Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholestyramine treatment in children with heterozygous familial hypercholesterolemia (FHHe) can interfere with fat absorption from the intestinal tract, and has the potential to decrease the absorption of fat-soluble vitamins. The aim of this study was to examine the effect of cholestyramine treatment on the levels of the fat soluble vitamins (vitamin E, beta-carotene and lycopene) in LDL, on the glutathione system and on the susceptibility of LDL to oxidation in FHHe children. Patients were 16 children (seven girls, nine boys), age 14+/-4 years, non-smokers. Plasma LDL level before cholestyramine treatment but after dietary treatment was 239+/-50 mg% with no secondary cause for hypercholesterolemia. A control group was comprised of ten children (seven girls, three boys), age 14+/-4 years with plasma LDL level of 100+/-14 mg%. Blood was drawn from 16 FHHe children and five control children after fasting for 14 h. Thereafter cholestyramine treatment was begun in the patient group, at a dose of 8 g/day for 2 months. At the end of this period the dose was increased to 12-16 g/day for an additional 2 months. After 4 months from the beginning of the treatment, blood was drawn again. Plasma LDL cholesterol decreased after treatment by 14% (from 239+/-67 mg% before treatment to 205+/-55 mg% after treatment, P=0.07). Malondialdehyde (MDA) levels measured by thiobarbituric reactive substances (TBARS) assay in LDL at the end of oxidation were 30% higher in FHHe children in comparison to controls (P=0.02). After treatment TBARS levels in LDL (after in vitro oxidation) from FHHe children were decreased by 23% (P=0.02). Vitamin E levels in LDL from FHHe children after treatment were decreased by 65%, while beta-carotene and lycopene contents in LDL, paradoxically increased by 90 and 102%, respectively. In red blood cells (RBC), glutathione peroxidase (GPx) and glutathione transferase (GTf) activities were decreased by 29 and 24%, respectively, while glutathione reductase activity, total and oxidized glutathione contents from FHHe children did not change after cholestyramine treatment. LDL was more prone to oxidation in FHHe children than in controls, when measured by TBARS levels after LDL oxidation (with 10 &mgr;M CuSO(4)). Cholestyramine treatment for 4 months normalized LDL susceptibility to oxidation measured by TBARS levels, despite the decrease in vitamin E content in LDL from treated FHHe children. This is presumably due to the increased LDL content of beta-carotene and lycopene after treatment. GPx and GTf activities decreased after treatment, presumably due to the drop in oxidative stress within the RBCs, in parallel to the decreased LDL tendency to oxidation. Cholestyramine treatment in FHHe children has an overall antioxidant effect on LDL.
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PMID:Reduced susceptibility of low density lipoprotein to lipid peroxidation after cholestyramine treatment in heterozygous familial hypercholesterolemic children. 1147 69

The aim of this study was to determine whether there are any disturbances of red/ox balance in the renal cortex of rats during the course of experimental diabetes. In the renal cortex of rats with streptozotocin-induced diabetes, the activity of superoxide dismutase (SOD) isoenzymes, glutathione peroxidase (GSH-Pox). glutathione S-transferase (GST) and glutathione reductase (GSH-RED) was measured in the 5th, 10th and 15th weeks of diabetes. Free radical cell damage was assessed on the basis of malonyldialdehyde (MDA) concentration. The influence of lipophilic antioxidant vitamin E on these analytes was also studied. An increase in MDA concentration in the 10th and 15th weeks of diabetes correlated significantly with plasma glucose concentration (r=0.47; p<0.001). Moreover, MDA concentration was influenced by time (+); p<0.001, diabetes (+); p<0.001, vitamin E (-) p<0.001 (ANOVA). Plasma creatinine concentration in rats was elevated by diabetes (p<0.001), whereas vitamin E decreased the concentration (p<0.05). Vitamin E lowered the activity of GSHPox (p<0.001) and GST (p<0.01) (ANOVA). Our results indicate that during experimental diabetes, disturbances of red/ox balance lead to disturbance in renal function manifested as increased creatinine blood concentration. We suggest that oral supplementation of vitamin E protects the renal cortex of rats during experimental diabetes.
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PMID:Evidence of oxidative stress in the renal cortex of diabetic rats: favourable effect of vitamin E. 1200 18

Phenobarbital (PB) is an efficacious hepatic tumor promoter. Although the promoting activity of PB is likely related to altered cell proliferation or apoptosis, the induction of an oxidative stress environment may also be important. PB has been shown to activate the transcription factor nuclear factor-kappaB (NF-kappaB). In this study, we hypothesized that PB-induced NF-kappaB activation can be decreased by dietary vitamin E in rats. Male Sprague-Dawley rats (n = 39) were fed a purified diet with varying levels of dietary vitamin E (10, 50 or 250 mg/kg of dl-alpha-tocopherol acetate) for 28 d, at which time 8 rats per level of dietary vitamin E were fed the same diet with 500 mg/kg PB for 10 d. In the rats fed the low vitamin E diet, PB increased NF-kappaB DNA binding, but it did not affect NF-kappaB activation in rats fed higher levels of vitamin E (50 and 250 mg/kg). Vitamin E may decrease the oxidative stress created by PB by also enhancing other antioxidants; therefore, we also measured hepatic glutathione S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase and NAD(P)H:quinone reductase (DT-diaphorase) activities and glutathione and ascorbic acid concentrations. Increased dietary alpha-tocopherol did not affect the antioxidants and antioxidant enzymes altered by PB treatment. Thus, the effect of alpha-tocopherol acetate on NF-kappaB activation does not appear to be mediated by alterations in the antioxidant system. These results demonstrate that the activation of NF-kappaB, a transcription factor that affects cell proliferation- and apoptosis-related gene expression, can be inhibited by dietary vitamin E.
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PMID:Vitamin E inhibits hepatic NF-kappaB activation in rats administered the hepatic tumor promoter, phenobarbital. 1236 15

The cellular antioxidant system appears to protect cochlear hair cells from oxidative stress due to noise and aging. The role of individual metabolic variables remains poorly understood, however. We examined the role of a number of metabolic factors on human cochlear function in noise-exposed individuals. In 58 factory workers we measured audiometry and distortion product otoacoustic emissions prior to a workshift. Simultaneously we measured levels of vitamin E, vitamin C, and polymorphism status for two metabolic genes related to glutathione S-transferase function (GSTM1 and GSTT1). Age and total noise exposure were predictive of hearing status. Vitamin E levels were negatively correlated with hearing function, and this effect was partly explained by an increase in vitamin E levels with age. No effect was found for vitamin C. Individuals possessing the GSTM1 gene had significantly better high frequency otoacoustic emissions compared to GSTM1 null individuals. The protective effect of GSTM1 was present even after adjusting for age, race, sex, and years of noise exposure. GSTT1 did not exhibit a similarly protective effect. While the cross-sectional nature of the study precludes drawing conclusions about causation, these data suggest that GSTM1, an antioxidant enzyme which is found in the mammalian cochlea, may play a protective role in humans against hair cell damage due to noise or aging.
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PMID:Antioxidant status and hearing function in noise-exposed workers. 1237 44

The food-derived heterocyclic amines (HCAs) 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are mutagenic in the Ames test and produce tumors in laboratory animals, including monkeys. These HCAs have also been shown to induce gene mutations in vivo. To assess the antimutagenic effects of dietary antioxidant vitamins, beta-carotene, ascorbic acid (vitamin C), and alpha-tocopherol (vitamin E), on food-borne mutagenes/carcinogens, we evaluated the mutagenic activity of the compounds alone or combined with antioxidant vitamins. We utilized the rat lymphocyte mutation assay at the hypoxanthine guanine phosphoribosyl transferase (Hprt) locus. Female Fischer 344 rats treated with different doses (0, 2.5, 5.0, 25.0, and 50.0 mg/kg) of the carcinogens were sacrificed 5 wk after mutagen treatment. Although IQ and MeIQ slightly increased mutation frequency (MF) at some doses, a significant (P < 0.0009) increase in MF was found in animals exposed to MeIQx at 25 mg/kg. PhIP was the most mutagenic of the HCAs, with increases (P < 0.0001) in MF detected at all dose levels compared with controls. Because PhIP was the most mutagenic, it was selected for studies using the dietary antioxidant vitamins. Addition of antioxidant vitamins, singly or in a mixture, caused a significant (P < 0.0001) decrease in PhIP-induced Hprt MF. Vitamin E was the most effective at decreasing Hprt MF. In addition, we determined whether carcinogen metabolism would be affected by ingestion of vitamins. The activities of endogenous detoxification enzymes, glutathione S-transferase and glutathione peroxidase (GPx), were thus examined. Intake of beta-carotene and vitamin C without the carcinogen resulted in an increase (P < 0.05) in GPx activity. Also a modest increase in GPx activity was seen in animals that received the antioxidant mixture alone. Although the mechanisms of action of the antioxidants remain to be determined, the results indicate that dietary-derived HCA treatment induced MF in rat lymphocytes and suggest that antioxidants in food or taken as supplements could, in part, counteract such mutagenic activities.
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PMID:Mutagenicity of food-derived carcinogens and the effect of antioxidant vitamins. 1246 41

The objective of this study was to determine the effects of supplementation of ascorbic acid, Vitamin E (Vit. E) and their combination in drinking water on sperm characteristics, lipid peroxidation (LPO) and seminal plasma enzymes of mature male rabbits. Twenty-four male New Zealand White rabbits (5 months old) were given drinking water supplemented with ascorbic acid (1.5 g/l), Vit. E (1.0 g/l) and ascorbic acid+Vit. E (1.5+1.0 g/l) for 12 weeks. Vitamin supplementation in drinking water increased feed intake, but body weight gain was not significantly affected. Concentrations of thiobarbituric acid-reactive substances (TBARS) were significantly (P<0.05) reduced in seminal plasma of treated groups compared with the control. Treatment with ascorbic acid, Vit. E, and their combination significantly (P<0.05) increased lipido (reaction time), ejaculate volume, sperm concentration, total sperm output, sperm motility index, total motile sperm, packed sperm volume, initial hydrogen ion concentration (pH), and semen initial fructose concentration. Abnormal and dead sperm were significantly (P<0.05) decreased in treated animals. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were significantly (P<0.05) decreased, whereas glutathione S-transferase (GST) showed a significant increase in seminal plasma of treated animals compared with the controls. The results from this study indicated that supplementation of drinking water with antioxidant ascorbic acid, Vit. E and their combination reduced the production of free radicals and can improve rabbit semen quality, but the greater improvement seemed to be from Vit. E.
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PMID:Effect of ascorbic acid and Vitamin E supplementation on semen quality and biochemical parameters of male rabbits. 1255 24

The presence of cyanobacterial toxins in drinking and recreational waters represents a potential public health risk. Microcystin-LR (MC-LR) is a potent cyclic heptapeptide hepatotoxin produced by the blue-green alga Microcystis aeruginosa. Chemoprotectant studies have indicated that membrane-active antioxidants such as vitamin E may offer protection against microcystin toxicity. This study investigated the effect of vitamin E supplementation on microcystin toxicity in mouse liver. Groups of mice were fed vitamin E supplements (8.33 or 33.3 U/mouse/day) for 4 weeks, with intraperitoneal doses of MC-LR extract (70% LD(50)) every 3 days from day 8. The potential benefits of vitamin E were evaluated based on lipid peroxidation, alanine transaminase (ALT), and glutathione S-transferase (GST) levels. Vitamin E supplementation at 33.3 U/mouse/day offered some protection against lipid peroxidation induced by repeated exposure to MC-LR extract and limited both the toxin-induced increase in ALT leakage and decrease in GST activity. Vitamin E supplementation at 66.6 U/mouse/day significantly increased the time to death and reduced the increase in liver percentage body weight induced in mice given a lethal dose challenge of MC-LR extract. Therefore, vitamin E, taken as a dietary supplement, may have a protective effect against chronic exposure to MC-LR.
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PMID:An investigation of the role of vitamin E in the protection of mice against microcystin toxicity. 1263 3

Oxidant effects of nicotine in the central nervous system is not clear. The aim of this study was to investigate whether nicotine induces oxidative stress in rat brain, and if it does, to test the effects of Hippophea rhamnoides L. extract (HRe-1) and also vitamin E as a positive control. The groups were: nicotine [0.5 mg/kg/day, intraperitoneal (i.p.)]; nicotine+vitamin E [75 mg/kg/day, intragastric (i.g.)]; nicotine+HRe-1 (250 mg/kg/day, i.g.); and control group (receiving only vehicles). There were eight rats per group and supplementation period was 3 weeks. Malondialdehyde (MDA) level was increased by nicotine in brain tissue, which was prevented by vitamin E whereas not affected by HRe-1. Brain tissue glutathione S-transferase activities of nicotine administered and HRe-1 supplemented groups were lower than control and vitamin E supplemented groups, while glutathione peroxidase (GSH-Px) activities of vitamin E and HRe-1 supplemented groups were lower than the nicotine administered group. Superoxide dismutase activity was not affected by any of the treatments. Total glutathione level was higher in the vitamin E supplemented group compared with control and nicotine administered groups. Vitamin E might have easily diffused to rat brain as a lipid soluble antioxidant, however, the plant extract, HRe-1, would not have sufficiently diffused to the brain to exert its antioxidant effect.
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PMID:Vitamin E but not Hippophea rhamnoides L. prevented nicotine-induced oxidative stress in rat brain. 1294 82

The effect of cadmium or manganese administration on rat liver glutathione S-transferase (GST) has been investigated. The activity of this enzyme in liver cytosol, where almost all the cellular activity is present, had increased by more than 36% 24 h after a single i.p. injection of CdCl(2) (2.5 mg kg(-1) b.w.) or MnCl(2) (2.0 mg kg(-1) b.w.). After shorter and longer time intervals, a lower enzyme activity stimulation was observed in both cases. When liver cytosol was incubated for 10 min with 75 microM CdCl(2) or 40 microM MnCl(2), no effect was observed on enzyme activity. The increase in GST following cadmium or manganese administration was blocked by prior administration of actinomycin D, indicative of a possible transcription-dependent response. The liver soluble GST from both control and metal-treated rats was not at all affected by Vitamin E, in the range of 20-300 microM. By contrast, hematin was seen to be a competitive inhibitor of this liver enzyme from both types of rats by using CDNB as substrate and the K(i) value was equal to 0.22 microM. The possibility that under the conditions used class alpha GST isoenzymes are affected by cadmium or manganese is discussed.
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PMID:Rat liver glutathione S-transferase activity stimulation following acute cadmium or manganese intoxication. 1515 61

Role of alpha-tocopherol (vitamin E), beta-carotene and/or their combination as antioxidants against the toxicity of fenvalerate on blood hematology, free radicals, biochemical parameters, and semen quality were studied in male rats. Fenvalerate (20 mg/kg BW), vitamin E (100 mg/kg BW), beta-carotene (10 mg/kg BW), and vitamin E plus beta-carotene (100 + 10 mg/kg BW, respectively) were given alone or in combination with fenvalerate. The tested doses were given to rats every other day for 30 days. Results obtained showed that fenvalerate significantly (P < 0.05) induced free radicals in plasma and brain and insignificantly in liver and testes. While, vitamin E, beta-carotene alone and/or in combination decreased the levels of free radicals in plasma, liver, testes, and brain. The activities of glutathione S-transferase (liver), alkaline phosphatase (plasma and liver), aspartate aminotransferase (plasma, liver, and testes) and alanine aminotransferase (plasma and liver) were significantly (P < 0.05) increased due to fenvalerate administration. The activity of acetylcholinesterase was significantly (P < 0.05) decreased in brain and plasma, while plasma glucose, urea, creatinine, and bilirubin concentrations were significantly (P < 0.05) increased in rats treated with fenvalerate. Also, results showed a significant (P < 0.05) alterations in plasma proteins, hematological parameters, body weight, and relative weights of organs. Sperm concentration and motility (%) were significantly (P < 0.05) decreased, while dead and abnormal sperm increased in rats exposed to fenvalerate. Vitamin E, beta-carotene alone and/or in combination did not cause any changes in the investigated parameters, but improved semen quality and minimized the toxic effect of fenvalerate. The obtained results demonstrated the beneficial influences of vitamin E, beta-carotene alone and/or in combination in reducing the harmful effects of fenvalerate.
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PMID:Role of alpha-tocopherol and beta-carotene in ameliorating the fenvalerate-induced changes in oxidative stress, hemato-biochemical parameters, and semen quality of male rats. 1518 33


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