700032 (India); Laskar, Aparna [CSIR-Indian Institute of Chemical Biology, Kolkata 700032 (India); Jana, Madhurya [Department of Life Science and Biotechnology, Jadavpur University, 188, Raja S C Mallick Road, Kolkata 700032 (India); Pramanik, Panchanan [Department of Chemistry, Indian Institute of Technology, Kharagpur 721302 (India); Karmakar, Parimal, E-mail: pkarmakar_28@yahoo.co.in [Department of Life Science and Biotechnology, Jadavpur University, 188, Raja S C Mallick Road, Kolkata 700032 (India)

2014-11-15

Highlights: • Spherical and sheet shaped copper oxide nanoparticles were synthesized. • Physical characterizations of these nanoparticles were done by TEM, DLS, XRD, FTIR. • They showed shape dependent antibacterial activity on different bacterial strain. • They induced both membrane damage and ROS mediated DNA damage in bacteria. - Abstract: In this work, we synthesized spherical and sheet shaped copper oxide nanoparticles and their physical characterizations were done by the X-ray diffraction, fourier transform infrared spectroscopy, transmission electron microscopy and dynamic light scattering. The antibacterial activity of these nanoparticles was determined on both gram positive and gram negative bacterial. Spherical shaped copper oxide nanoparticles showed more antibacterial property on gram positive bacteria where as sheet shaped copper oxide nanoparticles are more active on gram negative bacteria. We also demonstrated that copper oxide nanoparticles produced reactive oxygen species in both gram negative and gram positive bacteria. Furthermore, they induced membrane damage as determined by atomic force microscopy and scanning electron microscopy. Thus production of and membrane damage are major mechanisms of the bactericidal activity of these copper oxide nanoparticles. Finally it was concluded that antibacterial activity of nanoparticles depend on physicochemical properties of copper oxide nanoparticles and bacterial strain.

Chronic epigallocatechin-3-gallate ameliorates learning and memory deficits in diabetic rats via modulation of nitric oxide and oxidative stress.

Science.gov (United States)

Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad

2011-10-31

Due to anti-diabetic and antioxidant activity of green tea epigallocatechin gallate (EGCG) and the existence of evidence for its beneficial effect on cognition and memory, this research study was conducted to evaluate, for the first time, the efficacy of chronic EGCG on alleviation of learning and memory deficits in streptozotocin (STZ)-diabetic rats. Male Wistar rats were divided into control, diabetic, EGCG-treated-control and -diabetic groups. EGCG was administered at a dose of 20 and 40 mg/kg/day for 7 weeks. Learning and memory was evaluated using Y maze, passive avoidance, and radial 8-arm maze (RAM) tests. Oxidative stress markers and involvement of nitric oxide system were also evaluated. Alternation score of the diabetic rats in Y maze was lower than that of control and a significant impairment was observed in retention and recall in passive avoidance test (pRAM task and EGCG (40 mg/kg) significantly ameliorated these changes (pmemory respectively. Meanwhile, increased levels of malondialdehyde (MDA) and nitrite in diabetic rats significantly reduced due to EGCG treatment (pmemory deficits in STZ-diabetic rats through attenuation of oxidative stress and modulation of NO. Copyright © 2011 Elsevier B.V. All rights reserved.

Immunochemical detection of oxidatively damaged DNA

Czech Academy of Sciences Publication Activity Database

Rössner ml., Pavel; Šrám, Radim

2012-01-01

Roč. 46, č. 4 (2012), s. 492-522 ISSN 1071-5762 R&D Projects: GA MŽP(CZ) SP/1B3/50/07; GA MŠk 2B08005; GA ČR GAP503/11/0084 Institutional research plan: CEZ:AV0Z50390703 Institutional support: RVO:68378041 Keywords : oxidative DNA damage * ELISA * immunohistochemistry Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 3.279, year: 2012

Differential effects of experimental and cold-induced hyperthyroidism on factors inducing rat liver oxidative damage.

Science.gov (United States)

Venditti, P; Pamplona, R; Ayala, V; De Rosa, R; Caldarone, G; Di Meo, S

2006-03-01

Thyroid hormone-induced increase in metabolic rates is often associated with increased oxidative stress. The aim of the present study was to investigate the contribution of iodothyronines to liver oxidative stress in the functional hyperthyroidism elicited by cold, using as models cold-exposed and 3,5,3'-triiodothyronine (T3)- or thyroxine (T4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most extensive damage to lipids and proteins was found in T3-treated and cold-exposed rats, respectively. Increase in oxygen reactive species released by mitochondria and microsomes was found to contribute to tissue oxidative damage, whereas the determination of single antioxidants did not provide information about the possible contribution of a reduced effectiveness of the antioxidant defence system. Indeed, liver oxidative damage in hyperthyroid rats was scarcely related to levels of the liposoluble antioxidants and activities of antioxidant enzymes. Conversely, other biochemical changes, such as the degree of fatty acid unsaturation and hemoprotein content, appeared to predispose hepatic tissue to oxidative damage associated with oxidative challenge elicited by hyperthyroid state. As a whole, our results confirm the idea that T3 plays a key role in metabolic changes and oxidative damage found in cold liver. However, only data concerning changes in glutathione peroxidase activity and mitochondrial protein content favour the idea that dissimilarities in effects of cold exposure and T3 treatment could depend on differences in serum levels of T4.

Modification of radiation-induced oxidative damage in liposomal and microsomal membrane by eugenol

Energy Technology Data Exchange (ETDEWEB)

Pandey, B.N. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Lathika, K.M. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Mishra, K.P. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)]. E-mail: kpm@magnum.barc.ernet.in

2006-03-15

Radiation-induced membrane oxidative damage, and their modification by eugenol, a natural antioxidant, was investigated in liposomes and microsomes. Liposomes prepared with DPH showed decrease in fluorescence after {gamma}-irradiation, which was prevented significantly by eugenol and correlated with magnitude of oxidation of phospholipids. Presence of eugenol resulted in substantial inhibition in MDA formation in irradiated liposomes/microsomes, which was less effective when added after irradiation. Similarly, the increase in phospholipase C activity observed after irradiation in microsomes was inhibited in samples pre-treated with eugenol. Results suggest association of radio- oxidative membrane damage with alterations in signaling molecules, and eugenol significantly prevented these membrane damaging events.

Effects of GST Polymorphism on Ameliorative Effect of Curcumin and Carvacrol against DNA Damage Induced by Combined Treatment of Malathion and Parathion

Directory of Open Access Journals (Sweden)

Neeraj Kumar

2016-04-01

Full Text Available Background: Organophosphorus pesticides has been widely used in agriculture fields to control various crop insects and their extensive use pose human life at threat because of their adverse effects on human health. In this study, we checked the effects of GST polymorphism on ameliorative effect of curcumin and carvacrol against DNA damages. Methods: Comet assay was used to assess the DNA damage and results were expressed as Tail moment. Heparinised fresh blood from healthy individuals was treated with combined concentration of malathion and parathion (i.e. 30 µg/ml of malathion and 2.5 µg/ml of parathion in presence of combination of curcumin and carvacrol (25 µg/ml curcumin + 2.5 µg/ml carvacrol and 50 µg/ml curcumin + 5.0 µg/ml carvacrol in order to observe the ameliorative role of curcumin and carvacrol. Multiplex PCR was performed for GSTM1 and GSTT1 genotyping. Results: Curcumin in combination with carvacrol (i.e. 25 µg/ml curcumin + 2.5 µg/ml carvacrol and 50 µg/ml curcumin + 5.0 µg/ml carvacrol significantly reduced the DNA damage caused by combined action of malathion and parathion which supports their antigenotoxic property. No significant relationship of GSTT1 and GSTM1 polymorphism with genotoxicity of both the pesticides and antigenotoxic potential of curcumin and carvacrol was observed. Conclusion: Malathion and parathion were genotoxic in human PBL. Curcumin and carvacrol had an antigenotoxic effect against the malathion and parathion while there was not any significant effect of GSTT1 and GSTM1 polymorphism on genotoxicity of these pesticides and antigenotoxicity of curcumin and carvacrol.

Oxidative stress and nerve damage: Role in chemotherapy induced peripheral neuropathy

Directory of Open Access Journals (Sweden)

Aparna Areti

2014-01-01

Full Text Available Peripheral neuropathy is a severe dose limiting toxicity associated with cancer chemotherapy. Ever since it was identified, the clear pathological mechanisms underlying chemotherapy induced peripheral neuropathy (CIPN remain sparse and considerable involvement of oxidative stress and neuroinflammation has been realized recently. Despite the empirical use of antioxidants in the therapy of CIPN, the oxidative stress mediated neuronal damage in peripheral neuropathy is still debatable. The current review focuses on nerve damage due to oxidative stress and mitochondrial dysfunction as key pathogenic mechanisms involved in CIPN. Oxidative stress as a central mediator of apoptosis, neuroinflammation, metabolic disturbances and bioenergetic failure in neurons has been highlighted in this review along with a summary of research on dietary antioxidants and other nutraceuticals which have undergone prospective controlled clinical trials in patients undergoing chemotherapy.

Oxidative Damage to RPA Limits the Nucleotide Excision Repair Capacity of Human Cells.

Science.gov (United States)

Guven, Melisa; Brem, Reto; Macpherson, Peter; Peacock, Matthew; Karran, Peter

2015-11-01

Nucleotide excision repair (NER) protects against sunlight-induced skin cancer. Defective NER is associated with photosensitivity and a high skin cancer incidence. Some clinical treatments that cause photosensitivity can also increase skin cancer risk. Among these, the immunosuppressant azathioprine and the fluoroquinolone antibiotics ciprofloxacin and ofloxacin interact with UVA radiation to generate reactive oxygen species that diminish NER capacity by causing protein damage. The replication protein A (RPA) DNA-binding protein has a pivotal role in DNA metabolism and is an essential component of NER. The relationship between protein oxidation and NER inhibition was investigated in cultured human cells expressing different levels of RPA. We show here that RPA is limiting for NER and that oxidative damage to RPA compromises NER capability. Our findings reveal that cellular RPA is surprisingly vulnerable to oxidation, and we identify oxidized forms of RPA that are associated with impaired NER. The vulnerability of NER to inhibition by oxidation provides a connection between cutaneous photosensitivity, protein damage, and increased skin cancer risk. Our findings emphasize that damage to DNA repair proteins, as well as to DNA itself, is likely to be an important contributor to skin cancer risk.

Tempol, a Superoxide Dismutase Mimetic Agent, Ameliorates Cisplatin-Induced Nephrotoxicity through Alleviation of Mitochondrial Dysfunction in Mice

Science.gov (United States)

Ahmed, Lamiaa A.; Shehata, Nagwa I.; Abdelkader, Noha F.; Khattab, Mahmoud M.

2014-01-01

Background Mitochondrial dysfunction is a crucial mechanism by which cisplatin, a potent chemotherapeutic agent, causes nephrotoxicity where mitochondrial electron transport complexes are shifted mostly toward imbalanced reactive oxygen species versus energy production. In the present study, the protective role of tempol, a membrane-permeable superoxide dismutase mimetic agent, was evaluated on mitochondrial dysfunction and the subsequent damage induced by cisplatin nephrotoxicity in mice. Methods and Findings Nephrotoxicity was assessed 72 h after a single i.p. injection of cisplatin (25 mg/kg) with or without oral administration of tempol (100 mg/kg/day). Serum creatinine and urea as well as glucosuria and proteinuria were evaluated. Both kidneys were isolated for estimation of oxidative stress markers, adenosine triphosphate (ATP) content and caspase-3 activity. Moreover, mitochondrial oxidative phosphorylation capacity, complexes I–IV activities and mitochondrial nitric oxide synthase (mNOS) protein expression were measured along with histological examinations of renal tubular damage and mitochondrial ultrastructural changes. Tempol was effective against cisplatin-induced elevation of serum creatinine and urea as well as glucosuria and proteinuria. Moreover, pretreatment with tempol notably inhibited cisplatin-induced oxidative stress and disruption of mitochondrial function by restoring mitochondrial oxidative phosphorylation, complexes I and III activities, mNOS protein expression and ATP content. Tempol also provided significant protection against apoptosis, tubular damage and mitochondrial ultrastructural changes. Interestingly, tempol did not interfere with the cytotoxic effect of cisplatin against the growth of solid Ehrlich carcinoma. Conclusion This study highlights the potential role of tempol in inhibiting cisplatin-induced nephrotoxicity without affecting its antitumor activity via amelioration of oxidative stress and mitochondrial dysfunction

Elevated oxidative damage in kitchen workers in Chinese restaurants.

Science.gov (United States)

Wang, Jiajia; Luo, Xiaolin; Xu, Bin; Wei, Jun; Zhang, Zhenzhen; Zhu, Huilian

2011-01-01

To investigate associations between occupational exposure to cooking oil fumes (COFs) and potential oxidative and genotoxic effects in kitchen workers. Sixty-seven male kitchen workers and 43 male controls from Chinese restaurants in Guangzhou were recruited. For all the participants, the levels of 1-hydroxypyrene (1-OHP) and 8-hydroxy-2-deoxyguanosine (8-oxodG) in urine, binucleated micronucleus (BNMN) frequency, comet tail length and tail DNA% in peripheral blood lymphocytes (PBLs) and malondialdehyde (MDA) and superoxide dismutase (SOD) in serum were measured. The inhalable particulates (PM(10)) in their workplaces were also monitored. Our results showed that the exposed group had a significantly higher median level of urinary 1-OHP than that of the control group (pkitchen and cooking time per day. All these positive associations remained after adjusting for the four confounders in a subsequent multivariate linear regression analysis. Occupational exposure to COFs led to increased oxidative damage in Chinese kitchen workers. The health consequences of these oxidative changes need further investgation. Urinary 1-OHP and 8-oxodG are noninvasive and effective biomarkers for assessment of oxidative damage in restaurants workers.

Cancer risk and oxidative DNA damage in man

DEFF Research Database (Denmark)

Loft, S; Poulsen, H E

1996-01-01

with a mechanistically based increased risk of cancer, including Fanconi anemia, chronic hepatitis, cystic fibrosis, and various autoimmune diseases, the biomarker studies indicate an increased rate of oxidative DNA damage or in some instances deficient repair. Human studies support the experimentally based notion...

Moringa oleifera from Cambodia Ameliorates Oxidative Stress, Hyperglycemia, and Kidney Dysfunction in Type 2 Diabetic Mice.

Science.gov (United States)

Tang, Yujiao; Choi, Eun-Ju; Han, Weon Cheol; Oh, Mirae; Kim, Jin; Hwang, Ji-Young; Park, Pyo-Jam; Moon, Sang-Ho; Kim, Yon-Suk; Kim, Eun-Kyung

2017-05-01

Recent reports have shown the antidiabetic effect of Moringa oleifera from various parts of the world. However, M. oleifera from Cambodia has never determined. Therefore, the aim of this study was to assess the antidiabetic effect of M. oleifera extract from Cambodia. The leaf ethanolic extract contained flavonoids (31.90 mg/mL), polyphenols (53.03 mg/mL), lycopene (0.042 mg/mL), and ß-carotene (0.170 mg/mL), and possessed 2,2-diphenyl-1-picrylhydrazyl, hydrogen peroxide, and hydroxyl radical scavenging activities of 92.40, 99.25, and 83.57 TE/μM at 1 mg/mL, respectively. Db/db mice were orally administered the leaf extract (150 mg/kg/day) for 5 weeks. M. oleifera treatment significantly ameliorated the altered fasting plasma glucose (from 483 to 312 mg/dL), triglyceride (from 42.12 to 23.00 mg/dL), and low-density lipoprotein cholesterol (from 107.21 to 64.25 mg/dL) compared to control group, and increased the insulin levels from 946 ± 92 to 1678 ± 268 pg/mL. The histopathological damage and expression levels of tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, cyclooxygenase-2, and inducible nitric oxide synthase in renal tissue decreased. These results indicate the potential antidiabetic benefits of M. oleifera ethanolic leaf extract.

Oxidative stress/damage induces multimerization and interaction of Fanconi anemia proteins.

Science.gov (United States)

Park, Su-Jung; Ciccone, Samantha L M; Beck, Brian D; Hwang, Byounghoon; Freie, Brian; Clapp, D Wade; Lee, Suk-Hee

2004-07-16

Fanconi anemia (FANC) is a heterogeneous genetic disorder characterized by a hypersensitivity to DNA-damaging agents, chromosomal instability, and defective DNA repair. Eight FANC genes have been identified so far, and five of them (FANCA, -C, -E, -F, and -G) assemble in a multinuclear complex and function at least in part in a complex to activate FANCD2 by monoubiquitination. Here we show that FANCA and FANCG are redox-sensitive proteins that are multimerized and/or form a nuclear complex in response to oxidative stress/damage. Both FANCA and FANCG proteins exist as monomers under non-oxidizing conditions, whereas they become multimers following H2O2 treatment. Treatment of cells with oxidizing agent not only triggers the multimeric complex of FANCA and FANCG in vivo but also induces the interaction between FANCA and FANCG. N-Ethylmaleimide treatment abolishes multimerization and interaction of FANCA and FANCG in vitro. Taken together, our results lead us to conclude that FANCA and FANCG uniquely respond to oxidative damage by forming complex(es) via intermolecular disulfide linkage(s), which may be crucial in forming such complexes and in determining their function.

Treatment with glial derived neurotropic factor (GDNF attenuates oxidative damages of spinal

Directory of Open Access Journals (Sweden)

Tao Li

2016-05-01

Full Text Available Spinal cord injury (SCI is a serious and debilitating issue being suffered by wide population worldwide. Extensive treatment approaches have been tested and being verified for their efficacy. Owing to the nature of central nervous system (CNS, the resident stem cells would be triggered in response to any sort of trauma with nerve factors as their communication signals. Apart from physical injuries, damages due to oxidative stress also need to be addressed while CNS repair mechanism takes place. This study looks at the potential of glial derived nerve factor (GDNF in addressing the SCI in regard to oxidative damages. A total of 60 Wistar rats were clustered into five groups and GDNF at various concentrations was tested in each group. Assessments in terms of oxidative stress parameters were noted and analyzed accordingly. It was noted that GDNF had reduced oxidative damages and increased the levels of anti-oxidants in dose-dependent manner (p < 0.05. Though treatment with 10 mg/mL and 20 mg/mL showed significant changes as compared to control group, these treatment modalities remained insignificant among each other. In conclusion, we demonstrated that GDNF exerted a neuro-protective effect on CNS by inducing anti-oxidants and reducing the levels of oxidative stress in SCI induced rat models.

Involvement of inducible nitric oxide synthase in radiation-induced vascular endothelial damage

International Nuclear Information System (INIS)

Hong, Chang-Won; Lee, Joon-Ho; Kim, Suwan; Noh, Jae Myoung; Kim, Young-Mee; Pyo, Hongryull; Lee, Sunyoung

2013-01-01

The use of radiation therapy has been linked to an increased risk of cardiovascular disease. To understand the mechanisms underlying radiation-induced vascular dysfunction, we employed two models. First, we examined the effect of X-ray irradiation on vasodilation in rabbit carotid arteries. Carotid arterial rings were irradiated with 8 or 16 Gy using in vivo and ex vivo methods. We measured the effect of acetylcholine-induced relaxation after phenylephrine-induced contraction on the rings. In irradiated carotid arteries, vasodilation was significantly attenuated by both irradiation methods. The relaxation response was completely blocked by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a potent inhibitor of soluble guanylate cyclase. Residual relaxation persisted after treatment with L-N ω -nitroarginine (L-NA), a non-specific inhibitor of nitric oxide synthase (NOS), but disappeared following the addition of aminoguanidine (AG), a selective inhibitor of inducible NOS (iNOS). The relaxation response was also affected by tetraethylammonium, an inhibitor of endothelium-derived hyperpolarizing factor activity. In the second model, we investigated the biochemical events of nitrosative stress in human umbilical-vein endothelial cells (HUVECs). We measured iNOS and nitrotyrosine expression in HUVECs exposed to a dose of 4 Gy. The expression of iNOS and nitrotyrosine was greater in irradiated HUVECs than in untreated controls. Pretreatment with AG, L-N 6 -(1-iminoethyl) lysine hydrochloride (a selective inhibitor of iNOS), and L-NA attenuated nitrosative stress. While a selective target of radiation-induced vascular endothelial damage was not definitely determined, these results suggest that NO generated from iNOS could contribute to vasorelaxation. These studies highlight a potential role of iNOS inhibitors in ameliorating radiation-induced vascular endothelial damage. (author)

Endogenous melatonin and oxidatively damaged guanine in DNA

Directory of Open Access Journals (Sweden)

Poulsen Henrik E

2009-10-01

Full Text Available Abstract Background A significant body of literature indicates that melatonin, a hormone primarily produced nocturnally by the pineal gland, is an important scavenger of hydroxyl radicals and other reactive oxygen species. Melatonin may also lower the rate of DNA base damage resulting from hydroxyl radical attack and increase the rate of repair of that damage. This paper reports the results of a study relating the level of overnight melatonin production to the overnight excretion of the two primary urinary metabolites of the repair of oxidatively damaged guanine in DNA. Methods Mother-father-daughter(s families (n = 55 were recruited and provided complete overnight urine samples. Total overnight creatinine-adjusted 6-sulphatoxymelatonin (aMT6s/Cr has been shown to be highly correlated with total overnight melatonin production. Urinary 8-oxo-7,8-dihydro-guanine (8-oxoGua results from the repair of DNA or RNA guanine via the nucleobase excision repair pathway, while urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG may possibly result from the repair of DNA guanine via the nucleotide excision repair pathway. Total overnight urinary levels of 8-oxodG and 8-oxoGua are therefore a measure of total overnight guanine DNA damage. 8-oxodG and 8-oxoGua were measured using a high-performance liquid chromatography-electrospray ionization tandem mass spectrometry assay. The mother, father, and oldest sampled daughter were used for these analyses. Comparisons between the mothers, fathers, and daughters were calculated for aMT6s/Cr, 8-oxodG, and 8-oxoGua. Regression analyses of 8-oxodG and 8-oxoGua on aMT6s/Cr were conducted for mothers, fathers, and daughters separately, adjusting for age and BMI (or weight. Results Among the mothers, age range 42-80, lower melatonin production (as measured by aMT6s/CR was associated with significantly higher levels of 8-oxodG (p Conclusion Low levels of endogenous melatonin production among older individuals may lead to

The effect of obstructive sleep apnea on DNA damage and oxidative stress.

Science.gov (United States)

Kang, Il Gyu; Jung, Joo Hyun; Kim, Seon Tae

2013-06-01

Obstructive sleep apnea syndrome (OSAS) is associated with repeated hypoxia and re-oxygenation. This characteristic of OSAS may cause oxidative stress and DNA damage. However, the link of OSAS with oxidative stress and DNA damage is still controversial. In the current study, we investigated whether OSAS causes DNA damage using alkaline single-cell gel electrophoresis (comet assay) and measuring oxidative stress by monitoring serum malondialdehyde (MDA) levels. From March 2009 to August 2010, 51 patients who underwent polysomnography (PSG) during the night were enrolled in this study. We obtained serum from the patients at 6 AM. DNA damage and oxidative stress were evaluated using a comet assay and measuring serum MDA, respectively. We divided the patients into two groups according to the existence of comets appearing in the comet assay. Group 1 included 44 patients with negative assay results and group 2 consisted of seven patients with positive comet assay findings. We compared the age, gender proportion, PSG data (respiratory disturbance index [RDI], lowest O2 saturation level, and arousal index [AI]), time of disease onset, smoking habits, and serum MDA levels between the two groups. The average age and gender proportion of the two groups were not statistically different (P>0.05). The average of RDI for group 1 was 30.4±18.4 and 8.0±7.7 (P0.05). No relationship between positive comet assay results and OSAS severity was identified. Results of the current study showed that OSAS was not associated with DNA damage as measured by comet assays or oxidative stress according to serum MDA levels.

Stable markers of oxidant damage to proteins and their application in the study of human disease

DEFF Research Database (Denmark)

Davies, Michael Jonathan; Fu, S; Wang, H

1999-01-01

The mechanisms of formation and the nature of the altered amino acid side chains formed on proteins subjected to oxidant attack are reviewed. The use of stable products of protein side chain oxidation as potential markers for assessing oxidative damage in vivo in humans is discussed. The methods...... developed in the authors laboratories are outlined, and the advantages and disadvantages of these techniques compared with other methodologies for assessing oxidative damage to proteins and other macromolecules. Evidence is presented to show that protein oxidation products are sensitive markers of oxidative...... damage, that the pattern of products detected may yield information as to the nature of the original oxidative insult, and that the levels of oxidized side-chains can, in certain circumstances, be much higher than those of other markers of oxidation such as lipid hydroperoxides....

Allantoin ameliorates chemically-induced pancreatic β-cell damage through activation of the imidazoline I3 receptors

Directory of Open Access Journals (Sweden)

Marie Amitani

2015-08-01

Full Text Available Objective. Allantoin is the primary active compound in yams (Dioscorea spp.. Recently, allantoin has been demonstrated to activate imidazoline 3 (I3 receptors located in pancreatic tissues. Thus, the present study aimed to investigate the role of allantoin in the effect to improve damage induced in pancreatic β-cells by streptozotocin (STZ via the I3 receptors.Research Design and Methods. The effect of allantoin on STZ-induced apoptosis in pancreatic β-cells was examined using the ApoTox-Glo triplex assay, live/dead cell double staining assay, flow cytometric analysis, and Western blottings. The potential mechanism was investigated using KU14R: an I3 receptor antagonist, and U73122: a phospholipase C (PLC inhibitor. The effects of allantoin on serum glucose and insulin secretion were measured in STZ-treated rats.Results. Allantoin attenuated apoptosis and cytotoxicity and increased the viability of STZ-induced β-cells in a dose-dependent manner; this effect was suppressed by KU14R and U73112. Allantoin decreased the level of caspase-3 and increased the level of phosphorylated B-cell lymphoma 2 (Bcl-2 expression detected by Western blotting. The improvement in β-cells viability was confirmed using flow cytometry analysis. Daily injection of allantoin for 8 days in STZ-treated rats significantly lowered plasma glucose and increased plasma insulin levels. This action was inhibited by treatment with KU14R.Conclusion. Allantoin ameliorates the damage of β-cells induced by STZ. The blockade by pharmacological inhibitors indicated that allantoin can activate the I3 receptors through a PLC-related pathway to decrease this damage. Therefore, allantoin and related analogs may be effective in the therapy for β-cell damage.

Natural plant polyphenols for alleviating oxidative damage in man ...

African Journals Online (AJOL)

prevent the body from oxidative damage over human life span. This review .... Antioxidant supplementation/treatment has been adopted for .... deacetylase family regulates gene silencing and .... Drug News Perspect 2007; 20: 579-. 585. 12.

Ascorbic acid protects lipids in human plasma and low-density lipoprotein against oxidative damage

Energy Technology Data Exchange (ETDEWEB)

Frei, B. (Department of Nutrition, Harvard School of Public Health, Boston, MA (Unites States))

1991-12-01

The authors exposed human blood plasma and low-density lipoprotein (LDL) to many different oxidative challenges and followed the temporal consumption of endogenous antioxidants in relation to the initiation of oxidative damage. Under all types of oxidizing conditions, ascorbic acid completely protects lipids in plasma and LDL against detectable peroxidative damage as assessed by a specific and highly sensitive assay for lipid peroxidation. Ascorbic acid proved to be superior to the other water-soluble plasma antioxidants bilirubin, uric acid, and protein thiols as well as to the lipoprotein-associated antioxidants alpha-tocopherol, ubiquinol-10, lycopene, and beta-carotene. Although these antioxidants can lower the rate of detectable lipid peroxidation, they are not able to prevent its initiation. Only ascorbic acid is reactive enough to effectively intercept oxidants in the aqueous phase before they can attack and cause detectable oxidative damage to lipids.

Benfotiamine enhances antioxidant defenses and protects against cisplatin-induced DNA damage in nephrotoxic rats.

Science.gov (United States)

Harisa, Gamaleldin I

2013-08-01

The objective of the present study was to assess superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), paraoxonase (PON1), glutathione reductase (GR), and catalase (CAT) activities ratio and their relationship with DNA oxidative damage in rats treated with cisplatin (3 mg/kg bwt/day) in the presence and absence of benfotiamine (100 mg/kg/day) for 25 days. Cisplatin-induced renal damage was evidenced by renal dysfunction and elevated oxidative stress markers. SOD activity and levels of nitric oxide, protein carbonyl, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine were significantly increased by cisplatin treatment. Moreover, the ratios of GPx/GR, SOD/GPx, SOD/CAT, and SOD/PON1 were significantly increased compared to control. In contrast, glutathione levels were significantly decreased by cisplatin treatment. Simultaneous treatment of rats with cisplatin and benfotiamine ameliorate these variables to values near to those of control rats. This study suggests that benfotiamine can prevent cisplatin-induced nephrotoxicity by inhibiting formation reactive species of oxygen and nitrogen. © 2013 Wiley Periodicals, Inc.

Role of oxidative damage in toxicity of particulates

DEFF Research Database (Denmark)

Møller, Peter; Jacobsen, Nicklas R; Folkmann, Janne K

2010-01-01

composition play important roles in the oxidative potential of particulates. Studies in animal models indicate that particles from combustion processes (generated by combustion of wood or diesel oil), silicate, titanium dioxide and nanoparticles (C60 fullerenes and carbon nanotubes) produce elevated levels......Particulates are small particles of solid or liquid suspended in liquid or air. In vitro studies show that particles generate reactive oxygen species, deplete endogenous antioxidants, alter mitochondrial function and produce oxidative damage to lipids and DNA. Surface area, reactivity and chemical...

Biomarkers of oxidative damage to DNA and repair

DEFF Research Database (Denmark)

Loft, Steffen; Høgh Danielsen, Pernille; Mikkelsen, Lone

2008-01-01

environmental factors, including particulate air pollution, cause oxidative damage to DNA, whereas diets rich in fruit and vegetables or antioxidant supplements may reduce the levels and enhance repair. Urinary excretion of 8-oxodG, genotype and expression of OGG1 have been associated with risk of cancer...

Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis

Energy Technology Data Exchange (ETDEWEB)

Halliday, Gary M. [Dermatology Research Laboratories, Division of Medicine, Melanoma and Skin Cancer Research Institute, Royal Prince Alfred Hospital at the University of Sydney, Sydney, NSW (Australia)]. E-mail: garyh@med.usyd.edu.au

2005-04-01

Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans.

Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis

International Nuclear Information System (INIS)

Halliday, Gary M.

2005-01-01

Ultraviolet (UV) radiation causes inflammation, gene mutation and immunosuppression in the skin. These biological changes are responsible for photocarcinogenesis. UV radiation in sunlight is divided into two wavebands, UVB and UVA, both of which contribute to these biological changes, and therefore probably to skin cancer in humans and animal models. Oxidative damage caused by UV contributes to inflammation, gene mutation and immunosuppression. This article reviews evidence for the hypothesis that UV oxidative damage to these processes contributes to photocarcinogenesis. UVA makes a larger impact on oxidative stress in the skin than UVB by inducing reactive oxygen and nitrogen species which damage DNA, protein and lipids and which also lead to NAD+ depletion, and therefore energy loss from the cell. Lipid peroxidation induces prostaglandin production that in association with UV-induced nitric oxide production causes inflammation. Inflammation drives benign human solar keratosis (SK) to undergo malignant conversion into squamous cell carcinoma (SCC) probably because the inflammatory cells produce reactive oxygen species, thus increasing oxidative damage to DNA and the immune system. Reactive oxygen or nitrogen appears to cause the increase in mutational burden as SK progress into SCC in humans. UVA is particularly important in causing immunosuppression in both humans and mice, and UV lipid peroxidation induced prostaglandin production and UV activation of nitric oxide synthase is important mediators of this event. Other immunosuppressive events are likely to be initiated by UV oxidative stress. Antioxidants have also been shown to reduce photocarcinogenesis. While most of this evidence comes from studies in mice, there is supporting evidence in humans that UV-induced oxidative damage contributes to inflammation, gene mutation and immunosuppression. Available evidence implicates oxidative damage as an important contributor to sunlight-induced carcinogenesis in humans

DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment

International Nuclear Information System (INIS)

Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A.

2014-01-01

Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting

DNA Mismatch Repair and Oxidative DNA Damage: Implications for Cancer Biology and Treatment

Energy Technology Data Exchange (ETDEWEB)

Bridge, Gemma; Rashid, Sukaina; Martin, Sarah A., E-mail: sarah.martin@qmul.ac.uk [Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ (United Kingdom)

2014-08-05

Many components of the cell, including lipids, proteins and both nuclear and mitochondrial DNA, are vulnerable to deleterious modifications caused by reactive oxygen species. If not repaired, oxidative DNA damage can lead to disease-causing mutations, such as in cancer. Base excision repair and nucleotide excision repair are the two DNA repair pathways believed to orchestrate the removal of oxidative lesions. However, recent findings suggest that the mismatch repair pathway may also be important for the response to oxidative DNA damage. This is particularly relevant in cancer where mismatch repair genes are frequently mutated or epigenetically silenced. In this review we explore how the regulation of oxidative DNA damage by mismatch repair proteins may impact on carcinogenesis. We discuss recent studies that identify potential new treatments for mismatch repair deficient tumours, which exploit this non-canonical role of mismatch repair using synthetic lethal targeting.

Predicting storage-dependent damage to red blood cells using nitrite oxidation kinetics, peroxiredoxin-2 oxidation, and hemoglobin and free heme measurements.

Science.gov (United States)

Oh, Joo-Yeun; Stapley, Ryan; Harper, Victoria; Marques, Marisa B; Patel, Rakesh P

2015-12-01

Storage-dependent damage to red blood cells (RBCs) varies significantly. Identifying RBC units that will undergo higher levels of hemolysis during storage may allow for more efficient inventory management decision-making. Oxidative-stress mediates storage-dependent damage to RBCs and will depend on the oxidant:antioxidant balance. We reasoned that this balance or redox tone will serve as a determinant of how a given RBC unit stores and that its assessment in "young" RBCs will predict storage-dependent hemolysis. RBCs were sampled from bags and segments stored for 7 to 42 days. Redox tone was assessed by nitrite oxidation kinetics and peroxiredoxin-2 (Prx-2) oxidation. In parallel, hemolysis was assessed by measuring cell-free hemoglobin (Hb) and free heme (hemin). Correlation analyses were performed to determine if Day 7 measurements predicted either the level of hemolysis at Day 35 or the increase in hemolysis during storage. Higher Day 7 Prx-2 oxidation was associated with higher Day 35 Prx-2 oxidation, suggesting that early assessment of this variable may identify RBCs that will incur the most oxidative damage during storage. RBCs that oxidized nitrite faster on Day 7 were associated with the greatest levels of storage-dependent hemolysis and increases in Prx-2 oxidation. An inverse relationship between storage-dependent changes in oxyhemoglobin and free heme was observed underscoring an unappreciated reciprocity between these molecular species. Moreover, free heme was higher in the bag compared to paired segments, with opposite trends observed for free Hb. Measurement of Prx-2 oxidation and nitrite oxidation kinetics early during RBC storage may predict storage-dependent damage to RBC including hemolysis-dependent formation of free Hb and heme. © 2015 AABB.

Bisphenol a promotes cell survival following oxidative DNA damage in mouse fibroblasts.

Directory of Open Access Journals (Sweden)

Natalie R Gassman

Full Text Available Bisphenol A (BPA is a biologically active industrial chemical used in production of consumer products. BPA has become a target of intense public scrutiny following concerns about its association with human diseases such as obesity, diabetes, reproductive disorders, and cancer. Recent studies link BPA with the generation of reactive oxygen species, and base excision repair (BER is responsible for removing oxidatively induced DNA lesions. Yet, the relationship between BPA and BER has yet to be examined. Further, the ubiquitous nature of BPA allows continuous exposure of the human genome concurrent with the normal endogenous and exogenous insults to the genome, and this co-exposure may impact the DNA damage response and repair. To determine the effect of BPA exposure on base excision repair of oxidatively induced DNA damage, cells compromised in double-strand break repair were treated with BPA alone or co-exposed with either potassium bromate (KBrO3 or laser irradiation as oxidative damaging agents. In experiments with KBrO3, co-treatment with BPA partially reversed the KBrO3-induced cytotoxicity observed in these cells, and this was coincident with an increase in guanine base lesions in genomic DNA. The improvement in cell survival and the increase in oxidatively induced DNA base lesions were reminiscent of previous results with alkyl adenine DNA glycosylase-deficient cells, suggesting that BPA may prevent initiation of repair of oxidized base lesions. With laser irradiation-induced DNA damage, treatment with BPA suppressed DNA repair as revealed by several indicators. These results are consistent with the hypothesis that BPA can induce a suppression of oxidized base lesion DNA repair by the base excision repair pathway.

Ameliorative role of nano-ceria against amine coated Ag-NP induced toxicity in Labeo rohita

Science.gov (United States)

Khan, Muhammad Saleem; Qureshi, Naureen Aziz; Jabeen, Farhat

2018-03-01

Silver nanoparticles (Ag-NPs) and its byproducts can spread pollution in aquatic habitat. Liver and gills are key target for toxicity. Oxidative stress, tissue alterations, and hemotoxicity are assumed to be associated with Ag-NPs in target animals. Cerium oxide nanoparticles (nano-ceria) show antioxidant potential in scavenging the free radicals generated in Ag-NP-induced oxidative stress. We determined ameliorated role of nano-ceria against Ag-NP-induced toxicity in fresh water Labeo rohita (L. rohita). Four groups were used in study including control, nano-ceria, Ag-NPs, and Ag-NPs + nano-ceria. Ag-NPs (30 mg l-1) and nano-ceria (50 µg kg-1) were given through water and prepared feed, respectively. The samples were taken after 28 days. Results demonstrated that pre-treatment of nano-ceria recovered L. rohita from Ag-NP-induced toxicity and oxidative stress. Nano-ceria pre-treatment actively mimics the activity of GST, GSH, CAT, and SOD. Furthermore, Ag-NPs' treatment caused severe inflammation and necrosis in hepatic parenchyma which leaded to congestion of blood in hepatic tissues. Accumulation of a yellow pigment in hepatic tissue was also seen due to necrosis of affected cells. In nano-ceria pre-treatment, there was no congestion in hepatic tissue. Vacuolization of cells and necrosis in some area was recorded in nano-ceria pre-treated group, but the gill and hepatic tissue showed improvement against Ag-NP-induced damage. Nano-ceria pre-treatment also improved hematological parameters in Ag-NP-treated fish. This study concluded that Ag-NP-induced toxicity in treated fish and pre-treatment of nano-ceria show ameliorative role.

Density of oxidation-induced stacking faults in damaged silicon

NARCIS (Netherlands)

Kuper, F.G.; Hosson, J.Th.M. De; Verwey, J.F.

1986-01-01

A model for the relation between density and length of oxidation-induced stacking faults on damaged silicon surfaces is proposed, based on interactions of stacking faults with dislocations and neighboring stacking faults. The model agrees with experiments.

Ganoderma atrum polysaccharide ameliorates ROS generation and apoptosis in spleen and thymus of immunosuppressed mice.

Science.gov (United States)

Li, Wen-Juan; Li, Lu; Zhen, Weng-Ya; Wang, Le-Feng; Pan, Meng; Lv, Jia-Qian; Wang, Fan; Yao, Yu-Fei; Nie, Shao-Ping; Xie, Ming-Yong

2017-01-01

Ganoderma atrum polysaccharide (PSG-1) is a bioactive compound with antioxidant and immunomodulatory activities. The aim of this study was to determine the effect of PSG-1 on reactive oxygen species (ROS) generation and apoptosis in spleen and thymus of cyclophosphamide (CTX)-induced immunosuppressed mice. The results showed that PSG-1 protected mice against CTX-mediated immunosuppression, as evidenced by enhancing the ratios of thymus and spleen weights to body weight, promoting T cell and B cell survival, and increasing levels of TNF-α and IL-2. Apoptosis, ROS generation and lipid peroxidation in the immune organs of the immunosuppressed animals were ameliorated by PSG-1. The immune benefits of PSG-1 were associated with the enhancement of the activities of glutathione peroxidase, superoxide dismutase and catalase in the immune organs, implying that antioxidant activities of PSG-1 may play an important role in PSG-1-evoked immune protection. Taken together, these findings have demonstrated that PSG-1 may ameliorate CTX-induced immunosuppression through reducing apoptosis and oxidative damage in immunological system. Copyright © 2016. Published by Elsevier Ltd.

The HDAC Inhibitor TSA Ameliorates a Zebrafish Model of Duchenne Muscular Dystrophy.

Science.gov (United States)

Johnson, Nathan M; Farr, Gist H; Maves, Lisa

2013-09-17

Zebrafish are an excellent model for Duchenne muscular dystrophy. In particular, zebrafish provide a system for rapid, easy, and low-cost screening of small molecules that can ameliorate muscle damage in dystrophic larvae. Here we identify an optimal anti-sense morpholino cocktail that robustly knocks down zebrafish Dystrophin (dmd-MO). We use two approaches, muscle birefringence and muscle actin expression, to quantify muscle damage and show that the dmd-MO dystrophic phenotype closely resembles the zebrafish dmd mutant phenotype. We then show that the histone deacetylase (HDAC) inhibitor TSA, which has been shown to ameliorate the mdx mouse Duchenne model, can rescue muscle fiber damage in both dmd-MO and dmd mutant larvae. Our study identifies optimal morpholino and phenotypic scoring approaches for dystrophic zebrafish, further enhancing the zebrafish dmd model for rapid and cost-effective small molecule screening.

Epiphytes modulate Posidonia oceanica photosynthetic production, energetic balance, antioxidant mechanisms and oxidative damage

Directory of Open Access Journals (Sweden)

Monya Mendes Costa

2015-12-01

Full Text Available Epiphytes impose physical barriers to light penetration into seagrass leaves causing shading, which may decrease the production of oxygen reactive species (ROS, but also constitute a physical aggression that may trigger the production of ROS, leading to oxidative damage. Here we investigate the effects of epiphytes on Posidonia oceanica under both interactive perspectives, light attenuation and oxidative stress. Specifically the role of epiphytes in net photosynthesis, chlorophyll a and b, photoprotection (Violaxanthin+Anteraxanthin+Zeaxanthin cycle, soluble sugar and starch contents, enzymatic (ascorbate peroxidase (APX and dehydroascorbate reductase (DHAR and global (trolox equivalent antioxidant capacity (TEAC and oxygen radical antioxidant capacity (ORAC antioxidant responses, phenolics and oxidative damage (malondialdehyde are tested. Leaves with epiphytes showed higher chlorophyll b and lower content in VAZ cycle carotenoids. Epiphyte shading was the probable reason for the lower VAZ de-epoxidation-ratio of leaves with epiphytes. In spite of being shaded, leaves with epiphytes showed higher antioxidant levels, indicating that epiphytes trigger the production of ROS. Both ORAC and TEAC and also APX and DHAR activities were higher in leaves with epiphytes, indicating that this response was related with its presence. Malondialdehyde concentrations also suggest oxidative damage caused by epiphytes. We conclude that the epiphyte load causes oxidative stress in P. oceanica and the mechanisms to scavenge ROS were not completely effective to avoid cell damage.

Oxidative damage to DNA and lipids as biomarkers of exposure to air pollution

DEFF Research Database (Denmark)

Møller, Peter; Loft, Steffen

2010-01-01

BACKGROUND: Air pollution is thought to exert health effects through oxidative stress, which causes damage to DNA and lipids. OBJECTIVE: We determined whether levels of oxidatively damaged DNA and lipid peroxidation products in cells or bodily fluids from humans are useful biomarkers...... of biologically effective dose in studies of the health effects of exposure to particulate matter (PM) from combustion processes. DATA SOURCES: We identified publications that reported estimated associations between environmental exposure to PM and oxidative damage to DNA and lipids in PubMed and EMBASE. We also...... identified publications from reference lists and articles cited in the Web of Science. DATA EXTRACTION: For each study, we obtained information on the estimated effect size to calculate the standardized mean difference (unitless) and determined the potential for errors in exposure assessment and analysis...

Bicarbonate modulates oxidative and functional damage in ischemia-reperfusion.

Science.gov (United States)

Queliconi, Bruno B; Marazzi, Thire B M; Vaz, Sandra M; Brookes, Paul S; Nehrke, Keith; Augusto, Ohara; Kowaltowski, Alicia J

2013-02-01

The carbon dioxide/bicarbonate (CO(2)/HCO(3)(-)) pair is the main biological pH buffer. However, its influence on biological processes, and in particular redox processes, is still poorly explored. Here we study the effect of CO(2)/HCO(3)(-) on ischemic injury in three distinct models (cardiac HL-1 cells, perfused rat heart, and Caenorhabditis elegans). We found that, although various concentrations of CO(2)/HCO(3)(-) do not affect function under basal conditions, ischemia-reperfusion or similar insults in the presence of higher CO(2)/HCO(3)(-) resulted in greater functional loss associated with higher oxidative damage in all models. Because the effect of CO(2)/HCO(3)(-) was observed in all models tested, we believe this buffer is an important determinant of oxidative damage after ischemia-reperfusion. Copyright © 2012 Elsevier Inc. All rights reserved.

Role of berberine in ameliorating Schistosoma mansoni-induced hepatic injury in mice

Directory of Open Access Journals (Sweden)

Mohamed A Dkhi

2014-01-01

Full Text Available BACKGROUND: Schistosomiasis is caused by helminth parasites of the genus Schistosoma. Berberine chloride (BER, an isoquinoline alkaloid, has been used in vivo for its antiparasitic, antioxidant and hepatoprotective properties. In this study, the protective effect of BER and praziquantel has been compared for the extent of schistosomiasis-induced oxidative stress in hepatic tissue of mice. RESULTS: S. mansoni was able to induce inflammation and injury to the liver, evidenced (i by an increase in inflammatory cellular infiltrations, dilated sinusoids and vacuolated hepatocytes, (ii by decreased levels of alanine and aspartate aminotransferases and increased levels of alkaline phosphatase, γ-glutamyl transferase in the liver homogenate, (iii by increased production of nitric oxide and thiobarbituric acid reactive substances, and (iv by lowered glutathione levels and decreased activities of catalase and superoxide dismutase, respectively. All these infection-induced parameters were significantly altered during BER treatment. In particular, berberine counteracted the S. mansoni-induced loss of glutathione and the activities of catalase and superoxide dismutase. CONCLUSION: Based on these results, it is concluded that berberine could ameliorate pre-existing liver damage and oxidative stress conditions due to schistosomiasis.

A Comparison of the Effects of Neuronal Nitric Oxide Synthase and Inducible Nitric Oxide Synthase Inhibition on Cartilage Damage

Directory of Open Access Journals (Sweden)

Nevzat Selim Gokay

2016-01-01

Full Text Available The objective of this study was to investigate the effects of selective inducible nitric oxide synthase and neuronal nitric oxide synthase inhibitors on cartilage regeneration. The study involved 27 Wistar rats that were divided into five groups. On Day 1, both knees of 3 rats were resected and placed in a formalin solution as a control group. The remaining 24 rats were separated into 4 groups, and their right knees were surgically damaged. Depending on the groups, the rats were injected with intra-articular normal saline solution, neuronal nitric oxide synthase inhibitor 7-nitroindazole (50 mg/kg, inducible nitric oxide synthase inhibitor amino-guanidine (30 mg/kg, or nitric oxide precursor L-arginine (200 mg/kg. After 21 days, the right and left knees of the rats were resected and placed in formalin solution. The samples were histopathologically examined by a blinded evaluator and scored on 8 parameters. Although selective neuronal nitric oxide synthase inhibition exhibited significant (P=0.044 positive effects on cartilage regeneration following cartilage damage, it was determined that inducible nitric oxide synthase inhibition had no statistically significant effect on cartilage regeneration. It was observed that the nitric oxide synthase activation triggered advanced arthrosis symptoms, such as osteophyte formation. The fact that selective neuronal nitric oxide synthase inhibitors were observed to have mitigating effects on the severity of the damage may, in the future, influence the development of new agents to be used in the treatment of cartilage disorders.

The 6-hydroxychromanol derivative SUL-109 ameliorates renal injury after deep hypothermia and rewarming in rats.

Science.gov (United States)

Vogelaar, Pieter C; Roorda, Maurits; de Vrij, Edwin L; Houwertjes, Martin C; Goris, Maaike; Bouma, Hjalmar; van der Graaf, Adrianus C; Krenning, Guido; Henning, Robert H

2018-04-11

Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats. Human proximal tubule cell viability was assessed following exposure to H/R for 48/4 h in the presence of various 6-hydroxychromanols. Selected compounds (SUL-109, SUL-121) or vehicle were administered to ketamine-anaesthetized male Wistar rats (IV 135 µg/kg/h) undergoing H/R at 15°C for 3 h followed by rewarming and normothermia for 1 h. Metabolic parameters and body temperature were measured throughout. In addition, renal function, renal injury, histopathology and mitochondrial fitness were assessed. H/R injury in vitro lowered cell viability by 94 ± 1%, which was counteracted dose-dependently by multiple 6-hydroxychomanols derivatives. In vivo, H/R in rats showed kidney injury molecule 1 expression in the kidney and tubular dilation, accompanied by double-strand DNA breaks and protein nitrosylation. SUL-109 and SUL-121 ameliorated tubular kidney damage, preserved mitochondrial mass and maintained cortical adenosine 5'-triphosphate (ATP) levels, although SUL-121 did not reduce protein nitrosylation. The substituted 6-hydroxychromanols SUL-109 and SUL-121 ameliorate kidney injury during in vivo H/R by preserving mitochondrial mass, function and ATP levels. In addition, both 6-hydroxychromanols

Eccentric localization of catalase to protect chromosomes from oxidative damages during meiotic maturation in mouse oocytes.

Science.gov (United States)

Park, Yong Seok; You, Seung Yeop; Cho, Sungrae; Jeon, Hyuk-Joon; Lee, Sukchan; Cho, Dong-Hyung; Kim, Jae-Sung; Oh, Jeong Su

2016-09-01

The maintenance of genomic integrity and stability is essential for the survival of every organism. Unfortunately, DNA is vulnerable to attack by a variety of damaging agents. Oxidative stress is a major cause of DNA damage because reactive oxygen species (ROS) are produced as by-products of normal cellular metabolism. Cells have developed eloquent antioxidant defense systems to protect themselves from oxidative damage along with aerobic metabolism. Here, we show that catalase (CAT) is present in mouse oocytes to protect the genome from oxidative damage during meiotic maturation. CAT was expressed in the nucleus to form unique vesicular structures. However, after nuclear envelope breakdown, CAT was redistributed in the cytoplasm with particular focus at the chromosomes. Inhibition of CAT activity increased endogenous ROS levels, but did not perturb meiotic maturation. In addition, CAT inhibition produced chromosomal defects, including chromosome misalignment and DNA damage. Therefore, our data suggest that CAT is required not only to scavenge ROS, but also to protect DNA from oxidative damage during meiotic maturation in mouse oocytes.

The Ameliorative Effects of L-2-Oxothiazolidine-4-Carboxylate on Acetaminophen-Induced Hepatotoxicity in Mice

Directory of Open Access Journals (Sweden)

Jun Ho Shin

2013-03-01

Full Text Available The aim of the study was to investigate the ameliorative effects and the mechanism of action of L-2-oxothiazolidine-4-carboxylate (OTC on acetaminophen (APAP-induced hepatotoxicity in mice. Mice were randomly divided into six groups: normal control group, APAP only treated group, APAP + 25 mg/kg OTC, APAP + 50 mg/kg OTC, APAP + 100 mg/kg OTC, and APAP + 100 mg/kg N-acetylcysteine (NAC as a reference control group. OTC treatment significantly reduced serum alanine aminotransferase and aspartate aminotransferase levels in a dose dependent manner. OTC treatment was markedly increased glutathione (GSH production and glutathione peroxidase (GSH-px activity in a dose dependent manner. The contents of malondialdehyde and 4-hydroxynonenal in liver tissues were significantly decreased by administration of OTC and the inhibitory effect of OTC was similar to that of NAC. Moreover, OTC treatment on APAP-induced hepatotoxicity significantly reduced the formation of nitrotyrosin and terminal deoxynucleotidyl transferase dUTP nick end labeling positive areas of liver tissues in a dose dependent manner. Furthermore, the activity of caspase-3 in liver tissues was reduced by administration of OTC in a dose dependent manner. The ameliorative effects of OTC on APAP-induced liver damage in mice was similar to that of NAC. These results suggest that OTC has ameliorative effects on APAP-induced hepatotoxicity in mice through anti-oxidative stress and anti-apoptotic processes.

Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

Energy Technology Data Exchange (ETDEWEB)

Bakkal, B.H. [Department of Radiation Oncology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Gultekin, F.A. [Department of General Surgery, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Guven, B. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Turkcu, U.O. [Mugla School of Health Sciences, Mugla Sitki Kocman University, Mugla (Turkey); Bektas, S. [Department of Pathology, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey); Can, M. [Department of Biochemistry, School of Medicine, Bulent Ecevit University, Kozlu, Zonguldak (Turkey)

2013-09-27

Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage.

Effect of ozone oxidative preconditioning in preventing early radiation-induced lung injury in rats

International Nuclear Information System (INIS)

Bakkal, B.H.; Gultekin, F.A.; Guven, B.; Turkcu, U.O.; Bektas, S.; Can, M.

2013-01-01

Ionizing radiation causes its biological effects mainly through oxidative damage induced by reactive oxygen species. Previous studies showed that ozone oxidative preconditioning attenuated pathophysiological events mediated by reactive oxygen species. As inhalation of ozone induces lung injury, the aim of this study was to examine whether ozone oxidative preconditioning potentiates or attenuates the effects of irradiation on the lung. Rats were subjected to total body irradiation, with or without treatment with ozone oxidative preconditioning (0.72 mg/kg). Serum proinflammatory cytokine levels, oxidative damage markers, and histopathological analysis were compared at 6 and 72 h after total body irradiation. Irradiation significantly increased lung malondialdehyde levels as an end-product of lipoperoxidation. Irradiation also significantly decreased lung superoxide dismutase activity, which is an indicator of the generation of oxidative stress and an early protective response to oxidative damage. Ozone oxidative preconditioning plus irradiation significantly decreased malondialdehyde levels and increased the activity of superoxide dismutase, which might indicate protection of the lung from radiation-induced lung injury. Serum tumor necrosis factor alpha and interleukin-1 beta levels, which increased significantly following total body irradiation, were decreased with ozone oxidative preconditioning. Moreover, ozone oxidative preconditioning was able to ameliorate radiation-induced lung injury assessed by histopathological evaluation. In conclusion, ozone oxidative preconditioning, repeated low-dose intraperitoneal administration of ozone, did not exacerbate radiation-induced lung injury, and, on the contrary, it provided protection against radiation-induced lung damage

Silymarin and Nigella sativa extract ameliorate paracetamol induced oxidative stress and renal dysfunction in male mice

Directory of Open Access Journals (Sweden)

Reham Zakaria Hamza

2015-06-01

Full Text Available Objective: To evaluate the ameliorative role of silymarin or/and Nigella sativa (N. sativa water extract against N-acetyl-p-aminophenol (APAP-induced renal function deterioration in male mice at the biochemical levels. Methods: The mice were divided into seven groups (10/group. The first group was served as control. The second group was treated with dose of APAP. The third and fourth groups were treated with silymarin alone and N. sativa water extract alone, respectively. The fifth and sixth groups were treated with combination of APAP with silymarin and APAP with N. sativa water extract, respectively. The seventh group was treated with a combination of both ameliorative compounds (silymarin and N. sativa water extract with APAP and all animals were treated for a period of 30 days. Results: Exposure to APAP at the treated dose for mice led to an alteration of kidney function parameters, increase in the level of serum urea and creatinine. Also, paracetamol administration induced oxidative stress in kidney homogenates by increasing malondialdhyde level and decreasing superoxide dismutase and catalase activities and this stress was ameliorated by administration of either silymarin or N. sativa water extract. Conclusions: Administration of silymarin or/and N. sativa water extract to APAP-treated mice alleviate the toxicity of APAP, and this appeared clearly by biochemical improvement of kidney function parameters and antioxidant parameters. But, the alleviation is more pronounced with the both antioxidants. Thus, the pronounce effect of silymarin and N. sativa water extract is most effective in reducing the toxicity induced by APAP and improving the kidney function parameters and antioxidant status of kidney of male mice.

Coenzyme Q10 treatment ameliorates acute cisplatin nephrotoxicity in mice

International Nuclear Information System (INIS)

Fouad, Amr A.; Al-Sultan, Ali Ibrahim; Refaie, Shereen M.; Yacoubi, Mohamed T.

2010-01-01

The nephroprotective effect of coenzyme Q10 was investigated in mice with acute renal injury induced by a single i.p. injection of cisplatin (5 mg/kg). Coenzyme Q10 treatment (10 mg/kg/day, i.p.) was applied for 6 consecutive days, starting 1 day before cisplatin administration. Coenzyme Q10 significantly reduced blood urea nitrogen and serum creatinine levels which were increased by cisplatin. Coenzyme Q10 significantly compensated deficits in the antioxidant defense mechanisms (reduced glutathione level and superoxide dismutase activity), suppressed lipid peroxidation, decreased the elevations of tumor necrosis factor-α, nitric oxide and platinum ion concentration, and attenuated the reductions of selenium and zinc ions in renal tissue resulted from cisplatin administration. Also, histopathological renal tissue damage mediated by cisplatin was ameliorated by coenzyme Q10 treatment. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the cisplatin-induced overexpression of inducible nitric oxide synthase, nuclear factor-κB, caspase-3 and p53 in renal tissue. It was concluded that coenzyme Q10 represents a potential therapeutic option to protect against acute cisplatin nephrotoxicity commonly encountered in clinical practice.

Role of Cardamom (Elettaria cardamomum) in Ameliorating Radiation Induced Oxidative Stress In Rats

International Nuclear Information System (INIS)

Darwish, M.M.; Abd El Azime, A. Sh.

2013-01-01

Radiation is one of the most widespread sources of environmental stress in living environment which cause oxidative stress and metabolic changes. The present study aims to evaluate the antioxidant effect of Cardamom (Elettaria cardamomum) on gamma radiation-induced oxidative damage in liver and heart tis sues. The study was conducted on forty (40) rats which were classified into four equal groups. Group1: Control group, Group. 2: rats given cardamom in basal diet.Group3: Irradiated rats, rats were subjected to whole body gamma irradiation at 6 Gy delivere d as single exposure dose. Group 4: irradiated +cardamom: rats receiving cardamom for 4 weeks and irradiated. The animals were scarified 24h after irradiation. Irradiated animals had significant increase in oxidative stress markers in liver and heart tissues expressed by significant increase of malondialdehyde (MDA) content associated to significant depletion of superoxide dismutase (SOD) , catalase (CAT) activities, and reduced glutathione (GSH) content . Hepatic and cardiac changes included significant increases of serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) , total cholesterol(TC), triacylglycerol(TAG), low-density lipoprotein cholesterol(LDL-C), and iron concentration. While, a significant decre ase in high-density lipoprotein-cholesterol (HDL-C), manganese and copper were observed. Addition of cardamom to the basal diet prior to gamma radiation, improved the tested parameters . So it is a therapeutic alternative for oxidative stress, hyperlipidaemia and trace elements changes. . The data obtained in this study suggest that cardamom may prevent liver and heart from radiation-induced damage.

The Green Tea Catechin Epigallocatechin Gallate Ameliorates Graft-versus-Host Disease.

Directory of Open Access Journals (Sweden)

Sabine Westphal

Full Text Available Allogeneic hematopoetic stem cell transplantation (allo-HSCT is a standard treatment for leukemia and other hematologic malignancies. The major complication of allo-HSCT is graft-versus-host-disease (GVHD, a progressive inflammatory illness characterized by donor immune cells attacking the organs of the recipient. Current GVHD prevention and treatment strategies use immune suppressive drugs and/or anti-T cell reagents these can lead to increased risk of infections and tumor relapse. Recent research demonstrated that epigallocatechin gallate (EGCG, a component found in green tea leaves at a level of 25-35% at dry weight, may be useful in the inhibition of GVHD due to its immune modulatory, anti-oxidative and anti-angiogenic capacities. In murine allo-HSCT recipients treated with EGCG, we found significantly reduced GVHD scores, reduced target organ GVHD and improved survival. EGCG treated allo-HSCT recipients had significantly higher numbers of regulatory T cells in GVHD target organs and in the blood. Furthermore, EGCG treatment resulted in diminished oxidative stress indicated by significant changes of glutathione blood levels as well as glutathione peroxidase in the colon. In summary, our study provides novel evidence demonstrating that EGCG ameliorates lethal GVHD and reduces GVHD-related target organ damage. Possible mechanisms are increased regulatory T cell numbers and reduced oxidative stress.

Lycium chinense leaves extract ameliorates diabetic nephropathy by suppressing hyperglycemia mediated renal oxidative stress and inflammation.

Science.gov (United States)

Olatunji, Opeyemi Joshua; Chen, Hongxia; Zhou, Yifeng

2018-06-01

Diabetic nephropathy is one of the most serious and most frequently encountered diabetic complication, accounting for the highest cause of end-stage renal disease. This present study was aimed at exploring the protective/attenuative effect of Lycium chinense leaf extract (MELC) on streptozotocin induced diabetic nephropathy in experimental Sprague Dawley rats. The oral administration of diabetic rats with MELC markedly ameliorated renal dysfunction as observed in the significant reduction in the serum levels of creatinine, blood urea nitrogen (BUN), albumin and TGF-β1 as compared to the untreated diabetic control rats. In addition, the elevated levels of renal oxidative stress markers and pro-inflammatory parameters (GSH, SOD, CAT, MDA, TNF-α, IL-6 and IL-1β) were significantly reduced in MELC treated diabetic rats. The results obtained in this study suggests that L. chinense leaf might have the potential as possible pharmacological agent against diabetic nephropathy by suppressing renal oxidative stress and inflammation. Copyright © 2018. Published by Elsevier Masson SAS.

Single Molecule Scanning of DNA Radiation Oxidative Damage, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — This proposal will develop an assay to map genomic DNA, at the single molecule level and in a nanodevice, for oxidative DNA damage arising from radiation exposure;...

Cytosolic NADP(+)-dependent isocitrate dehydrogenase status modulates oxidative damage to cells.

Science.gov (United States)

Lee, Su Min; Koh, Ho-Jin; Park, Dong-Chan; Song, Byoung J; Huh, Tae-Lin; Park, Jeen-Woo

2002-06-01

NADPH is an important cofactor in many biosynthesis pathways and the regeneration of reduced glutathione, critically important in cellular defense against oxidative damage. It is mainly produced by glucose 6-phosphate dehydrogenase (G6PD), malic enzyme, and the cytosolic form of NADP(+)-dependent isocitrate dehydrogenase (IDPc). Little information is available about the role of IDPc in antioxidant defense. In this study we investigated the role of IDPc against cytotoxicity induced by oxidative stress by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 3-4-fold higher and 35% lower, respectively, than that in the parental cells carrying the vector alone. Although the activities of other antioxidant enzymes, such as superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, and G6PD, were comparable in all transformed cells, the ratio of GSSG to total glutathione was significantly higher in the cells expressing the lower level of IDPc. This finding indicates that IDPc is essential for the efficient glutathione recycling. Upon transient exposure to increasing concentrations of H(2)O(2) or menadione, an intracellular source of free radicals and reactive oxygen species, the cells with low levels of IDPc became more sensitive to oxidative damage by H(2)O(2) or menadione. Lipid peroxidation, oxidative DNA damage, and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly over-expressed IDPc exhibited enhanced resistance against oxidative stress, compared to the control cells. This study provides direct evidence correlating the activities of IDPc and the maintenance of the cellular redox state, suggesting that IDPc plays an important role in cellular defense against oxidative stress.

Imidacloprid enhances liver damage in Wistar rats: Biochemical, oxidative damage and histological assessment

Directory of Open Access Journals (Sweden)

Sana Chakroun

2017-12-01

Full Text Available Objective: To investigate the potential adverse effects of imidacloprid on biochemical parameters, oxidative stress and liver damage induced in the rat by oral sub-chronic imidaclopride exposure. Methods: Rats received three different doses of imidacloprid (1/45, 1/22 and 1/10 of LD50 given through gavage for 60 days. Two dozen of male Wistar rats were randomly divided into four experimental groups. Liver damage was determined by measuring aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase leakages. The prooxidant-antioxydant status in hepatic tissue homogenate was evaluated by measuring the degree of lipid peroxidation, the antioxidant enzymes activities such as catalase, superoxide dismutase and glutathione peroxidase (GPx. Results: The relative liver weight was significantly higher than that of control and other treated groups at the highest dose 1/10 of LD50 of imidacloprid. Additionally, treatment of rats with imidacloprid significantly increased liver lipid peroxidation (P ≤ 0.05 or 0.01 which went together with a significant decrease in the levels of superoxide dismutase and catalase activities. Parallel to these changes, imidacloprid treatment enhanced liver damage as evidence by sharp increase in the liver enzyme activities of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase. These results were also confirmed by histopathology. Conclusions: In light of the available data, it is our thought that after imidacloprid sub-chronic exposure, depletion of antioxidant enzymes is accompanied by induction of potential oxidative stress in the hepatic tissues that might affect the function of the liver which caused biochemical and histopathological alteration.

Oxidative DNA damage in lung tissue from patients with COPD is clustered in functionally significant sequences

Directory of Open Access Journals (Sweden)

Viktor M Pastukh

2011-03-01

Full Text Available Viktor M Pastukh1, Li Zhang2, Mykhaylo V Ruchko1, Olena Gorodnya1, Gina C Bardwell1, Rubin M Tuder2, Mark N Gillespie11Department of Pharmacology and Center for Lung Biology, University of South Alabama College of Medicine, Mobile, AL, USA; 2Program in Translational Lung Research, Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado at Denver, Aurora, CO, USAAbstract: Lung tissue from COPD patients displays oxidative DNA damage. The present study determined whether oxidative DNA damage was randomly distributed or whether it was localized in specific sequences in either the nuclear or mitochondrial genomes. The DNA damage-specific histone, gamma-H2AX, was detected immunohistochemically in alveolar wall cells in lung tissue from COPD patients but not control subjects. A PCR-based method was used to search for oxidized purine base products in selected 200 bp sequences in promoters and coding regions of the VEGF, TGF-β1, HO-1, Egr1, and β-actin genes while quantitative Southern blot analysis was used to detect oxidative damage to the mitochondrial genome in lung tissue from control subjects and COPD patients. Among the nuclear genes examined, oxidative damage was detected in only 1 sequence in lung tissue from COPD patients: the hypoxic response element (HRE of the VEGF promoter. The content of VEGF mRNA also was reduced in COPD lung tissue. Mitochondrial DNA content was unaltered in COPD lung tissue, but there was a substantial increase in mitochondrial DNA strand breaks and/or abasic sites. These findings show that oxidative DNA damage in COPD lungs is prominent in the HRE of the VEGF promoter and in the mitochondrial genome and raise the intriguing possibility that genome and sequence-specific oxidative DNA damage could contribute to transcriptional dysregulation and cell fate decisions in COPD.Keywords: DNA damage, VEGF hypoxic response element, mtDNA, COPD

Radio-oxidative membrane damage and its possible role as an indicator of radiation exposure

International Nuclear Information System (INIS)

Amit Kumar; Pandey, B.N.; Mishra, K.P.

2004-01-01

Cellular membranes have been recognized as a sensitive target in the mechanism of ionizing radiation-induced cell killing. In our laboratory, studies have been devoted to investigations on gamma radiation induced oxidative damage to model and cellular membrane damage by employing fluorescence and electron spin resonance (ESR) methods Considerable evidences has accumulated to suggest that radiation induced oxidative damage was related to apoptotic death of a variety of cells in culture. Radiation induced damage involving lipid peroxidation, altered bilayer fluidity, permeability changes and intracellular generated ROS have been evaluated by chemical and physical methods. Modification of damage by structural modulating agents such as cholesterol and antioxidants such as eugenol, ascorbic acid, ellagic acid, triphala have been extensively investigated. Generation of intracellular ROS in radiation stressed normal cell e.g. mouse thymocytes, tumor cells e.g. Ehrlich ascites cells and human cervical cell line were evaluated after exposure from low to moderate doses of α-radiation. Results suggest that modulation of intracellular ROS level may be an important approach to alter radio-cytotoxicity of cells. This presentation would describe results of our study together with an overview of free radical mediated oxidative damage to cellular membrane as an indicator of radiation exposure. (author)

Spectroellipsometric detection of silicon substrate damage caused by radiofrequency sputtering of niobium oxide

Science.gov (United States)

Lohner, Tivadar; Serényi, Miklós; Szilágyi, Edit; Zolnai, Zsolt; Czigány, Zsolt; Khánh, Nguyen Quoc; Petrik, Péter; Fried, Miklós

2017-11-01

Substrate surface damage induced by deposition of metal atoms by radiofrequency (rf) sputtering or ion beam sputtering onto single-crystalline silicon (c-Si) surface has been characterized earlier by electrical measurements. The question arises whether it is possible to characterize surface damage using spectroscopic ellipsometry (SE). In our experiments niobium oxide layers were deposited by rf sputtering on c-Si substrates in gas mixture of oxygen and argon. Multiple angle of incidence spectroscopic ellipsometry measurements were performed, a four-layer optical model (surface roughness layer, niobium oxide layer, native silicon oxide layer and ion implantation-amorphized silicon [i-a-Si] layer on a c-Si substrate) was created in order to evaluate the spectra. The evaluations yielded thicknesses of several nm for the i-a-Si layer. Better agreement could be achieved between the measured and the generated spectra by inserting a mixed layer (with components of c-Si and i-a-Si applying the effective medium approximation) between the silicon oxide layer and the c-Si substrate. High depth resolution Rutherford backscattering (RBS) measurements were performed to investigate the interface disorder between the deposited niobium oxide layer and the c-Si substrate. Atomic resolution cross-sectional transmission electron microscopy investigation was applied to visualize the details of the damaged subsurface region of the substrate.

An ECVAG trial on assessment of oxidative damage to DNA measured by the comet assay

DEFF Research Database (Denmark)

Johansson, Clara; Møller, Peter; Forchhammer, Lykke

2010-01-01

The increasing use of single cell gel electrophoresis (the comet assay) highlights its popularity as a method for detecting DNA damage, including the use of enzymes for assessment of oxidatively damaged DNA. However, comparison of DNA damage levels between laboratories can be difficult due...... to differences in assay protocols (e.g. lysis conditions, enzyme treatment, the duration of the alkaline treatment and electrophoresis) and in the end points used for reporting results (e.g. %DNA in tail, arbitrary units, tail moment and tail length). One way to facilitate comparisons is to convert primary comet...... assay end points to number of lesions/10(6) bp by calibration with ionizing radiation. The aim of this study was to investigate the inter-laboratory variation in assessment of oxidatively damaged DNA by the comet assay in terms of oxidized purines converted to strand breaks with formamidopyrimidine DNA...

Oxidative Damage Caused by Common Foodborne Pathogenic Bacteria in Egg Yolk

Directory of Open Access Journals (Sweden)

Reyhaneh Afshordi

2016-02-01

Full Text Available Background: Bacteria in foodstuff are the most important agent of foodborne disease. Aside from their infectious effects, obligate aerobes have a respiratory metabolism with oxygen as the terminal electron acceptor. Therefore, they can produce reactive oxygen species and free radicals in contaminated food. Malondialdehyde (MDA is a product of lipid peroxidation used as an indicator of oxidative stress. Objectives: This study aimed to evaluate the oxidative damage produced by two common food pathogenic bacteria in foodstuff. Materials and Methods: The egg yolks were incubated with different dilutions (105,106, and 107 of Staphylococcus aureus and Salmonella enteritidis at 37°C for 20 hours. The level of MDA in egg yolk was measured by fast and simple enzymatic or colorimetric methods, such as the thiobarbituric acid reactive species method. Results: The high group (107 had a higher MDA level of 1.97 ± 0.11 (μg MDA/g in S. aureus and 1.65 ± 0.27 (mg MDA/L in S. enteritidis than the control (0.90 ± 0.13 mg MDA/L. Conclusions: We concluded that common food pathogenic bacteria can induce oxidative damage in foodstuff aside from other common problems. Heating or sterilization methods cannot protect foodstuff from the damage caused by the presence of pathogenic bacteria.

Oxidative Damage to the Salivary Glands of Rats with Streptozotocin-Induced Diabetes-Temporal Study: Oxidative Stress and Diabetic Salivary Glands.

Science.gov (United States)

Knaś, M; Maciejczyk, M; Daniszewska, I; Klimiuk, A; Matczuk, J; Kołodziej, U; Waszkiel, D; Ładny, J R; Żendzian-Piotrowska, M; Zalewska, A

2016-01-01

Objective. This study evaluated oxidative damage caused to the salivary glands in streptozotocin-induced diabetes (DM). Materials and Methods. Rats were divided into 4 groups: groups 1 and 2, control rats, and groups 3 and 4, DM rats. 8-Hydroxy-2'-deoxyguanosine (8-OHdG), protein carbonyl (PC), 4-hydroxynonenal protein adduct (4-HNE), oxidized and/or MDA-modified LDL-cholesterol (oxy-LDL/MDA), 8-isoprostanes (8-isoP), and oxidative stress index (OSI) were measured at 7 (groups 1 and 3) and 14 (groups 2 and 4) days of experiment. Results. The unstimulated salivary flow in DM rats was reduced in the 2nd week, while the stimulated flow was decreased throughout the duration of the experiment versus control. OSI was elevated in both diabetic glands in the 1st and 2nd week, whereas 8-isoP and 8-OHdG were higher only in the parotid gland in the second week. PC and 4-HNE were increased in the 1st and 2nd week, whereas oxy-LDL/MDA was increased in the 2nd week in the diabetic parotid glands. Conclusions. Diabetes induces oxidative damage of the salivary glands, which seems to be caused by processes taking place in the salivary glands, independently of general oxidative stress. The parotid glands are more vulnerable to oxidative damage in these conditions.

Oxidative Damage to the Salivary Glands of Rats with Streptozotocin-Induced Diabetes-Temporal Study: Oxidative Stress and Diabetic Salivary Glands

Directory of Open Access Journals (Sweden)

M. Knaś

2016-01-01

Full Text Available Objective. This study evaluated oxidative damage caused to the salivary glands in streptozotocin-induced diabetes (DM. Materials and Methods. Rats were divided into 4 groups: groups 1 and 2, control rats, and groups 3 and 4, DM rats. 8-Hydroxy-2′-deoxyguanosine (8-OHdG, protein carbonyl (PC, 4-hydroxynonenal protein adduct (4-HNE, oxidized and/or MDA-modified LDL-cholesterol (oxy-LDL/MDA, 8-isoprostanes (8-isoP, and oxidative stress index (OSI were measured at 7 (groups 1 and 3 and 14 (groups 2 and 4 days of experiment. Results. The unstimulated salivary flow in DM rats was reduced in the 2nd week, while the stimulated flow was decreased throughout the duration of the experiment versus control. OSI was elevated in both diabetic glands in the 1st and 2nd week, whereas 8-isoP and 8-OHdG were higher only in the parotid gland in the second week. PC and 4-HNE were increased in the 1st and 2nd week, whereas oxy-LDL/MDA was increased in the 2nd week in the diabetic parotid glands. Conclusions. Diabetes induces oxidative damage of the salivary glands, which seems to be caused by processes taking place in the salivary glands, independently of general oxidative stress. The parotid glands are more vulnerable to oxidative damage in these conditions.

Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells.

Science.gov (United States)

Cellai, Filippo; Munnia, Armelle; Viti, Jessica; Doumett, Saer; Ravagli, Costanza; Ceni, Elisabetta; Mello, Tommaso; Polvani, Simone; Giese, Roger W; Baldi, Giovanni; Galli, Andrea; Peluso, Marco E M

2017-04-29

Nanotechnology is addressing major urgent needs for cancer treatment. We conducted a study to compare the frequency of 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3 H )-one deoxyguanosine (M₁dG) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) adducts, biomarkers of oxidative stress and/or lipid peroxidation, on human hepatocarcinoma HepG2 cells exposed to increasing levels of Fe₃O₄-nanoparticles (NPs) versus untreated cells at different lengths of incubations, and in the presence of increasing exposures to an alternating magnetic field (AMF) of 186 kHz using 32 P-postlabeling. The levels of oxidative damage tended to increase significantly after ≥24 h of incubations compared to controls. The oxidative DNA damage tended to reach a steady-state after treatment with 60 μg/mL of Fe₃O₄-NPs. Significant dose-response relationships were observed. A greater adduct production was observed after magnetic hyperthermia, with the highest amounts of oxidative lesions after 40 min exposure to AMF. The effects of magnetic hyperthermia were significantly increased with exposure and incubation times. Most important, the levels of oxidative lesions in AMF exposed NP treated cells were up to 20-fold greater relative to those observed in nonexposed NP treated cells. Generation of oxidative lesions may be a mechanism by which magnetic hyperthermia induces cancer cell death.

Anti-inflammatory and anti-oxidant activities of olmesartan medoxomil ameliorate experimental colitis in rats

Energy Technology Data Exchange (ETDEWEB)

Nagib, Marwa M. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Tadros, Mariane G., E-mail: mirogeogo@yahoo.com [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt); ELSayed, Moushira I. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo (Egypt); Khalifa, Amani E. [Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo (Egypt)

2013-08-15

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) driven through altered immune responses with production of proinflammatory cytokines. Many therapies are used, but side effects and loss of response limit long-term effectiveness. New therapeutic strategies are thus needed for patients who don't respond to current treatments. Recently, there is suggested involvement of the proinflammatory hormone angiotensin II in inflammatory bowel disease. The aim of this study was to investigate the possible role of olmesartan medoxomil (OLM-M), an angiotensin II receptor blocker in ameliorating ulcerative colitis. Colitis was induced in male Wistar rats by administration of 5% dextran sodium sulphate (DSS) in drinking water for 5 days. OLM-M (1, 3 and 10 mg/kg) was administered orally during 21 days prior to the induction of colitis, and for 5 days after. Sulfasalazine (500 mg/kg) was used as reference drug. All animals were tested for changes in colon length, disease activity index (DAI) and microscopic damage. Colon tissue concentration/activity of tumor necrosis alpha (TNF-α), myeloperoxidase (MPO), prostaglandin E2 (PGE2), reduced glutathione (GSH) and malondialdehyde (MDA) were assessed. Results showed that the OLM-M dose-dependently ameliorated the colonic histopathological and biochemical injuries, an effect that is comparable or even better than that of the standard sulfasalazine. These results suggest that olmesartan medoxomil may be effective in the treatment of UC through its anti-inflammatory and antioxidant effects. - Highlights: • Olmesartan medoximil reduced dextran sodium sulphate- induced colitis. • Mechanism involved anti-inflammatory and antioxidant effects dose- dependently. • It suppressed malondialdehyde and restored reduced glutathione levels. • It reduced inflammatory markers levels and histological changes.

Lactobacillus rhamnosus GR-1 Ameliorates Escherichia coli-Induced Inflammation and Cell Damage via Attenuation of ASC-Independent NLRP3 Inflammasome Activation.

Science.gov (United States)

Wu, Qiong; Liu, Ming-Chao; Yang, Jun; Wang, Jiu-Feng; Zhu, Yao-Hong

2016-02-15

Escherichia coli is a major environmental pathogen causing bovine mastitis, which leads to mammary tissue damage and cell death. We explored the effects of the probiotic Lactobacillus rhamnosus GR-1 on ameliorating E. coli-induced inflammation and cell damage in primary bovine mammary epithelial cells (BMECs). Increased Toll-like receptor 4 (TLR4), NOD1, and NOD2 mRNA expression was observed following E. coli challenge, but this increase was attenuated by L. rhamnosus GR-1 pretreatment. Immunofluorescence and Western blot analyses revealed that L. rhamnosus GR-1 pretreatment decreased the E. coli-induced increases in the expression of the NOD-like receptor family member pyrin domain-containing protein 3 (NLRP3) and the serine protease caspase 1. However, expression of the adaptor protein apoptosis-associated speck-like protein (ASC, encoded by the Pycard gene) was decreased during E. coli infection, even with L. rhamnosus GR-1 pretreatment. Pretreatment with L. rhamnosus GR-1 counteracted the E. coli-induced increases in interleukin-1β (IL-1β), -6, -8, and -18 and tumor necrosis factor alpha mRNA expression but upregulated IL-10 mRNA expression. Our data indicate that L. rhamnosus GR-1 reduces the adhesion of E. coli to BMECs, subsequently ameliorating E. coli-induced disruption of cellular morphology and ultrastructure and limiting detrimental inflammatory responses, partly via promoting TLR2 and NOD1 synergism and attenuating ASC-independent NLRP3 inflammasome activation. Although the residual pathogenic activity of L. rhamnosus, the dosage regimen, and the means of probiotic supplementation in cattle remain undefined, our data enhance our understanding of the mechanism of action of this candidate probiotic, allowing for development of specific probiotic-based therapies and strategies for preventing pathogenic infection of the bovine mammary gland. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Small Molecule Inhibiting Nuclear Factor-kB Ameliorates Oxidative Stress and Suppresses Renal Inflammation in Early Stage of Alloxan-Induced Diabetic Nephropathy in Rat.

Science.gov (United States)

Borgohain, Manash P; Lahkar, Mangala; Ahmed, Sahabuddin; Chowdhury, Liakat; Kumar, Saurabh; Pant, Rajat; Choubey, Abhinav

2017-05-01

Diabetic nephropathy is one of the major microvascular complications of diabetes mellitus which ultimately gives rise to cardiovascular diseases. Prolonged hyperglycaemia and chronic renal inflammation are the two key players in the development and progression of diabetic nephropathy. Nuclear factor kB (NF-kB)-mediated inflammatory cascade is a strong contributor to the renovascular inflammation in diabetic nephropathy. Here, we studied the effects of piceatannol, a potent NF-kB inhibitor, on various oxidative stress markers and NF-kB dependent diabetic renoinflammatory cascades in rat induced by alloxan (ALX). Experimental diabetes was induced in male Wistar rats by a single intraperitoneal dose, 150 mg/kg body-weight (b.w.) of ALX. Diabetic rats were treated with Piceatannol (PCTNL) at a dose of 30 and 50 mg/kg b.w. After 14 days of oral treatment, PCTNL significantly restored blood sugar level, glomerular filtration rate, serum markers and plasma lipids. PCTNL administration also reversed the declined activity of cellular antioxidant machineries namely superoxide dismutase and glutathione and the elevated levels of malondialdehyde and nitric oxide. Moreover, piceatannol-treated groups showed marked inhibition of renal pro-inflammatory cytokines and NF-kB p65/p50 binding to DNA. Renal histopathological investigations also supported its ameliorative effects against diabetic kidney damage. Importantly, effects were more prominent at a dose of 50 mg/kg, and in terms of body-weight gain, PCTNL failed to effect significantly. However, overall findings clearly demonstrated that PCTNL provides remarkable renoprotection in diabetes by abrogating oxidative stress and NF-kB activation - and might be helpful in early stage of diabetic nephropathy. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Oxidative DNA damage and its repair in rat spleen following subchronic exposure to aniline

International Nuclear Information System (INIS)

Ma Huaxian; Wang Jianling; Abdel-Rahman, Sherif Z.; Boor, Paul J.; Khan, M. Firoze

2008-01-01

The mechanisms by which aniline exposure elicits splenotoxic response, especially the tumorigenic response, are not well-understood. Splenotoxicity of aniline is associated with iron overload and generation of reactive oxygen species (ROS) which can cause oxidative damage to DNA, proteins and lipids (oxidative stress). 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is one of the most abundant oxidative DNA lesions resulting from ROS, and 8-oxoguanine glycosylase 1 (OGG1), a specific DNA glycosylase/lyase enzyme, plays a key role in the removal of 8-OHdG adducts. This study focused on examining DNA damage (8-OHdG) and repair (OGG1) in the spleen in an experimental condition preceding a tumorigenic response. To achieve that, male Sprague-Dawley rats were subchronically exposed to aniline (0.5 mmol/kg/day via drinking water for 30 days), while controls received drinking water only. Aniline treatment led to a significant increase in splenic oxidative DNA damage, manifested as a 2.8-fold increase in 8-OHdG levels. DNA repair activity, measured as OGG1 base excision repair (BER) activity, increased by ∼ 1.3 fold in the nuclear protein extracts (NE) and ∼ 1.2 fold in the mitochondrial protein extracts (ME) of spleens from aniline-treated rats as compared to the controls. Real-time PCR analysis for OGG1 mRNA expression in the spleen revealed a 2-fold increase in expression in aniline-treated rats than the controls. Likewise, OGG1 protein expression in the NEs of spleens from aniline-treated rats was ∼ 1.5 fold higher, whereas in the MEs it was ∼ 1.3 fold higher than the controls. Aniline treatment also led to stronger immunostaining for both 8-OHdG and OGG1 in the spleens, confined to the red pulp areas. It is thus evident from our studies that aniline-induced oxidative stress is associated with increased oxidative DNA damage. The BER pathway was also activated, but not enough to prevent the accumulation of oxidative DNA damage (8-OHdG). Accumulation of mutagenic oxidative

[Occupational hazards, DNA damage, and oxidative stress on exposure to waste anesthetic gases].

Science.gov (United States)

Lucio, Lorena M C; Braz, Mariana G; do Nascimento Junior, Paulo; Braz, José Reinaldo C; Braz, Leandro G

The waste anesthetic gases (WAGs) present in the ambient air of operating rooms (OR), are associated with various occupational hazards. This paper intends to discuss occupational exposure to WAGs and its impact on exposed professionals, with emphasis on genetic damage and oxidative stress. Despite the emergence of safer inhaled anesthetics, occupational exposure to WAGs remains a current concern. Factors related to anesthetic techniques and anesthesia workstations, in addition to the absence of a scavenging system in the OR, contribute to anesthetic pollution. In order to minimize the health risks of exposed professionals, several countries have recommended legislation with maximum exposure limits. However, developing countries still require measurement of WAGs and regulation for occupational exposure to WAGs. WAGs are capable of inducing damage to the genetic material, such as DNA damage assessed using the comet assay and increased frequency of micronucleus in professionals with long-term exposure. Oxidative stress is also associated with WAGs exposure, as it induces lipid peroxidation, oxidative damage in DNA, and impairment of the antioxidant defense system in exposed professionals. The occupational hazards related to WAGs including genotoxicity, mutagenicity and oxidative stress, stand as a public health issue and must be acknowledged by exposed personnel and responsible authorities, especially in developing countries. Thus, it is urgent to stablish maximum safe limits of concentration of WAGs in ORs and educational practices and protocols for exposed professionals. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Pulmonary dysfunctions, oxidative stress and DNA damage in brick kiln workers.

Science.gov (United States)

Kaushik, R; Khaliq, F; Subramaneyaan, M; Ahmed, R S

2012-11-01

Brick kilns in the suburban areas in developing countries pose a big threat to the environment and hence the health of their workers and people residing around them. The present study was planned to assess the lung functions, oxidative stress parameters and DNA damage in brick kiln workers. A total of 31 male subjects working in brick kiln, and 32 age, sex and socioeconomic status matched controls were included in the study. The lung volumes, capacities and flow rates, namely, forced expiratory volume in first second (FEV(1)), forced vital capacity (FVC), FEV(1)/FVC, expiratory reserve volume, inspiratory capacity (IC), maximal expiratory flow when 50% of FVC is remaining to be expired, maximum voluntary ventilation, peak expiratory flow rate and vital capacity were significantly decreased in the brick kiln workers. Increased oxidative stress as evidenced by increased malonedialdehyde levels and reduced glutathione content, glutathione S-transferase activity and ferric reducing ability of plasma were observed in the study group when compared with controls. Our results indicate a significant correlation between oxidative stress parameters and pulmonary dysfunction, which may be due to silica-induced oxidative stress and resulting lung damage.

Field oxide radiation damage measurements in silicon strip detectors

Energy Technology Data Exchange (ETDEWEB)

Laakso, M [Particle Detector Group, Fermilab, Batavia, IL (United States) Research Inst. for High Energy Physics (SEFT), Helsinki (Finland); Singh, P; Shepard, P F [Dept. of Physics and Astronomy, Univ. Pittsburgh, PA (United States)

1993-04-01

Surface radiation damage in planar processed silicon detectors is caused by radiation generated holes being trapped in the silicon dioxide layers on the detector wafer. We have studied charge trapping in thick (field) oxide layers on detector wafers by irradiating FOXFET biased strip detectors and MOS test capacitors. Special emphasis was put on studying how a negative bias voltage across the oxide during irradiation affects hole trapping. In addition to FOXFET biased detectors, negatively biased field oxide layers may exist on the n-side of double-sided strip detectors with field plate based n-strip separation. The results indicate that charge trapping occurred both close to the Si-SiO[sub 2] interface and in the bulk of the oxide. The charge trapped in the bulk was found to modify the electric field in the oxide in a way that leads to saturation in the amount of charge trapped in the bulk when the flatband/threshold voltage shift equals the voltage applied over the oxide during irradiation. After irradiation only charge trapped close to the interface is annealed by electrons tunneling to the oxide from the n-type bulk. (orig.).

Guidance for the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health (Revision 1)

DEFF Research Database (Denmark)

Sjödin, Anders Mikael

2018-01-01

of additional health claim applications related to antioxidants, oxidative damage and cardiovascular health, and the information collected from a Grant launched in 2014. This guidance is intended to assist applicants in preparing applications for the authorisation of health claims related to the antioxidants......EFSA asked the Panel on Dietetic Products, Nutrition and Allergies (NDA) to update the guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health published in 2011. The update takes into accounts experiences gained with evaluation......, oxidative damage and cardiovascular health. The document was subject to public consultation (from 12 July to 3 September 2017). This document supersedes the guidance on the scientific requirements for health claims related to antioxidants, oxidative damage and cardiovascular health published in 2011...

Essential fatty acid-rich diets protect against striatal oxidative damage induced by quinolinic acid in rats.

Science.gov (United States)

Morales-Martínez, Adriana; Sánchez-Mendoza, Alicia; Martínez-Lazcano, Juan Carlos; Pineda-Farías, Jorge Baruch; Montes, Sergio; El-Hafidi, Mohammed; Martínez-Gopar, Pablo Eliasib; Tristán-López, Luis; Pérez-Neri, Iván; Zamorano-Carrillo, Absalom; Castro, Nelly; Ríos, Camilo; Pérez-Severiano, Francisca

2017-09-01

Essential fatty acids have an important effect on oxidative stress-related diseases. The Huntington's disease (HD) is a hereditary neurologic disorder in which oxidative stress caused by free radicals is an important damage mechanism. The HD experimental model induced by quinolinic acid (QUIN) has been widely used to evaluate therapeutic effects of antioxidant compounds. The aim of this study was to test whether the fatty acid content in olive- or fish-oil-rich diet prevents against QUIN-related oxidative damage in rats. Rats were fed during 20 days with an olive- or a fish-oil-rich diet (15% w/w). Posterior to diet period, rats were striatally microinjected with QUIN (240 nmol/µl) or saline solution. Then, we evaluated the neurological damage, oxidative status, and gamma isoform of the peroxisome proliferator-activated receptor (PPARγ) expression. Results showed that fatty acid-rich diet, mainly by fish oil, reduced circling behavior, prevented the fall in GABA levels, increased PPARγ expression, and prevented oxidative damage in striatal tissue. In addition none of the enriched diets exerted changes neither on triglycerides or cholesterol blood levels, nor or hepatic function. This study suggests that olive- and fish-oil-rich diets exert neuroprotective effects.

Exercise Increases Cystathionine-γ-lyase Expression and Decreases the Status of Oxidative Stress in Myocardium of Ovariectomized Rats.

Science.gov (United States)

Tang, Zhiping; Wang, Yujun; Zhu, Xiaoyan; Ni, Xin; Lu, Jianqiang

2016-01-01

Exercise could be a therapeutic approach for cardiovascular dysfunction induced by estrogen deficiency. Our previous study has shown that estrogen maintains cystathionine-γ-lyase (CSE) expression and inhibits oxidative stress in the myocardium of female rats. In the present study, we investigated whether exercise improves CSE expression and oxidative stress status and ameliorates isoproterenol (ISO)-induced cardiac damage in ovariectomized (OVX) rats. The results showed that treadmill training restored the ovariectomy-induced reduction of CSE and estrogen receptor (ER)α and decrease of total antioxidant capacity (T-AOC) and increase of malondialdehyde (MDA). The level of CSE was positively correlated to T-AOC and ERα while inversely correlated to MDA. OVX rats showed increases in the serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) and the percentage of TUNEL staining in myocardium upon ISO insult compared to sham rats. Exercise training significantly reduced the serum levels of LDH and CK and the percentage of TUNEL staining in myocardium upon ISO insult in OVX rats. In cultured cardiomyocytes, ISO treatment decreased cell viability and increased LDH release, while overexpression of CSE increased cell viability and decreased LDH release in the cells upon ISO insult. The results suggest that exercise training improves the oxidative stress status and ameliorates the cardiac damage induced by oxidative stress in OVX rats. The improvement of oxidative stress status by exercise might be at least partially due to upregulation of CSE/H2S signaling.

Diabetic retinopathy pathogenesis and the ameliorating effects of melatonin; involvement of autophagy, inflammation and oxidative stress.

Science.gov (United States)

Dehdashtian, Ehsan; Mehrzadi, Saeed; Yousefi, Bahman; Hosseinzadeh, Azam; Reiter, Russel J; Safa, Majid; Ghaznavi, Habib; Naseripour, Masood

2018-01-15

Diabetic retinopathy (DR), a microvascular complication of diabetes mellitus (DM), remains as one of the major causes of vision loss worldwide. The release of pro-inflammatory cytokines and the adhesion of leukocytes to retinal capillaries are initial events in DR development. Inflammation, ER stress, oxidative stress and autophagy are major causative factors involved in the pathogenesis of DR. Diabetes associated hyperglycemia leads to mitochondrial electron transport chain dysfunction culminating in a rise in ROS generation. Since mitochondria are the major source of ROS production, oxidative stress induced by mitochondrial dysfunction also contributes to the development of diabetic retinopathy. Autophagy increases in the retina of diabetic patients and is regulated by ER stress, oxidative stress and inflammation-related pathways. Autophagy functions as a double-edged sword in DR. Under mild stress, autophagic activity can lead to cell survival while during severe stress, dysregulated autophagy results in massive cell death and may have a role in initiation and exacerbation of DR. Melatonin and its metabolites play protective roles against inflammation, ER stress and oxidative stress due to their direct free radical scavenger activities and indirect antioxidant activity via the stimulation antioxidant enzymes including glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase. Melatonin also acts as a cell survival agent by modulating autophagy in various cell types and under different conditions through amelioration of oxidative stress, ER stress and inflammation. Herein, we review the possible effects of melatonin on diabetic retinopathy, focusing on its ability to regulate autophagy processes. Copyright © 2017. Published by Elsevier Inc.

Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts.

Science.gov (United States)

Waly, Mostafa I; Al-Rawahi, Amani S; Al Riyami, Marwa; Al-Kindi, Mohamed A; Al-Issaei, Halima K; Farooq, Sardar A; Al-Alawi, Ahmed; Rahman, Mohammad S

2014-02-18

Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Eighty Sprague-Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities.

Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells

Directory of Open Access Journals (Sweden)

Filippo Cellai

2017-04-01

Full Text Available Nanotechnology is addressing major urgent needs for cancer treatment. We conducted a study to compare the frequency of 3-(2-deoxy-β-d-erythro-pentafuranosylpyrimido[1,2-α]purin-10(3H-one deoxyguanosine (M1dG and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG adducts, biomarkers of oxidative stress and/or lipid peroxidation, on human hepatocarcinoma HepG2 cells exposed to increasing levels of Fe3O4-nanoparticles (NPs versus untreated cells at different lengths of incubations, and in the presence of increasing exposures to an alternating magnetic field (AMF of 186 kHz using 32P-postlabeling. The levels of oxidative damage tended to increase significantly after ≥24 h of incubations compared to controls. The oxidative DNA damage tended to reach a steady-state after treatment with 60 μg/mL of Fe3O4-NPs. Significant dose–response relationships were observed. A greater adduct production was observed after magnetic hyperthermia, with the highest amounts of oxidative lesions after 40 min exposure to AMF. The effects of magnetic hyperthermia were significantly increased with exposure and incubation times. Most important, the levels of oxidative lesions in AMF exposed NP treated cells were up to 20-fold greater relative to those observed in nonexposed NP treated cells. Generation of oxidative lesions may be a mechanism by which magnetic hyperthermia induces cancer cell death.

Metabolic Imbalance Associated with Methylation Dysregulation and Oxidative Damage in Children with Autism

Science.gov (United States)

Melnyk, Stepan; Fuchs, George J.; Schulz, Eldon; Lopez, Maya; Kahler, Stephen G.; Fussell, Jill J.; Bellando, Jayne; Pavliv, Oleksandra; Rose, Shannon; Seidel, Lisa; Gaylor, David W.

2012-01-01

Oxidative stress and abnormal DNA methylation have been implicated in the pathophysiology of autism. We investigated the dynamics of an integrated metabolic pathway essential for cellular antioxidant and methylation capacity in 68 children with autism, 54 age-matched control children and 40 unaffected siblings. The metabolic profile of unaffected siblings differed significantly from case siblings but not from controls. Oxidative protein/DNA damage and DNA hypomethylation (epigenetic alteration) were found in autistic children but not paired siblings or controls. These data indicate that the deficit in antioxidant and methylation capacity is specific for autism and may promote cellular damage and altered epigenetic gene expression. Further, these results suggest a plausible mechanism by which pro-oxidant environmental stressors may modulate genetic predisposition to autism. PMID:21519954

Genetic damage caused by methyl-parathion in mouse spermatozoa is related to oxidative stress

International Nuclear Information System (INIS)

Pina-Guzman, B.; Solis-Heredia, M.J.; Rojas-Garcia, A.E.; Uriostegui-Acosta, M.; Quintanilla-Vega, B.

2006-01-01

Organophosphorous (OP) pesticides are considered genotoxic mainly to somatic cells, but results are not conclusive. Few studies have reported OP alterations on sperm chromatin and DNA, and oxidative stress has been related to their toxicity. Sperm cells are very sensitive to oxidative damage which has been associated with reproductive dysfunctions. We evaluated the effects of methyl-parathion (Me-Pa; a widely used OP) on sperm DNA, exploring the sensitive stage(s) of spermatogenesis and the relationship with oxidative stress. Male mice (10-12-weeks old) were administered Me-Pa (3-20 mg/kg bw/i.p.) and euthanized at 7- or 28-days post-treatment. Mature spermatozoa were obtained and evaluated for chromatin structure through SCSA (Sperm Chromatin Structure Assay; DNA Fragmentation Index parameters: Mean DFI and DFI%) and chromomycin-A 3 (CMA 3 )-staining, for DNA damage through in situ-nick translation (NT-positive) and for oxidative stress through lipid peroxidation (LPO; malondialdehyde production). At 7-days post-treatment (mature spermatozoa when Me-Pa exposure), dose-dependent alterations in chromatin structure (Mean DFI and CMA 3 -staining) were observed, as well as increased DNA damage, from 2-5-fold in DFI% and NT-positive cells. Chromatin alterations and DNA damage were also observed at 28-days post-treatment (cells at meiosis at the time of exposure); suggesting that the damage induced in spermatocytes was not repaired. Positive correlations were observed between LPO and sperm DNA-related parameters. These data suggest that oxidative stress is related to Me-Pa alterations on sperm DNA integrity and cells at meiosis (28-days post-treatment) and epididymal maturation (7-days post-treatment) are Me-Pa targets. These findings suggest a potential risk of Me-Pa to the offspring after transmission

Cytoprotective effect of phloroglucinol on oxidative stress induced cell damage via catalase activation.

Science.gov (United States)

Kang, Kyoung Ah; Lee, Kyoung Hwa; Chae, Sungwook; Zhang, Rui; Jung, Myung Sun; Ham, Young Min; Baik, Jong Seok; Lee, Nam Ho; Hyun, Jin Won

2006-02-15

We investigated the cytoprotective effect of phloroglucinol, which was isolated from Ecklonia cava (brown alga), against oxidative stress induced cell damage in Chinese hamster lung fibroblast (V79-4) cells. Phloroglucinol was found to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, hydrogen peroxide (H(2)O(2)), hydroxy radical, intracellular reactive oxygen species (ROS), and thus prevented lipid peroxidation. As a result, phloroglucinol reduced H(2)O(2) induced apoptotic cells formation in V79-4 cells. In addition, phloroglucinol inhibited cell damage induced by serum starvation and radiation through scavenging ROS. Phloroglucinol increased the catalase activity and its protein expression. In addition, catalase inhibitor abolished the protective effect of phloroglucinol from H(2)O(2) induced cell damage. Furthermore, phloroglucinol increased phosphorylation of extracellular signal regulated kinase (ERK). Taken together, the results suggest that phloroglucinol protects V79-4 cells against oxidative damage by enhancing the cellular catalase activity and modulating ERK signal pathway. (c) 2005 Wiley-Liss, Inc.

Carnosine attenuates cyclophosphamide-induced bone marrow suppression by reducing oxidative DNA damage

Directory of Open Access Journals (Sweden)

Jie Deng

2018-04-01

Full Text Available Oxidative DNA damage in bone marrow cells is the main side effect of chemotherapy drugs including cyclophosphamide (CTX. However, not all antioxidants are effective in inhibiting oxidative DNA damage. In this study, we report the beneficial effect of carnosine (β-alanyl-l-histidine, a special antioxidant with acrolein-sequestering ability, on CTX-induced bone marrow cell suppression. Our results show that carnosine treatment (100 and 200 mg/kg, i.p. significantly inhibited the generation of reactive oxygen species (ROS and 8-hydroxy-2′-deoxyguanosine (8-oxo-dG, and decreased chromosomal abnormalities in the bone marrow cells of mice treated with CTX (20 mg/kg, i.v., 24 h. Furthermore, carnosine evidently mitigated CTX-induced G2/M arrest in murine bone marrow cells, accompanied by reduced ratios of p-Chk1/Chk1 and p-p53/p53 as well as decreased p21 expression. In addition, cell apoptosis caused by CTX was also suppressed by carnosine treatment, as assessed by decreased TUNEL-positive cell counts, down-regulated expressions of Bax and Cyt c, and reduced ratios of cleaved Caspase-3/Caspase-3. These results together suggest that carnosine can protect murine bone marrow cells from CTX-induced DNA damage via its antioxidant activity. Keywords: Carnosine, Cyclophosphamide, Oxidative DNA damage, Sister chromatid exchange, Apoptosis, Cell cycle arrest

An association of cocoa consumption with improved physical fitness and decreased muscle damage and oxidative stress in athletes.

Science.gov (United States)

González-Garrido, José A; García-Sánchez, José R; Garrido-Llanos, Silvia; Olivares-Corichi, Ivonne M

2017-04-01

Several studies have demonstrated the protective effects of cocoa consumption, due to its anti-inflammatory and antioxidant properties. Acute exercise induces oxidative stress and causes muscular damage during training. This study was designed to examine the effect of cocoa consumption on the markers of muscle damage, oxidative stress and physical fitness in professional soccer players. Fifteen players (15-18 years old) were included in the study. Biochemical parameters, markers of muscle damage and oxidative stress, and physical performance were evaluated before and after cocoa consumption. Biochemical parameters determined the healthy metabolic status of the study group; biomarkers of muscle and oxidative damage were measured in blood to establish muscle and redox status. However, high levels of biomarkers of muscle damage were detected. Interestingly, cocoa consumption decreased the muscle damage biomarkers of CK and LDH by 39.4% and 23.03%, respectively. The redox status was modified by a decrease in oxidative damage (carbonyl groups, 26.31%; thiol groups, 27.52%; MDA, 32.42%) and an increase in total antioxidant capacity (15.98%) and GSH-Px activity (26.37%). In addition, we observed an increase in physical performance by 4% in the Cooper Test. Our findings suggest that a short period of cocoa consumption could be useful in maintaining a good physical fitness, due to the favourable effects on muscle and redox status in athletes during exhaustive exercise.

The Protective Effect of Antioxidants on Oxidative Stress in Rats Exposed to the 950 MHz Electromagnetic Field

International Nuclear Information System (INIS)

Ibrahim, N.K.; Gharib, O.A.

2010-01-01

Studies have linked cell phone radiation to health problems such as headaches, high blood pressure, cancer and more. There is a latency period for most diseases and it may take years and more studies before the required weight of evidence is established. But the effects are cumulative and precautions should be taken now before it is too late. The aim of the present study was to investigate if supplementation with antioxidants would protect heart and liver tissues from harmful radiation emitted by cell phone. Thirty two male albino rats were randomly divided into four equal groups: I- Control, II- Antioxidants treated group, III- 950 MHz EMR, IV- 950 MHz EMR + antioxidants. A 950 MHz EMR radiation (217-Hz pulse rate, 2-W maximum peak power, SAR Specific Absorption Rate 1 .6 W/Kg) was applied to groups III and IV 60 min/day, for 30 days using an experimental exposure device. Antioxidants supplement (Vitamins A, E and C + Se) was administered to rats daily, by gavages, during the period of exposure to EMR. Malondialdehyde (MDA) and nitric oxide (NO) were used as markers of oxidative damage. Catalase (CAT), and glutathione peroxidase (GSHPx) activities were studied to evaluate the changes of antioxidant status. Biochemical analysis performed at the end of EMR exposure showed that supplementation with antioxidants has significantly attenuated EMR-induced oxidative stress signified by a decrease in the amount of MDA and an increase the activity of CAT and GSHPx in heart and liver tissues. Amelioration of oxidative damage was substantiated by significant amelioration in the activity of serum enzymes creatine phosphokinase (CPK), lactate dehydrogenase (LDH), aspartate amino-transferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). According to the results obtained in the present study, it could be concluded that antioxidants supplementation may protect from mobile phone-induced oxidative damage in heart and liver tissues

Elevated levels of urinary markers of oxidatively generated DNA and RNA damage in bipolar disorder

DEFF Research Database (Denmark)

Munkholm, Klaus; Poulsen, Henrik Enghusen; Kessing, Lars Vedel

2015-01-01

OBJECTIVES: The pathophysiological mechanisms underlying bipolar disorder and its multi-system nature are unclear. Oxidatively generated damage to nucleosides has been demonstrated in metabolic disorders; however, the extent to which this occurs in bipolar disorder in vivo is unknown. We...... investigated oxidatively generated damage to DNA and RNA in patients with bipolar disorder and its relationship with the affective phase compared with healthy control subjects. METHODS: Urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), markers...... of oxidatively generated DNA and RNA damage, respectively, was measured in 37 rapid cycling patients with bipolar disorder and in 40 age- and gender-matched healthy control subjects. Employing a longitudinal design, repeated measurements of both markers were evaluated in various affective phases in patients...

Quantification of in vivo oxidative damage in Caenorhabditis elegans during aging by endogenous F3-isoprostane measurement

NARCIS (Netherlands)

Labuschagne, C.F.; Stigter, E.C.; Hendriks, M.M.; Berger, R.; Rokach, J.; Korswagen, H.C.; Brenkman, A.B.

2013-01-01

Oxidative damage is thought to be a major cause in development of pathologies and aging. However, quantification of oxidative damage is methodologically difficult. Here, we present a robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach for accurate, sensitive, and linear in vivo

Amelioration of soils contaminated with industrial exhalations in the Chvaletice region

Energy Technology Data Exchange (ETDEWEB)

Kozel, J

1966-01-01

In the area of the Chvaletice manganese and pyrite works, the pyrite fly dust decomposing into sulfuric acid causes considerable damage to agricultural production. Sulfuric acid is also formed from the escaping sulfur dioxide. The reaction of the affected soils is extremely acid and reaches from 4.5 to 6.5 pH, and in some cases it decreases to 2.5 pH. Soil devastation spreads to distant land in the direction of the predominating winds. Damage is caused to agricultural crops which decreases yields. It was decided to ameliorate the affected soils with high doses of calcareous composts of material obtained from fish-ponds and of marl. The purpose of the experiment, the partial results of which are described, was an operational checking of the suitability of the composts for the amelioration of contaminated soils and an estimation of the doses to be applied.

Protective Effect of Nitric Oxide (NO against Oxidative Damage in Larix gmelinii Seedlings under Ultraviolet-B Irradiation

Directory of Open Access Journals (Sweden)

Haiqing Hu

2016-10-01

Full Text Available Ultraviolet-B (UV-B stress appears to be more striking than other research works because of the thin ozone layer. The protective influence of an exogenous nitric oxide donor and sodium nitroprusside (SNP on the growth properties of Larix gmelinii seedlings was investigated under ultraviolet-B radiation conditions. The results indicated that 0.1 mM SNP could effectively alleviate the damage caused by ultraviolet-B radiation, and improved the seedling growth properties, the relative water content, and photosynthetic pigment content in leaves. Additionally, the photosynthetic capacity and antioxidant enzyme activity were increased during the exposure. On the contrary, the damage caused by active oxygen was decreased in SNP-treated seedling leaves. The damage caused by ultraviolet-B radiation was slightly reduced after treating with 0.01 mM SNP. Nevertheless, treatment with 0.5 mM SNP had a negative effect under ultraviolet-B radiation. Furthermore, supplementing NO (nitric oxide improved the photosynthetic capacity and antioxidant enzyme activity and alleviated the damage of caused by active oxygen. The best effective concentration of SNP was 0.1 mM. Therefore, a suitable amount of exogenous NO can protect the Larix gmelinii seedlings and increase their tolerance to ultraviolet-B radiation.

Prolonged fasting does not increase oxidative damage or inflammation in postweaned northern elephant seal pups.

Science.gov (United States)

Vázquez-Medina, José Pablo; Crocker, Daniel E; Forman, Henry Jay; Ortiz, Rudy M

2010-07-15

Elephant seals are naturally adapted to survive up to three months of absolute food and water deprivation (fasting). Prolonged food deprivation in terrestrial mammals increases reactive oxygen species (ROS) production, oxidative damage and inflammation that can be induced by an increase in the renin-angiotensin system (RAS). To test the hypothesis that prolonged fasting in elephant seals is not associated with increased oxidative stress or inflammation, blood samples and muscle biopsies were collected from early (2-3 weeks post-weaning) and late (7-8 weeks post-weaning) fasted seals. Plasma levels of oxidative damage, inflammatory markers and plasma renin activity (PRA), along with muscle levels of lipid and protein oxidation, were compared between early and late fasting periods. Protein expression of angiotensin receptor 1 (AT(1)), pro-oxidant (Nox4) and antioxidant enzymes (CuZn- and Mn-superoxide dismutases, glutathione peroxidase and catalase) was analyzed in muscle. Fasting induced a 2.5-fold increase in PRA, a 50% increase in AT(1), a twofold increase in Nox4 and a 70% increase in NADPH oxidase activity. By contrast, neither tissue nor systemic indices of oxidative damage or inflammation increased with fasting. Furthermore, muscle antioxidant enzymes increased 40-60% with fasting in parallel with an increase in muscle and red blood cell antioxidant enzyme activities. These data suggest that, despite the observed increases in RAS and Nox4, an increase in antioxidant enzymes appears to be sufficient to suppress systemic and tissue indices of oxidative damage and inflammation in seals that have fasted for a prolonged period. The present study highlights the importance of antioxidant capacity in mammals during chronic periods of stress to help avoid deleterious systemic consequences.

Can ebselen prevent cisplatin-induced ovarian damage?

Science.gov (United States)

Soyman, Zeynep; Uzun, Hafize; Bayindir, Nihan; Esrefoglu, Mukaddes; Boran, Birtan

2018-06-01

The occurrence of ovarian damage is a major shortcoming in treating tumors with cisplatin (CP). The present study investigates the beneficial effects of ebselen-a seleno-organic compound with antioxidant and antiinflammatory properties-vis-à-vis CP-induced ovarian damage. Twenty-eight adult female rats were divided into four study groups. Group 1 received no treatment. The rats in Groups 2, 3, and 4 were intraperitoneally administered CP (2 mg/kg/day) twice per week, for 5 weeks. Those in Group 2 received 0.3 ml saline (0.9% NaCl) intraperitoneally 60 min before each CP treatment, while those in Group 3 received 0.2 ml dimethyl sulfoxide (DMSO) and 0.3 ml saline intraperitoneally 60 min before each CP treatment. The rats in Group 4 were pretreated with an intraperitoneal injection of 15 mg/kg/day ebselen 60 min before each CP treatment. Ovarian tissue malondialdehyde (MDA), total nitric oxide (NOx), glutathione (GSH), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), and catalase levels, as well as histopathological damage scores (HDSs) and serum antimullerian hormone (AMH) levels, were assessed. Cu/Zn-SOD and GSH levels were significantly higher, and MDA and NOx levels significantly lower, in Group 4 than in Groups 2 and 3. Pretreatment with ebselen significantly improved serum AMH levels, relative to Groups 2 and 3. Additionally, HDS values were significantly lower in Group 4 than in Groups 2 and 3. Our results from using an experimental rat model of CP chemotherapy suggest that ebselen use may ameliorate ovarian damage by preventing oxidative injury.

Modelling of Zircaloy-steam-oxidation under severe fuel damage conditions

International Nuclear Information System (INIS)

Malang, S.; Neitzel, H.J.

1983-01-01

Small break loss-of-coolant accidents and special transients in an LWR, in combination with loss of required safety systems, may lead to an uncovered core for an extended period of time. As a consequence, the cladding temperature could rise up to the melting point due to the decay heat, resulting in severely damaged fuel rods. During heat-up the claddings oxidize due to oxygen uptake from the steam atmosphere in the core. The modeling and assessment of the Zircaloy-steam oxidation under such conditions is important, mainly for two reasons: The oxidation of the cladding influences the temperature transients due to the exothermic heat of reaction; the amount of liquified fuel depends on the oxide layer thickness and the oxygen content of the remaining Zircaloy metal when the melting point is reached. (author)

Glutathione S-transferase Mu 2-transduced mesenchymal stem cells ameliorated anti-glomerular basement membrane antibody-induced glomerulonephritis by inhibiting oxidation and inflammation.

Science.gov (United States)

Li, Yajuan; Yan, Mei; Yang, Jichen; Raman, Indu; Du, Yong; Min, Soyoun; Fang, Xiangdong; Mohan, Chandra; Li, Quan-Zhen

2014-01-30

Oxidative stress is implicated in tissue inflammation, and plays an important role in the pathogenesis of immune-mediated nephritis. Using the anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM-GN) mouse model, we found that increased expression of glutathione S-transferase Mu 2 (GSTM2) was related to reduced renal damage caused by anti-GBM antibodies. Furthermore, mesenchymal stem cell (MSC)-based therapy has shed light on the treatment of immune-mediated kidney diseases. The aim of this study was to investigate if MSCs could be utilized as vehicles to deliver the GSTM2 gene product into the kidney and to evaluate its potential therapeutic effect on anti-GBM-GN. The human GSTM2 gene (hGSTM2) was transduced into mouse bone marrow-derived MSCs via a lentivirus vector to create a stable cell line (hGSTM2-MSC). The cultured hGSTM2-MSCs were treated with 0.5 mM H2O2, and apoptotic cells were measured by terminal dUTP nick-end labeling (TUNEL) assay. The 129/svj mice, which were challenged with anti-GBM antibodies, were injected with 10⁶ hGSTM2-MSCs via the tail vein. Expression of hGSTM2 and inflammatory cytokines in the kidney was assayed by quantitative PCR and western blotting. Renal function of mice was evaluated by monitoring proteinuria and levels of blood urea nitrogen (BUN), and renal pathological changes were analyzed by histochemistry. Immunohistochemical analysis was performed to measure inflammatory cell infiltration and renal cell apoptosis. MSCs transduced with hGSTM2 exhibited similar growth and differentiation properties to MSCs. hGSTM2-MSCs persistently expressed hGSTM2 and resisted H2O2-induced apoptosis. Upon injection into 129/svj mice, hGSTM2-MSCs migrated to the kidney and expressed hGSTM2. The anti-GBM-GN mice treated with hGSTM2-MSCs exhibited reduced proteinuria and BUN (58% and 59% reduction, respectively) and ameliorated renal pathological damage, compared with control mice. Mice injected with hGSTM2-MSCs showed

Three job stress models/concepts and oxidative DNA damage in a sample of workers in Japan.

Science.gov (United States)

Inoue, Akiomi; Kawakami, Norito; Ishizaki, Masao; Tabata, Masaji; Tsuchiya, Masao; Akiyama, Miki; Kitazume, Akiko; Kuroda, Mitsuyo; Shimazu, Akihito

2009-04-01

Three job stress models/concepts (the job demands-control [DC] model, the effort-reward imbalance [ERI] model, and organizational justice) have been linked to coronary heart disease (CHD) at work. In recent years, oxidative DNA damage has been identified as a new risk factor for CHD. However, evidence for the association between these job stressors and oxidative DNA damage is limited. The present cross-sectional study investigated the association between these job stress models/concepts and oxidative DNA damage as a possible mediator of the adverse health effects of job stress. A total of 166 male and 51 female workers of a manufacturing factory in Japan were surveyed using a mailed questionnaire regarding job stressors and demographic, occupational, and lifestyle variables. Urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage, were also measured. In male subjects, the urinary concentrations of 8-OHdG were significantly higher among the group with lower interactional justice, one of the two components of organizational justice; however, no association was observed with the DC model or the ERI model. In female subjects, high job demands/control ratio was significantly and positively associated with the urinary concentrations of 8-OHdG. Interactional justice among male workers and the DC model-based strain among female workers may be associated with increased urinary concentrations of 8-OHdG which possibly reflects oxidative DNA damage.

An anthocyanin/polyphenolic-rich fruit juice reduces oxidative DNA damage and increases glutathione level in healthy probands.

Science.gov (United States)

Weisel, Tamara; Baum, Matthias; Eisenbrand, Gerhard; Dietrich, Helmut; Will, Frank; Stockis, Jean-Pierre; Kulling, Sabine; Rüfer, Corinna; Johannes, Christian; Janzowski, Christine

2006-04-01

Oxidative cell damage is involved in the pathogenesis of atherosclerosis, cancer, diabetes and other diseases. Uptake of fruit juice with especially high content of antioxidant flavonoids/polyphenols, might reduce oxidative cell damage. Therefore, an intervention study was performed with a red mixed berry juice [trolox equivalent antioxidative capacity (TEAC): 19.1 mmol/L trolox] and a corresponding polyphenol-depleted juice (polyphenols largely removed, TEAC 2.4 mmol/L trolox), serving as control. After a 3-week run-in period, 18 male probands daily consumed 700 mL juice, and 9 consumed control juice, in a 4-week intervention, followed by a 3-week wash-out. Samples were collected weekly to analyze DNA damage (comet assay), lipid peroxidation (plasma malondialdehyde: HPLC/fluorescence; urinary isoprostanes: GC-MS), blood glutathione (photometrically), DNA-binding activity of nuclear factor-kappaB (ELISA) and plasma carotenoid/alpha-tocopherol levels (HPLC-DAD). During intervention with the fruit juice, a decrease of oxidative DNA damage (p<5x10(-4)) and an increase of reduced glutathione (p<5x10(-4)) and of glutathione status (p<0.05) were observed, which returned to the run-in levels in the subsequent wash-out phase. The other biomarkers were not significantly modulated by the juice supplement. Intervention with the control juice did not result in reduction of oxidative damage. In conclusion, the fruit juice clearly reduces oxidative cell damage in healthy probands.

SIRT3 mediates decrease of oxidative damage and prevention of ageing in porcine fetal fibroblasts.

Science.gov (United States)

Xie, Xiaoxian; Wang, Liangliang; Zhao, Binggong; Chen, Yangyang; Li, Jiaqi

2017-05-15

Sirtuin 3 (SIRT3) is a mitochondria-specific protein required for the deacetylation of metabolic enzymes and the action of oxidative phosphorylation by acting as a nicotinamide adenine dinucleotide (NAD + )-dependent deacetylase. SIRT3 increases oxidative stress resistance and prevents mitochondrial decay associated with ageing in response to caloric restriction. However, the effects of SIRT3 on oxidative damage and ageing are not well understood. We investigated the physiological functions of porcine SIRT3 on the damage and ageing in porcine fetal fibroblasts (PFFs). Overexpression and knockdown of SIRT3 were confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis, respectively. All cells were treated with three different stress reagents 12-o-tetradecanoylphorbol-13-acetate (TPA), methanesulfonic acid methylester (MMS), and tert-butylhydroperoxide (t-BHP), respectively, and then examined by flow cytometry following JC-1 (5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimidazol-carbocyanine iodide) staining. SIRT3 overexpression enhanced the ability of superoxide dismutase 2 (SOD2) to reduce cellular reactive oxygen species (ROS), which further decreased the damage to the membranes and the organelles of the cells, especially to mitochondria. It inhibited the initial decrease of mitochondrial membrane potential, and prevented the decrease of adenosine triphosphate (ATP) production and activity of Nampt. In contrast, SIRT3 knockdown reduced the ability of SOD2 to increase cellular ROS which was directly correlated with stress-induced oxidative damage and ageing in PFFs. Our findings identify one function of SIRT3 in PFFs was to dampen cytotoxicity, and, therefore, to decrease oxidative damage and attenuate ageing possibly by enhancing the activity of SOD2. Copyright © 2017 Elsevier Inc. All rights reserved.

Oxidative Damage in Erythrocytes During Cold Storage With Organ Preservation Solution

OpenAIRE

MEMMEDOĞLU, Akif B.

1999-01-01

It is known that erythrocyte aggregation in renal tissue during preserva-tion is cause of microcirculation defects in the reperfusion period. The aim of our study is to investigate oxidative damage in erythrocytes relative to the time of cold ischemia during organ preservation and relationship between lipid peroxidation and development of these damages. In experiments with a rabbit model, explanted kidneys were exposed to perfusion and 96 hours preservation with Euro-Collins (EC) in the 1...

Environmental ozone exposure and oxidative DNA damage in adult residents of Florence, Italy

Energy Technology Data Exchange (ETDEWEB)

Palli, Domenico, E-mail: d.palli@ispo.toscana.i [Molecular and Nutritional Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139 Florence (Italy); Sera, Francesco, E-mail: f.sera@ispo.toscana.i [Molecular and Nutritional Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139 Florence (Italy); Giovannelli, Lisa, E-mail: lisag@pharm.unifi.i [Department of Pharmacology, University of Florence, Viale G.Pieraccini 6, 50139 Florence (Italy); Masala, Giovanna, E-mail: g.masala@ispo.toscana.i [Molecular and Nutritional Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139 Florence (Italy); Grechi, Daniele [Regional Environmental Protection Agency of Tuscany (ARPAT), Via Porpora 22, 50144 Florence (Italy); Bendinelli, Benedetta, E-mail: b.bendinelli@ispo.toscana.i [Molecular and Nutritional Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139 Florence (Italy); Caini, Saverio, E-mail: s.caini@ispo.toscana.i [Molecular and Nutritional Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139 Florence (Italy); Dolara, Piero, E-mail: piero.dolara@unifi.i [Department of Pharmacology, University of Florence, Viale G.Pieraccini 6, 50139 Florence (Italy); Saieva, Calogero, E-mail: c.saieva@ispo.toscana.i [Molecular and Nutritional Epidemiology Unit, Cancer Prevention and Research Institute (ISPO), Via Cosimo il Vecchio 2, 50139 Florence (Italy)

2009-05-15

In 71 adults residing in Florence, Italy, enrolled in a prospective study, we investigated the correlation between individual levels of oxidative DNA damage detected by the Comet assay in circulating lymphocytes, and a specific ozone exposure score calculated in 10 different time-windows (0-5 to 0-90 days) before blood drawing, based on daily measurements provided by the local environmental monitoring system. Overall, statistically significant positive correlations between average ozone concentrations and DNA damage emerged in almost all time-windows considered; correlations were more evident among males, non-smokers, and traffic-exposed workers. Multivariate regression analyses taking into account selected individual characteristics, showed an independent effect on DNA damage of average ozone concentrations in the last 60-90 days before blood drawing. Local residents showed a divergent pattern with correlations restricted to shorter time-windows. Our results suggest that ozone concentrations at ground levels modulate oxidative DNA damage in circulating lymphocytes of residents of polluted areas. - Ozone concentrations over the 60-90 days before blood drawing correlated with DNA damage in circulating lymphocytes of adults living in the metropolitan area of Florence, Italy.

Environmental ozone exposure and oxidative DNA damage in adult residents of Florence, Italy

International Nuclear Information System (INIS)

Palli, Domenico; Sera, Francesco; Giovannelli, Lisa; Masala, Giovanna; Grechi, Daniele; Bendinelli, Benedetta; Caini, Saverio; Dolara, Piero; Saieva, Calogero

2009-01-01

In 71 adults residing in Florence, Italy, enrolled in a prospective study, we investigated the correlation between individual levels of oxidative DNA damage detected by the Comet assay in circulating lymphocytes, and a specific ozone exposure score calculated in 10 different time-windows (0-5 to 0-90 days) before blood drawing, based on daily measurements provided by the local environmental monitoring system. Overall, statistically significant positive correlations between average ozone concentrations and DNA damage emerged in almost all time-windows considered; correlations were more evident among males, non-smokers, and traffic-exposed workers. Multivariate regression analyses taking into account selected individual characteristics, showed an independent effect on DNA damage of average ozone concentrations in the last 60-90 days before blood drawing. Local residents showed a divergent pattern with correlations restricted to shorter time-windows. Our results suggest that ozone concentrations at ground levels modulate oxidative DNA damage in circulating lymphocytes of residents of polluted areas. - Ozone concentrations over the 60-90 days before blood drawing correlated with DNA damage in circulating lymphocytes of adults living in the metropolitan area of Florence, Italy.

Urinary excretion of biomarkers of oxidatively damaged DNA and RNA in hereditary hemochromatosis

DEFF Research Database (Denmark)

Broedbaek, Kasper; Poulsen, Henrik E; Weimann, Allan

2009-01-01

Oxidatively generated damage to nucleic acids is considered to play a significant role in carcinogenesis, and it has been shown that people with hereditary hemochromatosis are at increased risk of cancer. In this study we used a new refined liquid chromatography-tandem mass spectrometry method...... of the iron overload seen in this disease. By this mechanism cellular damage resulting in end organ damage, typically seen in the liver of such patients, may be mediated....

Moderate Dose of Trolox Preventing the Deleterious Effects of Wi-Fi Radiation on Spermatozoa In vitro through Reduction of Oxidative Stress Damage

Science.gov (United States)

Ding, Shang-Shu; Sun, Ping; Zhang, Zhou; Liu, Xiang; Tian, Hong; Huo, Yong-Wei; Wang, Li-Rong; Han, Yan; Xing, Jun-Ping

2018-01-01

Background: The worsening of semen quality, due to the application of Wi-Fi, can be ameliorated by Vitamin E. This study aimed to demonstrate whether a moderate dose of trolox, a new Vitamin E, inhibits oxidative damage on sperms in vitro after exposure to Wi-Fi radiation. Methods: Each of the twenty qualified semen, gathered from June to October 2014 in eugenics clinic, was separated into four aliquots, including sham, Wi-Fi-exposed, Wi-Fi plus 5 mmol/L trolox, and Wi-Fi plus 10 mmol/L trolox groups. At 0 min, all baseline parameters of the 20 samples were measured in sequence. Reactive oxygen species, glutathione, and superoxide dismutase were evaluated in the four aliquots at 45 and 90 min, as were sperm DNA fragments, sperm mitochondrial potential, relative amplification of sperm mitochondrial DNA, sperm vitality, and progressive and immotility sperm. The parameters were analyzed by one-way analysis of variance and Tukey's posttest. Results: Among Wi-Fi plus 5 mmol/L trolox, Wi-Fi-exposed and Wi-Fi plus 10 mmol/L trolox groups, reactive oxygen species levels (45 min: 3.80 ± 0.41 RLU·10−6·ml−1 vs. 7.50 ± 0.35 RLU·10−6·ml−1 vs. 6.70 ± 0.47 RLU·10−6·ml−1, P Fi plus 5 mmol/L trolox group at 45 and 90 min, respectively. Other parameters were not affected, while the sham group maintained the baseline. Conclusion: This study found that 5 mmol/L trolox protected the Wi-Fi-exposed semen in vitro from the damage of electromagnetic radiation-induced oxidative stress. PMID:29451144

Effect of complex polyphenols and tannins from red wine on DNA oxidative damage of rat colon mucosa in vivo.

Science.gov (United States)

Giovannelli, L; Testa, G; De Filippo, C; Cheynier, V; Clifford, M N; Dolara, P

2000-10-01

Dietary polyphenols have been reported to have a variety of biological actions, including anti-carcinogenic, antioxidant and anti-inflammatory activities. In the present study we have evaluated the effect of an oral treatment with complex polyphenols and tannins from red wine and tea on DNA oxidative damage in the rat colon mucosa. Isolated colonocytes were prepared from the colon mucosa of rats treated for ten days with either wine complex polyphenols (57.2 mg/kg/d) or thearubigin (40 mg/kg/d) by oral gavage. Colonocyte oxidative DNA damage was analysed at the single cell level using a modification of the comet assay technique. The results show that wine complex polyphenols and tannins induce a significant decrease (-62% for pyrimidine and -57% for purine oxidation) in basal DNA oxidative damage in colon mucosal cells without affecting the basal level of single-strand breaks. On the other hand, tea polyphenols, namely a crude extract of thearubigin, did not affect either strand breaks or pyrimidine oxidation in colon mucosal cells. Our experiments are the first demonstration that dietary polyphenols can modulate in vivo oxidative damage in the gastrointestinal tract of rodents. These data support the hypothesis that dietary polyphenols might have both a protective and a therapeutic potential in oxidative damage-related pathologies.

Ameliorative effect of the hydroethanolic whole plant extract of ...

African Journals Online (AJOL)

At the end of the study, biochemical markers of nitrosative and oxidative stress status were determined. Results: DH (12.5, 50 and 100 mg/kg) significantly ameliorated haloperidol-induced catalepsy (bar test), spontaneous motor and working memory deficits (open field and elevated plus maze tests, respectively), ...

Oxidation of Carbon Nanotubes in an Ionizing Environment.

Science.gov (United States)

Koh, Ai Leen; Gidcumb, Emily; Zhou, Otto; Sinclair, Robert

2016-02-10

In this work, we present systematic studies on how an illuminating electron beam which ionizes molecular gas species can influence the mechanism of carbon nanotube oxidation in an environmental transmission electron microscope (ETEM). We found that preferential attack of the nanotube tips is much more prevalent than for oxidation in a molecular gas environment. We establish the cumulative electron doses required to damage carbon nanotubes from 80 keV electron beam irradiation in gas versus in high vacuum. Our results provide guidelines for the electron doses required to study carbon nanotubes within or without a gas environment, to determine or ameliorate the influence of the imaging electron beam. This work has important implications for in situ studies as well as for the oxidation of carbon nanotubes in an ionizing environment such as that occurring during field emission.

Mitochondrial DNA damage and oxidative damage in HL-60 cells exposed to 900 MHz radiofrequency fields

Energy Technology Data Exchange (ETDEWEB)

Sun, Yulong; Zong, Lin; Gao, Zhen [School of Public Health, Soochow University, Suzhou, Jiangsu Province (China); Zhu, Shunxing [Laboratory Animal Center, Nantong University, Nantong, Jiangsu Province (China); Tong, Jian [School of Public Health, Soochow University, Suzhou, Jiangsu Province (China); Cao, Yi, E-mail: yicao@suda.edu.cn [School of Public Health, Soochow University, Suzhou, Jiangsu Province (China)

2017-03-15

Highlights: • Increased reactive oxygen species. • Decreased mitochondrial transcription Factor A and polymerase gamma. • Decreased mitochondrial transcripts (ND1 and 16S) and mtDNA copy number. • Increased 8-hydroxy-2′deoxyguanosine. • Decreased adenosine triphosphate. - Abstract: HL-60 cells, derived from human promyelocytic leukemia, were exposed to continuous wave 900 MHz radiofrequency fields (RF) at 120 μW/cm{sup 2} power intensity for 4 h/day for 5 consecutive days to examine whether such exposure is capable damaging the mitochondrial DNA (mtDNA) mediated through the production of reactive oxygen species (ROS). In addition, the effect of RF exposure was examined on 8-hydroxy-2′-dexoyguanosine (8-OHdG) which is a biomarker for oxidative damage and on the mitochondrial synthesis of adenosine triphosphate (ATP) which is the energy required for cellular functions. The results indicated a significant increase in ROS and significant decreases in mitochondrial transcription factor A, mtDNA polymerase gamma, mtDNA transcripts and mtDNA copy number in RF-exposed cells compared with those in sham-exposed control cells. In addition, there was a significant increase in 8-OHdG and a significant decrease in ATP in RF-exposed cells. The response in positive control cells exposed to gamma radiation (GR, which is also known to induce ROS) was similar to those in RF-exposed cells. Thus, the overall data indicated that RF exposure was capable of inducing mtDNA damage mediated through ROS pathway which also induced oxidative damage. Prior-treatment of RF- and GR-exposed the cells with melatonin, a well-known free radical scavenger, reversed the effects observed in RF-exposed cells.

High-Intensity Exercise Induced Oxidative Stress and Skeletal Muscle Damage in Postpubertal Boys and Girls: A Comparative Study.

Science.gov (United States)

Pal, Sangita; Chaki, Biswajit; Chattopadhyay, Sreya; Bandyopadhyay, Amit

2018-04-01

Pal, S, Chaki, B, Chattopadhyay, S, and Bandyopadhyay, A. High-intensity exercise induced oxidative stress and skeletal muscle damage in post-pubertal boys and girls: a comparative study. J Strength Cond Res 32(4): 1045-1052, 2018-The purpose of this study was to examine the sex variation in high-intensity exercise induced oxidative stress and muscle damage among 44 sedentary postpubertal boys and girls through estimation of postexercise release pattern of muscle damage markers like creatine kinase, lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and oxidative stress markers like extent of lipid peroxidation (thiobarbituric acid-reactive substances) and catalase activity. Muscle damage markers like creatine kinase, LDH, ALT, and AST were measured before, immediately after, and 24 and 48 hours after high-intensity incremental treadmill running. Oxidative stress markers like thiobarbituric acid-reactive substances and catalase activity were estimated before and immediately after the exercise. Lipid peroxidation and serum catalase activity increased significantly in both groups after exercise (p exercise level at 24 and 48 hours after exercise in both the sexes, (p exercise, the pattern of postexercise release of these markers were found to be similar in both the groups. Accordingly, it has been concluded from the present investigation that high-intensity exercise induces significant oxidative stress and increases indices of skeletal muscle damage in both postpubertal girls and boys. However, postpubertal girls are relatively better protected from oxidative stress and muscle damage as compared to the boys of similar age and physical activity level. It is further evident that sex difference may not be apparent for all the biomarkers of muscle damage in this age group.

Oxidative stress damage-associated molecular signaling pathways differentiate spontaneous preterm birth and preterm premature rupture of the membranes.

Science.gov (United States)

Dutta, Eryn H; Behnia, Faranak; Boldogh, Istvan; Saade, George R; Taylor, Brandie D; Kacerovský, Marian; Menon, Ramkumar

2016-02-01

In women with preterm premature rupture of the membranes (PPROM), increased oxidative stress may accelerate premature cellular senescence, senescence-associated inflammation and proteolysis, which may predispose them to rupture. We demonstrate mechanistic differences between preterm birth (PTB) and PPROM by revealing differences in fetal membrane redox status, oxidative stress-induced damage, distinct signaling pathways and senescence activation. Oxidative stress-associated fetal membrane damage and cell cycle arrest determine adverse pregnancy outcomes, such as spontaneous PTB and PPROM. Fetal membranes and amniotic fluid samples were collected from women with PTB and PPROM. Molecular, biochemical and histologic markers were used to document differences in oxidative stress and antioxidant enzyme status, DNA damage, secondary signaling activation by Ras-GTPase and mitogen-activated protein kinases, and activation of senescence between membranes from the two groups. Oxidative stress was higher and antioxidant enzymes were lower in PPROM compared with PTB. PTB membranes had minimal DNA damage and showed activation of Ras-GTPase and ERK/JNK signaling pathway with minimal signs of senescence. PPROM had higher numbers of cells with DNA damage, prosenescence stress kinase (p38 MAPK) activation and signs of senescence. Samples were obtained retrospectively after delivery. The markers of senescence that we tested are specific but are not sufficient to confirm senescence as the pathology in PPROM. Oxidative stress-induced DNA damage and senescence are characteristics of fetal membranes from PPROM, compared with PTB with intact membranes. PTB and PPROM arise from distinct pathophysiologic pathways. Oxidative stress and oxidative stress-induced cellular damages are likely determinants of the mechanistic signaling pathways and phenotypic outcome. This study is supported by developmental funds to Dr R. Menon from the Department of Obstetrics and Gynecology at The University of

Enzymatic recognition of DNA damage induced by UVB-photosensitized titanium dioxide and biological consequences in Saccharomyces cerevisiae: Evidence for oxidatively DNA damage generation

International Nuclear Information System (INIS)

Pinto, A. Viviana; Deodato, Elder L.; Cardoso, Janine S.; Oliveira, Eliza F.; Machado, Sergio L.; Toma, Helena K.; Leitao, Alvaro C.; Padula, Marcelo de

2010-01-01

Although titanium dioxide (TiO 2 ) has been considered to be biologically inert, finding use in cosmetics, paints and food colorants, recent reports have demonstrated that when TiO 2 is attained by UVA radiation oxidative genotoxic and cytotoxic effects are observed in living cells. However, data concerning TiO 2 -UVB association is poor, even if UVB radiation represents a major environmental carcinogen. Herein, we investigated DNA damage, repair and mutagenesis induced by TiO 2 associated with UVB irradiation in vitro and in vivo using Saccharomyces cerevisiae model. It was found that TiO 2 plus UVB treatment in plasmid pUC18 generated, in addition to cyclobutane pyrimidine dimers (CPDs), specific damage to guanine residues, such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG), which are characteristic oxidatively generated lesions. In vivo experiments showed that, although the presence of TiO 2 protects yeast cells from UVB cytotoxicity, high mutation frequencies are observed in the wild-type (WT) and in an ogg1 strain (deficient in 8-oxoG and FapyG repair). Indeed, after TiO 2 plus UVB treatment, induced mutagenesis was drastically enhanced in ogg1 cells, indicating that mutagenic DNA lesions are repaired by the Ogg1 protein. This effect could be attenuated by the presence of metallic ion chelators: neocuproine or dipyridyl, which partially block oxidatively generated damage occurring via Fenton reactions. Altogether, the results indicate that TiO 2 plus UVB potentates UVB oxidatively generated damage to DNA, possibly via Fenton reactions involving the production of DNA base damage, such as 8-oxo-7,8-dihydroguanine.

Ameliorative Effect of Camel's Milk and Nigella Sativa Oil against Thioacetamide-induced Hepatorenal Damage in Rats.

Science.gov (United States)

Ahmad, Aftab; Al-Abbasi, Fahad A; Sadath, Saida; Ali, Soad Shaker; Abuzinadah, Mohammed F; Alhadrami, Hani A; Mohammad Alghamdi, Anwar Ali; Aseeri, Ali H; Khan, Shah Alam; Husain, Asif

2018-01-01

Camel milk (CM) and Nigella sativa (NS) have been traditionally claimed to cure wide range of diseases and used as medicine in different part of world, particularly in Saudi Arabia. Several research studies have been published that proved beneficial effects of CM and NS. This study was undertaken to investigate the antihepatotxic potential of CM and NS oil (NSO) against thioacetamide (TAA)-induced hepato and nephrotoxicity in rats. Thirty female Albino Wistar rats were randomly divided in to six groups having five rats in each group. A single subcutaneous injection of TAA (100 mg/kg b. w.) was administered to all the rats in Group-II to VI on 1 st day to induce hepatorenal damage. Group I served as a normal control while Group II served as toxic control for comparison purpose. Experimental animals in Group III, IV, and V were supplemented with fresh CM, (250 mL/24 h/cage), NSO (2 mL/kg/day p. o.), and NSO + fresh CM, respectively. Group VI was treated with a polyherbal hepatoprotective Unani medicine Jigreen (2 mL/kg/day p. o.) for 21 days. TAA-induced hepatorenal damage and protective effects of CM and NSO were assessed by analyzing liver and kidney function tests in the serum. Histopathology of liver and kidney tissues was also carried out to corroborate the findings of biochemical investigation. The results indicated that the TAA intoxicated rats showed significant increase in the alanine transaminase, aspartate transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase, lipid profile, urea, creatinine, uric acid, sodium, and potassium levels in serum. Treatment of rats with CM, NSO, and CM plus NSO combination and Jigreen significantly reversed the damage and brought down the serum biochemical parameters and lipid profile toward the normal levels. The histopathological studies also support the hepato and nephroprotective effects of CM and NSO. This study demonstrated the ameliorative effects of CM, NSO, and CM plus NSO combination against TAA

Tumour vasculature immaturity, oxidative damage and systemic inflammation stratify survival of colorectal cancer patients on bevacizumab treatment

Science.gov (United States)

Martin, Petra; Biniecka, Monika; Ó'Meachair, Shane; Maguire, Aoife; Tosetto, Miriam; Nolan, Blathnaid; Hyland, John; Sheahan, Kieran; O'Donoghue, Diarmuid; Mulcahy, Hugh; Fennelly, David; O'Sullivan, Jacintha

2018-01-01

Despite treatment of patients with metastatic colorectal cancer (mCRC) with bevacizumab plus chemotherapy, response rates are modest and there are no biomarkers available that will predict response. The aim of this study was to assess if markers associated with three interconnected cancer-associated biological processes, specifically angiogenesis, inflammation and oxidative damage, could stratify the survival outcome of this cohort. Levels of angiogenesis, inflammation and oxidative damage markers were assessed in pre-bevacizumab resected tumour and serum samples of mCRC patients by dual immunofluorescence, immunohistochemistry and ELISA. This study identified that specific markers of angiogenesis, inflammation and oxidative damage stratify survival of patients on this anti-angiogenic treatment. Biomarkers of immature tumour vasculature (% IMM, p=0.026, n=80), high levels of oxidative damage in the tumour epithelium (intensity of 8-oxo-dG in nuclear and cytoplasmic compartments, p=0.042 and 0.038 respectively, n=75) and lower systemic pro-inflammatory cytokines (IL6 and IL8, p=0.053 and 0.049 respectively, n=61) significantly stratify with median overall survival (OS). In summary, screening for a panel of biomarkers for high levels of immature tumour vasculature, high levels of oxidative DNA damage and low levels of systemic pro-inflammatory cytokines may be beneficial in predicting enhanced survival outcome following bevacizumab treatment for mCRC. PMID:29535825

Molecular Mechanisms Responsible for Increased Vulnerability of the Ageing Oocyte to Oxidative Damage

Science.gov (United States)

Redgrove, Kate A.; McLaughlin, Eileen A.

2017-01-01

In their midthirties, women experience a decline in fertility, coupled to a pronounced increase in the risk of aneuploidy, miscarriage, and birth defects. Although the aetiology of such pathologies are complex, a causative relationship between the age-related decline in oocyte quality and oxidative stress (OS) is now well established. What remains less certain are the molecular mechanisms governing the increased vulnerability of the aged oocyte to oxidative damage. In this review, we explore the reduced capacity of the ageing oocyte to mitigate macromolecular damage arising from oxidative insults and highlight the dramatic consequences for oocyte quality and female fertility. Indeed, while oocytes are typically endowed with a comprehensive suite of molecular mechanisms to moderate oxidative damage and thus ensure the fidelity of the germline, there is increasing recognition that the efficacy of such protective mechanisms undergoes an age-related decline. For instance, impaired reactive oxygen species metabolism, decreased DNA repair, reduced sensitivity of the spindle assembly checkpoint, and decreased capacity for protein repair and degradation collectively render the aged oocyte acutely vulnerable to OS and limits their capacity to recover from exposure to such insults. We also highlight the inadequacies of our current armoury of assisted reproductive technologies to combat age-related female infertility, emphasising the need for further research into mechanisms underpinning the functional deterioration of the ageing oocyte. PMID:29312475

Effect of complex polyphenols and tannins from red wine (WCPT) on chemically induced oxidative DNA damage in the rat.

Science.gov (United States)

Casalini, C; Lodovici, M; Briani, C; Paganelli, G; Remy, S; Cheynier, V; Dolara, P

1999-08-01

Flavonoids are polyphenolic antioxidants occurring in vegetables and fruits as well as beverages such as tea and wine which have been thought to influence oxidative damage. We wanted to verify whether a complex mixture of wine tannins (wine complex polyphenols and tannins, WCPT) prevent chemically-induced oxidative DNA damage in vivo. Oxidative DNA damage was evaluated by measuring the ratio of 8-hydroxy-2'-deoxyguanosine (80HdG)/ 2-deoxyguanosine (2dG) x 10(-6) in hydrolyzed DNA using HPLC coupled with electrochemical and UV detectors. We treated rats with WCPT (57 mg/kg p.o.) for 14 d, a dose 10-fold higher than what a moderate wine drinker would be exposed to. WCPT administration significantly reduced the ratio of 80HdG/2dG x 10(-6) in liver DNA obtained from rats treated with 2-nitropropane (2NP) relative to controls administered 2NP only (33. 3 +/- 2.5 vs. 44.9 +/- 3.2 x 10(-6) 2dG; micro +/- SE; p<0.05). On the contrary, pretreatment with WCPT for 10 d did not protect the colon mucosa from oxidative DNA damage induced by 1, 2-dimethylhydrazine (DMH). 2NP and DMH are hepatic and colon carcinogens, respectively, capable of inducing oxidative DNA damage. WCPT have protective action against some types of chemically-induced oxidative DNA damage in vivo.

Effects of forest road amelioration techniques on soil bulk density, surface runoff, sediment transport, soil moisture and seedling growth

Science.gov (United States)

Randy K. Kolka; Mathew F. Smidt

2004-01-01

Although numerous methods have been used to retire roads, new technologies have evolved that can potentially ameliorate soil damage, lessen ,the generation of nonpoint source pollution and increase tree productivity on forest roads. In this study we investigated the effects of three forest road amelioration techniques, subsoiling, recontouring and traditional...

Effects of a Brussels sprouts extract on oxidative DNA damage and metabolising enzymes in rat liver

DEFF Research Database (Denmark)

Sørensen, Mette; Jensen, B.R.; Poulsen, Henrik E.

2001-01-01

and catalase activity was also assessed in the kidneys. In order to examine a possible effect of the Brussels sprouts related to oxidative stress, we measured oxidative DNA damage in terms of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) and lipid peroxidation in terms of malondialdehyde (MDA) formation...... on MDA levels were found. The present results support the data obtained in several studies that consumption of cruciferous vegetables is capable of inducing various phase II enzyme systems. However, the observed increase in oxidative DNA damage raises the question of whether greatly increased ingestion...

Assessment of DNA damage and oxidative stress induced by radiation in Eisenia fetida

Energy Technology Data Exchange (ETDEWEB)

Ryu, Tae Ho; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Nili, Mohammad [Dawnesh Radiation Research Institute, Barcelona (Spain)

2012-04-15

Exposure of eukaryotic cells to ionizing radiation results in the immediate formation of free radicals and the occurrence of oxidative cell damage. Recently International Commission on Radiological Protection (ICRP) requires the effect data of ionizing radiation on non-human biota for the radiological protection of the environment. Based on their radioecological properties and their important role in the soil ecosystem, earthworms have been identified by the ICRP as one of the reference animals and plants (RAPs) to be used in environmental radiation protection. The investigation shows that oxidative stress is closely related to the exposed dose of radiation in the environment. To evaluate oxidative stress by ionizing radiation in the earthworm, we performed several experiments. The comet assay is known as a measurement which is one of the best techniques in assessing the DNA damage by oxidative stress. The SOD is a key enzyme in protecting cells against oxidative stress. An increase in the level of antioxidant enzyme such as SOD indicated that the exposure to radiation caused stress responses. Glutathione oxidation is considered as a maker for detection of reactive oxygen species (ROS). The GSSG levels increased progressively with increased exposure dose of ionizing radiation, which suggested a dose-dependent ROS generation.

Endomorphin 1 effectively protects cadmium chloride-induced hepatic damage in mice

International Nuclear Information System (INIS)

Gong Pin; Chen Fuxin; Ma Guofen; Feng Yun; Zhao Qianyu; Wang Rui

2008-01-01

The antioxidative capacity of endomorphin 1 (EM1), an endogenous μ-opioid receptor agonist, has been demonstrated by in vivo assays. The present study reports the effect of EM1 on hepatic damage induced by cadmium chloride (Cd(II)) in adult male mouse. Mouse were given intraperitoneally (i.p.) a single dose of Cd(II) (1 mg/kg body weight per day) and the animals were co-administrated with a dose of EM1 (50 μM/kg body weight per day) for 6 days. Since hepatic damage induced by Cd(II) is related to oxidative stress, lipid peroxidation (LPO), protein carbonyl (PCO), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH) were evaluated. The parameter indicating tissue damage such as liver histopathology was also determined. In addition, the concentrations of Cd and zinc (Zn) in the liver were analyzed. The intoxication of Cd(II) lead to the enhanced production of LPO and PCO, treatment with EM1 can effectively ameliorate the increase of LPO and PCO compared to the Cd(II) group. The increased activities of CAT, SOD and the elevated GSH induced by Cd(II) may relate to an adaptive-response to the oxidative damage, the effect of EM1 can restore the elevated antioxidant defense. Our results suggested that the structure features and the ability of chelating metal of EM1 may play a major role in the antioxidant effect of EM1 in vivo and opioid receptors may be involved in the protection of hepatic damage induced by Cd(II)

Antiretroviral therapy-induced insulin resistance and oxidative deoxy nucleic acid damage in human immunodeficiency virus-1 patients

Directory of Open Access Journals (Sweden)

Vaishali Kolgiri Honnapurmath

2017-01-01

Full Text Available Background and Objectives: Insulin resistance (IR is frequent in human immunodeficiency virus (HIV infection and may be related to antiretroviral therapy (ART. Increased oxidative stress parameters and carbonyl protein are linked to insulin sensitivity. The present study is aimed to determine IR, its association with oxidative deoxy nucleic acid (DNA damage in HIV-1-infected patients with different ART status. Materials and Methods: In this case–control study, a total 600 subjects were included. We used plasma levels of the oxidized base, 8-hydroxy-2-deoxyguanosine (8-OHdG, as our biomarker of oxidative DNA damage. 8-OHdG was measured with the highly sensitive 8-OHdG check enzyme-linked immunosorbent assay kit. IR was determined using homeostasis model assessment. Results: All subjects were randomly selected and grouped as HIV-negative (control group (n = 300, HIV-positive without ART (n = 100, HIV-positive with ART first line (n = 100, and HIV-positive with ART second line (n = 100. IR and oxidative DNA damage were significantly higher in HIV-positive patients with second-line ART and HIV-positive patients with first-line ART than ART-naive patients. In a linear regression analysis, increased IR was positively associated with the increased DNA damage (odds ratio: 3.052, 95% confidence interval: 2.595–3.509 P < 0.001. Interpretation and Conclusions: In this study, we observed that ART plays a significant role in the development of IR and oxidative DNA damage in HIV-positive patients taking ART. Awareness and knowledge of these biomarkers may prove helpful to clinicians while prescribing ART to HIV/AIDS patients. Larger studies are warranted to determine the exact role of ART in the induction of IR and DNA damage.

Deformability of Erythrocytes and Oxidative Damage in Alzheimer Disease

Directory of Open Access Journals (Sweden)

Mukerrem Betul Yerer

2012-04-01

Full Text Available Purpose: A lowered cerebral perfusion as a consequence of hemodynamic microcirculatory insufficiency is one of the factors underlying in Alzheimer's disease, which is a neurodegenerative disorder leading to progressive cognitive impairment. Erythrocyte deformability is one of the major factors affecting the microcirculatory hemodynamics which is closely related to the oxidative damage. The aim of this study is to investigate the relationship between the erythrocyte deformability, nitric oxide levels and oxidative stress in Alzheimer's disease. Methods: The blood samples of 30 elderly people in three groups consisting of healthy control and different severities of the disease (low and severe were used. Then the erythrocytes were isolated and the deformability of erythrocytes was determined by Rheodyne SSD evaluating the elongation indexes of the erythrocytes under different shear stress. The catalase, glutathione peroxidase and plasma nitric oxide levels were measured spectrophotometric ally. Results: The plasma nitric oxide levels, catalase activities were found significantly higher and glutathione peroxidase activity was significantly lower in severe Alzheimer's disease patients compared to the control group. However, the deformability of erythrocytes was not significantly affected from these alterations. Conclusion: the oxidant-antioxidant status is dramatically changed in Alzheimer's disease patients with the severity of the disease and similar alterations were seen in the nitric oxide levels without any significant change in erythrocyte deformability. [Cukurova Med J 2012; 37(2.000: 65-75

Repair of oxidative DNA damage by amino acids.

Science.gov (United States)

Milligan, J R; Aguilera, J A; Ly, A; Tran, N Q; Hoang, O; Ward, J F

2003-11-01

Guanyl radicals, the product of the removal of a single electron from guanine, are produced in DNA by the direct effect of ionizing radiation. We have produced guanyl radicals in DNA by using the single electron oxidizing agent (SCN)2-, itself derived from the indirect effect of ionizing radiation via thiocyanate scavenging of OH. We have examined the reactivity of guanyl radicals in plasmid DNA with the six most easily oxidized amino acids cysteine, cystine, histidine, methionine, tryptophan and tyrosine and also simple ester and amide derivatives of them. Cystine and histidine derivatives are unreactive. Cysteine, methionine, tyrosine and particularly tryptophan derivatives react to repair guanyl radicals in plasmid DNA with rate constants in the region of approximately 10(5), 10(5), 10(6) and 10(7) dm3 mol(-1) s(-1), respectively. The implication is that amino acid residues in DNA binding proteins such as histones might be able to repair by an electron transfer reaction the DNA damage produced by the direct effect of ionizing radiation or by other oxidative insults.

Green Synthesized Zinc Oxide (ZnO) Nanoparticles Induce Oxidative Stress and DNA Damage in Lathyrus sativus L. Root Bioassay System.

Science.gov (United States)

Panda, Kamal K; Golari, Dambaru; Venugopal, A; Achary, V Mohan M; Phaomei, Ganngam; Parinandi, Narasimham L; Sahu, Hrushi K; Panda, Brahma B

2017-05-18

Zinc oxide nanoparticles (ZnONP-GS) were synthesised from the precursor zinc acetate (Zn(CH₃COO)₂) through the green route using the milky latex from milk weed ( Calotropis gigantea L. R. Br) by alkaline precipitation. Formation of the ZnONP-GS was monitored by UV-visible spectroscopy followed by characterization and confirmation by energy-dispersive X-ray spectroscopy (EDX), transmission electron microscopy (TEM), and X-ray diffraction (XRD). Both the ZnONP-GS and the commercially available ZnONP-S (Sigma-Aldrich) and cationic Zn 2+ from Zn(CH₃COO)₂ were tested in a dose range of 0-100 mg·L -1 for their potency (i) to induce oxidative stress as measured by the generation reactive oxygen species (ROS: O₂ •- , H₂O₂ and • OH), cell death, and lipid peroxidation; (ii) to modulate the activities of antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), guaiacol peroxidase (GPX), and ascorbate peroxidase (APX); and (iii) to cause DNA damage as determined by Comet assay in Lathyrus sativus L. root bioassay system. Antioxidants such as Tiron and dimethylthiourea significantly attenuated the ZnONP-induced oxidative and DNA damage, suggesting the involvement of ROS therein. Our study demonstrated that both ZnONP-GS and ZnONP-S induced oxidative stress and DNA damage to a similar extent but were significantly less potent than Zn 2+ alone.

Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia

International Nuclear Information System (INIS)

Lundby, Carsten; Pilegaard, Henriette; Hall, Gerrit van; Sander, Mikael; Calbet, Jose; Loft, Steffen; Moeller, Peter

2003-01-01

Recent research suggests that high-altitude hypoxia may serve as a model for prolonged oxidative stress in healthy humans. In this study, we investigated the consequences of prolonged high-altitude hypoxia on the basal level of oxidative damage to nuclear DNA in muscle cells, a major oxygen-consuming tissue. Muscle biopsies from seven healthy humans were obtained at sea level and after 2 and 8 weeks of hypoxia at 4100 m.a.s.l. We found increased levels of strand breaks and endonuclease III-sensitive sites after 2 weeks of hypoxia, whereas oxidative DNA damage detected by formamidopyrimidine DNA glycosylase (FPG) protein was unaltered. The expression of 8-oxoguanine DNA glycosylase 1 (OGG1), determined by quantitative RT-PCR of mRNA levels did not significantly change during high-altitude hypoxia, although the data could not exclude a minor upregulation. The expression of heme oxygenase-1 (HO-1) was unaltered by prolonged hypoxia, in accordance with the notion that HO-1 is an acute stress response protein. In conclusion, our data indicate high-altitude hypoxia may serve as a good model for oxidative stress and that antioxidant genes are not upregulated in muscle tissue by prolonged hypoxia despite increased generation of oxidative DNA damage

Polysaccharides from Cordyceps sinensis mycelium ameliorate exhaustive swimming exercise-induced oxidative stress.

Science.gov (United States)

Yan, Feng; Wang, Beibei; Zhang, Yan

2014-02-01

Cordyceps sinensis (Berk.) Sacc. (Clavicipitaceae) is a famous medicinal fungus (mushroom) in Chinese herbal medicine. Polysaccharides from Cordyceps sinensis (CSP) have been identified as active ingredients responsible for its biological activities. Although many pharmacological actions of CSP have received a great deal of attention, research in this area continues. The current study was designed to investigate the effects of CSP on exhaustive exercise-induced oxidative stress. The mice were divided into four groups: control (C), low-dose CSP treated (LC), intermediate-dose CSP treated (IC) and high-dose CSP treated (HC). The treated groups received CSP (100, 200 and 400 mg/kg, ig), while the control group received drinking water for 28 days, followed by being forced to undergo exhaustive swimming exercise, and some biochemical parameters including superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were measured using detection kits according to the manufacturers' instructions. Compared with the C group, exhaustive swimming time was significantly prolonged in the LC, IC and HC groups (p activities in serum, liver and muscle were significantly higher in the IC and HC groups (p activities in serum, liver and muscle were significantly higher in the LC, IC and HC groups (p activities in serum, liver and muscle were significantly higher in the HC groups (p < 0.05); MDA and 8-OHdG levels in serum, liver and muscle were significantly lower in the LC, IC and HC groups (p < 0.05). The results obtained herein indicate that CSP could ameliorate exhaustive exercise-induced oxidative stress.

Protective effect of hemin against cadmium-induced testicular damage in rats

International Nuclear Information System (INIS)

Fouad, Amr A.; Qureshi, Habib A.; Al-Sultan, Ali Ibrahim; Yacoubi, Mohamed T.; Ali, Abdellah Abusrie

2009-01-01

The protective effect of hemin, the heme oxygenase-1 inducer, was investigated in rats with cadmium induced-testicular injury, in which oxidative stress and inflammation play a major role. Testicular damage was induced by a single i.p. injection of cadmium chloride (2 mg/kg). Hemin was given for three consecutive days (40 μmol/kg/day, s.c.), starting 1 day before cadmium administration. Hemin treatment significantly increased serum testosterone level that was reduced by cadmium. Hemin compensated deficits in the antioxidant defense mechanisms (reduced glutathione, and catalase and superoxide dismutase activities), and suppressed lipid peroxidation in testicular tissue resulted from cadmium administration. Also, hemin attenuated the cadmium-induced elevations in testicular tumor necrosis factor-α and nitric oxide levels, and caspase-3 activity. Additionally, hemin ameliorated cadmium-induced testicular tissue damage observed by light and electron microscopic examinations. The protective effect afforded by hemin was abolished by prior administration of zinc protoporphyrin-IX, the heme oxygenase-1 inhibitor. It was concluded that hemin, through its antioxidant, anti-inflammatory and antiapoptotic effects, represents a potential therapeutic option to protect the testicular tissue from the detrimental effects of cadmium

Resveratrol, an Nrf2 activator, ameliorates aging-related progressive renal injury.

Science.gov (United States)

Kim, Eun Nim; Lim, Ji Hee; Kim, Min Young; Ban, Tae Hyun; Jang, In-Ae; Yoon, Hye Eun; Park, Cheol Whee; Chang, Yoon Sik; Choi, Bum Soon

2018-01-11

Two important issues in the aging kidney are mitochondrial dysfunction and oxidative stress. An Nrf2 activator, resveratrol, is known to have various effects. Resveratrol may prevent inflammation and oxidative stress by activating Nrf2 and SIRT1 signaling. We examined whether resveratrol could potentially ameliorate the cellular condition, such as renal injury due to cellular oxidative stress and mitochondrial dysfunction caused by aging. Male 18-month-old C57BL/6 mice were used. Resveratrol (40 mg/kg) was administered to aged mice for 6 months. We compared histological changes, oxidative stress, and aging-related protein expression in the kidney between the resveratrol-treated group (RSV) and the control group (cont). We performed experiments using small-interfering RNAs (siRNAs) for Nrf2 and SIRT1 in cultured HK2 cells. Resveratrol improved renal function, proteinuria, histological changes and inflammation in aging mice. Also, expression of Nrf2-HO-1-NOQ-1 signaling and SIRT1-AMPK-PGC-1α signaling was increased in the RSV group. Transfection with Nrf2 and SIRT1 siRNA prevented resveratrol-induced anti-oxidative effect in HK2 cells in media treated with H 2 O 2 . Activation of the Nrf2 and SIRT1 signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Pharmacological targeting of Nrf2 signaling molecules may reduce the pathologic changes of aging in the kidney.

Oxidative Stress, DNA Damage and DNA Repair in Female Patients with Diabetes Mellitus Type 2.

Directory of Open Access Journals (Sweden)

Annemarie Grindel

Full Text Available Diabetes mellitus type 2 (T2DM is associated with oxidative stress which in turn can lead to DNA damage. The aim of the present study was to analyze oxidative stress, DNA damage and DNA repair in regard to hyperglycemic state and diabetes duration.Female T2DM patients (n = 146 were enrolled in the MIKRODIAB study and allocated in two groups regarding their glycated hemoglobin (HbA1c level (HbA1c≤7.5%, n = 74; HbA1c>7.5%, n = 72. In addition, tertiles according to diabetes duration (DD were created (DDI = 6.94±3.1 y, n = 49; DDII = 13.35±1.1 y, n = 48; DDIII = 22.90±7.3 y, n = 49. Oxidative stress parameters, including ferric reducing ability potential, malondialdehyde, oxidized and reduced glutathione, reduced thiols, oxidized LDL and F2-Isoprostane as well as the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were measured. Damage to DNA was analyzed in peripheral blood mononuclear cells and whole blood with single cell gel electrophoresis. DNA base excision repair capacity was tested with the modified comet repair assay. Additionally, mRNA expressions of nine genes related to base excision repair were analyzed in a subset of 46 matched individuals.No significant differences in oxidative stress parameters, antioxidant enzyme activities, damage to DNA and base excision repair capacity, neither between a HbA1c cut off />7.5%, nor between diabetes duration was found. A significant up-regulation in mRNA expression was found for APEX1, LIG3 and XRCC1 in patients with >7.5% HbA1c. Additionally, we observed higher total cholesterol, LDL-cholesterol, LDL/HDL-cholesterol, triglycerides, Framingham risk score, systolic blood pressure, BMI and lower HDL-cholesterol in the hyperglycemic group.BMI, blood pressure and blood lipid status were worse in hyperglycemic individuals. However, no major disparities regarding oxidative stress, damage to DNA and DNA repair were present which might be due to good medical

ATM-dependent pathways of chromatin remodelling and oxidative DNA damage responses.

Science.gov (United States)

Berger, N Daniel; Stanley, Fintan K T; Moore, Shaun; Goodarzi, Aaron A

2017-10-05

Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase with a master regulatory function in the DNA damage response. In this role, ATM commands a complex biochemical network that signals the presence of oxidative DNA damage, including the dangerous DNA double-strand break, and facilitates subsequent repair. Here, we review the current state of knowledge regarding ATM-dependent chromatin remodelling and epigenomic alterations that are required to maintain genomic integrity in the presence of DNA double-strand breaks and/or oxidative stress. We will focus particularly on the roles of ATM in adjusting nucleosome spacing at sites of unresolved DNA double-strand breaks within complex chromatin environments, and the impact of ATM on preserving the health of cells within the mammalian central nervous system.This article is part of the themed issue 'Chromatin modifiers and remodellers in DNA repair and signalling'. © 2017 The Author(s).

Increased urinary excretion of 8-oxo-2'-deoxyguanosine, a biomarker of oxidative DNA damage, in urban bus drivers

DEFF Research Database (Denmark)

Loft, S; Poulsen, H E; Vistisen, K

1999-01-01

Oxidative damage to DNA could be involved in the increased risk of cancer associated with exposure to polluted urban air, which contains a number of oxidants. CYP1A2 is induced by and metabolizes polyaromatic hydrocarbons (PAH) and aromatic amines and could modify effects of exposure to ambient air...... pollution. Similarly, DNA repair may be influenced by occupational and other exposures as well as modify the effect of DNA damaging agents. As part of a large investigation of the genotoxic burden to diesel exposed workers in transport sectors we studied oxidative DNA damage in 57 non-smoking bus drivers...... from the greater Copenhagen area. The drivers were studied on a workday and on a day off work. Comparisons were made between drivers from the central (n=30) and rural/suburban (n=27) areas of Copenhagen. The rate of oxidative DNA damage was estimated from 24 h urinary excretion of 8-oxo-2...

Enzymatic recognition of DNA damage induced by UVB-photosensitized titanium dioxide and biological consequences in Saccharomyces cerevisiae: evidence for oxidatively DNA damage generation.

Science.gov (United States)

Pinto, A Viviana; Deodato, Elder L; Cardoso, Janine S; Oliveira, Eliza F; Machado, Sérgio L; Toma, Helena K; Leitão, Alvaro C; de Pádula, Marcelo

2010-06-01

Although titanium dioxide (TiO(2)) has been considered to be biologically inert, finding use in cosmetics, paints and food colorants, recent reports have demonstrated that when TiO(2) is attained by UVA radiation oxidative genotoxic and cytotoxic effects are observed in living cells. However, data concerning TiO(2)-UVB association is poor, even if UVB radiation represents a major environmental carcinogen. Herein, we investigated DNA damage, repair and mutagenesis induced by TiO(2) associated with UVB irradiation in vitro and in vivo using Saccharomyces cerevisiae model. It was found that TiO(2) plus UVB treatment in plasmid pUC18 generated, in addition to cyclobutane pyrimidine dimers (CPDs), specific damage to guanine residues, such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG), which are characteristic oxidatively generated lesions. In vivo experiments showed that, although the presence of TiO(2) protects yeast cells from UVB cytotoxicity, high mutation frequencies are observed in the wild-type (WT) and in an ogg1 strain (deficient in 8-oxoG and FapyG repair). Indeed, after TiO(2) plus UVB treatment, induced mutagenesis was drastically enhanced in ogg1 cells, indicating that mutagenic DNA lesions are repaired by the Ogg1 protein. This effect could be attenuated by the presence of metallic ion chelators: neocuproine or dipyridyl, which partially block oxidatively generated damage occurring via Fenton reactions. Altogether, the results indicate that TiO(2) plus UVB potentates UVB oxidatively generated damage to DNA, possibly via Fenton reactions involving the production of DNA base damage, such as 8-oxo-7,8-dihydroguanine. Copyright 2010 Elsevier B.V. All rights reserved.

Enzymatic recognition of DNA damage induced by UVB-photosensitized titanium dioxide and biological consequences in Saccharomyces cerevisiae: Evidence for oxidatively DNA damage generation

Energy Technology Data Exchange (ETDEWEB)

Pinto, A. Viviana, E-mail: alicia.pinto@incqs.fiocruz.br [Laboratorio de Diagnostico Molecular e Hematologia, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21941-540, Rio de Janeiro (Brazil); Laboratorio de Radiobiologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21949-900, Rio de Janeiro (Brazil); Deodato, Elder L. [Laboratorio de Diagnostico Molecular e Hematologia, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21941-540, Rio de Janeiro (Brazil); Laboratorio de Radiobiologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21949-900, Rio de Janeiro (Brazil); Cardoso, Janine S. [Laboratorio de Radiobiologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21949-900, Rio de Janeiro (Brazil); Oliveira, Eliza F.; Machado, Sergio L.; Toma, Helena K. [Laboratorio de Diagnostico Molecular e Hematologia, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21941-540, Rio de Janeiro (Brazil); Leitao, Alvaro C. [Laboratorio de Radiobiologia Molecular, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21949-900, Rio de Janeiro (Brazil); Padula, Marcelo de [Laboratorio de Diagnostico Molecular e Hematologia, Faculdade de Farmacia, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude - Ilha do Fundao, CEP 21941-540, Rio de Janeiro (Brazil)

2010-06-01

Although titanium dioxide (TiO{sub 2}) has been considered to be biologically inert, finding use in cosmetics, paints and food colorants, recent reports have demonstrated that when TiO{sub 2} is attained by UVA radiation oxidative genotoxic and cytotoxic effects are observed in living cells. However, data concerning TiO{sub 2}-UVB association is poor, even if UVB radiation represents a major environmental carcinogen. Herein, we investigated DNA damage, repair and mutagenesis induced by TiO{sub 2} associated with UVB irradiation in vitro and in vivo using Saccharomyces cerevisiae model. It was found that TiO{sub 2} plus UVB treatment in plasmid pUC18 generated, in addition to cyclobutane pyrimidine dimers (CPDs), specific damage to guanine residues, such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG), which are characteristic oxidatively generated lesions. In vivo experiments showed that, although the presence of TiO{sub 2} protects yeast cells from UVB cytotoxicity, high mutation frequencies are observed in the wild-type (WT) and in an ogg1 strain (deficient in 8-oxoG and FapyG repair). Indeed, after TiO{sub 2} plus UVB treatment, induced mutagenesis was drastically enhanced in ogg1 cells, indicating that mutagenic DNA lesions are repaired by the Ogg1 protein. This effect could be attenuated by the presence of metallic ion chelators: neocuproine or dipyridyl, which partially block oxidatively generated damage occurring via Fenton reactions. Altogether, the results indicate that TiO{sub 2} plus UVB potentates UVB oxidatively generated damage to DNA, possibly via Fenton reactions involving the production of DNA base damage, such as 8-oxo-7,8-dihydroguanine.

Enantioselective oxidative stress and oxidative damage caused by Rac- and S-metolachlor to Scenedesmus obliquus.

Science.gov (United States)

Liu, Huijun; Xia, YiLu; Cai, Weidan; Zhang, Yina; Zhang, Xiaoqiang; Du, Shaoting

2017-04-01

The rational use and environmental security of chiral pesticides has gained the interest of many researchers. The enantioselective effects of Rac- and S-metolachlor on oxidative stress in Scenedesmus obliquus were determined in this study. Stronger green fluorescence was observed in response to S-metolachlor treatment than to Rac-metolachlor treatment, suggesting that more reactive oxygen species (ROS) were stimulated by S-metolachlor. ROS levels following S-metolachlor treatment were 1.92-, 8.31-, and 1.08-times higher than those observed following Rac-metolachlor treatment at 0.1, 0.2, and 0.3 mg/L, respectively. Superoxide dismutase (SOD) and catalase (CAT) were stimulated with increasing herbicide concentrations, with S-metolachlor exhibiting a greater effect. Oxidative damage in terms of chlorophyll (Chl) content, cellular membrane permeability, and cellular ultrastructures of S. obliquus were investigated. Chla and Chlb contents in algae treated with Rac-metolachlor were 2-6-fold higher than those in algae treated with S-metolachlor at 0.1, 0.2, and 0.3 mg/L. The cellular membrane permeability of algae exposed to 0.3 mg/L Rac- and S-metolachlor was 6.19- and 42.5-times that of the control. Correlation analysis implied that ROS are the major factor responsible for the oxidative damage caused by Rac- and S-metolachlor. Damage to the chloroplasts and cell membrane of S. obliquus, low production of starch granules, and an increased number of vacuoles were observed upon ultrastructural morphology analysis by transmission electron microscope. These results indicate that S-metolachlor has a greater effect on S. obliquus than Rac-metolachlor. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inhibition of myeloperoxidase oxidant production by N-acetyl lysyltyrosylcysteine amide reduces brain damage in a murine model of stroke.

Science.gov (United States)

Yu, Guoliang; Liang, Ye; Huang, Ziming; Jones, Deron W; Pritchard, Kirkwood A; Zhang, Hao

2016-05-24

Oxidative stress plays an important and causal role in the mechanisms by which ischemia/reperfusion (I/R) injury increases brain damage after stroke. Accordingly, reducing oxidative stress has been proposed as a therapeutic strategy for limiting damage in the brain after stroke. Myeloperoxidase (MPO) is a highly potent oxidative enzyme that is capable of inducing both oxidative and nitrosative stress in vivo. To determine if and the extent to which MPO-generated oxidants contribute to brain I/R injury, we treated mice subjected to middle cerebral artery occlusion (MCAO) with N-acetyl lysyltyrosylcysteine amide (KYC), a novel, specific and non-toxic inhibitor of MPO. Behavioral testing, ischemic damage, blood-brain-barrier disruption, apoptosis, neutrophils infiltration, microglia/macrophage activation, and MPO oxidation were analyzed within a 7-day period after MCAO. Our studies show that KYC treatment significantly reduces neurological severity scores, infarct size, IgG extravasation, neutrophil infiltration, loss of neurons, apoptosis, and microglia/macrophage activation in the brains of MCAO mice. Immunofluorescence studies show that KYC treatment reduces the formation of chlorotyrosine (ClTyr), a fingerprint biomarker of MPO oxidation, nitrotyrosine (NO2Tyr), and 4-hydroxynonenal (4HNE) in MCAO mice. All oxidative products colocalized with MPO in the infarcted brains, suggesting that MPO-generated oxidants are involved in forming the oxidative products. MPO-generated oxidants play detrimental roles in causing brain damage after stroke which is effectively reduced by KYC.

Beta-glucan ameliorates gamma-rays induced oxidative injury in male Swiss albino rats

International Nuclear Information System (INIS)

Salama, S.F.

2011-01-01

1,3-beta-D-Glucan is a natural polysaccharide derived from the cell walls of bakers yeast Saccharomyces cerevsiae with immunoenhancing and potent antioxidant effects. This study investigated the pathways through which beta-glucan gavage treatment (50mg/kg) exerts its effect on radiation-induced oxidative damage in male rats. Beta-glucan was given orally to male rats; 3 hours post gamma-irradiation at dose 5Gy, for 10 and 20 days post-irradiation level were assayed, being remarkable indicators in cell oxidative stress. Results pointed out that irradiation at 5Gy significantly depressed all blood parameters, such as erythrocytes count (RBCs), hemoglobin content (Hb), hematocrit value (Hct), total leucocytes count and absolute lymphocytes and neutrophils counts, blood glutathione (GSH) level and conversely elevated level of serum ascorbyl radical (AsR), product of lipid peroxidation (MDA melanodialdehyde), triglycerides and cholesterol. Total leucocytes count and absolute lymphocytes and neutrophils counts, RBCs, Hb, Hct, blood GSH and serum MDA of irradiated animals receiving beta-glucan administration were exhibited significant differences compared to the irradiated group. Marrow count and the percentage of viability and spleenocytes viability were also significantly decreased. Beta-glucan treatment accelerates recovery of cell damage induced by ionizing irradiation through its potential immune-enhancing activity and free radical scavenging ability that is partially mediated through stimulation of immunohaematological system thus could play a role in regulating irradiation complications

Honey bee (Apis mellifera) drones survive oxidative stress due to increased tolerance instead of avoidance or repair of oxidative damage.

Science.gov (United States)

Li-Byarlay, Hongmei; Huang, Ming Hua; Simone-Finstrom, Michael; Strand, Micheline K; Tarpy, David R; Rueppell, Olav

2016-10-01

Oxidative stress can lead to premature aging symptoms and cause acute mortality at higher doses in a range of organisms. Oxidative stress resistance and longevity are mechanistically and phenotypically linked; considerable variation in oxidative stress resistance exists among and within species and typically covaries with life expectancy. However, it is unclear whether stress-resistant, long-lived individuals avoid, repair, or tolerate molecular damage to survive longer than others. The honey bee (Apis mellifera L.) is an emerging model system that is well-suited to address this question. Furthermore, this species is the most economically important pollinator, whose health may be compromised by pesticide exposure, including oxidative stressors. Here, we develop a protocol for inducing oxidative stress in honey bee males (drones) via Paraquat injection. After injection, individuals from different colony sources were kept in common social conditions to monitor their survival compared to saline-injected controls. Oxidative stress was measured in susceptible and resistant individuals. Paraquat drastically reduced survival but individuals varied in their resistance to treatment within and among colony sources. Longer-lived individuals exhibited higher levels of lipid peroxidation than individuals dying early. In contrast, the level of protein carbonylation was not significantly different between the two groups. This first study of oxidative stress in male honey bees suggests that survival of an acute oxidative stressor is due to tolerance, not prevention or repair, of oxidative damage to lipids. It also demonstrates colony differences in oxidative stress resistance that might be useful for breeding stress-resistant honey bees. Copyright © 2016 Elsevier Inc. All rights reserved.

Oxidative stress and proinflammatory cytokines contribute to demyelination and axonal damage in a cerebellar culture model of neuroinflammation.

Science.gov (United States)

di Penta, Alessandra; Moreno, Beatriz; Reix, Stephanie; Fernandez-Diez, Begoña; Villanueva, Maite; Errea, Oihana; Escala, Nagore; Vandenbroeck, Koen; Comella, Joan X; Villoslada, Pablo

2013-01-01

Demyelination and axonal damage are critical processes in the pathogenesis of multiple sclerosis (MS). Oxidative stress and pro-inflammatory cytokines elicited by inflammation mediates tissue damage. To monitor the demyelination and axonal injury associated with microglia activation we employed a model using cerebellar organotypic cultures stimulated with lipopolysaccharide (LPS). Microglia activated by LPS released pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and increased the expression of inducible nitric oxide synthase (iNOS) and production of reactive oxygen species (ROS). This activation was associated with demyelination and axonal damage in cerebellar cultures. Axonal damage, as revealed by the presence of non-phosphorylated neurofilaments, mitochondrial accumulation in axonal spheroids, and axonal transection, was associated with stronger iNOS expression and concomitant increases in ROS. Moreover, we analyzed the contribution of pro-inflammatory cytokines and oxidative stress in demyelination and axonal degeneration using the iNOS inhibitor ethyl pyruvate, a free-scavenger and xanthine oxidase inhibitor allopurinol, as well as via blockage of pro-inflammatory cytokines using a Fc-TNFR1 construct. We found that blocking microglia activation with ethyl pyruvate or allopurinol significantly decreased axonal damage, and to a lesser extent, demyelination. Blocking TNFα significantly decreased demyelination but did not prevented axonal damage. Moreover, the most common therapy for MS, interferon-beta, was used as an example of an immunomodulator compound that can be tested in this model. In vitro, interferon-beta treatment decreased oxidative stress (iNOS and ROS levels) and the release of pro-inflammatory cytokines after LPS stimulation, reducing axonal damage. The model of neuroinflammation using cerebellar culture stimulated with endotoxin mimicked myelin and axonal damage mediated by the combination of oxidative stress and pro-inflammatory cytokines

Oxidation damage evaluation by non-destructive method for graphite components in high temperature gas-cooled reactor

International Nuclear Information System (INIS)

Shibata, Taiju; Tada, Tatsuya; Sumita, Junya; Sawa, Kazuhiro

2008-01-01

To develop non-destructive evaluation methods for oxidation damage on graphite components in High Temperature Gas-cooled Reactors (HTGRs), the applicability of ultrasonic wave and micro-indentation methods were investigated. Candidate graphites, IG-110 and IG-430, for core components of Very High Temperature Reactor (VHTR) were used in this study. These graphites were oxidized uniformly by air at 500degC. The following results were obtained from this study. (1) Ultrasonic wave velocities with 1 MHz can be expressed empirically by exponential formulas to burn-off, oxidation weight loss. (2) The porous condition of the oxidized graphite could be evaluated with wave propagation analysis with a wave-pore interaction model. It is important to consider the non-uniformity of oxidized porous condition. (3) Micro-indentation method is expected to determine the local oxidation damage. It is necessary to assess the variation of the test data. (author)

Weekend ethanol consumption and high-sucrose diet: resveratrol effects on energy expenditure, substrate oxidation, lipid profile, oxidative stress and hepatic energy metabolism.

Science.gov (United States)

Rocha, Katiucha Karolina Honório Ribeiro; Souza, Gisele Aparecida; Seiva, Fábio Rodrigues Ferreira; Ebaid, Geovana Xavier; Novelli, Ethel Lourenzi Barbosa

2011-01-01

The present study analyzed the association between weekend ethanol and high-sucrose diet on oxygen consumption, lipid profile, oxidative stress and hepatic energy metabolism. Because resveratrol (RS, 3,5,4'-trans-trihydroxystilbene) has been implicated as a modulator of alcohol-independent cardiovascular protection attributed to red wine, we also determined whether RS could change the damage done by this lifestyle. Male Wistar 24 rats receiving standard chow were divided into four groups (n = 6/group): (C) water throughout the experimental period; (E) 30% ethanol 3 days/week, water 4 days/week; (ES) a mixture of 30% ethanol and 30% sucrose 3 days/week, drinking 30% sucrose 4 days/week; (ESR) 30% ethanol and 30% sucrose containing 6 mg/l RS 3 days/week, drinking 30% sucrose 4 days/week. After 70 days the body weight was highest in ESR rats. E rats had higher energy expenditure (resting metabolic rate), oxygen consumption (VO(2)), fat oxidation, serum triacylglycerol (TG) and very low-density lipoprotein (VLDL) than C. ES rats normalized calorimetric parameters and enhanced carbohydrate oxidation. ESR ameliorated calorimetric parameters, reduced TG, VLDL and lipid hydroperoxide/total antioxidant substances, as well enhanced high-density lipoprotein (HDL) and HDL/TG ratio. Hepatic hydroxyacyl coenzyme-A dehydrogenase (OHADH)/citrate synthase ratio was lower in E and ES rats than in C. OHADH was highest in ESR rats. The present study brought new insights on weekend alcohol consumption, demonstrating for the first time, that this pattern of ethanol exposure induced dyslipidemic profile, calorimetric and hepatic metabolic changes which resemble that of the alcoholism. No synergistic effects were found with weekend ethanol and high-sucrose intake. RS was advantageous in weekend drinking and high-sucrose intake condition ameliorating hepatic metabolism and improving risk factors for cardiovascular damage.

Gefarnate stimulates mucin-like glycoprotein secretion in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models

Directory of Open Access Journals (Sweden)

Dota A

2013-01-01

Full Text Available Atsuyoshi Dota, Yuko Takaoka-Shichijo, Masatsugu NakamuraOphthalmic Research and Development Center, Santen Pharmaceutical Co, Ltd, Ikoma-shi, Nara, JapanPurpose: The aim of this study was to evaluate the effect of gefarnate on mucin-like glycoprotein secretion in isolated rabbit conjunctival tissue, and on corneal epithelial damage in rabbit and cat dry-eye models.Methods: Conjunctival tissue isolated from rabbits was treated with gefarnate. Mucin-like glycoprotein was detected in the culture supernatant by an enzyme-linked lectin assay. Gefarnate ointment was topically applied to eyes once daily for 7 days in the rabbit dry-eye model, in which the lacrimal glands, Harderian gland, and nictitating membrane were removed, or for 4 weeks in the cat dry-eye model, in which the lacrimal gland and nictitating membrane were removed. Corneal epithelial damage was evaluated by measurement of corneal permeability by rose bengal in the rabbit model or by fluorescein staining in the cat model.Results: Gefarnate stimulated mucin-like glycoprotein secretion in conjunctival tissue in a dose-dependent manner. In the rabbit dry-eye model, application of gefarnate ointment to the eyes resulted in a dose-dependent decrease in rose bengal permeability in the cornea, with the effect being significant at concentrations of ≥0.3%. In the cat dry-eye model, application of gefarnate ointment resulted in a significant decrease in the corneal fluorescein staining score.Conclusion: These results suggest that gefarnate stimulates in vitro secretion of mucin-like glycoprotein in conjunctival tissue and ameliorates corneal epithelial damage in animal dry-eye models. Gefarnate may therefore be effective for treating dry eye.Keywords: gefarnate, fluorescein staining, rose bengal permeability, rabbit, cat, dry eye

Oxidative DNA damage in vitamin C-supplemented guinea pigs after intratracheal instillation of diesel exhaust particles

DEFF Research Database (Denmark)

Moller, P.; Daneshvar, B.; Loft, S.

2003-01-01

. The concentrations of ascorbate in liver, lung, and plasma were unaltered by the DEP exposure. The results indicate that in guinea pigs DEP causes oxidative DNA damage rather than bulky DNA adducts in the lung. Guinea pigs, which are similar to humans with respect to vitamin C metabolism, may serve as a new model...... for the study of oxidative damage induced by particulate matter. (C) 2003 Elsevier Science (USA). All rights reserved....

Oxidative stress, activity behaviour and body mass in captive parrots.

Science.gov (United States)

Larcombe, S D; Tregaskes, C A; Coffey, J; Stevenson, A E; Alexander, L G; Arnold, K E

2015-01-01

Many parrot species are kept in captivity for conservation, but often show poor reproduction, health and survival. These traits are known to be influenced by oxidative stress, the imbalance between the production of reactive oxygen species (ROS) and ability of antioxidant defences to ameliorate ROS damage. In humans, oxidative stress is linked with obesity, lack of exercise and poor nutrition, all of which are common in captive animals. Here, we tested whether small parrots (budgerigars, Melopsittacus undulatus) maintained in typical pet cages and on ad libitum food varied in oxidative profile, behaviour and body mass. Importantly, as with many birds held in captivity, they did not have enough space to engage in extensive free flight. Four types of oxidative damage, single-stranded DNA breaks (low-pH comet assay), alkali-labile sites in DNA (high-pH comet assay), sensitivity of DNA to ROS (H2O2-treated comet assay) and malondialdehyde (a byproduct of lipid peroxidation), were uncorrelated with each other and with plasma concentrations of dietary antioxidants. Without strenuous exercise over 28 days in a relatively small cage, more naturally 'active' individuals had more single-stranded DNA breaks than sedentary birds. High body mass at the start or end of the experiment, coupled with substantial mass gain, were all associated with raised sensitivity of DNA to ROS. Thus, high body mass in these captive birds was associated with oxidative damage. These birds were not lacking dietary antioxidants, because final body mass was positively related to plasma levels of retinol, zeaxanthin and α-tocopherol. Individuals varied widely in activity levels, feeding behaviour, mass gain and oxidative profile despite standardized living conditions. DNA damage is often associated with poor immunocompetence, low fertility and faster ageing. Thus, we have candidate mechanisms for the limited lifespan and fecundity common to many birds kept for conservation purposes.

Green Tea Polyphenols Ameliorate the Early Renal Damage Induced by a High-Fat Diet via Ketogenesis/SIRT3 Pathway

Directory of Open Access Journals (Sweden)

Weijie Yi

2017-01-01

Full Text Available Scope. Several reports in the literature have suggested the renoprotective effects of ketone bodies and green tea polyphenols (GTPs. Our previous study found that GTP consumption could elevate the renal expression of the ketogenic rate-limiting enzyme, which was decreased by a high-fat diet (HFD in rats. Here, we investigated whether ketogenesis can mediate renoprotection by GTPs against an HFD. Methods and Results. Wistar rats were fed a standard or HFD with or without GTPs for 18 weeks. The renal oxidative stress level, kidney function, renal expression, and activity levels of mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA synthase 2 (HMGCS2 and sirtuin 3(SIRT3 were detected. The increased renal oxidative stress and the loss of renal function induced by the HFD were ameliorated by GTPs. Renal ketogenesis and SIRT3 expression and activity levels, which were reduced by the HFD, were restored by GTPs. In vitro, HEK293 cells were transfected with the eukaryotic expression plasmid pcDNA HMGCS2. GTP treatment could upregulate HMGCS2 and SIRT3 expression. Although SIRT3 expression was not affected by HMGCS2 transfection, the 4-hydroxy-2-nonenal (4-HNE level and the acetyl-MnSOD (K122/MnSOD ratio were reduced in HMGCS2-transfected cells in the context of H2O2. Conclusion. The ketogenesis/SIRT3 pathway mediates the renoprotection of GTPs against the oxidative stress induced by an HFD.

Grape (Vitis vinifera) extracts protect against radiation-induced oxidative stress and DNA damage

International Nuclear Information System (INIS)

Singha, Indrani; Das, Subir Kumar; Saxena, S.; Gautam, S.

2016-01-01

Ionizing radiation (IR) causes oxidative stress through the overwhelming generation of reactive oxygen species (ROS) in the living cells leading further to the oxidative damage to biomolecules. Grapes (Vitis vinifera) contain several bioactive phytochemicals and are the richest source of antioxidant. In this study, we investigated and compared in vitro antioxidant activity and DNA damage protective property of the grape extracts of four different cultivars, including the Thompson seedless, Flame seedless, Kishmish chorni and Red globe. The activities of ascorbic acid oxidase and catalase significantly (p<0.01) differed among extracts within the same cultivar, while that of peroxidase and polyphenol oxidase did not differ significantly among extracts of any cultivar. In vitro antioxidant activities were assessed by ferric-reducing antioxidant power (FRAP) assay and ABTS. The superoxide radical-scavenging activity was higher in the seed as compared to the skin or pulp of the same cultivar. DNA damage was evaluated in acellular system using pBR322 plasmid relaxation. Grape extract was able to effectively scavenge free radicals in vitro. It could significantly prevent radiation-induced DNA damage. Furthermore, the protective action of grape depends on the source of extract and type of the cultivars. (author)

Oxidative damage to biological macromolecules in Prague bus drivers and garagemen: impact of air pollution and genetic polymorphisms.

Science.gov (United States)

Bagryantseva, Yana; Novotna, Bozena; Rossner, Pavel; Chvatalova, Irena; Milcova, Alena; Svecova, Vlasta; Lnenickova, Zdena; Solansky, Ivo; Sram, Radim J

2010-11-10

DNA integrity was investigated in the lymphocytes of 50 bus drivers, 20 garagemen and 50 controls using the comet assay with excision repair enzymes. In parallel, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 15-F(2t)-isoprostane levels in the urine and protein carbonyl levels in the plasma were assessed as markers of oxidative damage to DNA, lipids and proteins. Exposure to carcinogenic polycyclic aromatic hydrocarbons (cPAHs) and volatile compounds was measured by personal samplers for 48 and 24h, respectively, before the collection of biological specimens. Both exposed groups exhibited a higher levels of DNA instability and oxidative damage to biological macromolecules than the controls. The incidence of oxidized lesions in lymphocyte DNA, but not the urinary levels of 8-oxodG, correlated with exposure to benzene and triglycerides increased this damage. Oxidative damage to lipids and proteins was associated with exposure to cPAHs and the lipid peroxidation levels positively correlated with age and LDL cholesterol, and negatively with vitamin C. The carriers of at least one variant hOGG1 (Cys) allele tended to higher oxidative damage to lymphocyte DNA than those with the wild genotype, while XPD23 (Gln/Gln) homozygotes were more susceptible to the induction of DNA strand breaks. In contrast, GSTM1 null variant seemed to protect DNA integrity. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Lack of association of colonic epithelium telomere length and oxidative DNA damage in Type 2 diabetes under good metabolic control

Directory of Open Access Journals (Sweden)

Kennedy Hugh

2008-10-01

Full Text Available Abstract Background Telomeres are DNA repeat sequences necessary for DNA replication which shorten at cell division at a rate directly related to levels of oxidative stress. Critical telomere shortening predisposes to cell senescence and to epithelial malignancies. Type 2 diabetes is characterised by increased oxidative DNA damage, telomere attrition, and an increased risk of colonic malignancy. We hypothesised that the colonic mucosa in Type 2 diabetes would be characterised by increased DNA damage and telomere shortening. Methods We examined telomere length (by flow fluorescent in situ hybridization and oxidative DNA damage (flow cytometry of 8 – oxoguanosine in the colonic mucosal cells of subjects with type 2 diabetes (n = 10; mean age 62.2 years, mean HbA1c 6.9% and 22 matched control subjects. No colonic pathology was apparent in these subjects at routine gastrointestinal investigations. Results Mean colonic epithelial telomere length in the diabetes group was not significantly different from controls (10.6 [3.6] vs. 12.1 [3.4] Molecular Equivalent of Soluble Fluorochrome Units [MESF]; P = 0.5. Levels of oxidative DNA damage were similar in both T2DM and control groups (2.6 [0.6] vs. 2.5 [0.6] Mean Fluorescent Intensity [MFI]; P = 0.7. There was no significant relationship between oxidative DNA damage and telomere length in either group (both p > 0.1. Conclusion Colonic epithelium in Type 2 diabetes does not differ significantly from control colonic epithelium in oxidative DNA damage or telomere length. There is no evidence in this study for increased oxidative DNA damage or significant telomere attrition in colonic mucosa as a carcinogenic mechanism.

Replication stress and oxidative damage contribute to aberrant constitutive activation of DNA damage signalling in human gliomas

DEFF Research Database (Denmark)

Bartkova, J; Hamerlik, P; Stockhausen, Marie

2010-01-01

brain and grade II astrocytomas, despite the degree of DDR activation was higher in grade II tumors. Markers indicative of ongoing DNA replication stress (Chk1 activation, Rad17 phosphorylation, replication protein A foci and single-stranded DNA) were present in GBM cells under high- or low...... and indicate that replication stress, rather than oxidative stress, fuels the DNA damage signalling in early stages of astrocytoma development.......Malignant gliomas, the deadliest of brain neoplasms, show rampant genetic instability and resistance to genotoxic therapies, implicating potentially aberrant DNA damage response (DDR) in glioma pathogenesis and treatment failure. Here, we report on gross, aberrant constitutive activation of DNA...

[Oxidative damage effects induced by CdTe quantum dots in mice].

Science.gov (United States)

Xie, G Y; Chen, W; Wang, Q K; Cheng, X R; Xu, J N; Huang, P L

2017-07-20

Objective: To investigate Oxidative damage effects induced by CdTe Quantum Dots (QDs) in mice. Methods: 40 ICR mice were randomly divided into 5 groups: one control group (normal saline) ; four CdTe QDs (exposed by intravenous injection of 0.2 ml of CdTe QDs at the concentration of 0、0.5、5.0、50.0 and 500.0 nmol/ml respectively) . After 24 h, the mice were decapitated and the blood was collected for serum biochemically indexes、hematology indexes, the activities of SOD、GSH-Px and the concentration of MDA were all detected. Results: The results showed in the four CdTe QDs exposure groups, the level of CRE、PLT and the concentration of MDA were all significantly lower than those of the control group ( P control group ( P <0.01) . Conclusion: It was suggested that CdTe QDs at 0.5 nmol/ml could induce Oxidative damage effects in mice.

Effect of Clonidine (an Antihypertensive Drug Treatment on Oxidative Stress Markers in the Heart of Spontaneously Hypertensive Rats

Directory of Open Access Journals (Sweden)

Nik Syamimi Nik Yusoff

2013-01-01

Full Text Available Hypertension is a risk factor for several cardiovascular diseases and oxidative stress suggested to be involved in the pathophysiology. Antihypertensive drug Clonidine action in ameliorating oxidative stress was not well studied. Therefore, this study investigate the effect of Clonidine on oxidative stress markers and nitric oxide (NO in SHR and nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME administered SHR. Male rats were divided into four groups [SHR, SHR+Clonidine (SHR-C, SHR+L-NAME, SHR+Clonidine+L-NAME(SHRC+L-NAME]. Rats (SHRC were administered with Clonidine (0.5 mg kg−1 day−1 from 4 weeks to 28 weeks in drinking water and L-NAME (25 mg kg−1 day−1 from 16 weeks to 28 weeks to SHRC+L-NAME. Systolic blood pressure (SBP was measured. At the end of 28 weeks, all rats were sacrificed and in their heart homogenate, oxidative stress parameters and NO was assessed. Clonidine treatment significantly enhanced the total antioxidant status (TAS (P<0.001 and reduced the thibarbituric acid reactive substances (TBARS (P<0.001 and protein carbonyl content (PCO (P<0.05. These data suggest that oxidative stress is involved in the hypertensive organ damage and Clonidine not only lowers the SBP but also ameliorated the oxidative stress in the heart of SHR and SHR+L-NAME.

Oxidative damage and cell-programmed death induced in Zea mays L. by allelochemical stress.

Science.gov (United States)

Ciniglia, Claudia; Mastrobuoni, Francesco; Scortichini, Marco; Petriccione, Milena

2015-05-01

The allelochemical stress on Zea mays was analyzed by using walnut husk washing waters (WHWW), a by-product of Juglans regia post-harvest process, which possesses strong allelopathic potential and phytotoxic effects. Oxidative damage and cell-programmed death were induced by WHWW in roots of maize seedlings. Treatment induced ROS burst, with excess of H2O2 content. Enzymatic activities of catalase were strongly increased during the first hours of exposure. The excess in malonildialdehyde following exposure to WHWW confirmed that oxidative stress severely damaged maize roots. Membrane alteration caused a decrease in NADPH oxidase activity along with DNA damage as confirmed by DNA laddering. The DNA instability was also assessed through sequence-related amplified polymorphism assay, thus suggesting the danger of walnut processing by-product and focusing the attention on the necessity of an efficient treatment of WHWW.

Ameliorating effects of traditional Chinese medicine preparation, Chinese materia medica and active compounds on ischemia/reperfusion-induced cerebral microcirculatory disturbances and neuron damage

Science.gov (United States)

Sun, Kai; Fan, Jingyu; Han, Jingyan

2015-01-01

Ischemic stroke and ischemia/reperfusion (I/R) injury induced by thrombolytic therapy are conditions with high mortality and serious long-term physical and cognitive disabilities. They have a major impact on global public health. These disorders are associated with multiple insults to the cerebral microcirculation, including reactive oxygen species (ROS) overproduction, leukocyte adhesion and infiltration, brain blood barrier (BBB) disruption, and capillary hypoperfusion, ultimately resulting in tissue edema, hemorrhage, brain injury and delayed neuron damage. Traditional Chinese medicine (TCM) has been used in China, Korea, Japan and other Asian countries for treatment of a wide range of diseases. In China, the usage of compound TCM preparation to treat cerebrovascular diseases dates back to the Han Dynasty. Even thousands of years earlier, the medical formulary recorded many classical prescriptions for treating cerebral I/R-related diseases. This review summarizes current information and underlying mechanisms regarding the ameliorating effects of compound TCM preparation, Chinese materia medica, and active components on I/R-induced cerebral microcirculatory disturbances, brain injury and neuron damage. PMID:26579420

Green Synthesized Zinc Oxide (ZnO Nanoparticles Induce Oxidative Stress and DNA Damage in Lathyrus sativus L. Root Bioassay System

Directory of Open Access Journals (Sweden)

Kamal K. Panda

2017-05-01

Full Text Available Zinc oxide nanoparticles (ZnONP-GS were synthesised from the precursor zinc acetate (Zn(CH3COO2 through the green route using the milky latex from milk weed (Calotropis gigantea L. R. Br by alkaline precipitation. Formation of the ZnONP-GS was monitored by UV-visible spectroscopy followed by characterization and confirmation by energy-dispersive X-ray spectroscopy (EDX, transmission electron microscopy (TEM, and X-ray diffraction (XRD. Both the ZnONP-GS and the commercially available ZnONP-S (Sigma-Aldrich and cationic Zn2+ from Zn(CH3COO2 were tested in a dose range of 0–100 mg·L−1 for their potency (i to induce oxidative stress as measured by the generation reactive oxygen species (ROS: O2•−, H2O2 and •OH, cell death, and lipid peroxidation; (ii to modulate the activities of antioxidant enzymes: catalase (CAT, superoxide dismutase (SOD, guaiacol peroxidase (GPX, and ascorbate peroxidase (APX; and (iii to cause DNA damage as determined by Comet assay in Lathyrus sativus L. root bioassay system. Antioxidants such as Tiron and dimethylthiourea significantly attenuated the ZnONP-induced oxidative and DNA damage, suggesting the involvement of ROS therein. Our study demonstrated that both ZnONP-GS and ZnONP-S induced oxidative stress and DNA damage to a similar extent but were significantly less potent than Zn2+ alone.

Personal exposure to ultrafine particles and oxidative DNA damage

DEFF Research Database (Denmark)

Vinzents, Peter S; Møller, Peter; Sørensen, Mette

2005-01-01

10), nitrous oxide, nitrogen dioxide, carbon monoxide, and/or number concentration of UFPs at urban background or busy street monitoring stations was not a significant predictor of DNA damage, although personal UFP exposure was correlated with urban background concentrations of CO and NO2...... the morning after exposure measurement. Cumulated outdoor and cumulated indoor exposures to UFPs each were independent significant predictors of the level of purine oxidation in DNA but not of strand breaks. Ambient air concentrations of particulate matter with an aerodynamic diameter of ..., particularly during bicycling in traffic. The results indicate that biologic effects of UFPs occur at modest exposure, such as that occurring in traffic, which supports the relationship of UFPs and the adverse health effects of air pollution....

Autophagy induction by SIRT6 is involved in oxidative stress-induced neuronal damage

Directory of Open Access Journals (Sweden)

Jiaxiang Shao

2016-03-01

Full Text Available Abstract SIRT6 is a NAD+-dependent histone deacetylase and has been implicated in the regulation of genomic stability, DNA repair, metabolic homeostasis and several diseases. The effect of SIRT6 in cerebral ischemia and oxygen/glucose deprivation (OGD has been reported, however the role of SIRT6 in oxidative stress damage remains unclear. Here we used SH-SY5Y neuronal cells and found that overexpression of SIRT6 led to decreased cell viability and increased necrotic cell death and reactive oxygen species (ROS production under oxidative stress. Mechanistic study revealed that SIRT6 induced autophagy via attenuation of AKT signaling and treatment with autophagy inhibitor 3-MA or knockdown of autophagy-related protein Atg5 rescued H2O2-induced neuronal injury. Conversely, SIRT6 inhibition suppressed autophagy and reduced oxidative stress-induced neuronal damage. These results suggest that SIRT6 might be a potential therapeutic target for neuroprotection.

The Role of Calcium in Ameliorating the Oxidative Stress of Fluoride in Rats.

Science.gov (United States)

Mohamed, N E

2016-03-01

The present study was carried out to investigate the effects of fluoride toxicity on some biochemical, hormonal, and histological parameters of female rats and the protective role of calcium against such effects. Adult female albino rats were divided into five groups; control group received distilled water for 60 days, calcium group received calcium carbonate with dose of 50 mg/kg three times per week for 60 days, fluoride group received sodium fluoride with dose of 20 mg/kg three times per week for 60 days, calcium + fluoride group received calcium carbonate (50 mg/kg) then after 2 h received sodium fluoride (20 mg/kg) three times per week for 60 days, and fluoride + calcium group received sodium fluoride (20 mg/kg) three times per week for 30 days then received calcium carbonate (50 mg/kg) three times per week for another 30 days. The results showed that the levels of thiobarbituric acid reactive substances, urea, creatinine, alkaline phosphatase, triiodothyronine, thyroxine, parathormone, phosphorous, magnesium, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma glutamyl transferase were significantly increased in rats treated with fluoride while serum estradiol, calcium, and organ glutathione were significantly decreased. The histological examination of the femur bone revealed that fluoride treatment induced thinning of bone trabeculae with wilding of marrow space, demineralization, and loss of trabeculae interconnections. Also, the histological examination of hepatic and renal tissues of fluoride-treated rats showed some damages in these tissues while administration of calcium carbonate for 30 or 60 days during fluoride treatment minimized such damages. It could be concluded that administration of calcium to female rats can ameliorate the hazardous effects of fluoride observed in the biochemical, hormonal, and histological parameters.

Role of antioxidant therapy in ameliorating the side effects of post-operative radiotherapy on genetic material of cancer cervix patients

International Nuclear Information System (INIS)

Korraa, S.; Elmaghraby, T.; Arian, F.; Mahfouz, M.

2003-01-01

The oxidative stress found in cancer patients and radiotherapy was resulted from the increased production of oxidants in the body and the inefficiency of endogenous antioxidant system to eliminate such oxidants. The present study was carried out to investigated whether supplementation of cancer cervix patients during radiotherapy with antioxidants can ameliorate the damaging effects of radiation on DNA of circulating lymphocytes or not. Accordingly, apoptosis, DNA-fragmentation, lipid peroxidation and the frequency of micronuclei among cancer cervix patient undergoing post-operative radiotherapy (n=40) were measured with and without the administration course of antioxidant antox (including 60 mg vitamin C 10 mg vitamin E, 1000 U I vitamin A and 50 mg selenium). Patients were divided into 2 groups each of 20 patients. The first group was administered the antioxidant antox, 200 mg per day, during radiotherapy and one week more post-cessation of radiotherapy , while the second group did not supplemented with antox. All parameters were investigated in a control group of 20 normal healthy women and in the 40 patient ones

Fisetin Protects DNA Against Oxidative Damage and Its Possible Mechanism.

Science.gov (United States)

Wang, Tingting; Lin, Huajuan; Tu, Qian; Liu, Jingjing; Li, Xican

2016-06-01

The paper tries to assess the protective effect of fisetin against •OH-induced DNA damage, then to investigate the possible mechanism. The protective effect was evaluated based on the content of malondialdehyde (MDA). The possible mechanism was analyzed using various antioxidant methods in vitro, including •OH scavenging (deoxyribose degradation), •O2 (-) scavenging (pyrogallol autoxidation), DPPH• scavenging, ABTS•(+) scavenging, and Cu(2+)-reducing power assays. Fisetin increased dose-dependently its protective percentages against •OH-induced DNA damage (IC50 value =1535.00±29.60 µM). It also increased its radical-scavenging percentages in a dose-dependent manner in various antioxidants assays. Its IC50 values in •OH scavenging, •O2(-) scavenging, DPPH• scavenging, ABTS•(+) scavenging, and Cu(2+)-reducing power assays, were 47.41±4.50 µM, 34.05±0.87 µM, 9.69±0.53 µM, 2.43±0.14 µM, and 1.49±0.16 µM, respectively. Fisetin can effectively protect DNA against •OH-induced oxidative damage possibly via reactive oxygen species (ROS) scavenging approach, which is assumed to be hydrogen atom (H•) and/or single electron (e) donation (HAT/SET) pathways. In the HAT pathway, the 3',4'-dihydroxyl moiety in B ring of fisetin is thought to play an important role, because it can be ultimately oxidized to a stable ortho-benzoquinone form.

[Endonuclease modified comet assay for oxidative DNA damage induced by detection of genetic toxicants].

Science.gov (United States)

Zhao, Jian; Li, Hongli; Zhai, Qingfeng; Qiu, Yugang; Niu, Yong; Dai, Yufei; Zheng, Yuxin; Duan, Huawei

2014-03-01

The aim of this study was to investigate the use of the lesion-specific endonucleases-modified comet assay for analysis of DNA oxidation in cell lines. DNA breaks and oxidative damage were evaluated by normal alkaline and formamidopyrimidine-DNA-glycosylase (FPG) modified comet assays. Cytotoxicity were assessed by MTT method. The human bronchial epithelial cell (16HBE) were treated with benzo (a) pyrene (B(a)P), methyl methanesulfonate (MMS), colchicine (COL) and vincristine (VCR) respectively, and the dose is 20 µmol/L, 25 mg/ml, 5 mg/L and 0.5 mg/L for 24 h, respectively. Oxidative damage was also detected by levels of reactive oxygen species in treated cells. Four genotoxicants give higher cytotoxicity and no significant changes on parameters of comet assay treated by enzyme buffer. Cell survival rate were (59.69 ± 2.60) %, (54.33 ± 2.81) %, (53.11 ± 4.00) %, (51.43 ± 3.92) % in four groups, respectively. There was the direct DNA damage induced by test genotoxicants presented by tail length, Olive tail moment (TM) and tail DNA (%) in the comet assay. The presence of FPG in the assays increased DNA migration in treated groups when compared to those without it, and the difference was statistically significant which indicated that the clastogen and aneugen could induce oxidative damage in DNA strand. In the three parameters, the Olive TM was changed most obviously after genotoxicants treatment. In the contrast group, the Olive TM of B(a) P,MMS, COL,VCR in the contrast groups were 22.99 ± 17.33, 31.65 ± 18.86, 19.86 ± 9.56 and 17.02 ± 9.39, respectively, after dealing with the FPG, the Olive TM were 34.50 ± 17.29, 43.80 ± 10.06, 33.10 ± 12.38, 28.60 ± 10.53, increased by 58.94%, 38.48%, 66.86% and 68.21%, respectively (t value was 3.91, 3.89, 6.66 and 3.87, respectively, and all P comet assay appears more specific for detecting oxidative DNA damage induced by genotoxicants exposure, and the application of comet assay will be expanded. The endonuclease

Oxidatively damaged DNA in animals exposed to particles

DEFF Research Database (Denmark)

Møller, Peter; Danielsen, Pernille Høgh; Jantzen, Kim

2013-01-01

on optimal methods. The majority of studies have used single intracavitary administration or inhalation with dose rates exceeding the pulmonary overload threshold, resulting in cytotoxicity and inflammation. It is unclear whether this is relevant for the much lower human exposure levels. Still...... not be equivocally determined. Roles of cytotoxicity or inflammation for oxidatively induced DNA damage could not be documented or refuted. Studies on exposure to particles in the gastrointestinal tract showed consistently increased levels of 8-oxo-7,8-dihydroguanine in the liver. Collectively, there is evidence...

Administration of red ginseng ameliorates memory decline in aged mice.

Science.gov (United States)

Lee, Yeonju; Oh, Seikwan

2015-07-01

It has been known that ginseng can be applied as a potential nutraceutical for memory impairment; however, experiments with animals of old age are few. To determine the memory enhancing effect of red ginseng, C57BL/6 mice (21 mo old) were given experimental diet pellets containing 0.12% red ginseng extract (approximately 200 mg/kg/d) for 3 mo. Young and old mice (4 mo and 21 mo old, respectively) were used as the control group. The effect of red ginseng, which ameliorated memory impairment in aged mice, was quantified using Y-maze test, novel objective test, and Morris water maze. Red ginseng ameliorated age-related declines in learning and memory in older mice. In addition, red ginseng's effect on the induction of inducible nitric oxide synthase and proinflammatory cytokines was investigated in the hippocampus of aged mice. Red ginseng treatment suppressed the production of age-processed inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-α, and interleukin-1β expressions. Moreover, it was observed that red ginseng had an antioxidative effect on aged mice. The suppressed glutathione level in aged mice was restored with red ginseng treatment. The antioxidative-related enzymes Nrf2 and HO-1 were increased with red ginseng treatment. The results revealed that when red ginseng is administered over long periods, age-related decline of learning and memory is ameliorated through anti-inflammatory activity.

Oxidative Damage, Inflammation, and Toll-Like Receptor 4 Pathway Are Increased in Preeclamptic Patients: A Case-Control Study

Directory of Open Access Journals (Sweden)

Fabiana C. B. Bernardi

2012-01-01

Full Text Available Problem. There was no direct correlation between plasma and placental oxidative damage parameters and inflammation and evidence of TLR4 pathway activation in the placenta in preeclamptic (PE patients. Method of Study. 33 PE patients and 33 normotensive pregnant women were included. The maternal section of the placenta and blood were collected to the determination of oxidative damage markers (thiobarbituric acid reactive species and protein carbonyls, inflammatory response (interleukin-6 and myeloperoxidase activity, and activation of the TLR-4-NF-kB pathway. Results. An increase of IL-6 levels in both plasma and placenta was observed, but myeloperoxidase activity was not significantly different comparing the groups. Oxidative damage parameters were increased in plasma and placenta in PE patients. A significant increase of the protein levels of TLR-4 and NF-kB was observed in the placenta. Conclusion. The TLR4-NF-kB pathway is upregulated in PE, probably generating local and systemic inflammatory response that is followed by local and systemic oxidative damage.

Photo-oxidative damage to isolated rat liver mitochondria induced by phenothiazines

Directory of Open Access Journals (Sweden)

T. RODRIGUES

2009-01-01

Full Text Available

Photosensitization is a well-known side-effect of phenothiazines that could involve photochemically promoted oxidative damage to mitochondria, leading to the impairment of metabolic functions and apoptosis. In this work, for the first time, we investigated the effects of photoexcited thioridazine (TR, trifluoperazine (TFP and fluphenazine (FP on isolated rat liver mitochondria. Under UV irradiation, the presence of these phenothiazines led to a dose-dependent lack of the respiratory control ratio. These effects were not accompanied by significant swelling and oxidation of protein thiol groups but were accompanied by lipid peroxidation. Lycopene and sorbate, well-known quenchers of singlet oxygen and triplet species, respectively, were ineffective at protecting mitochondrial lipids against the damage promoted by the excited phenothiazines, suggesting that photochemically-produced cation radicals were the prooxidant species. Corroborating this proposal, butylated hydroxytoluene (BHT completely inhibited the lipid peroxidation induced by UV irradiation in the presence of phenothiazines. These novel results make a significant contribution to the understanding of the photochemical properties of phenothiazines in biological systems. Keywords: Trifluoperazine, thioridazine, fluphenazine, rat liver mitochondria, oxidative stress, photochemistry, photodamage, respiratory chain.

Extract of Bauhinia vahlii Shows Antihyperglycemic Activity, Reverses Oxidative Stress, and Protects against Liver Damage in Streptozotocin-induced Diabetic Rats

Science.gov (United States)

Elbanna, Ahmed H.; Nooh, Mohammed M.; Mahrous, Engy A.; Khaleel, Amal E.; Elalfy, Taha S.

2017-01-01

Background: Several studies have affirmed the effectiveness of some Bauhinia plants as antihyperglycemic agents. Objective: We investigated the possible effect of Bauhinia vahlii leaves extract in reducing hyperglycemia and reversing signs of organ damage associated with diabetes in streptozotocin (STZ) rat model. Materials and Methods: Both polar fraction of the B. vahlii leaves (defatted ethanolic extract [DEE]) and nonpolar fraction (n-hexane extract) were evaluated in vitro for α-glucosidase inhibition and 2,2-diphenyl-1-picrylhydrazyl radical scavenging potential. DEE was selected for further in vivo studies and was administered at two doses, i.e., 150 or 300 mg/kg to STZ-diabetic rats for 4 weeks. Results: Only DEE exhibited in vitro antioxidant and antihyperglycemic activities and its oral administration at both dose levels resulted in significant reduction in fasting blood glucose and glycated hemoglobin. Furthermore, signs of oxidative stress as indicated by hepatic reduced glutathione, nitric oxide, and malondialdehyde levels were completely reversed. In addition, histopathological examination and measurement of serum aspartate transaminase and alanine transaminase levels showed that DEE protected the liver from signs of liver pathogenesis when compared to diabetic untreated animals and those treated with metformin. Phytochemical analysis of DEE showed high flavonoids content with quercitrin as the major constituent along with other quercetin glycosides. Conclusion: This study strongly highlights the possible beneficial effect of B. vahlii leaves extract in relieving hyperglycemia and liver damage in STZ-diabetic rats and recommends further investigation of the value of quercetin derivatives in controlling diabetes and ameliorating liver damage associated with it. SUMMARY The polar fraction of the Bauhinia vahlii leaves (defatted ethanolic extract [DEE]) exhibited both in vitro antioxidant activity in 2,2-diphenyl-1-picrylhydrazyl scavenging assay and

Potential Damage to Modern Building Materials from 21st Century Air Pollution

Directory of Open Access Journals (Sweden)

Peter Brimblecombe

2010-01-01

Full Text Available The evolution of damage to building materials has been estimated for the 21st century, with a particular focus on aluminum, zinc, copper, plastic, paint, and rubber in urban areas. We set idealized air pollution and climates to represent London and Prague across the period 1950–2100. Environmental parameters were used to estimate future recession, corrosion, and loss of properties through published damage or dose-response functions. The 21st century seems to provide a less aggressive environment for stone and metals than recent times. Improvements in air quality are the most relevant drivers for this amelioration. Changes in climate predicted for the 21st century do not alter this picture. On the other hand, polymeric materials, plastic, paint, and rubber might show slightly increased rates of degradation, to some extent the result of enhanced oxidant concentrations, but also the possibility of contributions from more solar radiation.

CaNa2EDTA chelation attenuates cell damage in workers exposed to lead--a pilot study.

Science.gov (United States)

Čabarkapa, A; Borozan, S; Živković, L; Stojanović, S; Milanović-Čabarkapa, M; Bajić, V; Spremo-Potparević, B

2015-12-05

Lead induced oxidative cellular damage and long-term persistence of associated adverse effects increases risk of late-onset diseases. CaNa2EDTA chelation is known to remove contaminating metals and to reduce free radical production. The objective was to investigate the impact of chelation therapy on modulation of lead induced cellular damage, restoration of altered enzyme activities and lipid homeostasis in peripheral blood of workers exposed to lead, by comparing the selected biomarkers obtained prior and after five-day CaNa2EDTA chelation intervention. The group of smelting factory workers diagnosed with lead intoxication and current lead exposure 5.8 ± 1.2 years were administered five-day CaNa2EDTA chelation. Elevated baseline activity of antioxidant enzymes Cu, Zn-SOD and CAT as well as depleted thiols and increased protein degradation products-carbonyl groups and nitrites, pointing to Pb induced oxidative damage, were restored toward normal values following the treatment. Lead showed inhibitor potency on both RBC AChE and BChE in exposed workers, and chelation re-established the activity of BChE, while RBC AChE remained unaffected. Also, genotoxic effect of lead detected in peripheral blood lymphocytes was significantly decreased after therapy, exhibiting 18.9% DNA damage reduction. Administration of chelation reversed the depressed activity of serum PON 1 and significantly decreased lipid peroxidation detected by the post-chelation reduction of MDA levels. Lactate dehydrogenase LDH1-5 isoenzymes levels showed evident but no significant trend of restoring toward normal control values following chelation. CaNa2EDTA chelation ameliorates the alterations linked with Pb mediated oxidative stress, indicating possible benefits in reducing health risks associated with increased oxidative damage in lead exposed populations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Nickel exposure induces oxidative damage to mitochondrial DNA in Neuro2a cells: the neuroprotective roles of melatonin.

Science.gov (United States)

Xu, Shang-Cheng; He, Min-Di; Lu, Yong-Hui; Li, Li; Zhong, Min; Zhang, Yan-Wen; Wang, Yuan; Yu, Zheng-Ping; Zhou, Zhou

2011-11-01

Recent studies suggest that oxidative stress and mitochondrial dysfunction play important roles in the neurotoxicity of nickel. Because mitochondrial DNA (mtDNA) is highly vulnerable to oxidative stress and melatonin can efficiently protect mtDNA against oxidative damage in various pathological conditions, the aims of this study were to determine whether mtDNA oxidative damage was involved in the neurotoxicity of nickel and to assay the neuroprotective effects of melatonin in mtDNA. In this study, we exposed mouse neuroblastoma cell lines (Neuro2a) to different concentrations of nickel chloride (NiCl(2), 0.125, 0.25, and 0.5 mm) for 24 hr. We found that nickel significantly increased reactive oxygen species (ROS) production and mitochondrial superoxide levels. In addition, nickel exposure increased mitochondrial 8-hydroxyguanine (8-OHdG) content and reduced mtDNA content and mtDNA transcript levels. Consistent with this finding, nickel was found to destroy mtDNA nucleoid structure and decrease protein levels of Tfam, a key protein component for nucleoid organization. However, all the oxidative damage to mtDNA induced by nickel was efficiently attenuated by melatonin pretreatment. Our results suggest that oxidative damage to mtDNA may account for the neurotoxicity of nickel. Melatonin has great pharmacological potential in protecting mtDNA against the adverse effects of nickel in the nervous system. © 2011 John Wiley & Sons A/S.

Ultrafine titanium dioxide particles in the absence of photoactivation can induce oxidative damage to human bronchial epithelial cells

International Nuclear Information System (INIS)

Gurr, J.-R.; Wang, Alexander S.S.; Chen, C.-H.; Jan, K.-Y.

2005-01-01

Ultrafine titanium dioxide (TiO 2 ) particles have been shown to exhibit strong cytotoxicity when exposed to UVA radiation, but are regarded as a biocompatible material in the absence of photoactivation. In contrast to this concept, the present results indicate that anatase-sized (10 and 20 nm) TiO 2 particles in the absence of photoactivation induced oxidative DNA damage, lipid peroxidation, and micronuclei formation, and increased hydrogen peroxide and nitric oxide production in BEAS-2B cells, a human bronchial epithelial cell line. However, the treatment with anatase-sized (200 and >200 nm) particles did not induce oxidative stress in the absence of light irradiation; it seems that the smaller the particle, the easier it is for the particle to induce oxidative damage. The photocatalytic activity of the anatase form of TiO 2 was reported to be higher than that of the rutile form. In contrast to this notion, the present results indicate that rutile-sized 200 nm particles induced hydrogen peroxide and oxidative DNA damage in the absence of light but the anatase-sized 200 nm particles did not. In total darkness, a slightly higher level of oxidative DNA damage was also detected with treatment using an anatase-rutile mixture than with treatment using either the anatase or rutile forms alone. These results suggest that intratracheal instillation of ultrafine TiO 2 particles may cause an inflammatory response

Nitroxides are more efficient inhibitors of oxidative damage to calf skin collagen than antioxidant vitamins.

Science.gov (United States)

Venditti, Elisabetta; Scirè, Andrea; Tanfani, Fabio; Greci, Lucedio; Damiani, Elisabetta

2008-01-01

Reactive oxygen species generated upon UV-A exposure appear to play a major role in dermal connective tissue transformations including degradation of skin collagen. Here we investigate on oxidative damage to collagen achieved by exposure to (i) UV-A irradiation and to (ii) AAPH-derived radicals and on its possible prevention using synthetic and natural antioxidants. Oxidative damage was identified through SDS-PAGE, circular dichroism spectroscopy and quantification of protein carbonyl residues. Collagen (2 mg/ml) exposed to UV-A and to AAPH-derived radicals was degraded in a time- and dose-dependent manner. Upon UV-A exposure, maximum damage was observable at 730 kJ/m2 UV-A, found to be equivalent to roughly 2 h of sunshine, while exposure to 5 mM AAPH for 2 h at 50 degrees C lead to maximum collagen degradation. In both cases, dose-dependent protection was achieved by incubation with muM concentrations of nitroxide radicals, where the extent of protection was shown to be dictated by their structural differences whereas the vitamins E and C proved less efficient inhibitors of collagen damage. These results suggest that nitroxide radicals may be able to prevent oxidative injury to dermal tissues in vivo alternatively to commonly used natural antioxidants.

Female plumage colour influences seasonal oxidative damage and testosterone profiles in a songbird.

Science.gov (United States)

Vitousek, Maren N; Stewart, Rosemary A; Safran, Rebecca J

2013-10-23

Across diverse taxa, morphological traits mediate social interactions and mate selection. Physiological constraints on signal elaboration have been widely documented, but the potential for trait display to influence physiological state remains poorly understood. We tested for the presence of causal links between ventral plumage colour-a trait known to covary with reproductive performance-and physiological measures in female North American barn swallows, Hirundo rustica erythrogaster. Naturally darker swallows have lower levels of plasma oxidative damage. Females manipulated to display darker ventral plumage during reproduction rapidly decreased oxidative damage, adopting the physiological state of naturally darker individuals. These results support the presence of a social mechanism that links static plumage traits with the physiological state of their bearer during trait advertisement, long after the completion of signal development.

Sulfotanshinone IIA Sodium Ameliorates Glucose Peritoneal Dialysis Solution-Induced Human Peritoneal Mesothelial Cell Injury via Suppression of ASK1-P38-mediated Oxidative Stress

Directory of Open Access Journals (Sweden)

Yao Zhou

2018-05-01

Full Text Available Background/Aims: Long-term use of high-glucose peritoneal dialysis solution (PDS induces peritoneal mesothelial cell (PMC injury, peritoneal dysfunction, and peritoneal dialysis (PD failure in patients with end-stage renal disease. How to preserve PMCs in PD is a major challenge for nephrologists worldwide. In this study, we aimed to elucidate the efficacy and mechanisms of sulfotanshinone IIA sodium (Tan IIa in ameliorating high-glucose PDS-induced human PMC injury. Methods: The human PMC line HMrSV5 was incubated with 4.25% PDS in vitro to mimic the high-glucose conditions in PD. Cellular viability was measured by Cell Counting Kit 8. Generation of superoxide and reactive oxygen species (ROS was assessed using a Total ROS/Superoxide Detection Kit. Oxidative modification of protein was evaluated by OxyBlot Protein Oxidation Detection Kit. TUNEL (dT-mediated dUTP nick end labeling assay and DAPI (4,6-diamidino-2-phenylindole staining were used to evaluate apoptosis. Western blot analysis was performed to evaluate the efficacy and mechanisms of Tan IIa. Results: Tan IIa protected PMCs against PDS-induced injury as evidenced by alleviating changes in morphology and loss of cell viability. Consistent with their antioxidant properties, N-acetyl-L-cysteine (NAC and Tan IIa suppressed superoxide and ROS production, protein oxidation, and apoptosis elicited by PDS. Apoptosis signal-regulating kinase 1 (ASK1-p38 signaling was activated by PDS. Both Tan IIa and NAC suppressed ASK1 and p38 phosphorylation elicited by PDS. Moreover, genetic downregulation of ASK1 ameliorated cell injury and inhibited the phosphorylation of p38 and activation of caspase 3. Conclusion: Tan IIa protects PMCs against PDS-induced oxidative injury through suppression of ASK1-p38 signaling.

Assessment of evidence for nanosized titanium dioxide-generated DNA strand breaks and oxidatively damaged DNA in cells and animal models

DEFF Research Database (Denmark)

Møller, Peter; Jensen, Ditte Marie; Wils, Regitze Sølling

2017-01-01

Nanosized titanium dioxide (TiO2) has been investigated in numerous studies on genotoxicity, including comet assay endpoints and oxidatively damaged DNA in cell cultures and animal models. The results have been surprisingly mixed, which might be attributed to physico-chemical differences...... culture studies also demonstrate increased levels of oxidatively damaged DNA after exposure to TiO2. There are relatively few studies on animal models where DNA strand breaks and oxidatively damaged DNA have been tested with reliable methods. Collectively, this review shows that exposure to nanosized TiO2...... of the tested TiO2. In the present review, we assess the role of certain methodological issues and publication bias. The analysis shows that studies on DNA strand breaks without proper assay controls or very low intra-group variation tend to show statistically significant effects. Levels of oxidatively damaged...

2- and 4-Aminobiphenyls induce oxidative DNA damage in human hepatoma (Hep G2) cells via different mechanisms

International Nuclear Information System (INIS)

Wang Shuchi; Chung, Jing-Gung; Chen, C.-H.; Chen, S.-C.

2006-01-01

4-Aminobiphenyl (4-ABP) and its analogue, 2-aminobiphenyl (2-ABP), were examined for their ability to induce oxidative DNA damage in Hep G2 cells. Using the alkaline comet assay, we showed that 2-ABP and 4-ABP (25-200 μM) were able to induce the DNA damage in Hep G2 cells. With both compounds, formation of intracellular reactive oxygen species (ROS) was detected using flow cytometry analysis. Post-treatment of 2-ABP and 4-ABP-treated cells by endonuclease III (Endo III) or formamidopyrimidine-DNA glycosylase (Fpg) to determine the formation of oxidized pyrimidines or oxidized purines showed a significant increase of the extent of DNA migration. This indicated that oxidative DNA damage occurs in Hep G2 cells after exposure to 2-ABP and 4-ABP. This assumption was further substantiated by the fact that the spin traps, 5,5-dimethyl-pyrroline-N-oxide (DMPO) and N-tert-butyl-α-phenylnitrone (PBN), decreased DNA damage significantly. Furthermore, addition of the catalase (100 U/ml) caused a decrease in the DNA damage induced by 2-ABP or 4-ABP, indicating that H 2 O 2 is involved in ABP-induced DNA damage. Pre-incubation of the cells with the iron chelator desferrioxamine (DFO) (1 mM) and with the copper chelator neocupronine (NC) (100 μM) also decreased DNA damage in cells treated with 200 μM 2-ABP or 200 μM 4-ABP, while the calcium chelator {1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid acetoxymethyl ester}(BAPTA/AM) (10 μM) decreased only DNA strand breaks in cells exposed to 4-ABP. This suggested that ions are involved in the formation of DNA strand breaks. Using RT-PCR and Western blotting, lower inhibition of the expression of the OGG1 gene and of the OGG1 protein was observed in cells treated with 4-ABP, and 2-ABP-treated cells showed a marked reduction in the expression of OGG1 gene and OGG1 protein. Taken together, our finding indicated the mechanisms of induced oxidative DNA damage in Hep G2 cell by 2-ABP and 4-ABP are different, although both

To Analyze the Amelioration of Phenobarbital Induced Oxidative Stress by Erucin, as Indicated by Biochemical and Histological Alterations.

Science.gov (United States)

Arora, Rohit; Bhushan, Sakshi; Kumar, Rakesh; Mannan, Rahul; Kaur, Pardeep; Singh, Bikram; Sharma, Ritika; Vig, Adarsh Pal; Singh, Balbir; Singh, Amrit Pal; Arora, Saroj

2016-01-01

Phenobarbital is a commonly employed antidepressant and anti-epileptic drug. The cancer promoting activity of this genotoxic xenobiotic is often ignored. It is responsible for oxidative stress leading to modulation in xenobiotic and antioxidative enzymes. Glucosinolates and more specifically their hydrolytic products are known for their antioxidative and anticancer activities. The present study involves the analysis of hepatoprotective effect of erucin (isolated from Eruca sativa (Mill.) Thell.) against phenobarbital mediated hepatic damage in male wistar rats. The liver homogenate was analyzed for oxidative stress (superoxide dismutase, catalase, guaiacol peroxidase, ascorbate peroxidase, glutathione reductase and lactate dehydrogenase), other oxidative parameters (thiobarbituric acid reactive species, conjugated dienes and lipid hydroperoxide), phase I enzymes (NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, cytochrome P420, cytochrome P450 and cytochrome b5), phase II enzymes (γ-glutamyl transpeptidase, DT-diaphorase and glutathione-S-transferase), serum parameters (alkaline phosphatase, serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, direct bilirubin and total bilirubin) and certain histological parameters. Erucin accorded protection from phenobarbital induced hepatic damage by normalizing antioxidative enzymes, other oxidative parameters, phase I, II, and serum parameters. Erucin, an analogue of sulforaphane has the potential to act as an anticancer agent by regulating various biochemical parameters.

NEIL2 protects against oxidative DNA damage induced by sidestream smoke in human cells.

Directory of Open Access Journals (Sweden)

Altaf H Sarker

Full Text Available Secondhand smoke (SHS is a confirmed lung carcinogen that introduces thousands of toxic chemicals into the lungs. SHS contains chemicals that have been implicated in causing oxidative DNA damage in the airway epithelium. Although DNA repair is considered a key defensive mechanism against various environmental attacks, such as cigarette smoking, the associations of individual repair enzymes with susceptibility to lung cancer are largely unknown. This study investigated the role of NEIL2, a DNA glycosylase excising oxidative base lesions, in human lung cells treated with sidestream smoke (SSS, the main component of SHS. To do so, we generated NEIL2 knockdown cells using siRNA-technology and exposed them to SSS-laden medium. Representative SSS chemical compounds in the medium were analyzed by mass spectrometry. An increased production of reactive oxygen species (ROS in SSS-exposed cells was detected through the fluorescent detection and the induction of HIF-1α. The long amplicon-quantitative PCR (LA-QPCR assay detected significant dose-dependent increases of oxidative DNA damage in the HPRT gene of cultured human pulmonary fibroblasts (hPF and BEAS-2B epithelial cells exposed to SSS for 24 h. These data suggest that SSS exposure increased oxidative stress, which could contribute to SSS-mediated toxicity. siRNA knockdown of NEIL2 in hPF and HEK 293 cells exposed to SSS for 24 h resulted in significantly more oxidative DNA damage in HPRT and POLB than in cells with control siRNA. Taken together, our data strongly suggest that decreased repair of oxidative DNA base lesions due to an impaired NEIL2 expression in non-smokers exposed to SSS would lead to accumulation of mutations in genomic DNA of lung cells over time, thus contributing to the onset of SSS-induced lung cancer.

Oxidative Stress and Proinflammatory Cytokines Contribute to Demyelination and Axonal Damage in a Cerebellar Culture Model of Neuroinflammation

Science.gov (United States)

di Penta, Alessandra; Moreno, Beatriz; Reix, Stephanie; Fernandez-Diez, Begoña; Villanueva, Maite; Errea, Oihana; Escala, Nagore; Vandenbroeck, Koen; Comella, Joan X.; Villoslada, Pablo

2013-01-01

Background Demyelination and axonal damage are critical processes in the pathogenesis of multiple sclerosis (MS). Oxidative stress and pro-inflammatory cytokines elicited by inflammation mediates tissue damage. Methods/Principal Findings To monitor the demyelination and axonal injury associated with microglia activation we employed a model using cerebellar organotypic cultures stimulated with lipopolysaccharide (LPS). Microglia activated by LPS released pro-inflammatory cytokines (IL-1β, IL-6 and TNFα), and increased the expression of inducible nitric oxide synthase (iNOS) and production of reactive oxygen species (ROS). This activation was associated with demyelination and axonal damage in cerebellar cultures. Axonal damage, as revealed by the presence of non-phosphorylated neurofilaments, mitochondrial accumulation in axonal spheroids, and axonal transection, was associated with stronger iNOS expression and concomitant increases in ROS. Moreover, we analyzed the contribution of pro-inflammatory cytokines and oxidative stress in demyelination and axonal degeneration using the iNOS inhibitor ethyl pyruvate, a free-scavenger and xanthine oxidase inhibitor allopurinol, as well as via blockage of pro-inflammatory cytokines using a Fc-TNFR1 construct. We found that blocking microglia activation with ethyl pyruvate or allopurinol significantly decreased axonal damage, and to a lesser extent, demyelination. Blocking TNFα significantly decreased demyelination but did not prevented axonal damage. Moreover, the most common therapy for MS, interferon-beta, was used as an example of an immunomodulator compound that can be tested in this model. In vitro, interferon-beta treatment decreased oxidative stress (iNOS and ROS levels) and the release of pro-inflammatory cytokines after LPS stimulation, reducing axonal damage. Conclusion The model of neuroinflammation using cerebellar culture stimulated with endotoxin mimicked myelin and axonal damage mediated by the combination of

Gum acacia mitigates genetic damage in adenine-induced chronic renal failure in rats.

Science.gov (United States)

Ali, B H; Al Balushi, K; Al-Husseini, I; Mandel, P; Nemmar, A; Schupp, N; Ribeiro, D A

2015-12-01

Subjects with chronic renal failure (CRF) exhibit oxidative genome damage, which may predispose to carcinogenesis, and Gum acacia (GumA) ameliorates this condition in humans and animals. We evaluated here renal DNA damage and urinary excretion of four nucleic acid oxidation adducts namely 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxoguanosine (8-oxoGuo) and 8-hydroxy-2-deoxyguanisone (8-OHdg) in rats with adenine (ADE)-induced CRF with and without GumA treatment. Twenty-four rats were divided into four equal groups and treated for 4 weeks. The first group was given normal food and water (control). The second group was given normal food and GumA (15% w/v) in drinking water. The third group was fed powder diet containing adenine (ADE) (0·75% w/w in feed). The fourth group was fed like in the third group, plus GumA in drinking water (15%, w/v). ADE feeding induced CRF (as measured by several physiological, biochemical and histological indices) and also caused a significant genetic damage and significant decreases in urinary 8-oxo Gua and 8-oxoGuo, but not in the other nucleic acids. However, concomitant GumA treatment reduced the level of genetic damage in kidney cells as detected by Comet assay and significantly reversed the effect of adenine on urinary 8-oxoGuo. Treatment with GumA is able to mitigate genetic damage in renal tissues of rats with ADE-induced CRF. © 2015 Stichting European Society for Clinical Investigation Journal Foundation.

Curcumin Attenuates Gamma Radiation Induced Intestinal Damage in Rats

International Nuclear Information System (INIS)

EI-Tahawy, N.A.

2009-01-01

Small Intestine exhibits numerous morphological and functional alterations during radiation exposure. Oxidative stress, a factor implicated in the intestinal injury may contribute towards some of these alterations. The present work was designed to evaluate the efficacy of curcumin, a yellow pigment of turmeric on y-radiation-induced oxidative damage in the small intestine by measuring alterations in the level of thiobarbituric acid reactive substances (TSARS), serotonin metabolism, catecholamine levels, and monoamine oxidase (MAO) activity in parallel to changes in the architecture of intestinal tissues. In addition, monoamine level, MAO activity and TSARS level were determined in the serum. Curcumin was supplemented orally via gavages, to rats at a dose of (45 mg/ Kg body wt/ day) for 2 weeks pre-irradiation and the last supplementation was 30 min pre exposure to 6.5 Gy gamma radiations (applied as one shot dose). Animals were sacrificed on the 7th day after irradiation. The results demonstrated that, whole body exposure of rats to ionizing radiation has induced oxidative damage in small intestine obvious by significant increases of TSARS content, MAO activity and 5-hydroxy indole acetic acid (5-HIAA) and by significant decreases of serotonin (5-HT), dopamine (DA), norepinephrine (NE) and epinephrine (EPI) levels. In parallel histopathological studies of the small intestine of irradiated rats through light microscopic showed significant decrease in the number of villi, villus height, mixed sub mucosa layer with more fibres and fibroblasts. Intestinal damage was in parallel to significant alterations of serum MAO activity, TBARS, 5-HT, DA, NE and EPI levels. Administration of curcumin before irradiation has significantly improved the levels of monoamines in small intestine and serum of irradiated rats, which was associated with significant amelioration in MAO activity and TBARS contents

Ochratoxin A: induction of (oxidative) DNA damage, cytotoxicity and apoptosis in mammalian cell lines and primary cells

International Nuclear Information System (INIS)

Kamp, Hennicke G.; Eisenbrand, Gerhard; Schlatter, Josef; Wuerth, Kirsten; Janzowski, Christine

2005-01-01

Ochratoxin A (OTA) is a nephrotoxic/-carcinogenic mycotoxin, produced by several Aspergillus- and Penicillium-strains. Humans are exposed to OTA via food contamination, a causal relationship of OTA to human endemic Balkan nephropathy is still under debate. Since DNA-adducts of OTA or its metabolites could not be identified unambiguously, its carcinogenic effectiveness might be related to secondary effects, such as oxidative cell damage or cell proliferation. In this study, OTA mediated induction of (oxidative) DNA damage, cytotoxicity (necrosis, growth inhibition, apoptosis) and modulation of glutathione were investigated in cell lines (V79, CV-1) and primary rat kidney cells. After 24 h incubation, viability of V79 cells was strongly decreased by OTA concentrations >2.5 μmol/L, whereas CV-1 cells were clearly less sensitive. Strong growth inhibition occurred in both cell lines (IC 50 ∼2 μmol/L). Apoptosis, detected with an immunochemical test and with flow cytometry, was induced by >1 μmol/L OTA. Oxidative DNA damage, detected by comet assay after additional treatment with repair enzymes, was induced in all cell systems already at five-fold lower concentrations. Glutathione in CV-1 cells was depleted after 1 h incubation (>100 μmol/L). In contrast, an increase was measured after 24 h incubation (>0.5 μmol/L). In conclusion, OTA induces oxidative DNA damage at low, not yet cytotoxic concentrations. Oxidative DNA damage might initiate cell transformation eventually in connection with proliferative response following cytotoxic cell death. Both events might represent pivotal factors in the chain of cellular events leading into nephro-carcinogenicity of OTA

The Efficacy of Coffee and Green Tea in Ameliorating Histological and Biochemical Changes Induced By γ-Irradiation in Albino Rats

International Nuclear Information System (INIS)

Rezk, R.G.; Darwish, M.M.

2009-01-01

Exposure to ionizing radiation results in oxidative damage, organ dysfunction and metabolic disturbances. The aim of the present study was to investigate the efficacy of coffee, green tea, or coffee + green tea consumption on radiation-induced damage in liver and heart tissues of rats. Rats received/day, by gavages, the water extract of 0.3 g green tea and/or 0.2 g coffee, for a period of 7 days. The last dose was given 60 min before irradiation with a dose of 6.5 Gy. Histological examination through light microscope of sections in the liver and heart tissues on the 3rd day post-irradiation revealed that all treatments has attenuated radiation-induced oxidative damage. Necrosis, apoptosis, cell death and rupture of cell membrane in both tissues were less severe and were associated with significant decrease of serum malonaldehyde (MDA) content and significant increase in superoxide dismutase (SOD) and catalase (Cat) activities, and glutathione (GSH) content, compared to their corresponding value in non irradiated rats. The results were substantiated by significant amelioration in the activity of serum lactate dehydrogenase (LDH), aspartate amino transferase (AST), alanine amino transferase (ALT), gamma glutamyl transferase (GGT), and alkaline phosphatase (ALP) and the content of triglycerides (TG) and total cholesterol (TC), markers of liver and heart functions. No significant changes were recorded between the 3 treatments. However, coffee + green tea provoked better results with respect to radiation-induced lipid peroxidation, which might be attributed to their synergistic effect as free radical scavengers. It could be concluded that drinking coffee associated with green tea is healthier than drinking coffee or green tea alone to protect liver and heart tissues from oxidative stress

Metoprolol induces oxidative damage in common carp (Cyprinus carpio).

Science.gov (United States)

Martínez-Rodríguez, Héctor; Donkor, Kingsley; Brewer, Sharon; Galar-Martínez, Marcela; SanJuan-Reyes, Nely; Islas-Flores, Hariz; Sánchez-Aceves, Livier; Elizalde-Velázquez, Armando; Gómez-Oliván, Leobardo Manuel

2018-04-01

During the last decade, β-blockers such as metoprolol (MTP) have been frequently detected in surface water, aquatic systems and municipal water at concentrations of ng/L to μg/L. Only a small number of studies exist on the toxic effects induced by this group of pharmaceuticals on aquatic organisms. Therefore, the present study aimed to evaluate the oxidative damage induced by MTP in the common carp Cyprinus carpio, using oxidative stress biomarkers. To this end, indicators of cellular oxidation such as hydroperoxide content (HPC), lipid peroxidation (LPX) and protein carbonyl content (PCC) were determined, as well as the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Also, concentrations of MTP and its metabolite O-desmethyl metoprolol were determined in water as well as carp gill, liver, kidney, brain and blood, along with the partial uptake pattern of these compounds. Results show that carp takes up MTP and its metabolite in the different organs evaluated, particularly liver and gill. The oxidative stress biomarkers, HPC, LPX, and PCC, as well as SOD and CAT activity all increased significantly at most exposure times in all organs evaluated. Results indicate that MTP and its metabolite induce oxidative stress on the teleost C. carpio and that the presence of these compounds may constitute a risk in water bodies for aquatic species. Copyright © 2018 Elsevier B.V. All rights reserved.

Oxidative Damage to the Salivary Glands of Rats with Streptozotocin-Induced Diabetes-Temporal Study: Oxidative Stress and Diabetic Salivary Glands

OpenAIRE

Kna?, M.; Maciejczyk, M.; Daniszewska, I.; Klimiuk, A.; Matczuk, J.; Ko?odziej, U.; Waszkiel, D.; ?adny, J. R.; ?endzian-Piotrowska, M.; Zalewska, A.

2016-01-01

Objective. This study evaluated oxidative damage caused to the salivary glands in streptozotocin-induced diabetes (DM). Materials and Methods. Rats were divided into 4 groups: groups 1 and 2, control rats, and groups 3 and 4, DM rats. 8-Hydroxy-2′-deoxyguanosine (8-OHdG), protein carbonyl (PC), 4-hydroxynonenal protein adduct (4-HNE), oxidized and/or MDA-modified LDL-cholesterol (oxy-LDL/MDA), 8-isoprostanes (8-isoP), and oxidative stress index (OSI) were measured at 7 (groups 1 and 3) and 14...

Damage recovery and optical activity in europium implanted wide gap oxides

International Nuclear Information System (INIS)

Alves, E.; Marques, C.; Franco, N.; Alves, L.C.; Peres, M.; Soares, M.J.; Monteiro, T.

2010-01-01

In this study we compare and discuss the defects and optical behaviour of sapphire and magnesium oxide single crystals implanted at room temperature with different fluences (1 x 10 15 -1 x 10 16 cm -2 ) of europium ions. Rutherford backscattering channelling shows that for fluences above 5 x 10 15 cm -2 the surface disorder level in the Al-sublattice reaches the random level. Implantation damage recovers fast for annealing in oxidizing atmosphere but even for the highest fluence we recover almost completely all the damage after annealing at 1300 o C, independently of the annealing environment (reducing or oxidizing). Annealing above 1000 o C promotes the formation of Eu 2 O 3 in the samples with higher concentration of Eu. The optical activation of the rare earth ions at room temperature was observed after annealing at 800 o C by photoluminescence and ionoluminescence. In Al 2 O 3 lattice the highest intensity line of the Eu 3+ ions corresponds to the forced electric dipole 5 D 0 → 7 F 2 transition that occurs ∼616 nm. For the MgO samples the Eu 3+ optical activation was also achieved after implantation with different fluences. Here, the lanthanide recombination is dominated by the magnetic dipole 5 D 0 → 7 F 1 transition near by 590 nm commonly observed for samples were Eu 3+ is placed in a high symmetry local site. The results clearly demonstrate the possibility to get Eu incorporated in optical active regular lattice sites in wide gap oxides.

GSTP1 Loss results in accumulation of oxidative DNA base damage and promotes prostate cancer cell survival following exposure to protracted oxidative stress.

Science.gov (United States)

Mian, Omar Y; Khattab, Mohamed H; Hedayati, Mohammad; Coulter, Jonathan; Abubaker-Sharif, Budri; Schwaninger, Julie M; Veeraswamy, Ravi K; Brooks, James D; Hopkins, Lisa; Shinohara, Debika Biswal; Cornblatt, Brian; Nelson, William G; Yegnasubramanian, Srinivasan; DeWeese, Theodore L

2016-02-01

Epigenetic silencing of glutathione S-transferase π (GSTP1) is a hallmark of transformation from normal prostatic epithelium to adenocarcinoma of the prostate. The functional significance of this loss is incompletely understood. The present study explores the effects of restored GSTP1 expression on glutathione levels, accumulation of oxidative DNA damage, and prostate cancer cell survival following oxidative stress induced by protracted, low dose rate ionizing radiation (LDR). GSTP1 protein expression was stably restored in LNCaP prostate cancer cells. The effect of GSTP1 restoration on protracted LDR-induced oxidative DNA damage was measured by GC-MS quantitation of modified bases. Reduced and oxidized glutathione levels were measured in control and GSTP1 expressing populations. Clonogenic survival studies of GSTP1- transfected LNCaP cells after exposure to protracted LDR were performed. Global gene expression profiling and pathway analysis were performed. GSTP1 expressing cells accumulated less oxidized DNA base damage and exhibited decreased survival compared to control LNCaP-Neo cells following oxidative injury induced by protracted LDR. Restoration of GSTP1 expression resulted in changes in modified glutathione levels that correlated with GSTP1 protein levels in response to protracted LDR-induced oxidative stress. Survival differences were not attributable to depletion of cellular glutathione stores. Gene expression profiling and pathway analysis following GSTP1 restoration suggests this protein plays a key role in regulating prostate cancer cell survival. The ubiquitous epigenetic silencing of GSTP1 in prostate cancer results in enhanced survival and accumulation of potentially promutagenic DNA adducts following exposure of cells to protracted oxidative injury suggesting a protective, anti-neoplastic function of GSTP1. The present work provides mechanistic backing to the tumor suppressor function of GSTP1 and its role in prostate carcinogenesis. © 2015

Differential effects of experimental and cold-induced hyperthyroidism on factors inducing rat liver oxidative damage

OpenAIRE

Venditti, Paola; Pamplona Gras, Reinald; Ayala, Victoria; Rosa, R. de; Caldarone, G.; Di Meo, S.

2006-01-01

Thyroid hormone-induced increase in metabolic rates is often associated with increased oxidative stress. The aim of the present study was to investigate the contribution of iodothyronines to liver oxidative stress in the functional hyperthyroidism elicited by cold, using as models cold-exposed and 3,5,3'-triiodothyronine (T-3)- or thyroxine (T-4)-treated rats. The hyperthyroid state was always associated with increases in both oxidative capacity and oxidative damage of the tissue. The most ex...

Andrographis paniculata ameliorates carbon tetrachloride (CCl(4))-dependent hepatic damage and toxicity: diminution of oxidative stress.

Science.gov (United States)

Koh, Pei Hoon; Mokhtar, Ruzaidi Azli Mohd; Iqbal, Mohammad

2011-01-01

Andrographis paniculata (hempedu bumi) is a plant that possesses many medicinal values in treating several diseases and for health care maintenance. However, its hepatoprotective activity and mechanism of action have not been fully investigated. Therefore, this study aimed to evaluate the hepatoprotective effects of A. paniculata and its mechanism of action in rats. Carbon tetrachloride (CCl(4)) challenge of rats at a dose of 1.2 ml/kg body weight-induced oxidative stress in the liver. This was evidenced by augmentation in lipid peroxidation, which was accompanied by a decrease in the activities of antioxidant enzymes and depletion in the level of reduced glutathione (P paniculata (P paniculata to scavenge the 2,2-Diphenyl-2-picrylhydrazyl radical was determined through its EC(50) value. The EC(50) value of A. paniculata was 583.60 ± 4.25 µg/ml. In addition, A. paniculata was found to contain 65.37 ± 1.20 mg/g total phenolics expressed as gallic acid equivalent. From these studies, it is concluded that A. paniculata could be used as a hepatoprotective agent and possesses the potential to treat or prevent degenerative diseases where oxidative stress is implicated.

Amelioration of Gamma-hexachlorocyclohexane (Lindane induced renal toxicity by Camellia sinensis in Wistar rats

Directory of Open Access Journals (Sweden)

W. L. N. V. Vara Prasad

2016-11-01

Full Text Available Aim: A study to assess the toxic effects of gamma-hexachlorocyclohexane (γ-HCH (lindane and ameliorative effects of Camellia sinensis on renal system has been carried out in male Wistar rats. Materials and Methods: Four groups of rats with 18 each were maintained under standard laboratory hygienic conditions and provided feed and water ad libitum. γ-HCH was gavaged at 20 mg/kg b.wt. using olive oil as vehicle to Groups II. C. sinensis at 100 mg/kg b.wt. was administered orally in distilled water to Group IV in addition to γ-HCH 20 mg/kg b.wt. up to 45 days to study ameliorative effects. Groups I and III were treated with distilled water and C. sinensis (100 mg/kg b.wt., respectively. Six rats from each group were sacrificed at fortnight intervals. Serum was collected for creatinine estimation. The kidney tissues were collected in chilled phosphate buffer saline for antioxidant profile and in also 10% buffered formalin for histopathological studies. Results: γ-HCH treatment significantly increased serum creatinine and significantly reduced the renal antioxidative enzymes catalase, superoxide dismutase, and glutathione peroxidase. Grossly, severe congestion was noticed in the kidneys. Microscopically, kidney revealed glomerular congestion, atrophy, intertubular hemorrhages, degenerative changes in tubular epithelium with vacuolated cytoplasm, desquamation of epithelium and urinary cast formation. A significant reduction in serum creatinine levels, significant improvement in renal antioxidant enzyme activities and near to normal histological appearance of kidneys in Group IV indicated that the green tea ameliorated the effects of γ-HCH, on renal toxicity. Conclusion: This study suggested that C. sinensis extract combined with γ-HCH could enhance antioxidant/detoxification system which consequently reduced the oxidative stress thus potentially reducing γ-HCH toxicity and tissue damage.

Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice.

Directory of Open Access Journals (Sweden)

Naoto Terami

Full Text Available Inhibition of sodium glucose cotransporter 2 (SGLT2 has been reported as a new therapeutic strategy for treating diabetes. However, the effect of SGLT2 inhibitors on the kidney is unknown. In addition, whether SGLT2 inhibitors have an anti-inflammatory or antioxidative stress effect is still unclear. In this study, to resolve these issues, we evaluated the effects of the SGLT2 inhibitor, dapagliflozin, using a mouse model of type 2 diabetes and cultured proximal tubular epithelial (mProx24 cells. Male db/db mice were administered 0.1 or 1.0 mg/kg of dapagliflozin for 12 weeks. Body weight, blood pressure, blood glucose, hemoglobin A1c, albuminuria and creatinine clearance were measured. Mesangial matrix accumulation and interstitial fibrosis in the kidney and pancreatic β-cell mass were evaluated by histological analysis. Furthermore, gene expression of inflammatory mediators, such as osteopontin, monocyte chemoattractant protein-1 and transforming growth factor-β, was evaluated by quantitative reverse transcriptase-PCR. In addition, oxidative stress was evaluated by dihydroethidium and NADPH oxidase 4 staining. Administration of 0.1 or 1.0 mg/kg of dapagliflozin ameliorated hyperglycemia, β-cell damage and albuminuria in db/db mice. Serum creatinine, creatinine clearance and blood pressure were not affected by administration of dapagliflozin, but glomerular mesangial expansion and interstitial fibrosis were suppressed in a dose-dependent manner. Dapagliflozin treatment markedly decreased macrophage infiltration and the gene expression of inflammation and oxidative stress in the kidney of db/db mice. Moreover, dapagliflozin suppressed the high-glucose-induced gene expression of inflammatory cytokines and oxidative stress in cultured mProx24 cells. These data suggest that dapagliflozin ameliorates diabetic nephropathy by improving hyperglycemia along with inhibiting inflammation and oxidative stress.

Curcumin ameliorates cardiac dysfunction induced by mechanical trauma.

Science.gov (United States)

Li, Xintao; Cao, Tingting; Ma, Shuo; Jing, Zehao; Bi, Yue; Zhou, Jicheng; Chen, Chong; Yu, Deqin; Zhu, Liang; Li, Shuzhuang

2017-11-05

Curcumin, a phytochemical component derived from turmeric (Carcuma longa), has been extensively investigated because of its anti-inflammatory and anti-oxidative properties. Inflammation and oxidative stress play critical roles in posttraumatic cardiomyocyte apoptosis, which contributes to secondary cardiac dysfunction. This research was designed to identify the protective effect of curcumin on posttraumatic cardiac dysfunction and investigate its underlying mechanism. Noble-Collip drum was used to prepare a mechanical trauma (MT) model of rats, and the hemodynamic responses of traumatized rats were observed by ventricular intubation 12h after trauma. Myocardial apoptosis was determined through terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and caspase-3 activity assay. Tumor necrosis factor-α (TNF-α) and reactive oxygen species (ROS) generated by monocytes and myocardial cells were identified through enzyme-linked immunosorbent assay (ELISA), and the intracellular alteration of Ca 2+ in cardiomyocytes was examined through confocal microscopy. In vivo, curcumin effectively ameliorated MT-induced secondary cardiac dysfunction and significantly decreased the apoptotic indices of the traumatized myocardial cells. In vitro, curcumin inhibited TNF-α production by monocytes and reduced the circulating TNF-α levels. With curcumin pretreatment, ROS production and Ca 2+ overload in H9c2 cells were attenuated when these cells were incubated with traumatic plasma. Therefore, curcumin can effectively ameliorate MT-induced cardiac dysfunction mainly by inhibiting systemic inflammatory responses and by weakening oxidative stress reaction and Ca 2+ overload in cardiomyocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

Wine and oxidative stress: up-to-date evidence of the effects of moderate wine consumption on oxidative damage in humans.

Science.gov (United States)

Covas, María Isabel; Gambert, Philippe; Fitó, Montserrat; de la Torre, Rafael

2010-02-01

Wine and alcohol consumption has been considered to be protective against coronary heart disease development, an oxidative stress associated disease. Wine contains polyphenols displaying antioxidant properties tested in in vitro and in vivo studies. Due to this, a general consensus exists, both among the general public and the scientific community, that wine, particularly red wine, is an antioxidant beverage. Alcohol consumption, however, is associated with oxidative damage. Several studies have been carried out on the antioxidant health benefits of wine and wine polyphenols. However, adequate scientific evidence (Level I or II) is required to be provided before recommendations or statements which can reach the general public can be formulated. Here, we summarize the state of the art of the up-to-date body of knowledge, and the extent to which there exists evidence of the benefits of moderate wine consumption on oxidative damage in humans. From the available data, there is no evidence, at present, that sustained wine consumption provides antioxidant benefits in healthy volunteers other than to counteract a possible pro-oxidative effect of the alcohol. On the contrary, data on the antioxidant protective effect of red wine in oxidative stress situations are promising. In this way, the postprandial oxidative stress after a meal, despite the diversity of biomarkers used for its evaluation, is counteracted by the ingestion of wine. Further studies are warranted. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Chafuroside B, an Oolong tea polyphenol, ameliorates UVB-induced DNA damage and generation of photo-immunosuppression related mediators in human keratinocytes.

Directory of Open Access Journals (Sweden)

Tatsuya Hasegawa

Full Text Available Chafuroside B was recently isolated as a new polyphenolic constituent of oolong tea leaves. However, the effects of chafuroside B on skin function have not been examined. In this study, we investigated the protective effects of chafuroside B against UVB-induced DNA damage, apoptosis and generation of photo-immunosuppression related mediators in cultured normal human epidermal keratinocytes (NHEK. Chafuroside B at 1 µM attenuated both UVB-induced apoptosis, evaluated in terms of caspase-3/7 activity, and UVB-induced DNA damage, evaluated in terms of formation of cyclobutane pyrimidine dimers (CPD, in NHEK exposed to UVB (20 mJ/cm2. In addition, chafuroside B at 0.3 or 1 µM suppressed the UVB-induced production of interleukin (IL-10, tumor necrosis factor (TNF-α, and prostaglandin E2 (PGE2, as determined by ELISA, and conversely enhanced IL-12 mRNA expression and production, as measured by RT-PCR and ELISA. Further, chafuroside B at 1 µM also suppressed UVB-induced expression of receptor activator of nuclear factor κB ligand (RANKL mRNA. These results indicate that chafuroside B promotes repair of UVB-induced DNA damage and ameliorates the generation of IL-10, TNF-α, PGE2, and RANKL, all of which are UVB-induced immunosuppression related mediators. These effects of chafuroside B may be mediated at least in part through induction of IL-12 synthesis in human keratinocytes. Because chafuroside B might have practical value as a photoprotective agent, a further study of the in vivo effects of chafuroside B seems warranted.

Vitamin-E reduces the oxidative damage on delta-aminolevulinic dehydratase induced by lead intoxication in rat erythrocytes.

Science.gov (United States)

Rendón-Ramirez, A; Cerbón-Solórzano, J; Maldonado-Vega, M; Quintanar-Escorza, M A; Calderón-Salinas, J V

2007-09-01

Lead intoxication induces oxidative damage on lipids and proteins. In the present paper we study in vivo and in vitro the antioxidant effect of vitamin-E and trolox, on the oxidative effects of lead intoxication in rat erythrocytes. Vitamin-E simultaneously administered to erythrocytes treated with lead was capable to prevent the inhibition of delta-aminolevulinic dehydratase activity and lipid oxidation. Partial but important protective effects were found when vitamin-E was administered either after or before lead exposure in rats. In vitro, the antioxidant trolox protected delta-ALA-D activity against damage induced by lead or menadione. These results indicate that vitamin-E could be useful in order to protect membrane-lipids and, notably, to prevent protein oxidation produced by lead intoxication.

Ramadan fasting ameliorates arterial pulse pressure and lipid profile, and alleviates oxidative stress in hypertensive patients.

Science.gov (United States)

Al-Shafei, Ahmad I M

2014-06-01

Effects of Ramadan fasting on health are important. Its effects on arterial pulse pressure (PP), lipid profile and oxidative stress were characterized in hypertensives. PP, indices of lipid profile and oxidative stress were measured pre-, during and post-fasting in equal (40 each), sex- and age-matched groups (age 55 ± 5 years) of hypertensives (HT) and controls (C). Fasting reduced PP significantly by 17.2% and insignificantly by 9.3% in the HT and C groups, respectively. Total cholesterol (TC) was lowered insignificantly by 11.7% and 4.7% in the HT and C patients, respectively. Triglycerides (TG) and malondialdehyde (MDA) were significantly lowered by: TG: 24.5% and 22.8%; MDA: 45.6% and 54.3%; while glutathione (GSH) elevated by 56.8% and 52.6% in the HT and C groups, respectively. High-density lipoproteins (HDL) were raised significantly by 33.3% and insignificantly by 6.7%, whereas low-density lipoproteins (LDL) decreased significantly by 17.7% and insignificantly by 4.0% in the HT and C groups, respectively. At 6 weeks post-fasting, MDA remained significantly lower than the pre-fasting level by 24.3% and 25.7%, and GSH higher by 30.2% and 26.3% in the HT and C groups, respectively, while PP and TC returned to pre-fasting values in both groups. The post-fasting, HDL was significantly higher by 20.3% and LDL lower by 12.0% than the fasting levels in the HT patients. Fasting improves PP and lipids profile and ameliorates oxidative stress in hypertensives.

Oxidative DNA damage and repair in skeletal muscle of humans exposed to high-altitude hypoxia

DEFF Research Database (Denmark)

Lundby, Carsten; Pilegaard, Henriette; van Hall, Gerrit

2003-01-01

Recent research suggests that high-altitude hypoxia may serve as a model for prolonged oxidative stress in healthy humans. In this study, we investigated the consequences of prolonged high-altitude hypoxia on the basal level of oxidative damage to nuclear DNA in muscle cells, a major oxygen-consuming...

[Damage effects of chronic hypoxia on medulla oblongata associated with oxidative stress and cell apoptosis].

Science.gov (United States)

Hou, Xuefei; Ding, Yan; Nie, Zheng; Li, Hui; Tang, Yuhong; Zhou, Hua; Chen, Li; Zheng, Yu

2012-08-01

The aim of this study is to study the damage effects of chronic hypoxia on medulla oblongata and to explore whether the damage is associated with oxidative stress and cell apoptosis. Adult male SD rats were randomly divided into two groups: control group and chronic hypoxia group. Medulla oblongata was obtained for the following methods of analyses. Nissl's staining was used to examine the Niss bodies of neurons in medullary respiratory related nuclei, biochemistry methods were utilized to examine oxidant stress damage induced by chronic hypoxia on medulla oblongata through measuring malondialdehyde (MDA) content and superoxide dismutase (SOD) activity, and RT-PCR technique was used to study the influence of apoptosis induced by chronic hypoxia on medulla oblongata through analyzing the levels of Bax mRNA and Bcl-2 mRNA. The results showed the optical densities of Nissl's staining in pre-BötC, NA, NTS, FN, and 12N were significantly decreased in chronic hypoxia group in comparison with that in control group (P 0.05). Bax mRNA expression had no obvious change and Bcl-2 mRNA expression significantly decreased in chronic hypoxia group in comparison with that in control group (P < 0.05). The results suggest that chronic hypoxia could bring about serious damage to medullary respiratory centers through aggravating oxidative stress and increasing cell apoptosis.

Submaximal exercise training, more than dietary selenium supplementation, improves antioxidant status and ameliorates exercise-induced oxidative damage to skeletal muscle in young equine athletes.

Science.gov (United States)

White, S H; Warren, L K

2017-02-01

Exercise is associated with increased production of reactive oxygen species (ROS) as metabolism is upregulated to fuel muscle activity. If antioxidant systems become overwhelmed, ROS can negatively affect health and performance. Adaptation to exercise through regular training has been shown to improve defense against oxidative insult. Given selenium's role as an antioxidant, we hypothesized that increased Se intake would further enhance skeletal muscle adaptations to training. Quarter Horse yearlings (18 ± 0.2 mo; 402 ± 10 kg) were randomly assigned to receive either 0.1 or 0.3 mg Se/kg DM and placed in either an untrained or a trained (30 min walk-trot-canter, 4 d/wk) group for 14 wk. Phase 1 (wk 1 to 8) consisted of 4 treatments: trained and fed 0.1 mg Se/kg DM through wk 14 (CON-TR; n = 10), trained and fed 0.3 mg Se/kg DM through wk 14 (HIGH-TR; n = 10), untrained and fed 0.1 mg Se/kg DM through wk 14 (CON-UN; n = 5), or untrained and fed 0.3 mg Se/kg DM through wk 14 (HIGH-UN; n = 5). During Phase 2 (wk 9 to 14), dietary Se level in half of the trained horses was reversed, resulting in 6 treatments: CON-TR (n = 5), trained and fed 0.1 mg/kg Se in Phase 1 and then switched to 0.3 mg/kg Se for Phase 2 (ADD-TR; n = 5), trained and fed 0.3 mg/kg Se in Phase 1 and then switched to 0.1 mg/kg Se for Phase 2 (DROP-TR; n = 5), HIGH-TR (n = 5), CON-UN (n = 5), or HIGH-UN (n = 5). All horses underwent a 120-min submaximal exercise test (SET) at the end of Phase 1 (SET 1) and 2 (SET 2). Blood samples and biopsies from the middle gluteal muscle were collected before and after each phase of the study and in response to each SET and analyzed for markers of oxidative damage and antioxidant enzyme activity. In both phases, serum Se was higher (P creatine kinase (CK) activity was lower in trained horses than in untrained horses (P < 0.0001), indicating less muscle damage, but plasma lipid hydroperoxides (LPO) and muscle GPx and SOD activities were unaffected by training or Se

Effect of vitamin E and C supplementation on oxidative damage and total antioxidant capacity in lead-exposed workers.

Science.gov (United States)

Rendón-Ramírez, Adela-Leonor; Maldonado-Vega, María; Quintanar-Escorza, Martha-Angelica; Hernández, Gerardo; Arévalo-Rivas, Bertha-Isabel; Zentella-Dehesa, Alejandro; Calderón-Salinas, José-Víctor

2014-01-01

The molecular response of the antioxidant system and the effects of antioxidant supplementation against oxidative insult in lead-exposed workers has not been sufficiently studied. In this work, antioxidants (vitamin E 400 IU+vitamin C 1g/daily) were supplemented for one year to 15 workers exposed to lead (73 μg of lead/dl of blood) and the results were compared with those on 19 non-lead exposed workers (6.7 μg of lead/dl). Lead intoxication was accompanied by a high oxidative damage and an increment in the erythrocyte antioxidant response due to increased activity of catalase and superoxide dismutase. Antioxidant supplementations decreased significantly the oxidative damage as well as the total antioxidant capacity induced by lead intoxication with reduction of the antioxidant enzyme activities. We conclude that antioxidant supplementation is effective in reducing oxidative damage and induces modifications in the physiopathological status of the antioxidant response in lead-exposed workers. Copyright © 2013 Elsevier B.V. All rights reserved.

Maltol, a Food Flavoring Agent, Attenuates Acute Alcohol-Induced Oxidative Damage in Mice

Directory of Open Access Journals (Sweden)

Ye Han

2015-01-01

Full Text Available The purpose of this study was to evaluate the hepatoprotective effect of maltol, a food-flavoring agent, on alcohol-induced acute oxidative damage in mice. Maltol used in this study was isolated from red ginseng (Panax ginseng C.A Meyer and analyzed by high performance liquid chromatography (HPLC and mass spectrometry. For hepatoprotective activity in vivo, pretreatment with maltol (12.5, 25 and 50 mg/kg; 15 days drastically prevented the elevated activities of aspartate transaminase (AST, alanine transaminase (ALT, alkaline phosphatase (ALP and triglyceride (TG in serum and the levels of malondialdehyde (MDA, tumor necrosis factor-α (TNF-α, interleukin-1β (IL-1β in liver tissue (p < 0.05. Meanwhile, the levels of hepatic antioxidant, such as catalase (CAT, superoxide dismutase (SOD, glutathione peroxidase (GSH-Px were elevated by maltol pretreatment, compared to the alcohol group (p < 0.05. Histopathological examination revealed that maltol pretreatment significantly inhibited alcohol-induced hepatocyte apoptosis and fatty degeneration. Interestingly, pretreatment of maltol effectively relieved alcohol-induced oxidative damage in a dose-dependent manner. Maltol appeared to possess promising anti-oxidative and anti-inflammatory capacities. It was suggested that the hepatoprotective effect exhibited by maltol on alcohol-induced liver oxidative injury may be due to its potent antioxidant properties.

Oxidative damage to DNA by diesel exhaust particle exposure in co-cultures of human lung epithelial cells and macrophages

DEFF Research Database (Denmark)

Jantzen, Kim; Roursgaard, Martin; Madsen, Claus Desler

2012-01-01

Studies in mono-culture of cells have shown that diesel exhaust particles (DEPs) increase the production of reactive oxygen species (ROS) and oxidative stress-related damage to DNA. However, the level of particle-generated genotoxicity may depend on interplay between different cell types, e.g. lung...... treatment with standard reference DEPs, SRM2975 and SRM1650b. The exposure to DEPs did not affect the colony-forming ability of A549 cells in co-culture with THP-1a cells. The DEPs generated DNA strand breaks and oxidatively damaged DNA, measured using the alkaline comet assay as formamidopyrimidine...... relationship between levels of respiration and ROS production. In conclusion, exposure of mono-cultured cells to DEPs generated oxidative stress to DNA, whereas co-cultures with macrophages had lower levels of oxidatively damaged DNA than A549 epithelial cells....

Electroacupuncture ameliorates post-stroke learning and memory through minimizing ultrastructural brain damage and inhibiting the expression of MMP-2 and MMP-9 in cerebral ischemia-reperfusion injured rats.

Science.gov (United States)

Lin, Ruhui; Yu, Kunqiang; Li, Xiaojie; Tao, Jing; Lin, Yukun; Zhao, Congkuai; Li, Chunyan; Chen, Li-Dian

2016-07-01

The aim of the present study was to investigate the potential neuroprotective effects of electroacupuncture (EA) in the treatment of cerebral ischemia/reperfusion (I/R) injury, and to elucidate the association between this neuroprotective effect and brain ultrastructure and expression of matrix metalloproteinase (MMP)‑2 and 9. Rats underwent focal cerebral I/R injury by arterial ligation and received in vivo therapeutic EA at the Baihui (DU20) and Shenting (DU24) acupoints. The therapeutic efficacy was then evaluated following the surgery. The results of the current study demonstrated that EA treatment significantly ameliorated neurological deficits and reduced cerebral infarct volume compared with I/R injured rats. Furthermore, EA improved the learning and memory ability of rats following I/R injury, inhibited blood brain barrier breakdown and reduced neuronal damage in the ischemic penumbra. Furthermore, EA attenuated ultrastructural changes in the brain tissue following ischemia and inhibited MMP‑2/MMP‑9 expression in cerebral I/R injured rats. The results suggest that EA ameliorates anatomical deterioration, and learning and memory deficits in rats with cerebral I/R injury.

Cellular defense against singlet oxygen-induced oxidative damage by cytosolic NADP+-dependent isocitrate dehydrogenase.

Science.gov (United States)

Kim, Sun Yee; Park, Jeen-Woo

2003-03-01

Singlet oxygen (1O2) is a highly reactive form of molecular oxygen that may harm living systems by oxidizing critical cellular macromolecules. Recently, we have shown that NADP+-dependent isocitrate dehydrogenase is involved in the supply of NADPH needed for GSH production against cellular oxidative damage. In this study, we investigated the role of cytosolic form of NADP+-dependent isocitrate dehydrogenase (IDPc) against singlet oxygen-induced cytotoxicity by comparing the relative degree of cellular responses in three different NIH3T3 cells with stable transfection with the cDNA for mouse IDPc in sense and antisense orientations, where IDPc activities were 2.3-fold higher and 39% lower, respectively, than that in the parental cells carrying the vector alone. Upon exposure to singlet oxygen generated from photoactivated dye, the cells with low levels of IDPc became more sensitive to cell killing. Lipid peroxidation, protein oxidation, oxidative DNA damage and intracellular peroxide generation were higher in the cell-line expressing the lower level of IDPc. However, the cells with the highly over-expressed IDPc exhibited enhanced resistance against singlet oxygen, compared to the control cells. The data indicate that IDPc plays an important role in cellular defense against singlet oxygen-induced oxidative injury.

Baicalin Ameliorates Experimental Liver Cholestasis in Mice by Modulation of Oxidative Stress, Inflammation, and NRF2 Transcription Factor

Directory of Open Access Journals (Sweden)

Kezhen Shen

2017-01-01

Full Text Available Experimental cholestatic liver fibrosis was performed by bile duct ligation (BDL in mice, and significant liver injury was observed in 15 days. Administration of baicalin in mice significantly ameliorates liver fibrosis. Experimental cholestatic liver fibrosis was associated with induced gene expression of fibrotic markers such as collagen I, fibronectin, alpha smooth muscle actin (SMA, and connective tissue growth factor (CTGF; increased inflammatory cytokines (TNFα, MIP1α, IL1β, and MIP2; increased oxidative stress and reactive oxygen species- (ROS- inducing enzymes (NOX2 and iNOS; dysfunctional mitochondrial electron chain complexes; and apoptotic/necrotic cell death markers (DNA fragmentation, caspase 3 activity, and PARP activity. Baicalin administration on alternate day reduced fibrosis along with profibrotic gene expression, proinflammatory cytokines, oxidative stress, and cell death whereas improving the function of mitochondrial electron transport chain. We observed baicalin enhanced NRF2 activation by nuclear translocation and induced its target genes HO-1 and GCLM, thus enhancing antioxidant defense. Interplay of oxidative stress/inflammation and NRF2 were key players for baicalin-mediated protection. Stellate cell activation is crucial for initiation of fibrosis. Baicalin alleviated stellate cell activation and modulated TIMP1, SMA, collagen 1, and fibronectin in vitro. This study indicates that baicalin might be beneficial for reducing inflammation and fibrosis in liver injury models.

Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection

Energy Technology Data Exchange (ETDEWEB)

Sahu, Bidya Dhar [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Tatireddy, Srujana [National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037 (India); Koneru, Meghana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Borkar, Roshan M. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Kumar, Jerald Mahesh [CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad 500 007 (India); Kuncha, Madhusudana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Srinivas, R. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Shyam Sunder, R. [Faculty of Pharmacy, Osmania University, Hyderabad 500 007 (India); Sistla, Ramakrishna, E-mail: sistla@iict.res.in [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India)

2014-05-15

Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in

Over-expression of heme oxygenase-1 promotes oxidative mitochondrial damage in rat astroglia.

Science.gov (United States)

Song, Wei; Su, Haixiang; Song, Sisi; Paudel, Hemant K; Schipper, Hyman M

2006-03-01

Glial heme oxygenase-1 is over-expressed in the CNS of subjects with Alzheimer disease (AD), Parkinson disease (PD) and multiple sclerosis (MS). Up-regulation of HO-1 in rat astroglia has been shown to facilitate iron sequestration by the mitochondrial compartment. To determine whether HO-1 induction promotes mitochondrial oxidative stress, assays for 8-epiPGF(2alpha) (ELISA), protein carbonyls (ELISA) and 8-OHdG (HPLC-EC) were used to quantify oxidative damage to lipids, proteins, and nucleic acids, respectively, in mitochondrial fractions and whole-cell compartments derived from cultured rat astroglia engineered to over-express human (h) HO-1 by transient transfection. Cell viability was assessed by trypan blue exclusion and the MTT assay, and cell proliferation was determined by [3H] thymidine incorporation and total cell counts. In rat astrocytes, hHO-1 over-expression (x 3 days) resulted in significant oxidative damage to mitochondrial lipids, proteins, and nucleic acids, partial growth arrest, and increased cell death. These effects were attenuated by incubation with 1 microM tin mesoporphyrin, a competitive HO inhibitor, or the iron chelator, deferoxamine. Up-regulation of HO-1 engenders oxidative mitochondrial injury in cultured rat astroglia. Heme-derived ferrous iron and carbon monoxide (CO) may mediate the oxidative modification of mitochondrial lipids, proteins and nucleic acids in these cells. Glial HO-1 hyperactivity may contribute to cellular oxidative stress, pathological iron deposition, and bioenergetic failure characteristic of degenerating and inflamed neural tissues and may constitute a rational target for therapeutic intervention in these conditions. Copyright 2005 Wiley-Liss, Inc.

Association between Urinary Excretion of Cortisol and Markers of Oxidatively Damaged DNA and RNA in Humans

DEFF Research Database (Denmark)

Joergensen, Anders; Broedbaek, Kasper; Weimann, Allan

2011-01-01

Chronic psychological stress is associated with accelerated aging, but the underlying biological mechanisms are not known. Prolonged elevations of the stress hormone cortisol is suspected to play a critical role. Through its actions, cortisol may potentially induce oxidatively generated damage...... to cellular constituents such as DNA and RNA, a phenomenon which has been implicated in aging processes. We investigated the relationship between 24 h excretion of urinary cortisol and markers of oxidatively generated DNA and RNA damage, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 8-oxo-7,8-dihydroguanosine......, in a sample of 220 elderly men and women (age 65 - 83 years). We found a robust association between the excretion of cortisol and the oxidation markers (R(2)¿=¿0.15, P...

Nitric oxide synthase inhibition ameliorates nicotine-induced sperm function decline in male rats

Directory of Open Access Journals (Sweden)

Ibukun P. Oyeyipo

2015-09-01

Conclusion: Taken together, the present data indicate the abilities of l-NAME to ameliorate nicotine-induced spermatotoxic effects in male rats via a mechanism dependent on the circulating testosterone level.

Application of lipid peroxidation and protein oxidation biomarkers for oxidative damage in mammalian cells. A comparison with two fluorescent probes

NARCIS (Netherlands)

Orhan, H.; Gurer-Orhan, H.; Vriese, E.; Vermeulen, N.P.E.; Meerman, J.H.N.

2006-01-01

We recently developed two biomarker sets for oxidative damage: one for determination of lipid peroxidation (LPO) degradation products; acetaldehyde, propanal, butanal, pentanal, hexanal, heptanal, octanal, nonanal, malondialdehyde and acetone, by a gas chromatography-electron capture detection

4β-Hydroxywithanolide E selectively induces oxidative DNA damage for selective killing of oral cancer cells.

Science.gov (United States)

Tang, Jen-Yang; Huang, Hurng-Wern; Wang, Hui-Ru; Chan, Ya-Ching; Haung, Jo-Wen; Shu, Chih-Wen; Wu, Yang-Chang; Chang, Hsueh-Wei

2018-03-01

Reactive oxygen species (ROS) induction had been previously reported in 4β-hydroxywithanolide (4βHWE)-induced selective killing of oral cancer cells, but the mechanism involving ROS and the DNA damage effect remain unclear. This study explores the role of ROS and oxidative DNA damage of 4βHWE in the selective killing of oral cancer cells. Changes in cell viability, morphology, ROS, DNA double strand break (DSB) signaling (γH2AX foci in immunofluorescence and DSB signaling in western blotting), and oxidative DNA damage (8-oxo-2'deoxyguanosine [8-oxodG]) were detected in 4βHWE-treated oral cancer (Ca9-22) and/or normal (HGF-1) cells. 4βHWE decreased cell viability, changed cell morphology and induced ROS generation in oral cancer cells rather than oral normal cells, which were recovered by a free radical scavenger N-acetylcysteine (NAC). For immunofluorescence, 4βHWE also accumulated more of the DSB marker, γH2AX foci, in oral cancer cells than in oral normal cells. For western blotting, DSB signaling proteins such as γH2AX and MRN complex (MRE11, RAD50, and NBS1) were overexpressed in 4βHWE-treated oral cancer cells in different concentrations and treatment time. In the formamidopyrimidine-DNA glycolyase (Fpg)-based comet assay and 8-oxodG-based flow cytometry, the 8-oxodG expressions were higher in 4βHWE-treated oral cancer cells than in oral normal cells. All the 4βHWE-induced DSB and oxidative DNA damage to oral cancer cells were recovered by NAC pretreatment. Taken together, the 4βHWE selectively induced DSB and oxidative DNA damage for the ROS-mediated selective killing of oral cancer cells. © 2017 Wiley Periodicals, Inc.

D-saccharic acid-1,4-lactone ameliorates alloxan-induced diabetes mellitus and oxidative stress in rats through inhibiting pancreatic beta-cells from apoptosis via mitochondrial dependent pathway

Energy Technology Data Exchange (ETDEWEB)

Bhattacharya, Semantee [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Manna, Prasenjit [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India); Gachhui, Ratan [Department of Life Sciences and Biotechnology, Jadavpur University, 188, Raja S C Mullick Road, Kolkata 700 032 (India); Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in [Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054 (India)

2011-12-15

Oxidative stress plays a vital role in diabetic complications. To suppress the oxidative stress mediated damage in diabetic pathophysiology, a special focus has been given on naturally occurring antioxidants present in normal diet. D-saccharic acid 1,4-lactone (DSL), a derivative of D-glucaric acid, is present in many dietary plants and is known for its detoxifying and antioxidant properties. The aim of the present study was to evaluate the beneficial role of DSL against alloxan (ALX) induced diabetes in the pancreas tissue of Swiss albino rats. A dose-dependent study for DSL (20-120 mg/kg body weight) was carried out to find the effective dose of the compound in ALX-induced diabetic rats. ALX exposure elevated the blood glucose, glycosylated Hb, decreased the plasma insulin and disturbed the intra-cellular antioxidant machineries whereas oral administration of DSL at a dose of 80 mg/kg body weight restored these alterations close to normal. Investigating the mechanism of the protective activity of DSL we observed that it prevented the pancreatic {beta}-cell apoptosis via mitochondria-dependent pathway. Results showed decreased mitochondrial membrane potential, enhanced cytochrome c release in the cytosol and reciprocal regulation of Bcl-2 family proteins in the diabetic rats. These events were also found to be associated with increased level of Apaf-1, caspase 9, and caspase 3 that ultimately led to pancreatic {beta}-cell apoptosis. DSL treatment, however, counteracted these changes. In conclusion, DSL possesses the capability of ameliorating the oxidative stress in ALX-induced diabetes and thus could be a promising approach in lessening diabetic complications. Highlights: Black-Right-Pointing-Pointer Oxidative stress is suggested as a key event in the pathogenesis of diabetes. Black-Right-Pointing-Pointer D-saccharic acid 1,4-lactone (DSL) reduces the alloxan-induced diabetes mellitus. Black-Right-Pointing-Pointer DSL normalizes cellular antioxidant machineries

D-saccharic acid-1,4-lactone ameliorates alloxan-induced diabetes mellitus and oxidative stress in rats through inhibiting pancreatic beta-cells from apoptosis via mitochondrial dependent pathway

International Nuclear Information System (INIS)

Bhattacharya, Semantee; Manna, Prasenjit; Gachhui, Ratan; Sil, Parames C.

2011-01-01

Oxidative stress plays a vital role in diabetic complications. To suppress the oxidative stress mediated damage in diabetic pathophysiology, a special focus has been given on naturally occurring antioxidants present in normal diet. D-saccharic acid 1,4-lactone (DSL), a derivative of D-glucaric acid, is present in many dietary plants and is known for its detoxifying and antioxidant properties. The aim of the present study was to evaluate the beneficial role of DSL against alloxan (ALX) induced diabetes in the pancreas tissue of Swiss albino rats. A dose-dependent study for DSL (20–120 mg/kg body weight) was carried out to find the effective dose of the compound in ALX-induced diabetic rats. ALX exposure elevated the blood glucose, glycosylated Hb, decreased the plasma insulin and disturbed the intra-cellular antioxidant machineries whereas oral administration of DSL at a dose of 80 mg/kg body weight restored these alterations close to normal. Investigating the mechanism of the protective activity of DSL we observed that it prevented the pancreatic β-cell apoptosis via mitochondria-dependent pathway. Results showed decreased mitochondrial membrane potential, enhanced cytochrome c release in the cytosol and reciprocal regulation of Bcl-2 family proteins in the diabetic rats. These events were also found to be associated with increased level of Apaf-1, caspase 9, and caspase 3 that ultimately led to pancreatic β-cell apoptosis. DSL treatment, however, counteracted these changes. In conclusion, DSL possesses the capability of ameliorating the oxidative stress in ALX-induced diabetes and thus could be a promising approach in lessening diabetic complications. Highlights: ► Oxidative stress is suggested as a key event in the pathogenesis of diabetes. ► D-saccharic acid 1,4-lactone (DSL) reduces the alloxan-induced diabetes mellitus. ► DSL normalizes cellular antioxidant machineries disturbed due to alloxan toxicity. ► DSL inhibits pancreatic β-cells apoptosis

Screening SIRT1 Activators from Medicinal Plants as Bioactive Compounds against Oxidative Damage in Mitochondrial Function

Directory of Open Access Journals (Sweden)

Yi Wang

2016-01-01

Full Text Available Sirtuin type 1 (SIRT1 belongs to the family of NAD+ dependent histone deacetylases and plays a critical role in cellular metabolism and response to oxidative stress. Traditional Chinese medicines (TCMs, as an important part of natural products, have been reported to exert protective effect against oxidative stress in mitochondria. In this study, we screened SIRT1 activators from TCMs and investigated their activities against mitochondrial damage. 19 activators were found in total by in vitro SIRT1 activity assay. Among those active compounds, four compounds, ginsenoside Rb2, ginsenoside F1, ginsenoside Rc, and schisandrin A, were further studied to validate the SIRT1-activation effects by liquid chromatography-mass spectrometry and confirm their activities against oxidative damage in H9c2 cardiomyocytes exposed to tert-butyl hydroperoxide (t-BHP. The results showed that those compounds enhanced the deacetylated activity of SIRT1, increased ATP content, and inhibited intracellular ROS formation as well as regulating the activity of Mn-SOD. These SIRT1 activators also showed moderate protective effects on mitochondrial function in t-BHP cells by recovering oxygen consumption and increasing mitochondrial DNA content. Our results suggested that those compounds from TCMs attenuated oxidative stress-induced mitochondrial damage in cardiomyocytes through activation of SIRT1.

Oxidative stress generated damage to DNA by gastrointestinal exposure to insoluble particles

DEFF Research Database (Denmark)

Møller, Peter; Folkmann, J K; Danielsen, P H

2012-01-01

that gastrointestinal exposure to single-walled carbon nanotubes (SWCNT), fullerenes C60, carbon black, titanium dioxide and diesel exhaust particles generates oxidized DNA base lesions in organs such as the bone marrow, liver and lung. Oral exposure to nanosized carbon black has also been associated with increased...... level of lipid peroxidation derived exocyclic DNA adducts in the liver, suggesting multiple pathways of oxidative stress for particle-generated damage to DNA. At equal dose, diesel exhaust particles (SRM2975) generated larger levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine in rat liver than carbon black...

Role of oxidative DNA damage in genome instability and cancer

International Nuclear Information System (INIS)

Bignami, M.; Kunkel, T.

2009-01-01

Inactivation of mismatch repair (MMR) is associated with a dramatic genomic instability that is observed experimentally as a mutator phenotype and micro satellite instability (MSI). It has been implicit that the massive genetic instability in MMR defective cells simply reflects the accumulation of spontaneous DNA polymerase errors during DNA replication. We recently identified oxidation damage, a common threat to DNA integrity to which purines are very susceptible, as an important cofactor in this genetic instability

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 (CdCl 2 , 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.

Zingiber officinale Roscoe ameliorates anticancer antibiotic doxorubicin-induced acute cardiotoxicity in rat.

Science.gov (United States)

Ajith, Thekkuttuparambil Ananthanarayanan; Hema, Unnikrishnan; Aswathi, Sreedharan

2016-07-01

Oxidative stress (OS) has been suggested in the cardiotoxicity induced by anticancer antibiotic doxorubicin (DXN). The cardioprotective effects of aqueous ethanol extract of Zingiber officinale was evaluated against DXN-induced acute cardiac damage in rat. The results of the study demonstrated that Z. officinale significantly and dose dependently protected the cardiotoxicity induced by DXN. The activities of serum glutamate oxaloacetate transaminase and serum lactate dehydrogenase activity in the DXN alone treated group of animals were significantly (pofficinale (200 and 400 mg/kg, p.o) plus DXN treated groups. The cardiac malondialdehyde was elevated in the DXN alone treated group and declined significantly in the Z. officinale (400 mg/kg) plus DXN treated group. The results concluded that aqueous ethanol extract of Z. officinale ameliorated DXN-induced cardiotoxicity. The protection can be ascribed to the free radical scavenging activity of Z. officinale. This protective effect may suggest the adjuvant role of Z. officinale against OS induced by cancer chemotherapeutants, which warrant further research. © 2016 Old City Publishing, Inc.

Levels of oxidative damage and lipid peroxidation in thyroid neoplasia.

LENUS (Irish Health Repository)

Young, Orla

2012-02-01

BACKGROUND: This study assessed the presence of oxidative damage and lipid peroxidation in thyroid neoplasia. METHODS: Using tissue microarrays and immunohistochemistry, we assessed levels of DNA damage (8-oxo-dG) and lipid peroxidation (4-HNE) in 71 follicular thyroid adenoma (FTA), 45 papillary thyroid carcinoma (PTC), and 17 follicular thyroid carcinoma (FTC) and matched normal thyroid tissue. RESULTS: Cytoplasmic 8-oxo-dG and 4-HNE expression was significantly higher in FTA, FTC, and PTC tissue compared to matched normal tissue (all p values < .001). Similarly, elevated nuclear levels of 8-oxo-dG were seen in all in FTA, FTC, and PTC tissue compared to matched normal (p values < .07, < .001, < .001, respectively). In contrast, a higher level of 4-HNE expression was detected in normal thyroid tissue compared with matched tumor tissue (p < .001 for all groups). Comparing all 3 groups, 4-HNE levels were higher than 8-oxo-dG levels (p < .001 for all groups) except that cytoplasmic levels of 8-oxo-dG were higher than 4-HNE in all (p < .001). These results were independent of proliferation status. CONCLUSION: High levels of DNA damage and lipid peroxidation in benign and malignant thyroid neoplasia indicates this damage is an early event that may influence disease progression.

Nicotinamide mononucleotide inhibits post-ischemic NAD(+) degradation and dramatically ameliorates brain damage following global cerebral ischemia.

Science.gov (United States)

Park, Ji H; Long, Aaron; Owens, Katrina; Kristian, Tibor

2016-11-01

Nicotinamide adenine dinucleotide (NAD(+)) is an essential cofactor for multiple cellular metabolic reactions and has a central role in energy production. Brain ischemia depletes NAD(+) pools leading to bioenergetics failure and cell death. Nicotinamide mononucleotide (NMN) is utilized by the NAD(+) salvage pathway enzyme, nicotinamide adenylyltransferase (Nmnat) to generate NAD(+). Therefore, we examined whether NMN could protect against ischemic brain damage. Mice were subjected to transient forebrain ischemia and treated with NMN or vehicle at the start of reperfusion or 30min after the ischemic insult. At 2, 4, and 24h of recovery, the proteins poly-ADP-ribosylation (PAR), hippocampal NAD(+) levels, and expression levels of NAD(+) salvage pathway enzymes were determined. Furthermore, animal's neurologic outcome and hippocampal CA1 neuronal death was assessed after six days of reperfusion. NMN (62.5mg/kg) dramatically ameliorated the hippocampal CA1 injury and significantly improved the neurological outcome. Additionally, the post-ischemic NMN treatment prevented the increase in PAR formation and NAD(+) catabolism. Since the NMN administration did not affect animal's temperature, blood gases or regional cerebral blood flow during recovery, the protective effect was not a result of altered reperfusion conditions. These data suggest that administration of NMN at a proper dosage has a strong protective effect against ischemic brain injury. Published by Elsevier Inc.

Effects of prior surface damage on high-temperature oxidation of Fe-, Ni-, and Co-based alloys

Energy Technology Data Exchange (ETDEWEB)

Blau, Peter Julian [ORNL; Lowe, Tracie M [ORNL; Pint, Bruce A [ORNL

2009-01-01

Multi-component metallic alloys have been developed to withstand high-temperature service in corrosive environments. Some of these applications, like exhaust valve seats in internal combustion engines, must also resist sliding, impact, and abrasion. The conjoint effects of temperature, oxidation, and mechanical contact can result in accelerated wear and the formation of complex surface layers whose properties differ from those of the base metal and the oxide scale that forms in the absence of mechanical contact. The authors have investigated the effects of prior surface damage, produced by scratch tests, on the localized reformation of oxide layers. Three high-performance commercial alloys, based on iron, nickel, and cobalt, were used as model materials. Thermogravimetric analysis (TGA) was used to determine their static oxidation rates at elevated temperature (850o C). A micro-abrasion, ball-cratering technique was used to measure oxide layer thickness and to compare it with TGA results. By using taper-sectioning techniques and energy-dispersive elemental mapping, a comparison was made between oxide compositions grown on non-damaged surfaces and oxides that formed on grooves produced by a diamond stylus. Microindentation and scratch hardness data revealed the effects of high temperature exposure on both the substrate hardness and the nature of oxide scale disruption. There were significant differences in elemental distribution between statically-formed oxides and those that formed on scratched regions

Frequency of polymorphism -262 c/t in catalase gene and oxidative damage in Slovak children with bronchial asthma.

Science.gov (United States)

Babusikova, Eva; Jesenak, Milos; Evinova, Andrea; Banovcin, Peter; Dobrota, Dusan

2013-12-01

Bronchial asthma is a complex disease in which genetic factors, environmental factors and oxidative damage are responsible for the initiation and modulation of disease progression. If antioxidant mechanisms fail, reactive oxygen species damage the biomolecules followed by progression of the disease. Catalase is one of the most important endogenous enzymatic antioxidants. In the present study, we examined the hypothesis that increased oxidative damage and polymorphism in the CAT gene (-262 promoter region, C/T) are associated with childhood bronchial asthma. Genotyping of the polymorphisms in the CAT gene in healthy (249) and asthmatic children (248) was performed using polymerase chain reaction-restriction fragment length polymorphism. Markers of oxidative damage: content of sulfhydryl groups and thiobarbituric acid-reactive substances were determined by spectrophotometry in children. The TT genotype of catalase was more frequent among the asthmatic patients (22.6%) than in healthy children (4.8%) (odds ratio=5.63; 95% confidence interval=2.93-10.81, P<.001). The amount of sulfhydryl groups decreased significantly and conversely, the content of thiobarbituric acid-reactive substances increased significantly in bronchial asthma and in catalase TT genotype compared to other catalase genotypes of this gene. These results suggest that catalase polymorphism might participate in development of bronchial asthma and in enhanced oxidative damage in asthmatic children. Genetic variation of enzymatic antioxidants may modulate disease risk. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

Relation between both oxidative and metabolic-osmotic cell damages and initial injury severity in bombing casualties

Directory of Open Access Journals (Sweden)

Vučeljić Marina

2006-01-01

Full Text Available Background/Aim. We have recently reported the development of oxidative cell damages in bombing casualties within a very early period after the initial injury. The aim of this study, was to investigate malondialdehyde (MDA, as an indicator of lipid peroxidation, and osmolal gap (OG, as a good indicator of metabolic cell damages and to assess their relationship with the initial severity of the injury in bombing casualties. Methods. The study included the males (n = 52, injured during the bombing with the Injury Severity Score (ISS ranging from 3 to 66. The whole group of casualties was devided into a group of less severely (ISS < 25, n = 24 and a group of severely (ISS ≥ 26, n = 28 injured males. The uninjured volunteers (n = 10 were the controls. Osmolality, MDA, sodium, glucose, urea, creatinine, total bilirubin and total protein levels were measured in the venous blood, sampled daily, within a ten-day period. Results. In both groups of casualties, MDA and OG levels increased, total protein levels decreased, while other parameters were within the control limits. MDA alterations correlated with ISS (r = 0.414, p < 0.01, while a statistically significant correlation between OG and ISS was not obtained. Interestingly, in spite of some differences in MDA and OG trends, at the end of the examined period they were at the similar level in both groups. Conclusion. The initial oxidative damages of the cellular membrane with intracellular metabolic disorders contributed to the gradual development of metabolic-osmotic damages of cells, which, consequently caused the OG increase. In the bombing casualties, oxidative cell damages were dependent on the initial injury severity, while metabolic-osmotic cell damages were not.

Echinacoside Induces Apoptosis in Human SW480 Colorectal Cancer Cells by Induction of Oxidative DNA Damages

Directory of Open Access Journals (Sweden)

Liwei Dong

2015-06-01

Full Text Available Echinacoside is a natural compound with potent reactive oxygen species (ROS-scavenging and anti-oxidative bioactivities, which protect cells from oxidative damages. As cancer cells are often under intense oxidative stress, we therefore tested if Echinacoside treatment would promote cancer development. Surprisingly, we found that Echinacoside significantly inhibited the growth and proliferation of a panel of cancer cell lines. Treatment of the human SW480 cancer cells with Echinacoside resulted in marked apoptosis and cell cycle arrest, together with a significant increase in active caspase 3 and cleaved PARP, and upregulation of the G1/S-CDK blocker CDKN1B (p21. Interestingly, immunocytochemistry examination of drug-treated cancer cells revealed that Echinacoside caused a significant increase of intracellular oxidized guanine, 8-oxoG, and dramatic upregulation of the double-strand DNA break (DSB-binding protein 53BP1, suggesting that Echinacoside induced cell cycle arrest and apoptosis in SW480 cancer cells via induction of oxidative DNA damages. These results establish Echinacoside as a novel chemical scaffold for development of anticancer drugs.

Evaluation of Cassia tora Linn. against oxidative stress-induced DNA and cell membrane damage

Directory of Open Access Journals (Sweden)

R Sunil Kumar

2017-01-01

Full Text Available Objective: The present study aims to evaluate antioxidants and protective role of Cassia tora Linn. against oxidative stress-induced DNA and cell membrane damage. Materials and Methods: The total and profiles of flavonoids were identified and quantified through reversed-phase high-performance liquid chromatography. In vitro antioxidant activity was determined using standard antioxidant assays. The protective role of C. tora extracts against oxidative stress-induced DNA and cell membrane damage was examined by electrophoretic and scanning electron microscopic studies, respectively. Results: The total flavonoid content of CtEA was 106.8 ± 2.8 mg/g d.w.QE, CtME was 72.4 ± 1.12 mg/g d.w.QE, and CtWE was 30.4 ± 0.8 mg/g d.w.QE. The concentration of flavonoids present in CtEA in decreasing order: quercetin >kaempferol >epicatechin; in CtME: quercetin >rutin >kaempferol; whereas, in CtWE: quercetin >rutin >kaempferol. The CtEA inhibited free radical-induced red blood cell hemolysis and cell membrane morphology better than CtME as confirmed by a scanning electron micrograph. CtEA also showed better protection than CtME and CtWE against free radical-induced DNA damage as confirmed by electrophoresis. Conclusion: C. tora contains flavonoids and inhibits oxidative stress and can be used for many health benefits and pharmacotherapy.

Erythrocytes Membrane Alterations Reflecting Liver Damage in CCl₄-Induced Cirrhotic Rats: The Ameliorative Effect of Naltrexone

Directory of Open Access Journals (Sweden)

Fatemeh Sarhadi Kholari

2016-11-01

Full Text Available Cirrhosis is the consequence of chronic liver disease. Deleterious effects of oxidative stress on hepatocytes may be reflected in the erythrocyte membrane. Naltrexone (NTX has been shown to attenuate hepatocellular injury in fibrotic animal models. The aim of this study was to investigate the progressive effect of CCl4 on the liver and whether the improvement of liver cirrhosis can be monitored through alterations in the erythrocyte membrane. In this study, 84 male Wistar rats were divided into 4 groups and received reagents (i.p. as follows: 1- CCl₄, 2- NTX + CCl₄, 3- Mineral Oil (M, and 4- NTX + M. After 2, 6 and 8 weeks, the blood and liver tissue samples were collected. Plasma enzyme activities, the content of erythrocyte GSH and some membrane compositions, including protein carbonyl, protein sulfhydryl, and malondialdehyde were assessed. After 6 and 8 weeks, plasma enzyme activities and the content of protein carbonyl were higher in CCl4 group significantly, as compared to other groups (P<0.001. NTX significantly diminished protein carbonyl and plasma enzyme activities (P<0.001. GSH did not change until the 6th week. However, CCl4+NTX increased it significantly as compared to CCl₄ group (P<0.05. Protein sulfhydryl showed changes in NTX+CCl₄ group which indicated a significant increase in protein sulfhydryl content in a 6th week compared to CCl4 group (P<0.05. MDA did not show any significant alteration. CCl₄-induced cirrhosis is accompanied by increased content of oxidative stress markers, especially protein carbonyl of RBC membrane and plasma enzyme activities. This study shows that the progression of liver cirrhosis and the ameliorative effect of NTX can be followed through alterations of these markers.

Oxidative Damage and Its Possible Mechanism

Directory of Open Access Journals (Sweden)

Tingting Wang

2016-06-01

Full Text Available Purpose: The paper tries to assess the protective effect of fisetin against •OH-induced DNAdamage, then to investigate the possible mechanism.Methods: The protective effect was evaluated based on the content of malondialdehyde(MDA. The possible mechanism was analyzed using various antioxidant methods in vitro,including •OH scavenging (deoxyribose degradation, •O2- scavenging (pyrogallolautoxidation, DPPH• scavenging, ABTS•+ scavenging, and Cu2+-reducing power assays.Results: Fisetin increased dose-dependently its protective percentages against •OH-inducedDNA damage (IC50 value =1535.00±29.60 μM. It also increased its radical-scavengingpercentages in a dose-dependent manner in various antioxidants assays. Its IC50 values in•OH scavenging, •O2- scavenging, DPPH• scavenging, ABTS•+ scavenging, and Cu2+-reducing power assays, were 47.41±4.50 μM, 34.05±0.87 μM, 9.69±0.53 μM, 2.43±0.14μM, and 1.49±0.16 μM, respectively.Conclusion: Fisetin can effectively protect DNA against •OH-induced oxidative damagepossibly via reactive oxygen species (ROS scavenging approach, which is assumed to behydrogen atom (H• and/or single electron (e donation (HAT/SET pathways. In the HATpathway, the 3’,4’-dihydroxyl moiety in B ring of fisetin is thought to play an importantrole, because it can be ultimately oxidized to a stable ortho-benzoquinone form.

Mild Oxidative Damage in the Diabetic Rat Heart Is Attenuated by Glyoxalase-1 Overexpression

Directory of Open Access Journals (Sweden)

Casper G. Schalkwijk

2013-07-01

Full Text Available Diabetes significantly increases the risk of heart failure. The increase in advanced glycation endproducts (AGEs and oxidative stress have been associated with diabetic cardiomyopathy. We recently demonstrated that there is a direct link between AGEs and oxidative stress. Therefore, the aim of the current study was to investigate if a reduction of AGEs by overexpression of the glycation precursor detoxifying enzyme glyoxalase-I (GLO-I can prevent diabetes-induced oxidative damage, inflammation and fibrosis in the heart. Diabetes was induced in wild-type and GLO-I transgenic rats by streptozotocin. After 24-weeks of diabetes, cardiac function was monitored with ultrasound under isoflurane anesthesia. Blood was drawn and heart tissue was collected for further analysis. Analysis with UPLC-MSMS showed that the AGE Nε-(1-carboxymethyllysine and its precursor 3-deoxyglucosone were significantly elevated in the diabetic hearts. Markers of oxidative damage, inflammation, and fibrosis were mildly up-regulated in the heart of the diabetic rats and were attenuated by GLO-I overexpression. In this model of diabetes, these processes were not accompanied by significant changes in systolic heart function, i.e., stroke volume, fractional shortening and ejection fraction. This study shows that 24-weeks of diabetes in rats induce early signs of mild cardiac alterations as indicated by an increase of oxidative stress, inflammation and fibrosis which are mediated, at least partially, by glycation.

Ameliorative potential of Ocimum sanctum in chronic constriction injury-induced neuropathic pain in rats

Directory of Open Access Journals (Sweden)

GURPREET KAUR

2015-03-01

Full Text Available The present study was designed to investigate the ameliorative potential of Ocimumsanctum and its saponin rich fraction in chronic constriction injury-induced neuropathic pain in rats. The chronic constriction injury was induced by placing four loose ligatures around the sciatic nerve, proximal to its trifurcation. The mechanical hyperalgesia, cold allodynia, paw heat hyperalgesia and cold tail hyperalgesia were assessed by performing the pinprick, acetone, hot plate and cold tail immersion tests, respectively. Biochemically, the tissue thio-barbituric acid reactive species, super-oxide anion content (markers of oxidative stress and total calcium levels were measured. Chronic constriction injury was associated with the development of mechanical hyperalgesia, cold allodynia, heat and cold hyperalgesia along with an increase in oxidative stress and calcium levels. However, administration of Ocimumsanctum (100 and 200 mg/kg p.o. and its saponin rich fraction (100 and 200 mg/kg p.o. for 14 days significantly attenuated chronic constriction injury-induced neuropathic pain as well as decrease the oxidative stress and calcium levels. It may be concluded that saponin rich fraction of Ocimum sanctum has ameliorative potential in attenuating painful neuropathic state, which may be attributed to a decrease in oxidative stress and calcium levels.

Base excision repair of oxidative DNA damage and association with cancer and aging

DEFF Research Database (Denmark)

Maynard, Scott; Schurman, Shepherd H; Harboe, Charlotte

2009-01-01

Aging has been associated with damage accumulation in the genome and with increased cancer incidence. Reactive oxygen species (ROS) are produced from endogenous sources, most notably the oxidative metabolism in the mitochondria, and from exogenous sources, such as ionizing radiation. ROS attack DNA...

Repair of oxidative DNA base damage in the host genome influences the HIV integration site sequence preference.

Directory of Open Access Journals (Sweden)

Geoffrey R Bennett

Full Text Available Host base excision repair (BER proteins that repair oxidative damage enhance HIV infection. These proteins include the oxidative DNA damage glycosylases 8-oxo-guanine DNA glycosylase (OGG1 and mutY homolog (MYH as well as DNA polymerase beta (Polβ. While deletion of oxidative BER genes leads to decreased HIV infection and integration efficiency, the mechanism remains unknown. One hypothesis is that BER proteins repair the DNA gapped integration intermediate. An alternative hypothesis considers that the most common oxidative DNA base damages occur on guanines. The subtle consensus sequence preference at HIV integration sites includes multiple G:C base pairs surrounding the points of joining. These observations suggest a role for oxidative BER during integration targeting at the nucleotide level. We examined the hypothesis that BER repairs a gapped integration intermediate by measuring HIV infection efficiency in Polβ null cell lines complemented with active site point mutants of Polβ. A DNA synthesis defective mutant, but not a 5'dRP lyase mutant, rescued HIV infection efficiency to wild type levels; this suggested Polβ DNA synthesis activity is not necessary while 5'dRP lyase activity is required for efficient HIV infection. An alternate hypothesis that BER events in the host genome influence HIV integration site selection was examined by sequencing integration sites in OGG1 and MYH null cells. In the absence of these 8-oxo-guanine specific glycosylases the chromatin elements of HIV integration site selection remain the same as in wild type cells. However, the HIV integration site sequence preference at G:C base pairs is altered at several positions in OGG1 and MYH null cells. Inefficient HIV infection in the absence of oxidative BER proteins does not appear related to repair of the gapped integration intermediate; instead oxidative damage repair may participate in HIV integration site preference at the sequence level.

Amelioration of both early and late radiation-induced damage to pig skin by essential fatty acids

International Nuclear Information System (INIS)

Hopewell, J.W.; Van den Aardweg, G.J.M.J.; Morris, G.M.

1994-01-01

To evaluate the possible role of essential fatty acids, specifically gamma-linolenic and eicosapentaenoic acid, in the amelioration of early and late radiation damage to the skin. Skin sites on the flank of 22-25 kg female large white pigs were irradiated with either single or fractionated doses (20 F/28 days) of β-rays from 22.5 mm diameter 90 Sr/ 90 Y plaques at a dose rate of ∼3 Gy/min. Essential fatty acids were administered orally in the form of two open-quotes activeclose quotes oils, So-1100 and So-5407, which contained gamma-linolenic acid and a mixture of that oil with eicosapentaenoic acid, respectively. Oils (1.5-6.0 ml) were given daily for 4 weeks prior, both 4 weeks prior and 10-16 weeks after, or in the case of one single dose study, just for 10 weeks after irradiation. Control animals received a open-quotes placeboclose quotes oil, So-1129, containing no gamma linolenic acid or eicosapentaenoic acid over similar time scales before and after irradiation. Acute and late skin reactions were assessed visually and the dose-related incidence of a specific reaction used to compare the effects of different treatment schedules. A reduction in the severity of both the early and late radiation reactions in the skin was only observed when open-quotes activeclose quotes oils were given over the time course of the expression of radiation damage. Prior treatment with oils did not modify the radiation reaction. A 3.0 ml daily dose of either So-1100 or So-5407 given prior to, but also after irradiation with single and fractionated doses of β-rays produced the most significant modification to the radiation reactions, effects consistent with dose modification factors between 1.06-1.24 for the acute reactions of bright red erythema and/or moist desquamation, and of 1.14-1.35 for the late reactions of dusky/mauve erythema and dermal necrosis. 38 refs., 5 tabs

Zataria multiflora ameliorates testicular and spermatological damages induced by cisplatin in mice model

Directory of Open Access Journals (Sweden)

2017-11-01

Full Text Available Background and objectives: Cisplatin (CP, a highly effective antineoplastic drug, causes testicular damage. Zataria multiflora Boiss. (ZM, a medicinal plant, has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects of ZM against cisplatin-induced testicular toxicity. Methods: Thirty-two adult male mice were randomly divided into four groups. The control group received normal saline with oral gavage during 7 days; ZM group received ZM (200 mg/kg during 7 days by gavage; CP group received CP (10 mg/kg i.p. in 5th day of study; ZM + CP group received ZM during 7 days and CP was injected in 5th day. Sperm parameters (including motility, sperm count, sperm viability rate and morphological sperm abnormalities, biochemical (malondialdehyde (MDA, glutathione (GSH and protein carbonyl (PC levels, serum testosterone levels, histological and immunochemistry assays of testis were examined one day after the last receipt of the drug. Results: CP treatment caused significant damage via changed of sperm parameters, increased oxidative stress (increased MDA, PC levels and decreased GSH level, histological changes (degeneration, necrosis, arrest of spermatogenesis, congestion and decrease in thickness of the germinal epithelium, diameter of seminiferous tubules and Johnsen’s Score, decreased serum testosterone level and increased caspase-3 immunoreactivity. ZM preserved spermatogenesis and mitigated the toxic effects of CP on the testis tissue. In addition, pretreatment with ZM significantly reduced caspase-3 immunoreactivity. Conclusion: The findings of this study suggested ZM as a potential antioxidant compound which showed protective effect against cisplatin-induced testicular toxicity.

Stress proteins and oxidative damage in a renal derived cell line exposed to inorganic mercury and lead

International Nuclear Information System (INIS)

Stacchiotti, Alessandra; Morandini, Fausta; Bettoni, Francesca; Schena, Ilaria; Lavazza, Antonio; Grigolato, Pier Giovanni; Apostoli, Pietro; Rezzani, Rita; Aleo, Maria Francesca

2009-01-01

A close link between stress protein up-regulation and oxidative damage may provide a novel therapeutic tool to counteract nephrotoxicity induced by toxic metals in the human population, mainly in children, of industrialized countries. Here we analysed the time course of the expression of several heat shock proteins, glucose-regulated proteins and metallothioneins in a rat proximal tubular cell line (NRK-52E) exposed to subcytotoxic doses of inorganic mercury and lead. Concomitantly, we used morphological and biochemical methods to evaluate metal-induced cytotoxicity and oxidative damage. In particular, as biochemical indicators of oxidative stress we detected reactive oxygen species (ROS) and nitrogen species (RNS), total glutathione (GSH) and glutathione-S-transferase (GST) activity. Our results clearly demonstrated that mercury increases ROS and RNS levels and the expressions of Hsp25 and inducible Hsp72. These findings are corroborated by evident mitochondrial damage, apoptosis or necrosis. By contrast, lead is unable to up-regulate Hsp72 but enhances Grp78 and activates nuclear Hsp25 translocation. Furthermore, lead causes endoplasmic reticulum (ER) stress, vacuolation and nucleolar segregation. Lastly, both metals stimulate the over-expression of MTs, but with a different time course. In conclusion, in NRK-52E cell line the stress response is an early and metal-induced event that correlates well with the direct oxidative damage induced by mercury. Indeed, different chaperones are involved in the specific nephrotoxic mechanism of these environmental pollutants and work together for cell survival.

Metallothionein blocks oxidative DNA damage induced by acute inorganic arsenic exposure

Energy Technology Data Exchange (ETDEWEB)

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

2015-02-01

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

Protective property of mulberry digest against oxidative stress - A potential approach to ameliorate dietary acrylamide-induced cytotoxicity.

Science.gov (United States)

Zhang, Linxia; Xu, Yang; Li, Yuting; Bao, Tao; Gowd, Vemana; Chen, Wei

2017-09-01

The aim of this study was investigating the protective effect of mulberry digest (MBD) on acrylamide-induced oxidative stress. Composition analysis of MBD revealed that it contained six major phenolic compounds (quercetin-3-O-rutinoside, quercetin hexoside, quercetin rhamnosylhexoside hexoside, kaempferol rhamnosylhexoside, cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside). After in vitro digestion, the contents of two anthocyanins were both decreased significantly, while the contents of four flavonoid glycosides were all increased. In addition, MBD was found to successfully suppress acrylamide-induced ROS overproduction, restore the mitochondrial membrane potential, and inhibit the mitochondrial membrane lipid peroxidation and glutathione depletion. More interestingly, the protective effect of MBD against acrylamide-induced oxidative damage was enhanced compared with mulberry fruits without digestion (MBE). Further study revealed that MBD enhanced the cell resistance capacity to acrylamide-induced oxidative stress, rather than its direct reaction with acrylamide. Overall, our results indicate that MBD provides a potent protection against acrylamide-induced oxidative stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

Zerumbone, a Bioactive Sesquiterpene, Ameliorates Diabetes-Induced Retinal Microvascular Damage through Inhibition of Phospho-p38 Mitogen-Activated Protein Kinase and Nuclear Factor-κB Pathways

Directory of Open Access Journals (Sweden)

Wayne Young Liu

2016-12-01

Full Text Available Zerumbone ameliorates retinal damage by blocking advanced glycation end products and their receptor system in streptozotocin-diabetic rats. Because of the multiple factors involved in diabetic retinopathy (DR etiology, the mechanisms of zerumbone that are mainly responsible for its ameliorative effect on DR need to be further clarified. In the present study, zerumbone (20 mg or 40 mg/kg or fenofibric acid (100 mg/kg was orally administered to diabetic rats by intragastric gavage once daily for three consecutive months. Zerumbone displayed similar characteristics to fenofibric acid in reducing retinal vascular permeability and leukostasis in diabetic rats. Fundus photographs showed that large retinal vessel diameters were decreased in zerumbone-treated diabetic rats. Zerumbone not only down-regulated the gene expression of retinal angiogenic parameters, but also reduced the expression of inflammatory cytokines and chemokines in the retina of diabetic rats. Moreover, zerumbone reduced the p38 MAPK phosphorylation and abrogated the nuclear translocation of NF-κB p65 in the retina of diabetic rats. In conclusion, treatment of diabetic rats with zerumbone attenuates the severity of retinal inflammation and angiogenesis, via inhibition of p38 MAPK and NF-κB signaling pathways. These benefits of zerumbone for DR appear to be linked to its antihyperglycemic and antihyperlipidemic effects.

The possible influences of dietary oil supplementation in ameliorating metabolic disturbances and oxidative stress in Alloxan injected rats

International Nuclear Information System (INIS)

Farag, M.F.S.; Osman, N.N.; Darwish, M.M.

2005-01-01

Diabetes mellitus (DM) is a multifactor disease that is associated with a number of different metabolic abnormalities. Clinical research has confirmed the efficacy of several plant extracts in the modulation of oxidative stress associated with DM. The present work was conducted to examine the protective or treating effects of two different dietary oils rich in medium chain fatty acids (MCFA) as coconut oil (CO) or omega-3-polyunsaturated fatty acids (ω-3-PUFAs)as flaxseed oil (FO) on the severity of DM induced experimentally by alloxan injection. Wistar strain albino rats (17 Og) were fed commercial rat chow diet supplemented with either CO or FO for four weeks. A single dose of alloxan (150 mg/kg) resulted in hyperglycemia, decreases in serum insulin, thyroxine (T 4 ), and high density lipoprotein-cholesterol levels, elevated triglycerides, total cholesterol and low density lipoprotein-cholesterol concentrations. Concurrent with those changes, an increased liver malonaldehyde (MDA) level was observed. This oxidative stress was related to decreases in superoxide dismutase (SOD) activity and glutathione (GSH) content in the liver of alloxan diabetic rats. Oils supplementation after diabetes induction ameliorated hyperglycemia, increased insulin and thyroxine hormone levels, improved lipid profiles, blunted the increase in MDA, modulated the levels of hepatic SOD activity and GSH content of alloxan treated rats. It could be suggested that each of CO or FO could be used as antidiabetic complement in case of DM. This may be related to their anti oxidative properties

Oxidative stress damage as a detrimental factor in preterm birth pathology.

Science.gov (United States)

Menon, Ramkumar

2014-01-01

Normal term and spontaneous preterm births (PTB) are documented to be associated with oxidative stress (OS), and imbalances in the redox system (balance between pro- and antioxidant) have been reported in the maternal-fetal intrauterine compartments. The exact mechanism of labor initiation either at term or preterm by OS is still unclear, and this lack of understanding can partially be blamed for failure of antioxidant supplementation trials in PTB prevention. Based on recent findings from our laboratory, we postulate heterogeneity in host OS response. The physiologic (at term) and pathophysiologic (preterm) pathways of labor are not mediated by OS alone but by OS-induced damage to intrauterine tissues, especially fetal membranes of the placenta. OS damage affects all major cellular elements in the fetal cells, and this damage promotes fetal cell senescence (aging). The aging of the fetal cells is predominated by p38 mitogen activated kinase (p38MAPK) pathways. Senescing cells generate biomolecular signals that are uterotonic, triggering labor process. The aging of fetal cells is normal at term. However, aging is premature in PTB, especially in those PTBs complicated by preterm premature rupture of the membranes, where elements of redox imbalances and OS damage are more dominant. We postulate that fetal cell senescence signals generated by OS damage are likely triggers for labor. This review highlights the mechanisms involved in senescence development at term and preterm by OS damage and provides insight into novel fetal signals of labor initiation pathways.

Ballet dancers cardiorespiratory, oxidative and muscle damage responses to classes and rehearsals.

Science.gov (United States)

Rodrigues-Krause, Josianne; Krause, Mauricio; Cunha, Giovani Dos Santos; Perin, Diana; Martins, Jocelito B; Alberton, Cristine Lima; Schaun, Maximiliano I; De Bittencourt, Paulo Ivo Homem; Reischak-Oliveira, Alvaro

2014-01-01

This study aimed to describe and compare ballet dancers' cardiorespiratory responses, muscle damage and oxidative stress levels during a ballet class (practice of isolated ballet exercises performed with barre/hand-rail support and across-the-floor movements to improve technical skills) and rehearsal (practice of ballet choreography involving technical-artistic skills to improve dancers' performance for shows). The 12 advanced female ballet dancers undertook three exercise sessions: maximum effort test, class and rehearsal. Heart rate (HR) and oxygen consumption (VO2) were continuously measured. Lactate was determined before 15 min and after class and rehearsal. Blood was sampled pre, post and 48 h after class and rehearsal for creatine kinase (CK), lipid peroxides (LPO) and glutathione analysis (GSSG/GSH). Class was of lower intensity than rehearsal as shown by VO2, HR and lactate values: VO2 (mL.kg(-1).min(-1)): 14.5±2.1 vs. 19.1±1.7 (p Ballet dancers' muscle damage and oxidative stress responses seem not to be dependent on exercise intensity based on VO2 responses.

Biologically relevant oxidants and terminology, classification and nomenclature of oxidatively generated damage to nucleobases and 2-deoxyribose in nucleic acids

DEFF Research Database (Denmark)

Cadet, Jean; Loft, Steffen; Olinski, Ryszard

2012-01-01

A broad scientific community is involved in investigations aimed at delineating the mechanisms of formation and cellular processing of oxidatively generated damage to nucleic acids. Perhaps as a consequence of this breadth of research expertise, there are nomenclature problems for several of the ...

Hydroxytyrosol Protects against Oxidative DNA Damage in Human Breast Cells

Directory of Open Access Journals (Sweden)

José J. Gaforio

2011-10-01

Full Text Available Over recent years, several studies have related olive oil ingestion to a low incidence of several diseases, including breast cancer. Hydroxytyrosol and tyrosol are two of the major phenols present in virgin olive oils. Despite the fact that they have been linked to cancer prevention, there is no evidence that clarifies their effect in human breast tumor and non-tumor cells. In the present work, we present hydroxytyrosol and tyrosol’s effects in human breast cell lines. Our results show that hydroxytyrosol acts as a more efficient free radical scavenger than tyrosol, but both fail to affect cell proliferation rates, cell cycle profile or cell apoptosis in human mammary epithelial cells (MCF10A or breast cancer cells (MDA-MB-231 and MCF7. We found that hydroxytyrosol decreases the intracellular reactive oxygen species (ROS level in MCF10A cells but not in MCF7 or MDA-MB-231 cells while very high amounts of tyrosol is needed to decrease the ROS level in MCF10A cells. Interestingly, hydroxytyrosol prevents oxidative DNA damage in the three breast cell lines. Therefore, our data suggest that simple phenol hydroxytyrosol could contribute to a lower incidence of breast cancer in populations that consume virgin olive oil due to its antioxidant activity and its protection against oxidative DNA damage in mammary cells.

Antioxidant treatment ameliorates experimental diabetes-induced depressive-like behaviour and reduces oxidative stress in brain and pancreas.

Science.gov (United States)

Réus, Gislaine Z; Dos Santos, Maria Augusta B; Abelaira, Helena M; Titus, Stephanie E; Carlessi, Anelise S; Matias, Beatriz I; Bruchchen, Livia; Florentino, Drielly; Vieira, Andriele; Petronilho, Fabricia; Ceretta, Luciane B; Zugno, Alexandra I; Quevedo, João

2016-03-01

Studies have shown a relationship between diabetes mellitus (DM) and the development of major depressive disorder. Alterations in oxidative stress are associated with the pathophysiology of both diabetes mellitus and major depressive disorder. This study aimed to evaluate the effects of antioxidants N-acetylcysteine and deferoxamine on behaviour and oxidative stress parameters in diabetic rats. To this aim, after induction of diabetes by a single dose of alloxan, Wistar rats were treated with N-acetylcysteine or deferoxamine for 14 days, and then depressive-like behaviour was evaluated. Oxidative stress parameters were assessed in the prefrontal cortex, hippocampus, amygdala, nucleus accumbens and pancreas. Diabetic rats displayed depressive-like behaviour, and treatment with N-acetylcysteine reversed this alteration. Carbonyl protein levels were increased in the prefrontal cortex, hippocampus and pancreas of diabetic rats, and both N-acetylcysteine and deferoxamine reversed these alterations. Lipid damage was increased in the prefrontal cortex, hippocampus, amygdala and pancreas; however, treatment with N-acetylcysteine or deferoxamine reversed lipid damage only in the hippocampus and pancreas. Superoxide dismutase activity was decreased in the amygdala, nucleus accumbens and pancreas of diabetic rats. In diabetic rats, there was a decrease in catalase enzyme activity in the prefrontal cortex, amygdala, nucleus accumbens and pancreas, but an increase in the hippocampus. Treatment with antioxidants did not have an effect on the activity of antioxidant enzymes. In conclusion, animal model of diabetes produced depressive-like behaviour and oxidative stress in the brain and periphery. Treatment with antioxidants could be a viable alternative to treat behavioural and biochemical alterations induced by diabetes. Copyright © 2015 John Wiley & Sons, Ltd.

Antidepressant activity of vorinostat is associated with amelioration of oxidative stress and inflammation in a corticosterone-induced chronic stress model in mice.

Science.gov (United States)

Kv, Athira; Madhana, Rajaram Mohanrao; Js, Indu Chandran; Lahkar, Mangala; Sinha, Swapnil; Naidu, V G M

2018-05-15

Major depressive disorder (MDD) is a multifactorial neuropsychiatric disorder. Chronic administration of corticosterone (CORT) to rodents is used to mimic the stress associated dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, a well-established feature found in depressive patients. Recently, preclinical studies have demonstrated the antidepressant potential of histone deacetylase (HDAC) inhibitors. So, we examined the antidepressant potential of vorinostat (VOR), a HDAC inhibitor against CORT injections in male mice. VOR (25 mg/kg; intraperitoneal) and fluoxetine (FLX) (15 mg/kg; oral) treatments were provided to CORT administered mice. At the end of dosing schedule, neurobehavioral tests were conducted; followed by mechanistic evaluation through biochemical analysis, RTPCR and western blot in serum and hippocampus. Neurobehavioral tests revealed the development of anxiety/depressive-like behavior in CORT mice as compared to the vehicle control. Depressive-mice showed concomitant HPA axis dysregulation as observed from the significant increase in serum CORT and ACTH. Chronic CORT administration was found to significantly increase hippocampal malondialdehyde (MDA) and iNOS levels while lowering glutathione (GSH) content, as compared to vehicle control. VOR treatment, in a similar manner to the classical antidepressant FLX, significantly ameliorated anxiety/depressive-like behavior along with HPA axis alterations induced by CORT. The antidepressant-like ability of drug treatments against chronic CORT induced stress model, as revealed in our study, may be due to their potential to mitigate inflammatory damage and oxidative stress via modulation of hippocampal NF-κB p65, COX-2, HDAC2 and phosphorylated JNK levels. Copyright © 2018 Elsevier B.V. All rights reserved.

[Effect of germacrone in alleviating HUVECs damaged by H2O2-induced oxidative stress].

Science.gov (United States)

Chen, Qiong-Fang; Wang, Gang; Tang, Li-Qing; Yu, Xian-Wen; Li, Zhao-Fei; Yang, Xiu-Fen

2017-09-01

This study focuses on the protective effect of germacrone on human umbilical vein endothelial cells(HUVECs) damaged by H2O2-induced oxidative stress and its possible mechanisms. The oxidative damage model was established by using 500 μmol•L⁻¹ H2O2 to treat HUVECs for 3 hours, and then protected with different concentrations of germacrone for 24 hours. The effect of germacrone on cell viability of HUVECs damaged by H2O2 was detected by MTT. The contents of PGI2, TXB2, ET-1, t-PA, PAI-1, TNF-α and IL-6 were detected by ELISA. The content of NO was detected by using nitrate reductase method. Colorimetry was used to detect NOS and GSH-Px. The contents of MDA, SOD and LDH were detected by TBA, WST-1 and microplate respectively. Apoptosis was observed by Hoechst 33258 fluorescent staining. The mRNA expressions of Bax, Bcl-2 and Caspase-3 in cells were detected by RT-PCR. The results showed that the cell damage rate was 52% after treated with 500 μmol•L⁻¹ H2O2 for 3 hours. The cell activity was increasing with the rise of germacrone concentration within the range of 20-200 mol•L⁻¹. Compared with normal group, the contents of PGI2, NO, T-NOS, t-PA, SOD, GSH-Px and Bcl-2 mRNA expressions were lower after damaged with H2O2. The contents of PAI-1, ET-1, IL-6, TNF-α, TXB2, LDH, MDA, Bax mRNA and Caspase-3 mRNA expressions were increased. Compared with model group, the contents of PGI2, NO, T-NOS, t-PA, SOD, GSH-Px and Bcl-2 mRNA expressions were increased after treated with germacrone. The contents of PAI-1, ET-1, IL-6, TNF-α, TXB2, LDH, MDA, Bax mRNA and Caspase-3 mRNA expressions were lower after treated with germacrone. According to Hoechst 33258 fluorescence staining, compared with normal group, the cell membrane and the nucleus showed strong dense blue fluorescence, and the number of cells significantly decreased in model group. Compared with model group, blue fluorescence intensity decreased in drug group. The above findings demonstrate that

Effect of lemon verbena supplementation on muscular damage markers, proinflammatory cytokines release and neutrophils' oxidative stress in chronic exercise.

Science.gov (United States)

Funes, Lorena; Carrera-Quintanar, Lucrecia; Cerdán-Calero, Manuela; Ferrer, Miguel D; Drobnic, Franchek; Pons, Antoni; Roche, Enrique; Micol, Vicente

2011-04-01

Intense exercise is directly related to muscular damage and oxidative stress due to excessive reactive oxygen species (ROS) in both, plasma and white blood cells. Nevertheless, exercise-derived ROS are essential to regulate cellular adaptation to exercise. Studies on antioxidant supplements have provided controversial results. The purpose of this study was to determine the effect of moderate antioxidant supplementation (lemon verbena extract) in healthy male volunteers that followed a 90-min running eccentric exercise protocol for 21 days. Antioxidant enzymes activities and oxidative stress markers were measured in neutrophils. Besides, inflammatory cytokines and muscular damage were determined in whole blood and serum samples, respectively. Intense running exercise for 21 days induced antioxidant response in neutrophils of trained male through the increase of the antioxidant enzymes catalase, glutathione peroxidase and glutathione reductase. Supplementation with moderate levels of an antioxidant lemon verbena extract did not block this cellular adaptive response and also reduced exercise-induced oxidative damage of proteins and lipids in neutrophils and decreased myeloperoxidase activity. Moreover, lemon verbena supplementation maintained or decreased the level of serum transaminases activity indicating a protection of muscular tissue. Exercise induced a decrease of interleukin-6 and interleukin-1β levels after 21 days measured in basal conditions, which was not inhibited by antioxidant supplementation. Therefore, moderate antioxidant supplementation with lemon verbena extract protects neutrophils against oxidative damage, decreases the signs of muscular damage in chronic running exercise without blocking the cellular adaptation to exercise.

Effects of environmental pollution on endogenous oxidative DNA damage in humans

Czech Academy of Sciences Publication Activity Database

Singh, R.; Kaur, B.; Kalina, I.; Popov, T. A.; Georgieva, T.; Garte, S.; Binková, Blanka; Šrám, Radim; Taioli, E.; Farmer, P. B.

2007-01-01

Roč. 620, - (2007), s. 71-82 ISSN 0027-5107 Grant - others:EU(NO) 2000 -00091; EU(NO) G0100873 Institutional research plan: CEZ:AV0Z50390512 Source of funding: R - rámcový projekt EK ; R - rámcový projekt EK Keywords : oxidative DNA damage * polycyclic aromatic hydrocarbons * -oxo-deoxyguanosine Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 4.159, year: 2007

Oxidative Stress Measures of Lipid and DNA Damage in Human Tears.

Science.gov (United States)

Haworth, Kristina M; Chandler, Heather L

2017-05-01

We evaluate feasibility and repeatability of measures for lipid peroxidation and DNA oxidation in human tears, as well as relationships between outcome variables, and compared our findings to previously reported methods of evaluation for ocular sun exposure. A total of 50 volunteers were seen for 2 visits 14 ± 2 days apart. Tear samples were collected from the inferior tear meniscus using a glass microcapillary tube. Oxidative stress biomarkers were quantified using enzyme-linked immunosorbent assay (ELISA): lipid peroxidation by measurement of hexanoyl-lysine (HEL) expression; DNA oxidation by measurement of 8-oxo-2'-deoxyguinosone (8OHdG) expression. Descriptive statistics were generated. Repeatability estimates were made using Bland-Altman plots with mean differences and 95% limits of agreement were calculated. Linear regression was conducted to evaluate relationships between measures. Mean (±SD) values for tear HEL and 8OHdG expression were 17368.02 (±9878.42) nmol/L and 66.13 (±19.99) ng/mL, respectively. Repeatability was found to be acceptable for both HEL and 8OHdG expression. Univariate linear regression supported tear 8OHdG expression and spring season of collection to be predictors of higher tear HEL expression; tear HEL expression was confirmed as a predictor of higher tear 8OHdG expression. We demonstrate feasibility and repeatability of estimating previously unreported tear 8OHdG expression. Seasonal temperature variation and other factors may influence tear lipid peroxidation. Support is demonstrated to suggest lipid damage and DNA damage occur concurrently on the human ocular surface.

Chromosome and oxidative damage biomarkers in lymphocytes of Parkinson's disease patients.

Science.gov (United States)

Migliore, L; Scarpato, R; Coppede, F; Petrozzi, L; Bonuccelli, U; Rodilla, V

2001-10-01

As cancer development usually results from exposure to several environmental risk factors in interaction with the genetic susceptibility of the host, it could be of interest to investigate if neurodegeneration, as occurs in Parkinson's disease (PD) patients can be attributed at least partially, to environmental risk factors. There is growing evidence that oxidative stress could play a significant role as a risk factor in the aetiology and pathogenesis of neurodegenerative diseases, emphasising the need for new individual and human-based approaches. The aim of our research is to explore the relation between chromosome instability and oxidative stress biomarkers in Parkinson's disease using a variety of strategies. We determined peripheral markers for oxidative damage in PD by testing for spontaneous and induced chromosomal damage, DNA strand breaks, oxidised pyrimidines and altered purines both in peripheral blood and cultured lymphocytes. We also measured glutathione S-transferase activity in the plasma of patients and controls. Compared to healthy controls, PD patients show higher frequencies of micronuclei (17.2 +/- 4.8 vs. 9.0 +/- 3.4, p < 0.001) and a significant increase in the levels of single strand breaks (SSB). Significant differences were also obtained in the distribution of oxidised purine bases between the two groups. Preliminary data obtained by fluorescence in situ hybridization analysis showed that the percentage of centromere negative micronuclei is higher than that of centromere positive micronuclei. Glutathione S-transferase activity in plasma from PD patients and controls was also measured and the enzymatic activity in PD patients was lower than in healthy controls.

Systemic oxidatively generated DNA/RNA damage in clinical depression

DEFF Research Database (Denmark)

Jorgensen, Anders; Krogh, Jesper; Miskowiak, Kamilla

2013-01-01

oxidatively generated DNA and RNA damage, 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), respectively, were determined in healthy controls (N=28), moderately depressed, non-medicated patients (N=26) and severely depressed patients eligible for electroconvulsive therapy...... for trend=0.004). The 8-oxoGuo excretion was further increased after clinically effective ECT compared with pre-ECT values (P=0.006). There were no differences in 8-oxodG excretion between the groups or pre- vs. post-ECT. LIMITATIONS: Small sample size and the inclusion of both unipolar and bipolar patients...

Herpes simplex virus induces neural oxidative damage via microglial cell Toll-like receptor-2

Directory of Open Access Journals (Sweden)

Little Morgan R

2010-06-01

Full Text Available Abstract Background Using a murine model of herpes simplex virus (HSV-1 encephalitis, our laboratory has determined that induction of proinflammatory mediators in response to viral infection is largely mediated through a Toll-like receptor-2 (TLR2-dependent mechanism. Published studies have shown that, like other inflammatory mediators, reactive oxygen species (ROS are generated during viral brain infection. It is increasingly clear that ROS are responsible for facilitating secondary tissue damage during central nervous system infection and may contribute to neurotoxicity associated with herpes encephalitis. Methods Purified microglial cell and mixed neural cell cultures were prepared from C57B/6 and TLR2-/- mice. Intracellular ROS production in cultured murine microglia was measured via 2', 7'-Dichlorofluorescin diacetate (DCFH-DA oxidation. An assay for 8-isoprostane, a marker of lipid peroxidation, was utilized to measure free radical-associated cellular damage. Mixed neural cultures obtained from β-actin promoter-luciferase transgenic mice were used to detect neurotoxicity induced by HSV-infected microglia. Results Stimulation with HSV-1 elevated intracellular ROS in wild-type microglial cell cultures, while TLR2-/- microglia displayed delayed and attenuated ROS production following viral infection. HSV-infected TLR2-/- microglia produced less neuronal oxidative damage to mixed neural cell cultures in comparison to HSV-infected wild-type microglia. Further, HSV-infected TLR2-/- microglia were found to be less cytotoxic to cultured neurons compared to HSV-infected wild-type microglia. These effects were associated with decreased activation of p38 MAPK and p42/p44 ERK in TLR2-/- mice. Conclusions These studies demonstrate the importance of microglial cell TLR2 in inducing oxidative stress and neuronal damage in response to viral infection.

SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages

International Nuclear Information System (INIS)

Lee, Ae Sin; Jung, Yu Jin; Kim, Dal; Nguyen-Thanh, Tung; Kang, Kyung Pyo; Lee, Sik; Park, Sung Kwang; Kim, Won

2014-01-01

Highlights: • Knockout of SIRT2 attenuates lipopolysaccharide-induced iNOS expression. • Lipopolysaccharide-induced NO production is decreased in SIRT2 KO macrophage. • SIRT2 deficiency suppresses lipopolysaccharide-induced ROS production in macrophage. • M1-macrophage related factors are decreased in SIRT2 deficient cells. • SIRT2 deficiency decreases lipopolysaccharide-induced activation of NFκB. - Abstract: Introduction: SIRT2 is a NAD(+)-dependent deacetylases and associated with numerous processes such as infection, carcinogenesis, DNA damage and cell cycle regulation. However, the role of SIRT2 in inflammatory process in macrophage remains unclear. Materials and methods: In the present study, we have evaluated the regulatory effects of SIRT2 in lipopolysaccharide (LPS)-stimulated macrophages isolated from SIRT2 knockout (KO) and wild type (WT) mice or Raw264.7 macrophage cells. As inflammatory parameters, expression of inducible nitric oxide synthase (iNOS), the productions of nitric oxide, reactive oxygen species (ROS) and M1-macrophage-related factors were evaluated. We also examined the effects of SIRT2 on activation of nuclear factor-kappaB (NFκB) signaling. Results: SIRT2 deficiency inhibits LPS-induced iNOS mRNA and protein expression in bone marrow derived macrophages. SIRT2-siRNA transfection also suppressed LPS-induced iNOS expression in Raw264.7 macrophage cells. Bone marrow derived macrophages isolated from SIRT2 KO mice produced lower nitric oxide and expressed lower levels of M1-macrophage related markers including iNOS and CD86 in response to LPS than WT mice. Decrease of SIRT2 reduced the LPS-induced reactive oxygen species production. Deficiency of SIRT2 resulted in inhibition of NFκB activation through reducing the phosphorylation and degradation of IκBα. The phosphorylation and nuclear translocation of p65 was significantly decreased in SIRT2-deficient macrophages after LPS stimulation. Discussion: Our data suggested that

SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages

Energy Technology Data Exchange (ETDEWEB)

Lee, Ae Sin; Jung, Yu Jin; Kim, Dal; Nguyen-Thanh, Tung [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kang, Kyung Pyo [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Lee, Sik [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Park, Sung Kwang [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Kim, Won, E-mail: kwon@jbnu.ac.kr [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of)

2014-08-08

Highlights: • Knockout of SIRT2 attenuates lipopolysaccharide-induced iNOS expression. • Lipopolysaccharide-induced NO production is decreased in SIRT2 KO macrophage. • SIRT2 deficiency suppresses lipopolysaccharide-induced ROS production in macrophage. • M1-macrophage related factors are decreased in SIRT2 deficient cells. • SIRT2 deficiency decreases lipopolysaccharide-induced activation of NFκB. - Abstract: Introduction: SIRT2 is a NAD(+)-dependent deacetylases and associated with numerous processes such as infection, carcinogenesis, DNA damage and cell cycle regulation. However, the role of SIRT2 in inflammatory process in macrophage remains unclear. Materials and methods: In the present study, we have evaluated the regulatory effects of SIRT2 in lipopolysaccharide (LPS)-stimulated macrophages isolated from SIRT2 knockout (KO) and wild type (WT) mice or Raw264.7 macrophage cells. As inflammatory parameters, expression of inducible nitric oxide synthase (iNOS), the productions of nitric oxide, reactive oxygen species (ROS) and M1-macrophage-related factors were evaluated. We also examined the effects of SIRT2 on activation of nuclear factor-kappaB (NFκB) signaling. Results: SIRT2 deficiency inhibits LPS-induced iNOS mRNA and protein expression in bone marrow derived macrophages. SIRT2-siRNA transfection also suppressed LPS-induced iNOS expression in Raw264.7 macrophage cells. Bone marrow derived macrophages isolated from SIRT2 KO mice produced lower nitric oxide and expressed lower levels of M1-macrophage related markers including iNOS and CD86 in response to LPS than WT mice. Decrease of SIRT2 reduced the LPS-induced reactive oxygen species production. Deficiency of SIRT2 resulted in inhibition of NFκB activation through reducing the phosphorylation and degradation of IκBα. The phosphorylation and nuclear translocation of p65 was significantly decreased in SIRT2-deficient macrophages after LPS stimulation. Discussion: Our data suggested that

Shikonin ameliorates isoproterenol (ISO)-induced myocardial damage through suppressing fibrosis, inflammation, apoptosis and ER stress.

Science.gov (United States)

Yang, Jun; Wang, Zhao; Chen, Dong-Lin

2017-09-01

Shikonin, isolated from the roots of herbal plant Lithospermum erythrorhizon, is a naphthoquinone. It has been reported to exert beneficial anti-inflammatory effects and anti-oxidant properties in various diseases. Isoproterenol (ISO) has been widely used to establish cardiac injury in vivo and in vitro. However, shikonin function in ISO-induced cardiac injury remains uncertain. In our study, we attempted to investigate the efficiency and possible molecular mechanism of shikonin in cardiac injury treatment induced by ISO. In vivo, C57BL6 mice were subcutaneously injected with 5mg/kg ISO to induce heart failure. And mice were given a gavage of shikonin (2 or 4mg/kg/d, for four weeks). Cardiac function, fibrosis indices, inflammation response, apoptosis and endoplasmic reticulum (ER) stress were calculated. Pathological alterations, fibrosis-, inflammation-, apoptosis- and ER stress-related molecules were examined. In ISO-induced cardiac injury, shikonin significantly ameliorated heart function, decreased myocardial fibrosis, suppressed inflammation, attenuated apoptosis and ER stress through impeding collagen accumulation, Toll like receptor 4/nuclear transcription factor κB (TLR4/NF-κB), Caspase-3 and glucose-regulated protein 78 (GRP78) signaling pathways activity, relieving heart failure in vivo. Also, in vitro, shikonin attenuated ISO-induced cardiac muscle cells by reducing fibrosis, inflammation, apoptosis and ER stress. Our findings indicated that shikonin treatment attenuated ISO-induced heart injury, providing an effective therapeutic strategy for heart failure treatment for future. Copyright © 2017. Published by Elsevier Masson SAS.

Studies on Ameliorative Effects of Polyphenolic Extract from Paullinia pinnata L. (Sapindaceae on Carbon Tetrachloride - Induced Hepatotoxicity and Oxidative Stress: an in vivo Assessment

Directory of Open Access Journals (Sweden)

Mikhail O. NAFIU

2018-03-01

Full Text Available The current study investigates the effects of polyphenolic extract from the leaf of Paullinia pinnata against CCl4 – induced oxidative stress and liver damage in female albino rats. Thirty albino rats were randomly distributed into six groups (A-F. Rats in group A were given 1 ml normal saline orally to serve as control. The rats in groups B, C, D, E, and F were respectively induced intraperitoneally with single administration of 1 ml/kg body weight (b. wt CCl4 dissolved in liquid paraffin (1:1. Thirty minutes after induction, the rats in the respective groups were orally treated with normal saline, 50 mg/kg b. wt. Silymarin, 50, 100 and 200 mg/kg b. wt. polyphenolic extract from P. pinnata respectively, once daily for 7 days.  Levels of liver function indices and the activities of antioxidant enzymes were determined. Administration of polyphenolic extract from P. pinnata significantly (p < 0.05 ameliorated CCl4- induced hepatotoxicity with respect to liver function indices, antioxidant and lipid peroxidation parameters. The biochemical changes observed were also consistent with histopathological observations on the rat liver, as architectural degeneration and severe cellular necrosis were restored after the administration of polyphenolic extract from P. pinnata in the treated groups. The study suggests that polyphenolic extract from P. pinnata is a potential hepatoprotective agent against CCl4-mediated hepatic injury through fortification of antioxidant defense mechanisms.

Age and metabolic risk factors associated with oxidatively damaged DNA in human peripheral blood mononuclear cells

DEFF Research Database (Denmark)

Løhr, Mille; Jensen, Annie; Eriksen, Louise

2015-01-01

Aging is associated with oxidative stress-generated damage to DNA and this could be related to metabolic disturbances. This study investigated the association between levels of oxidatively damaged DNA in peripheral blood mononuclear cells (PBMCs) and metabolic risk factors in 1,019 subjects, aged...... 18-93 years. DNA damage was analyzed as strand breaks by the comet assay and levels of formamidopyrimidine (FPG-) and human 8-oxoguanine DNA glycosylase 1 (hOGG1)-sensitive sites There was an association between age and levels of FPG-sensitive sites for women, but not for men. The same tendency......, cholesterol and glycosylated hemoglobin (HbA1c). In the group of men, there were significant positive associations between alcohol intake, HbA1c and FPG-sensitive sites in multivariate analysis. The levels of metabolic risk factors were positively associated with age, yet only few subjects fulfilled all...

Structural influences on the laser damage resistance of optical oxide coatings for use at 1064 nm

Energy Technology Data Exchange (ETDEWEB)

Hacker, E; Lauth, H; Meyer, J; Weissbrodt, P [Zeiss Jena GmbH, Jena (Germany, F.R.); Wolf, R; Zscherpe, G [Ingenieurhochschule Mittweida (Germany, F.R.); Heyer, H [Sektion Physik, Friedrich-Schiller-Univ. Jena (Germany, F.R.)

1990-11-01

Optical coatings of titania (TiO{sub 2}) and tantala (Ta{sub 2}O{sub 5}) prepared by reactive r.f. diode and d.c. plasmatron sputtering were investigated for the influence of structural properties on the 1064 nm laser damage resistance. Using various methods of characterizing the compositional, crystallographic, microstructural and optical properties, it was found that the damage thresholds are directly related to the content of oxygen in the films in excess of the stoichiometric values, whereas grain sizes and refractive indices show no systematic influences valid for both oxide materials. The highest oxygen-to-metal atomic ratios and thus the highest damage threshold were achieved by the use of r.f diode sputtering. X-ray photospectroscopy investigations of tantala coatings with different oxygen-to-tantalum atomic ratios up to 2.75 revealed for both constituents of the oxide only binding energies representative for tantalum pentoxide. (orig.).

The Neuroprotective Effects of Brazilian Green Propolis on Neurodegenerative Damage in Human Neuronal SH-SY5Y Cells

Directory of Open Access Journals (Sweden)

Junjun Ni

2017-01-01

Full Text Available Oxidative stress and synapse dysfunction are the major neurodegenerative damage correlated to cognitive impairment in Alzheimer’s disease (AD. We have found that Brazilian green propolis (propolis improves the cognitive functions of mild cognitive impairment patients living at high altitude; however, mechanism underlying the effects of propolis is unknown. In the present study, we investigated the effects of propolis on oxidative stress, expression of brain-derived neurotrophic factor (BDNF, and activity-regulated cytoskeleton-associated protein (Arc, the critical factors of synapse efficacy, using human neuroblastoma SH-SY5Y cells. Pretreatment with propolis significantly ameliorated the hydrogen peroxide- (H2O2- induced cytotoxicity in SH-SY5Y cells. Furthermore, propolis significantly reduced the H2O2-generated reactive oxygen species (ROS derived from mitochondria and 8-oxo-2′-deoxyguanosine (8-oxo-dG, the DNA oxidative damage marker but significantly reversed the fibrillar β-amyloid and IL-1β-impaired BDNF-induced Arc expression in SH-SY5Y cells. Furthermore, propolis significantly upregulated BDNF mRNA expression in time- and dose-dependent manners. In addition, propolis induced Arc mRNA and protein expression via phosphoinositide-3 kinase (PI3K. These observations strongly suggest that propolis protects from the neurodegenerative damage in neurons through the properties of various antioxidants. The present study provides a potential molecular mechanism of Brazilian green propolis in prevention of cognitive impairment in AD as well as aging.

DNA damage and defence gene expression after oxidative stress induced by x-rays and diesel exhaust particles

Energy Technology Data Exchange (ETDEWEB)

Risom, Lotte

2004-07-01

Particulate air pollution is one the most important environmental health factors for people living in cities. Especially the exhaust particles from traffic are possible causes for cancer and cardiopulmonary diseases. The aim of this thesis was to characterize the health effects of diesel exhaust particles (DEP) by inducing oxidative stress and analyse the underlying mechanisms. Methods for determining oxidative stress, DNA damage, and gene expression were validated and calibrated in lung tissue by studying the dose response relations after ionizing radiation. The study showed the feasibility of partial-body x-ray irradiation as an in vivo model for induction and repair of oxidative DNA damage, of DNA repair enzymes expression, and antioxidant defense genes. A 'nose-only' mouse model for inhalation of ultra-fine particles showed that particles induce oxidative DNA damage in lung tissue and in bronchoalveolar lavage cells. The exposure increased the expression of HO-1 mRNA and oxoguanine DNA glycosylase OGG1 mRNA. The levels of 8-oxodG and OGG1 mRNA were mirror images. Colon and liver were analysed after administration of DEP in the diet with or without increasing doses of sucrose. This study indicated that DEP induces DNA adducts and oxidative stress through formation of DNA strand breaks, DNA repair enzyme expression, apoptosis, and protein oxidisation in colon and liver at relatively low exposure doses. The thesis is based on four published journal articles. (ln)

DNA damage and defence gene expression after oxidative stress induced by x-rays and diesel exhaust particles

International Nuclear Information System (INIS)

Risom, Lotte

2004-01-01

Particulate air pollution is one the most important environmental health factors for people living in cities. Especially the exhaust particles from traffic are possible causes for cancer and cardiopulmonary diseases. The aim of this thesis was to characterize the health effects of diesel exhaust particles (DEP) by inducing oxidative stress and analyse the underlying mechanisms. Methods for determining oxidative stress, DNA damage, and gene expression were validated and calibrated in lung tissue by studying the dose response relations after ionizing radiation. The study showed the feasibility of partial-body x-ray irradiation as an in vivo model for induction and repair of oxidative DNA damage, of DNA repair enzymes expression, and antioxidant defense genes. A 'nose-only' mouse model for inhalation of ultra-fine particles showed that particles induce oxidative DNA damage in lung tissue and in bronchoalveolar lavage cells. The exposure increased the expression of HO-1 mRNA and oxoguanine DNA glycosylase OGG1 mRNA. The levels of 8-oxodG and OGG1 mRNA were mirror images. Colon and liver were analysed after administration of DEP in the diet with or without increasing doses of sucrose. This study indicated that DEP induces DNA adducts and oxidative stress through formation of DNA strand breaks, DNA repair enzyme expression, apoptosis, and protein oxidisation in colon and liver at relatively low exposure doses. The thesis is based on four published journal articles. (ln)

Dietary Berries and Ellagic Acid Prevent Oxidative DNA Damage and Modulate Expression of DNA Repair Genes

Directory of Open Access Journals (Sweden)

Ramesh C. Gupta

2008-03-01

Full Text Available DNA damage is a pre-requisite for the initiation of cancer and agents that reduce this damage are useful in cancer prevention. In this study, we evaluated the ability of whole berries and berry phytochemical, ellagic acid to reduce endogenous oxidative DNA damage. Ellagic acid was selected based on > 95% inhibition of 8-oxodeoxyguosine (8-oxodG and other unidentified oxidative DNA adducts induced by 4-hydroxy-17B;-estradiol and CuCl2 in vitro. Inhibition of the latter occurred at lower concentrations (10 u(microM than that for 8-oxodG (100 u(microM. In the in vivo study, female CD-1 mice (n=6 were fed either a control diet or diet supplemented with ellagic acid (400 ppm and dehydrated berries (5% w/w with varying ellagic acid contents -- blueberry (low, strawberry (medium and red raspberry (high, for 3 weeks. Blueberry and strawberry diets showed moderate reductions in endogenous DNA adducts (25%. However, both red raspberry and ellagic acid diets showed a significant reduction of 59% (p < 0.001 and 48% (p < 0.01, respectively. Both diets also resulted in a 3-8 fold over-expression of genes involved in DNA repair such as xeroderma pigmentosum group A complementing protein (XPA, DNA excision repair protein (ERCC5 and DNA ligase III (DNL3. These results suggest that red raspberry and ellagic acid reduce endogenous oxidative DNA damage by mechanisms which may involve increase in DNA repair.

Curcumin ameliorates skeletal muscle atrophy in type 1 diabetic mice by inhibiting protein ubiquitination.

Science.gov (United States)

Ono, Taisuke; Takada, Shingo; Kinugawa, Shintaro; Tsutsui, Hiroyuki

2015-09-01

What is the central question of this study? We sought to examine whether curcumin could ameliorate skeletal muscle atrophy in diabetic mice by inhibiting protein ubiquitination, inflammatory cytokines and oxidative stress. What is the main finding and its importance? We found that curcumin ameliorated skeletal muscle atrophy in streptozotocin-induced diabetic mice by inhibiting protein ubiquitination without affecting protein synthesis. This favourable effect of curcumin was possibly due to the inhibition of inflammatory cytokines and oxidative stress. Curcumin may be beneficial for the treatment of muscle atrophy in type 1 diabetes mellitus. Skeletal muscle atrophy develops in patients with diabetes mellitus (DM), especially in type 1 DM, which is associated with chronic inflammation. Curcumin, the active ingredient of turmeric, has various biological actions, including anti-inflammatory and antioxidant properties. We hypothesized that curcumin could ameliorate skeletal muscle atrophy in mice with streptozotocin-induced type 1 DM. C57BL/6 J mice were injected with streptozotocin (200 mg kg(-1) i.p.; DM group) or vehicle (control group). Each group of mice was randomly subdivided into two groups of 10 mice each and fed a diet with or without curcumin (1500 mg kg(-1) day(-1)) for 2 weeks. There were significant decreases in body weight, skeletal muscle weight and cellular cross-sectional area of the skeletal muscle in DM mice compared with control mice, and these changes were significantly attenuated in DM+Curcumin mice without affecting plasma glucose and insulin concentrations. Ubiquitination of protein was increased in skeletal muscle from DM mice and decreased in DM+Curcumin mice. Gene expressions of muscle-specific ubiquitin E3 ligase atrogin-1/MAFbx and MuRF1 were increased in DM and inhibited in DM+Curcumin mice. Moreover, nuclear factor-κB activation, concentrations of the inflammatory cytokines tumour necrosis factor-α and interleukin-1β and oxidative

Riboflavin ameliorates cisplatin induced toxicities under photoillumination.

Directory of Open Access Journals (Sweden)

Iftekhar Hassan

Full Text Available BACKGROUND: Cisplatin is an effective anticancer drug that elicits many side effects mainly due to induction of oxidative and nitrosative stresses during prolonged chemotherapy. The severity of these side effects consequently restricts its clinical use under long term treatment. Riboflavin is an essential vitamin used in various metabolic redox reactions in the form of flavin adenine dinucleotide and flavin mononucleotide. Besides, it has excellent photosensitizing property that can be used to ameliorate these toxicities in mice under photodynamic therapy. METHODS AND FINDINGS: Riboflavin, cisplatin and their combinations were given to the separate groups of mice under photoilluminated condition under specific treatment regime. Their kidney and liver were excised for comet assay and histopathological studies. Furthermore, Fourier Transform Infrared Spectroscopy of riboflavin-cisplatin combination in vitro was also conducted to investigate any possible interaction between the two compounds. Their comet assay and histopathological examination revealed that riboflavin in combination with cisplatin was able to protect the tissues from cisplatin induced toxicities and damages. Moreover, Fourier Transform Infrared Spectroscopy analysis of the combination indicated a strong molecular interaction among their constituent groups that may be assigned for the protective effect of the combination in the treated animals. CONCLUSION: Inclusion of riboflavin diminishes cisplatin induced toxicities which may possibly make the cisplatin-riboflavin combination, an effective treatment strategy under chemoradiotherapy in pronouncing its antineoplastic activity and sensitivity towards the cancer cells as compared to cisplatin alone.

Oxidative damage in response to natural levels of UV-B radiation in larvae of the tropical sea urchin Tripneustes gratilla.

Science.gov (United States)

Lister, Kathryn Naomi; Lamare, Miles D; Burritt, David J

2010-01-01

To assess the effects of UV radiation (280-400nm) on development, oxidative damage and antioxidant defence in larvae of the tropical sea urchin Tripneustes gratilla, a field experiment was conducted at two depths in Aitutaki, Cook Islands (18.85°S, 159.75°E) in May 2008. Compared with field controls (larvae shielded from UV-R but exposed to VIS-radiation), UV-B exposure resulted in developmental abnormality and increases in oxidative damage to proteins (but not lipids) in embryos of T. gratilla held at 1m depth. Results also indicated that larvae had the capacity to increase the activities of protective antioxidant enzymes when exposed to UV-B. The same trends in oxidative damage and antioxidant defence were observed for embryos held at 4m, although the differences were smaller and more variable. In contrast to UV-B exposure, larvae exposed to UV-A only showed no significant increases in abnormality or oxidative damage to lipids and proteins compared with field controls. This was true at both experimental depths. Furthermore, exposure to UV-A did not cause a significant increase in the activities of antioxidants. This study indicates that oxidative stress is an important response of tropical sea urchin larvae to exposure to UV radiation. © 2010 The Authors. Journal Compilation. The American Society of Photobiology.

Effect of recoiled O on damage regrowth and electrical properties of through-oxide implanted Si

International Nuclear Information System (INIS)

Sadana, D.K.; Wu, N.R.; Washburn, J.; Current, M.; Morgan, A.; Reed, D.; Maenpaa, M.

1982-10-01

High dose (4 to 7.5 x 10 15 cm -2 ) As implantations into p-type (100) Si have been carried out through a screen-oxide of thicknesses less than or equal to 775A and without screen oxide. The effect of recoiled O on damage annealing and electrical properties of the implanted layers has been investigated using a combination of the following techniques: TEM, RBS/MeV He + channeling, SIMS and Hall measurements in conjunction with chemical stripping and sheet resistivity measurements. The TEM results show that there is a dramatically different annealing behavior of the implantation damage for the through oxide implants (Case I) as compared to implants into bare silicon (Case II). Comparison of the structural defect profiles with O distributions obtained by SIMS demonstrated that retardation in the secondary damage growth in Case I can be directly related with the presence of O. Weak-beam TEM showed that a high density of fine defect clusters (less than or equal to 50A) were present both in Case I and Case II. The electrical profiles showed only 30% of the total As to be electrically active. The structural and electrical results have been explained by a model that entails As-O, Si-O and As-As complex formation and their interaction with the dislocations

Oxidative stress damage as a detrimental factor in preterm birth pathology

Directory of Open Access Journals (Sweden)

Ramkumar eMenon

2014-11-01

Full Text Available Normal term and spontaneous preterm births (PTB are documented to be associated with oxidative stress (OS, and imbalances in the redox system (balance between pro- and antioxidant have been reported in the maternal-fetal intrauterine compartments. The exact mechanism of labor initiation either at term or preterm by OS is still unclear, and this lack of understanding can partially be blamed for failure of antioxidant supplementation trials in PTB prevention. Based on recent findings from our laboratory, we postulate heterogeneity in host OS response. The physiologic (at term and pathophysiologic (preterm pathways of labor are not mediated by OS alone but by OS-induced damage to intrauterine tissues, especially fetal membranes of the placenta. OS damage affects all major cellular elements in the fetal cells, and this damage promotes fetal cell senescence (aging. The aging of the fetal cells are predominated by p38 mitogen activated kinase (p38MAPK pathways. Senescing cells generate biomolecular signals that are uterotonic, triggering labor process. The aging of fetal cells is normal at term. However, aging is premature in PTB, especially in those PTBs complicated by preterm premature rupture of the membranes (pPROM, where elements of redox imbalances and OS damage are more dominant. We postulate that fetal cell senescence signals generated by OS damage are likely triggers for labor. This review highlights the mechanisms involved in senescence development at term and preterm by OS damage and provides insight into novel fetal signals of labor initiation pathways.

The ameliorative effect of ascorbic acid on the oxidative status, live weight and recovery rate in road transport stressed goats in a hot humid tropical environment.

Science.gov (United States)

Nwunuji, Tanko Polycarp; Mayowa, Opeyemi Onilude; Yusoff, Sabri Mohd; Bejo, Siti-Khairani; Salisi, Shahrom; Mohd, Effendy Abd Wahid

2014-05-01

The ameliorative effect of ascorbic acid (AA) on live weight following transportation is vital in animal husbandry. This study investigated the influence of AA on live weight, rectal temperature (rt), and oxidative status of transport stressed goats in a hot humid tropical environment. Twenty-four goats were divided into four groups, A, B, C and D of six animals each. Group A were administered AA 100 mg/kg intramuscularly 30 min prior to 3.5 h transportation. Group B was administered AA following transportation. Group C were transported but not administered AA as positive controls while group D were not transported but were administered normal saline as negative controls. Live weight, rt and blood samples were collected before, immediately post-transport (pt), 24 h, 3 days, 7 days and 10 days pt. Plasma was used for malondialdehyde (MDA) analysis while hemolysates were used for superoxide dismutase (SOD) analysis. There was minimal live weight loss in group A compared to groups B and C. Group A recorded reduced MDA activities and increased SOD activities compared to groups B and C which recorded significantly high MDA activities. This study revealed that AA administration ameliorated the stress responses induced by transportation in animals in hot humid tropical environments. The administration of AA to goats prior to transportation could ameliorate stress and enhance productivity. © 2014 Japanese Society of Animal Science.

Radiation-induced oxidative damage to the DNA-binding domain of the lactose repressor

Czech Academy of Sciences Publication Activity Database

Gillard, N.; Goffinont, S.; Buré, C.; Davídková, Marie; Maurizot, J. C.; Cadene, M.; Spotheim-Maurizot, M.

2007-01-01

Roč. 403, part 3 (2007), s. 463-472 ISSN 0264-6021 R&D Projects: GA MŠk 1P05OC085 Institutional research plan: CEZ:AV0Z10480505 Keywords : ionizing radiation * oxidative damage * DNA binding domain * lac repressor Subject RIV: CE - Biochemistry Impact factor: 4.009, year: 2007

FOXO3 Transcription Factor Is Essential for Protecting Hematopoietic Stem and Progenitor Cells from Oxidative DNA Damage.

Science.gov (United States)

Bigarella, Carolina L; Li, Jianfeng; Rimmelé, Pauline; Liang, Raymond; Sobol, Robert W; Ghaffari, Saghi

2017-02-17

Accumulation of damaged DNA in hematopoietic stem cells (HSC) is associated with chromosomal abnormalities, genomic instability, and HSC aging and might promote hematological malignancies with age. Despite this, the regulatory pathways implicated in the HSC DNA damage response have not been fully elucidated. One of the sources of DNA damage is reactive oxygen species (ROS) generated by both exogenous and endogenous insults. Balancing ROS levels in HSC requires FOXO3, which is an essential transcription factor for HSC maintenance implicated in HSC aging. Elevated ROS levels result in defective Foxo3 -/- HSC cycling, among many other deficiencies. Here, we show that loss of FOXO3 leads to the accumulation of DNA damage in primitive hematopoietic stem and progenitor cells (HSPC), associated specifically with reduced expression of genes implicated in the repair of oxidative DNA damage. We provide further evidence that Foxo3 -/- HSPC are defective in DNA damage repair. Specifically, we show that the base excision repair pathway, the main pathway utilized for the repair of oxidative DNA damage, is compromised in Foxo3 -/- primitive hematopoietic cells. Treating mice in vivo with N -acetylcysteine reduces ROS levels, rescues HSC cycling defects, and partially mitigates HSPC DNA damage. These results indicate that DNA damage accrued as a result of elevated ROS in Foxo3 -/- mutant HSPC is at least partially reversible. Collectively, our findings suggest that FOXO3 serves as a protector of HSC genomic stability and health. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Anacardic Acids from Cashew Nuts Ameliorate Lung Damage Induced by Exposure to Diesel Exhaust Particles in Mice

Directory of Open Access Journals (Sweden)

Ana Laura Nicoletti Carvalho

2013-01-01

Full Text Available Anacardic acids from cashew nut shell liquid, a Brazilian natural substance, have antimicrobial and antioxidant activities and modulate immune responses and angiogenesis. As inflammatory lung diseases have been correlated to environmental pollutants exposure and no reports addressing the effects of dietary supplementation with anacardic acids on lung inflammation in vivo have been evidenced, we investigated the effects of supplementation with anacardic acids in a model of diesel exhaust particle- (DEP- induced lung inflammation. BALB/c mice received an intranasal instillation of 50 μg of DEP for 20 days. Ten days prior to DEP instillation, animals were pretreated orally with 50, 150, or 250 mg/kg of anacardic acids or vehicle (100 μL of cashew nut oil for 30 days. The biomarkers of inflammatory and antioxidant responses in the alveolar parenchyma, bronchoalveolar lavage fluid (BALF, and pulmonary vessels were investigated. All doses of anacardic acids ameliorated antioxidant enzyme activities and decreased vascular adhesion molecule in vessels. Animals that received 50 mg/kg of anacardic acids showed decreased levels of neutrophils and tumor necrosis factor in the lungs and BALF, respectively. In summary, we demonstrated that AAs supplementation has a potential protective role on oxidative and inflammatory mechanisms in the lungs.

Parental exposure to the herbicide diuron results in oxidative DNA damage to germinal cells of the Pacific oyster Crassostrea gigas.

Science.gov (United States)

Barranger, Audrey; Heude-Berthelin, Clothilde; Rouxel, Julien; Adeline, Béatrice; Benabdelmouna, Abdellah; Burgeot, Thierry; Akcha, Farida

2016-02-01

Chemical pollution by pesticides has been identified as a possible contributing factor to the massive mortality outbreaks observed in Crassostrea gigas for several years. A previous study demonstrated the vertical transmission of DNA damage by subjecting oyster genitors to the herbicide diuron at environmental concentrations during gametogenesis. This trans-generational effect occurs through damage to genitor-exposed gametes, as measured by the comet-assay. The presence of DNA damage in gametes could be linked to the formation of DNA damage in other germ cells. In order to explore this question, the levels and cell distribution of the oxidized base lesion 8-oxodGuo were studied in the gonads of exposed genitors. High-performance liquid chromatography coupled with UV and electrochemical detection analysis showed an increase in 8-oxodGuo levels in both male and female gonads after exposure to diuron. Immunohistochemistry analysis showed the presence of 8-oxodGuo at all stages of male germ cells, from early to mature stages. Conversely, the oxidized base was only present in early germ cell stages in female gonads. These results indicate that male and female genitors underwent oxidative stress following exposure to diuron, resulting in DNA oxidation in both early germ cells and gametes, such as spermatozoa, which could explain the transmission of diuron-induced DNA damage to offspring. Furthermore, immunostaining of early germ cells seems indicates that damages caused by exposure to diuron on germ line not only affect the current sexual cycle but also could affect future gametogenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

Critical role of NADPH oxidase in neuronal oxidative damage and microglia activation following traumatic brain injury.

Directory of Open Access Journals (Sweden)

Quan-Guang Zhang

Full Text Available BACKGROUND: Oxidative stress is known to play an important role in the pathology of traumatic brain injury. Mitochondria are thought to be the major source of the damaging reactive oxygen species (ROS following TBI. However, recent work has revealed that the membrane, via the enzyme NADPH oxidase can also generate the superoxide radical (O(2(-, and thereby potentially contribute to the oxidative stress following TBI. The current study thus addressed the potential role of NADPH oxidase in TBI. METHODOLOGY/PRINCIPAL FINDINGS: The results revealed that NADPH oxidase activity in the cerebral cortex and hippocampal CA1 region increases rapidly following controlled cortical impact in male mice, with an early peak at 1 h, followed by a secondary peak from 24-96 h after TBI. In situ localization using oxidized hydroethidine and the neuronal marker, NeuN, revealed that the O(2(- induction occurred in neurons at 1 h after TBI. Pre- or post-treatment with the NADPH oxidase inhibitor, apocynin markedly inhibited microglial activation and oxidative stress damage. Apocynin also attenuated TBI-induction of the Alzheimer's disease proteins β-amyloid and amyloid precursor protein. Finally, both pre- and post-treatment of apocynin was also shown to induce significant neuroprotection against TBI. In addition, a NOX2-specific inhibitor, gp91ds-tat was also shown to exert neuroprotection against TBI. CONCLUSIONS/SIGNIFICANCE: As a whole, the study demonstrates that NADPH oxidase activity and superoxide production exhibit a biphasic elevation in the hippocampus and cortex following TBI, which contributes significantly to the pathology of TBI via mediation of oxidative stress damage, microglial activation, and AD protein induction in the brain following TBI.

Oxidative stress induced damage in benign and malignant breast diseases: histopathological and biochemical aspects

Directory of Open Access Journals (Sweden)

Seema Khanna

2012-04-01

Full Text Available Increasing evidences indicate involvement of free radicals in the pathogenesis of benign and malignant breast diseases. Free radicals are highly reactive molecules and react with non–radicals in chain reaction leading to formation of new free radicals. If the defense mechanism of body fails to combat them, these free radicals pose a threat of injuring tissues by reacting with cell lipids. Lipids in the cell membrane undergo degradation to form hydroperoxides, which decompose to form a variety of products including malondialdehyde (MDA. MDA therefore was used as a marker to assess oxidative damage of cells and tissues. The aim of the present study was to assess the status of oxidative stress in the patients of benign and malignant breast diseases. Study has been made on the blood samples of 25 cases of benign breast disease and on an equal number of breast carcinoma patients. 20 healthy subjects were taken as the control cases.Mean MDA levels were significantly raised with depletion of antioxidant activity in all the patients in comparison to their control group suggesting the role of oxidative damage in the aetiopathogenesis of disease.

Oligomeric proanthocyanidins (OPCs) modulating radiation-induced oxidative stress on functional and structural performance of eye in male rats

International Nuclear Information System (INIS)

Said, U.Z.; Soliman, S.M.; Azab, Kh.Sh.; El-Tahawy, N.A.

2005-01-01

Eye oxidative stress may play a major role in the etiology and pathogenesis of eye disorders such as macular degeneration and photic injury of retinal degeneration that lead to vision loss. Proanthocyanidins derived from pine bark and from grape seeds have various anti pathophysiological functions. This study was performed to evaluate the role of oligomeric proanthocyanidins (OPCs) on the radiation-induced changes in rat eye tissues. OPCs were supplemented to rats (100 mg /kg body weight/ day) for 14 successive days before and 7 successive days after exposure to 7 Gy (single dose) of whole body gamma irradiation. The results revealed radiation-induced depletion in the activities of eye endogenous antioxidant enzymes and rise in pro-oxidant levels. Supplementation of OPCs pre- and post-irradiation has significantly reduced the levels of thiobarbituric acid reactive substances, xanthine oxidase, and significantly ameliorated the activities of xanthine dehydrogenase and reactive oxygen scavenging enzymes such as superoxide dismutase, glutathione peroxidase and catalase activities in eye tissues. OPCs significantly ameliorated the radiation-induced changes in levels of insulin and glucose in the serum. The oxidative stress induced cellular damage as indicated by retardation in the responses of eye to photo stimulation as well as histopathological changes in the eye tissues. Severe intra-retinal hemorrhages, cornea swelling, disruption of photoreceptor layer of the retina and epithelial necrosis were seen. The eye tissues of rats that received OPCs supplement showed significant less severe histological damage and remarkable improvement in photo stimulation responses when compared to irradiated rats on the 7 T h and 21 s t days after exposure to gamma irradiation. According to the results obtained, it could be concluded that OPCs might protect the eye tissues from the oxidative stress possibly by virtue of its anti oxidative activity through augmentation of antioxidant

Articulation of Native Cartilage Against Different Femoral Component Materials. Oxidized Zirconium Damages Cartilage Less Than Cobalt-Chrome.

Science.gov (United States)

Vanlommel, Jan; De Corte, Ronny; Luyckx, Jean Philippe; Anderson, Melissa; Labey, Luc; Bellemans, Johan

2017-01-01

Oxidized zirconium (OxZr) is produced by thermally driven oxidization creating an oxidized surface with the properties of a ceramic at the top of the Zr metal substrate. OxZr is much harder and has a lower coefficient of friction than cobalt-chrome (CoCr), both leading to better wear characteristics. We evaluated and compared damage to the cartilage of porcine patella plugs, articulating against OxZr vs CoCr. Our hypothesis was that, owing to its better wear properties, OxZr would damage cartilage less than CoCr. If this is true, OxZr might be a better material for the femoral component during total knee arthroplasty if the patella is not resurfaced. Twenty-one plugs from porcine patellae were prepared and tested in a reciprocating pin-on-disk machine while lubricated with bovine serum and under a constant load. Three different configurations were tested: cartilage-cartilage as the control group, cartilage-OxZr, and cartilage-CoCr. Macroscopic appearance, cartilage thickness, and the modified Mankin score were evaluated after 400,000 wear cycles. The control group showed statistically significant less damage than plugs articulating against both other materials. Cartilage plugs articulating against OxZr were statistically significantly less damaged than those articulating against CoCr. Although replacing cartilage by an implant always leads to deterioration of the cartilage counterface, OxZr results in less damage than CoCr. The use of OxZr might thus be preferable to CoCr in case of total knee arthroplasty without patella resurfacing. Copyright © 2016 Elsevier Inc. All rights reserved.

Secoisolariciresinol diglucoside abrogates oxidative stress-induced damage in cardiac iron overload condition.

Directory of Open Access Journals (Sweden)

Stephanie Puukila

Full Text Available Cardiac iron overload is directly associated with cardiac dysfunction and can ultimately lead to heart failure. This study examined the effect of secoisolariciresinol diglucoside (SDG, a component of flaxseed, on iron overload induced cardiac damage by evaluating oxidative stress, inflammation and apoptosis in H9c2 cardiomyocytes. Cells were incubated with 50 μ5M iron for 24 hours and/or a 24 hour pre-treatment of 500 μ M SDG. Cardiac iron overload resulted in increased oxidative stress and gene expression of the inflammatory mediators tumor necrosis factor-α, interleukin-10 and interferon γ, as well as matrix metalloproteinases-2 and -9. Increased apoptosis was evident by increased active caspase 3/7 activity and increased protein expression of Forkhead box O3a, caspase 3 and Bax. Cardiac iron overload also resulted in increased protein expression of p70S6 Kinase 1 and decreased expression of AMP-activated protein kinase. Pre-treatment with SDG abrogated the iron-induced increases in oxidative stress, inflammation and apoptosis, as well as the increased p70S6 Kinase 1 and decreased AMP-activated protein kinase expression. The decrease in superoxide dismutase activity by iron treatment was prevented by pre-treatment with SDG in the presence of iron. Based on these findings we conclude that SDG was cytoprotective in an in vitro model of iron overload induced redox-inflammatory damage, suggesting a novel potential role for SDG in cardiac iron overload.

Base excision repair of both uracil and oxidatively damaged bases contribute to thymidine deprivation-induced radiosensitization

International Nuclear Information System (INIS)

Allen, Bryan G.; Johnson, Monika; Marsh, Anne E.; Dornfeld, Kenneth J.

2006-01-01

Purpose: Increased cellular sensitivity to ionizing radiation due to thymidine depletion is the basis of radiosensitization with fluoropyrimidine and methotrexate. The mechanism responsible for cytotoxicity has not been fully elucidated but appears to involve both the introduction of uracil into, and its removal from, DNA. The role of base excision repair of uracil and oxidatively damaged bases in creating the increased radiosensitization during thymidine depletion is examined. Methods and Materials: Isogenic strains of S. cerevisiae differing only at loci involved in DNA repair functions were exposed to aminopterin and sulfanilamide to induce thymidine deprivation. Cultures were irradiated and survival determined by clonogenic survival assay. Results: Strains lacking uracil base excision repair (BER) activities demonstrated less radiosensitization than the parental strain. Mutant strains continued to show partial radiosensitization with aminopterin treatment. Mutants deficient in BER of both uracil and oxidatively damaged bases did not demonstrate radiosensitization. A recombination deficient rad52 mutant strain was markedly sensitive to radiation; addition of aminopterin increased radiosensitivity only slightly. Radiosensitization observed in rad52 mutants was also abolished by deletion of the APN1, NTG1, and NTG2 genes. Conclusion: These data suggest radiosensitization during thymidine depletion is the result of BER activities directed at both uracil and oxidatively damaged bases

Beneficial effect of honokiol on lipopolysaccharide induced anxiety-like behavior and liver damage in mice.

Science.gov (United States)

Sulakhiya, Kunjbihari; Kumar, Parveen; Gurjar, Satendra S; Barua, Chandana C; Hazarika, Naba K

2015-02-26

Anxiety disorders are commonly occurring co-morbid neuropsychiatric disorders with chronic inflammatory conditions such as live damage. Numerous studies revealed that peripheral inflammation, oxidative stress and brain derived neurotrophic factor (BDNF) play important roles in the pathophysiology of anxiety disorders. Honokiol (HNK) is a polyphenol, possessing multiple biological activities including antioxidant, anti-inflammatory, anxiolytic, antidepressant and hepatoprotection. The present study was designed to investigate the effect of HNK, in lipopolysaccharide (LPS)-induced anxiety-like behavior and liver damage in mice. Mice (n=6-10/group) were pre-treated with different doses of HNK (2.5 and 5mg/kg; i.p.) for two days, and challenged with saline or LPS (0.83mg/kg; i.p.) on third day. Anxiety-like behavior was monitored using elevated plus maze (EPM) and open field test (OFT). Animals were sacrificed to evaluate various biochemical parameters in plasma and liver. HNK pre-treatment provided significant (P<0.01) protection against LPS-induced reduction in body weight, food and water intake in mice. HNK at higher dose significantly (P<0.05) attenuated LPS-induced anxiety-like behavior by increasing the number of entries and time spent in open arm in EPM test, and by increasing the frequency in central zone in OFT. HNK pre-treatment ameliorated LPS-induced peripheral inflammation by reducing plasma IL-1β, IL-6, TNF-α level, and also improved the plasma BDNF level, prevented liver damage via attenuating transaminases (AST, ALT), liver oxidative stress and TNF-α activity in LPS challenged mice. In conclusion, the current investigation suggests that HNK provided beneficial effect against LPS-induced anxiety-like behavior and liver damage which may be governed by inhibition of cytokines production, oxidative stress and depletion of plasma BDNF level. Our result suggests that HNK could be a therapeutic approach for the treatment of anxiety and other

Low intensity microwave radiation induced oxidative stress, inflammatory response and DNA damage in rat brain.

Science.gov (United States)

Megha, Kanu; Deshmukh, Pravin Suryakantrao; Banerjee, Basu Dev; Tripathi, Ashok Kumar; Ahmed, Rafat; Abegaonkar, Mahesh Pandurang

2015-12-01

Over the past decade people have been constantly exposed to microwave radiation mainly from wireless communication devices used in day to day life. Therefore, the concerns over potential adverse effects of microwave radiation on human health are increasing. Until now no study has been proposed to investigate the underlying causes of genotoxic effects induced by low intensity microwave exposure. Thus, the present study was undertaken to determine the influence of low intensity microwave radiation on oxidative stress, inflammatory response and DNA damage in rat brain. The study was carried out on 24 male Fischer 344 rats, randomly divided into four groups (n=6 in each group): group I consisted of sham exposed (control) rats, group II-IV consisted of rats exposed to microwave radiation at frequencies 900, 1800 and 2450 MHz, specific absorption rates (SARs) 0.59, 0.58 and 0.66 mW/kg, respectively in gigahertz transverse electromagnetic (GTEM) cell for 60 days (2h/day, 5 days/week). Rats were sacrificed and decapitated to isolate hippocampus at the end of the exposure duration. Low intensity microwave exposure resulted in a frequency dependent significant increase in oxidative stress markers viz. malondialdehyde (MDA), protein carbonyl (PCO) and catalase (CAT) in microwave exposed groups in comparison to sham exposed group (pmicrowave exposed groups (pmicrowave exposed animal (pmicrowave exposed groups as compared to their corresponding values in sham exposed group (pmicrowave radiation induces oxidative stress, inflammatory response and DNA damage in brain by exerting a frequency dependent effect. The study also indicates that increased oxidative stress and inflammatory response might be the factors involved in DNA damage following low intensity microwave exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

Proceedings of damage and oxidation protection in high temperature composites

International Nuclear Information System (INIS)

Haritos, G.K.; Ochoa, O.O.

1991-01-01

This book contains proceedings of Damage and Oxidation Protection in High Temperature Composites. Topics covered include: current issues in the development of new materials and structural concepts for the aerospace structures of the future; transportation vehicles of the future; materials and structural concepts; fundamental understanding and quantitative descriptions of the physical processes and mechanisms controlling the behavior of emerging materials and structures; and the critical need for advances in our understanding of how the interaction of service loads and environment influences the lifecycle of emerging structures and materials

Screening for oxidative damage by engineered nanomaterials: a comparative evaluation of FRAS and DCFH

Science.gov (United States)

Pal, Anoop K.; Hsieh, Shu-Feng; Khatri, Madhu; Isaacs, Jacqueline A.; Demokritou, Philip; Gaines, Peter; Schmidt, Daniel F.; Rogers, Eugene J.; Bello, Dhimiter

2014-02-01

Several acellular assays are routinely used to measure oxidative stress elicited by engineered nanomaterials (ENMs), yet little comparative evaluations of such methods exist. This study compares for the first time the performance of the dichlorofluorescein (DCFH) assay which measures reactive oxygen species (ROS) generation, to that of the ferric-reducing ability of serum (FRAS) assay, which measures biological oxidant damage in serum. A diverse set of 28 commercially important and extensively characterized ENMs were tested on both the assays. Intracellular oxidative stress was also assessed on a representative subset of seven ENMs in THP-1 (phorbol 12-myristate 13-acetate matured human monocytes) cells. Associations between assay responses and ENM physicochemical properties were assessed via correlation and regression analysis. DCFH correlated strongly with FRAS after dose normalization for mass ( R 2 = 0.78) and surface area ( R 2 = 0.68). Only 10/28 ENMs were positive in DCFH versus 21/28 in FRAS. Both assays were strongly associated with specific surface area and transition metal content. Qualitatively, a similar response ranking was observed for acellular FRAS and intracellular reduced:oxidized glutathione ratio (GSH:GSSG) in cells. Quantitatively, weak correlation was found between intracellular GSSG and FRAS or DCFH ( R 2 < 0.25) even after calculating effective dose to cells. The FRAS assay was more sensitive than DCFH, especially for ENMs with low to moderate oxidative damage potential, and may serve as a more biologically relevant substitute for acellular ROS measurements of ENMs. Further in vitro and in vivo validations of FRAS against other toxicological endpoints with larger datasets are recommended.

Salidroside Suppresses HUVECs Cell Injury Induced by Oxidative Stress through Activating the Nrf2 Signaling Pathway

Directory of Open Access Journals (Sweden)

Yao Zhu

2016-08-01

Full Text Available Oxidative stress plays an important role in the pathogenesis of cardiovascular diseases. Salidroside (SAL, one of the main effective constituents of Rhodiola rosea, has been reported to suppress oxidative stress-induced cardiomyocyte injury and necrosis by promoting transcription of nuclear factor E2-related factor 2 (Nrf2-regulated genes such as heme oxygenase-1 (HO-1 and NAD(PH dehydrogenase (quinone1 (NQO1. However, it has not been indicated whether SAL might ameliorate endothelial injury induced by oxidative stress. Here, our study demonstrated that SAL might suppress HUVEC cell injury induced by oxidative stress through activating the Nrf2 signaling pathway. The results of our study indicated that SAL decreased the levels of intercellular reactive oxygen species (ROS and malondialdehyde (MDA, and improved the activities of superoxide dismutase (SOD and catalase (CAT, resulting in protective effects against oxidative stress-induced cell damage in HUVECs. It suppressed oxidative stress damage by inducing Nrf2 nuclear translocation and activating the expression of Nrf2-regulated antioxidant enzyme genes such as HO-1 and NQO1 in HUVECs. Knockdown of Nrf2 with siRNA abolished the cytoprotective effects against oxidative stress, decreased the expression of Nrf2, HO-1, and NQO1, and inhibited the nucleus translocation of Nrf2 in HUVECs. This study is the first to demonstrate that SAL suppresses HUVECs cell injury induced by oxidative stress through activating the Nrf2 signaling pathway.

Fungicidal Drugs Induce a Common Oxidative-Damage Cellular Death Pathway

Directory of Open Access Journals (Sweden)

Peter Belenky

2013-02-01

Full Text Available Amphotericin, miconazole, and ciclopirox are antifungal agents from three different drug classes that can effectively kill planktonic yeast, yet their complete fungicidal mechanisms are not fully understood. Here, we employ a systems biology approach to identify a common oxidative-damage cellular death pathway triggered by these representative fungicides in Candida albicans and Saccharomyces cerevisiae. This mechanism utilizes a signaling cascade involving the GTPases Ras1 and Ras2 and protein kinase A, and it culminates in death through the production of toxic reactive oxygen species in a tricarboxylic-acid-cycle- and respiratory-chain-dependent manner. We also show that the metabolome of C. albicans is altered by antifungal drug treatment, exhibiting a shift from fermentation to respiration, a jump in the AMP/ATP ratio, and elevated production of sugars; this coincides with elevated mitochondrial activity. Lastly, we demonstrate that DNA damage plays a critical role in antifungal-induced cellular death and that blocking DNA-repair mechanisms potentiates fungicidal activity.

Ginger and alpha lipoic acid ameliorate age-related ultrastructural changes in rat liver.