Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1260386 (GSH)
 38,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study has been initiated to investigate whether endogenous carnitine depletion and/or carnitine deficiency is a risk factor during development of cisplatin (CDDP)-induced cardiomyopathy and if so, whether carnitine supplementation by propionyl-L-carnitine (PLC) could offer protection against this toxicity. To achieve the ultimate goal of this study, a total of 60 adult male Wistar albino rats were divided into six groups. The first three groups were injected intraperitoneally with normal saline, PLC (500 mg kg(-1)), and d-carnitine (500 mg kg(-1)) respectively, for 10 successive days. The 4th, 5th, and 6th groups were injected intraperitoneally with the same doses of normal saline, PLC and D-carnitine, respectively, for 5 successive days before and after a single dose of CDDP (7 mg kg(-1)). On day 6 after CDDP treatment, animals were sacrificed, serum as well as hearts were isolated and analyzed. CDDP resulted in a significant increase in serum creatine phosphokinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH), thiobarbituric acid reactive substances (TBARS) and total nitrate/nitrite (NO(x)) and a significant decrease in reduced glutathione (GSH), total carnitine, and adenosine triphosphate (ATP) content in cardiac tissues. In the carnitine-depleted rat model, CDDP induced dramatic increase in serum cardiomyopathy enzymatic indices, CK-MB and LDH, as well as progressive reduction in total carnitine and ATP content in cardiac tissue. Interestingly, PLC supplementation resulted in a complete reversal of the increase in cardiac enzymes, TBARS and NO(x), and the decrease in total carnitine, GSH and ATP, induced by CDDP, to the control values. Moreover, histopathological examination of cardiac tissues confirmed the biochemical data, where PLC prevents CDDP-induced cardiac degenerative changes while d-carnitine aggravated CDDP-induced cardiac tissue damage. In conclusion, data from this study suggest for the first time that carnitine deficiency and oxidative stress are risk factors and should be viewed as mechanisms during development of CDDP-related cardiomyopathy and that carnitine supplementation, using PLC, prevents the progression of CDDP-induced cardiotoxicity.
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PMID:Propionyl-L-carnitine prevents the progression of cisplatin-induced cardiomyopathy in a carnitine-depleted rat model. 1643 31

The present study was to investigate the effects of l-arginine (l-Arg) supplementation on cardiac oxidative stress and the inflammatory response in rats following acute exhaustive exercise on a treadmill. Rats were randomly divided into four groups: sedentary control (SC); SC with l-Arg treatment (SC+Arg); exhaustive exercise (E); exhaustive exercise with l-Arg treatment (E+Arg). Rats in groups SC+Arg and E+Arg received a 2 % l-Arg diet. Rats in groups E and E+Arg performed an exhaustive running test on a treadmill at a final speed of 30 m/min, 10 % grade, at approximately 70-75 % VO2max. The results showed a significant increase in cardiac xanthine oxidase (XO) and myeloperoxidase activities and membrane lipid peroxidation endproduct (malondialdehyde; MDA) levels of exercised rats compared with SC rats. The increased cardiac XO activity and MDA levels in exercised rats were significantly decreased in exercised rats supplemented with l-Arg. Myocardial GSSG content increased whereas the GSH:GSSG ratio was depressed in exercised rats compared with SC rats. Cardiac GSSG levels significantly decreased, whereas total glutathione, GSH and the GSH:GSSG ratio increased in exercised rats supplemented with l-Arg compared with exercised rats. The activities of creatinine kinase (CK) and lactate dehydrogenase (LDH), and lactate, uric acid, and nitrite and nitrate levels in the plasma significantly increased in exercised rats compared with SC rats. The activities of plasma CK and LDH were significantly decreased in l-Arg-supplemented plus exercised rats compared with exercised rats. These findings suggest that l-Arg supplementation reduces the oxidative damage and inflammatory response on the myocardium caused by exhaustive exercise in rats.
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PMID:L-Arginine attenuates xanthine oxidase and myeloperoxidase activities in hearts of rats during exhaustive exercise. 1644 18

Carvedilol, a beta-blocker has shown clinically to attenuate the development of nitroglycerin (NTG) tolerance. The present study was designed to investigate the possible mechanisms whereby carvedilol could prevent NTG tolerance, particularly at the level of vascular superoxide anion (O2-) production (an important factor in nitrate tolerance) as well as modulation of certain aortic antioxidants. Rabbits were treated with NTG patch (1.5 microg/kg/min) and/or cavedilol (10 mg/kg/day) for 3 days. Relaxation of aortic segments was studied in organ chamber and rate of vascular O2- production was determined. In addition, aortic glutathione (GSH) level and superoxide dismutase (SOD) activity was also assessed. Aortic segments from NTG-treated rabbits showed a significant decrease in maximal relaxation in response to various vasodilators. Also, NTG treatment increased vascular O2- production by two-fold as compared with untreated control group. The potential source of O2- production was found to be the adventitia. In addition, treatment of rabbits with NTG induced a significant decrease in total GSH level and SOD activity by 46 and 53%, respectively, as compared with the control values. Concomitant treatment of NTG with carvedilol significantly prevented the development of NTG tolerance and normalized the rate of vascular O2- production. Moreover, carvedilol restored the normal level of aortic antioxidants mainly, total GSH and SOD.
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PMID:Evidences for prevention of nitroglycerin tolerance by carvedilol. 1650 7

Resveratrol is as an antioxidant with free radical-scavenging activity and finds its clinical application in the prevention of postischemic tissue injury following solid organ transplantation. This study investigates the effect of Resveratrol on spleen and ileum tissues subjected to hepatic ischemia-reperfusion (I/R) in rats. Twenty-four rats were recruited in the study as follows: group A: I/R (n = 8), group B: I/R + Resveratrol (n = 8), and group C: sham operation (n = 8). After intraperitonealy pretreatment of eight rats with resveratrol (15 mg/kg/d) for 5 days, 16 rats were subjected to 45 minutes of hepatic ischemia followed by 30 minutes reperfusion period. Resveratrol was given 15 minutes prior to ischemia and just before the reperfusion in rats. After reperfusion period all rats were sacrificed. Spleen and ileum tissues were examined spectrophotometrically to measure malondialdehyde (MDA), glutathione (GSH), and total nitrite, nitrate as an end product of nitric oxide (NO) levels. Concerning the spleen, statistically significant decrease of GSH and increase of MDA and NO levels were found group A when compared to groups B and C (P = .040, P = .004, and P = .001 group A vs group B; P = .05, P = .003, and P = .001 group A vs group C, respectively). Parallel results were obtained in ileum. A statistically significant decrease in GSH and an increase in MDA and NO levels in group A in respect to group B and group C was obtained (P = .048, P = .034, and P = .001 group A vs group B; P = .004, P = .001, and P = .003 group A vs group C, respectively). The result of this study shows that resveratrol has a protective effect on spleen and ileal mitochondrial oxidative stress in rats subjected to I/R.
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PMID:Protective effects of resveratrol on spleen and ileum in rats subjected to ischemia-reperfusion. 1654 24

Cardiotoxicity is an important consideration in the evaluation of cancer chemotherapy, because chemotherapy-induced myocardial damage might be irreversible and lethal. This in-vivo study investigated the cardiotoxicity of either arsenic trioxide or imatinib mesilate, or a combination of both drugs, following repeated administration in male Wistar rats. Both arsenic trioxide and imatinib mesilate were administered daily at a dose of 5 mg kg(-1) intraperitoneally and 30 mg kg(-1) orally for 10 days, respectively. Cardiotoxicity was evaluated by biochemical and histopathological examination 48 h after the last dose. Treatment with either arsenic or imatinib, or both, resulted in significant increases in serum creatine kinase isoenzyme (CK-MB), glutathione peroxidase (GPx), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) activity levels. Cardiac tissue of rats treated with arsenic showed significant increases in levels of reduced glutathione (GSH) content, GPx activity, malondialdehyde (MDA) and total nitrate/nitrite (NOx), whereas imatinib treatment significantly increased cardiac GSH content and MDA production level and decreased GPx activity level and NOx content. A combination of arsenic and imatinib produced significant increases in cardiac GSH content, GPx activity and MDA production levels, in addition to a reduction in NOx content. Combination arsenic/imatinib treatment extensively increased GPx activity and MDA production levels compared with imatinib treatment alone. Moreover, rats treated with arsenic or imatinib, or both, showed a significant increase in serum bilirubin, creatinine and urea levels. Histopathological examination of cardiac tissue of the combination-treated group revealed fibroblastic proliferation, myocardial disorganization and myocardial necrosis. Liver peroxidative alterations revealed that treatment with either arsenic or imatinib, or the two combined, increased levels of reduced-GSH and MDA production levels. However, imatinib treatment depleted liver GPx activity level contrary to treatment with the combination. Rats treated with arsenic alone or arsenic/imatinib combination showed significant elevation in liver NOx. In conclusion, both arsenic trioxide and imatinib mesilate might have significant cardiotoxicity and cardiac function should be monitored during treatment with them alone or in combination, as well as in the presence of pre-existing cardiac dysfunction.
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PMID:Cardiotoxic effects of arsenic trioxide/imatinib mesilate combination in rats. 1659 75

Nitric oxide ((*)NO)-derived reactive species nitrate unsaturated fatty acids, yielding nitroalkene derivatives, including the clinically abundant nitrated oleic and linoleic acids. The olefinic nitro group renders these derivatives electrophilic at the carbon beta to the nitro group, thus competent for Michael addition reactions with cysteine and histidine. By using chromatographic and mass spectrometric approaches, we characterized this reactivity by using in vitro reaction systems, and we demonstrated that nitroalkene-protein and GSH adducts are present in vivo under basal conditions in healthy human red cells. Nitro-linoleic acid (9-, 10-, 12-, and 13-nitro-9,12-octadecadienoic acids) (m/z 324.2) and nitro-oleic acid (9- and 10-nitro-9-octadecaenoic acids) (m/z 326.2) reacted with GSH (m/z 306.1), yielding adducts with m/z of 631.3 and 633.3, respectively. At physiological concentrations, nitroalkenes inhibited glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which contains a critical catalytic Cys (Cys-149). GAPDH inhibition displayed an IC(50) of approximately 3 microM for both nitroalkenes, an IC(50) equivalent to the potent thiol oxidant peroxynitrite (ONOO(-)) and an IC(50) 30-fold less than H(2)O(2), indicating that nitroalkenes are potent thiol-reactive species. Liquid chromatography-mass spectrometry analysis revealed covalent adducts between fatty acid nitroalkene derivatives and GAPDH, including at the catalytic Cys-149. Liquid chromatography-mass spectrometry-based proteomic analysis of human red cells confirmed that nitroalkenes readily undergo covalent, thiol-reversible post-translational modification of nucleophilic amino acids in GSH and GAPDH in vivo. The adduction of GAPDH and GSH by nitroalkenes significantly increased the hydrophobicity of these molecules, both inducing translocation to membranes and suggesting why these abundant derivatives had not been detected previously via traditional high pressure liquid chromatography analysis. The occurrence of these electrophilic nitroalkylation reactions in vivo indicates that this reversible post-translational protein modification represents a new pathway for redox regulation of enzyme function, cell signaling, and protein trafficking.
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PMID:Reversible post-translational modification of proteins by nitrated fatty acids in vivo. 1668 16

The aim of the present work was to investigate the role of inducible nitric oxide (NO) synthase (iNOS) in CCl(4)-induced cirrhosis by utilizing iNOS knock out mice (iNOS(-/-)). Cirrhosis was produced by i.p. administration of CCl(4) (1 ml kg(-1) of body weight) dissolved in olive oil three times a week for 3 months to iNOS(-/-) or iNOS(+/+) (wild type) mice; appropriate olive oil controls were performed. Nitrite plus nitrate levels were lower in iNOS(-/-) compared with iNOS(+/+) mice, but CCl(4) did not produce a significant effect in any mice. Reduced (GSH) glutathione was increased in iNOS(-/-) mice receiving vehicle and in both groups receiving CCl(4); lipid peroxidation increased significantly in iNOS(+/+) but not in iNOS(-/-) mice. Bilirubins, alanine aminotransferase and collagen (measured as the hepatic hydroxyproline content) were increased significantly by the chronic intoxication with CCl(4) in both iNOS(-/-) and iNOS(+/+) mice; importantly there was no difference between these groups. This study clearly suggests that NO derived from iNOS does not participate in cholestasis, necrosis or fibrosis induced by CCl(4) in the mice. The present results are in disagreement with several studies indicating a beneficial or detrimental effect of this molecule utilizing different experimental approaches and in agreement with some studies indicating that NO does not affect liver damage in some models. It must be pointed out that this is the first report in iNOS knock out mice utilizing the chronic model of intoxication with CCl(4); thus, comparisons with other models or approaches are difficult to reconcile.
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PMID:Inducible nitric oxide synthase is not essential for the development of fibrosis and liver damage induced by CCl4 in mice. 1670 56

The aim of this study was to investigate the antioxidant effect of acetyl-L-carnitine (ALC) against gamma-irradiation-induced oxidative damage in liver and lung tissue after total body irradiation with a single dose of 6Gy. To achieve the ultimate goal of this study, 40 adult rats were randomly divided into 4 groups of 10 animals each. Group I was injected intraperitoneally with saline solution for 5 consecutive days and served as control group. Group II was irradiated with a single dose of 6Gy. Group III was daily injected with ALC (250 mg kg(-1), i.p.) for 5 consecutive days. Group IV received a daily i.p. injection of ALC (250 mg kg(-1), i.p.) for 5 consecutive days and 1h after the last dose, rats were irradiated with a single dose (6Gy). The animals were sacrified after 24h. Administration of ALC for 5 consecutive days resulted in a significant increase in the activities of both superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) and the level of reduced glutathione (GSH), in lung and liver tissues which were reduced by radiation treatment. Also, ALC resulted in a significant decrease in total nitrate/nitrite (NO(x)) and malondialdehyde (MDA) levels in both lung and liver tissues and a significant decrease in triglycerides, low-density lipoprotein-cholesterol (LDL), high-density lipoprotein-cholesterol (HDL), total cholesterol, Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels and Gamma glutamyl transpeptidase (GGTP) compared to irradiated group. In conclusion, data obtained from this study indicate that ALC could increase the endogenous antioxidant defense mechanism in rat and there by protect the animals from radiation-induced organs toxicity.
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PMID:Protective role of carnitine ester against radiation-induced oxidative stress in rats. 1675 76

In this study we assessed activities of antioxidant enzymes, lipid peroxidation end-products, and nitric oxide (NO) levels in women with postmenopausal osteoporosis (PMO). Relationship between oxidative stress parameters and NO levels with bone mineral density (BMD) and clinical variables influencing bone mass and health related quality of life measures was also investigated in women with PMO. Postmenopausal women (n=87), aged 40-65, without previous diagnosis or treatment for osteoporosis and independent in daily living activities were included. BMD was measured at the lumbar spine and proximal femur using dual-X-ray absorptiometry (DXA). Erythrocyte catalase (CATe) enzyme activity, erythrocyte and plasma enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and lipid peroxidation end-product malondialdehyde (MDA) and nitrite/nitrate levels, by product of NO were studied. A total of 23 healthy non-porotic women were included as controls. Women with PMO had significantly lower erythrocyte CATe enzyme activity and higher erythrocyte malondialdehyde (MDAe) and erythrocyte nitric oxide (NOe) levels in comparison to controls whereas erythrocyte SODe and GSH-Px enzyme activity was similar. In plasma, osteoporotic women had significantly higher SOD enzyme activity and higher MDA levels whereas similar GSH-Px enzyme activity and NO levels compared to non-porotic controls. Significant correlation was found between erythrocyte SODe, CATe enzyme activity and NOe levels with proximal femur BMD. Some of the quality of life scores as pain, mental, and social functions correlated with antioxidant enzyme activities and NO levels.Consequently, oxidative stress markers may be an important indicator for bone loss in postmenopausal women. Further researches assessing the oxidative stress markers and NO in bone tissue and changes with anti-osteoporotic drugs would be valuable to better understand the role of free radicals, antioxidants, and NO in the regulation of bone mass.
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PMID:Role of antioxidant systems, lipid peroxidation, and nitric oxide in postmenopausal osteoporosis. 1684 Nov 80

Nitroglycerin (GTN) is metabolized to 1,2-dinitroglycerin (1,2-GDN) and 1,3-dinitroglycerin (1,3-GDN) in vivo and in liver homogenates. 1,2-GDN and 1,3-GDN are converted to isomers of glyceryl mononitrate (GMN) in vivo. The denitration reactions yield inorganic nitrite (NO(-)(2)) which is oxidized to inorganic nitrate (NO(-)(3)). Denitration involves utilization of glutathione (GSH). In attempting to use the Bratton-Marshall assay for NO(-)(2) in studies of GTN metabolism in vitro, and in attempting to use Ellman's reagent for GSH in the same research, apparent concentrations of both NO(-)(2) and GSH were noticed lower than anticipated. Apparent mutual interference by NO(-)(2) and GSH in their respective assays was then found. Development of a specific liquid chromatographic method for measurement of NO(-)(2), NO(-)(3), GSH and oxidized glutathione (GSSG) permitted the study of the interaction of NO(-)(2) and GSH, which yielded NO(-)(3) and GSSG.
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PMID:Analysis of solutions containing glutathione and inorganic nitrite: application to nitroglycerin metabolism studies. 1686 24


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