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)

Both acidosis and oxidative stress contribute to ischemic brain injury. The present study examines interactions between acidosis and oxidative stress in murine cortical cultures. Acidosis (pH 6.2) was found to potentiate markedly neuronal death induced by H2O2 exposure. To determine if this effect was mediated by decreased antioxidant capacity at low pH, the activities of several antioxidant enzymes were measured. Acidosis was found to reduce the activities of glutathione peroxidase and glutathione S-transferase by 50-60% (p < 0.001) and the activity of glutathione reductase by 20% (p < 0.01) in lysates of the cortical cultures. Like acidosis, direct inhibition of glutathione peroxidase with mercaptosuccinate also potentiated H2O2 toxicity. Because acidosis may accelerate hydroxyl radical production by the Fenton reaction, the effect of iron chelators was also examined. Both desferrioxamine and N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine, two structurally different iron chelators, significantly reduced H2O2-induced neuronal death under both pH 7.2 and pH 6.2 conditions. These results suggest that the increased cell death produced by severe acidosis during cerebral ischemia may result in part from exacerbation of oxidative injury. This exacerbation may result from both impaired antioxidant enzyme functions and increased intracellular free iron levels.
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PMID:Acidosis potentiates oxidative neuronal death by multiple mechanisms. 1050 Dec

The influence of ionol (100mg/kg) on the rate of superoxide generation (V) and activities of antioxidant enzymes: CuZn- and Mn-SOD, glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) in different subcellular organelles of mice liver was studied. Ionol is shown to result in realiable a synchronous changes of all studied antioxidant enzyme activities in cytosol and whole blood. On the first day the level of these enzymes increased by 1.5 times and on the third day it returned to normal. The obtained data indicate retention of regulatory relation in antioxidant system in liver cytosol within the sector SOD-GSH-Px. In the mitochondria the Mn-SOD activity changes in antibate manner as compared CuZn-SOD activity, on the first day Mn-SOD activity decreases and remains on lowered level during the whole period investigated. In microsomes the value of V is found to be reduced. In the case of SMP on the first day after the administration of ionol V value didn't increase significantly. However, owing to Mn-SOD activity decrease the ratio V/A, showing the level of superoxide radicals in subcellular organelles grows 3-fold. In nuclei V value increases 4-6-fold during 1-3 hours after ionol injection. The data obtained show that administration of high dose of ionol to intact mice suppresses antioxidant enzyme system of mitochondria, induces abrupt production of superoxide radicals in nuclei and reduces of functioning of electron transport chaine in microsomes. The observed disturbances have short-lived character and are normalized during 3 days after administration of ionol. The toxic effects of ionol may be connected with the action of oxidative modification products formed in organism.
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PMID:[Effect of ionol on superoxide radical metabolism in murine liver]. 1054 81

The current experiments were designed to study the effect of moderate treadmill training exercise on lipid peroxides and antioxidant enzyme activity in various tissues of ICR mice. Three-month-old female mice were trained on a treadmill to run daily from 45 to 50 minutes, at 1 km per hour, 6 days a week for a total of 8 weeks. At the end of the 8-week endurance-training period, both sedentary control (SC) and exercise-trained (ET) mice were sacrificed, and various tissues were collected to measure antioxidant enzyme activity. The results showed weight gain and serum lipid peroxides significantly decreased in ET mice compared to SC mice. Also, although lipid peroxide levels in kidney and salivary glands were found to be significantly decreased in ET mice, these mice showed higher lipid peroxide levels in the liver compared to SC mice. No change was observed in heart and calf muscle tissue of the ET mice. Exercise was also noted to increase superoxide dismutase (SOD) activity in kidney, heart, and calf muscle homogenates. Increases in catalase activity were present in liver, heart, calf muscle, and salivary gland homogenates of ET mice compared to their SC counterparts. Exercise was also shown to increase glutathione peroxidase activity in liver, kidney, and heart homogenates, as well as glutathione transferase activity in liver and salivary gland homogenates. In addition, exercise training was found to increase reduced and total glutathione levels in heart, calf muscle, and salivary gland. These results indicate that moderate exercise is beneficial to the lowering of lipid peroxides and the increasing of antioxidant enzyme activity specifically in the salivary gland, and also in various organs. However, its beneficial effect on elevation of antioxidant enzymes and suppression of lipid peroxide, varies from organ to organ.
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PMID:Modulation of antioxidant enzymes and lipid peroxidation in salivary gland and other tissues in mice by moderate treadmill exercise. 1060 13

Limited information is available on the upregulation of endogenous antioxidant enzymes by means of administering various pharmaceuticals and/or chemicals. It has been reported that ursodeoxycholic acid (UDCA), a bile acid originally identified from black bear bile (a Chinese medicine, Yutan) increased glutathione S-transferase (GST) activities in mouse livers, resulting in a decrease in systemic lethal toxicity of orally challenged 1-2-dichloro-4-nitrobenzene (DCNB). Also, ursolic acid found in herbal medicines (e.g. leaves of loquat) was reported to increase catalase (CAT) activities in mouse liver. Interestingly, the chemical structures of these two compounds are surprisingly similar to each other, despite the difference in their original sources. These results suggest that in the future, more and more compounds will be found to have effects on increasing endogenous antioxidant enzyme activities. Deprenyl is a monoamine oxidase B inhibitor but also possesses many other different pharmacological activities. Among these various pharmacological effects of deprenyl, a possible causal relationship between two effects of deprenyl, namely the prolongation of the survival of animals and upregulation of antioxidant enzymes in selective brain regions, has been postulated by the authors. In at least four different animal species (rats, mice, hamsters and dogs), a significant prolongation of survival by chronic administration of the drug has been reported by different groups including that of the authors. This group has reported that repeated administration of the drug for 2-3 weeks can significantly increase activities of both types of superoxide dismutase (SODs) (Cu, Zn-, and Mn-SODs) as well as of CAT selectively in brain dopaminergic regions. Both effects are dose dependent but excessive dosages become less effective and even cause an adverse effect (i.e. a decrease in enzyme activities and shortening of life span). The parallelism of the dose-effect relationship between the two phenomena suggests that modification of SOD and CAT levels is one possible mechanism for deprenyl's ability to prolong the life span of animals.
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PMID:Pharmacological modifications of endogenous antioxidant enzymes with special reference to the effects of deprenyl: a possible antioxidant strategy. 1065 38

We previously reported that antisense c-jun suppressed apoptosis induced by serum deprivation in F-MEL cells. To elucidate the molecular mechanisms responsible for this suppression of apoptosis we investigated the activities and protein expression of antioxidant materials in the cell under serum deprivation. In the parental F-MEL cells enzyme activities of catalase, glutathione S-transferase (GST), and glutathione peroxidase (GPx) increased to reach the maximum at 24-72 h after removal of serum and then decreased to initial levels or a little less. Superoxide dismutase (SOD) maintained the initial level for 72 h and increased 1.5- to 2-fold at 96 h. Glutathione (GSH) levels increased at 24 h and then dropped significantly to one-third the initial level. On the other hand, in c-junAS (+) cells, in which antisense c-jun was expressed and c-Jun protein expression was reduced to undetectable level. We found 1.9-, 2.7-, 4.8-, and 15. 8-fold increase in the activities of catalase, GST, SOD, and GPx, respectively, at 96 h. GSH maintained almost the same level as the initial. Enhancement of these enzyme activities in c-junAS (+) cells was induced under serum deprivation. Western blottings for catalase, GST, and SOD also showed enhanced increase in protein expression, supporting the increase in enzyme activities. Cellular peroxide level under serum deprivation was monitored by flow cytometry using DCFH-DA as a probe. We found that the peroxide level increased at 24 h and then decreased at 72 and 96 h in c-junAS (+) cells, and reduction of the peroxide level coincided with an increase in antioxidant enzyme activities. These results indicate that antioxidant materials such as catalase, GST, SOD, GPx, and GSH are induced by serum deprivation when c-jun expression is inhibited in F-MEL cells. The link between inhibition of c-jun expression and enhancement of cellular antioxidant defense is discussed.
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PMID:Inhibition of c-Jun expression induces antioxidant enzymes under serum deprivation. 1066 16

We examined the effects of garlic oil (GO) and two of its organosulfur compounds, diallyl sulfide (DAS) and diallyl disulfide (DADS), on the drug-metabolizing and antioxidant systems in rats and sought to determine whether these effects are associated with dietary fat. Rats were fed a high-fat diet and received GO or DADS (200 mg/kg body wt) or DAS (100 mg/kg) orally three times a week for seven weeks. Control animals received corn oil alone. Another group of rats was fed a low-fat diet, with or without GO. GO and DADS significantly reduced the body weight gain of rats (p < 0.05). GO, however, dramatically increased the spleen weight and spleen weight-to-body weight ratio (p < 0.05). DAS increased glutathione S-transferase (GST) and 7-pentoxyresorufin O-dealkylase activities, whereas DADS increased only GST activity (p < 0.05). Immunoblot assay showed GO-, DAS-, and DADS-enhanced expression of the placental form of GST and cytochrome P-450 IIBI but suppressed cytochrome P-450 IIEI expression. Hepatic antioxidant enzyme activities were also modulated by these garlic components. GO and DADS inhibited glutathione peroxidase activity (p < 0.05), and DADS and DAS enhanced glutathione reductase activity (p < 0.05). Only GO enhanced the superoxide dismutase activity (p < 0.05). All these garlic components increased glutathione levels in red blood cells (p < 0.05) but did not influence hepatic glutathione levels. Although the amount of fat in the diet modulated drug-metabolizing and antioxidant functions, no interactions between GO and dietary fat were observed. These results indicate that GO and its allyl sulfide components, as well as dietary lipid, modulate drug-metabolizing and antioxidant enzyme activities. The action of GO appears to be independent of dietary lipid content.
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PMID:Effects of garlic oil and its organosulfur compounds on the activities of hepatic drug-metabolizing and antioxidant enzymes in rats fed high- and low-fat diets. 1069 70

It has been reported that several cis-unsaturated fatty acids (c-UFAs) could increase doxorubicin (DOX) accumulation in cancer cells and hence elevate its cytotoxicity. However, some researchers showed that c-UFA pretreatment did not affect its cytotoxicity in special cell lines. It is possible that the different results occurred due to different cellular characteristics. We hypothesized that c-UFA treatment might modulate the activities of some antioxidant enzymes to affect the resistance of cells to DOX. In the present study, we examined how c-UFA pretreatment affected DOX cytotoxicity on mouse leukemia cell line, P388, and its resistant subline, P388/DOX, which we found to have significantly higher glutathione peroxidase (GPx) activity as well as P-glycoprotein (p-gp) overexpression. We chose two c-UFAs, gamma-linolenic acid (GLA) (18:3n-6) and docosahexaenoic acid (DHA) (22:6n-3). Cytotoxicity was measured by MTT (3-(4.5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and trypan blue exclusion assays. DOX accumulation and p-gp expression were measured by flow cytometry. The activities of catalase (CAT), superoxide dismutase (SOD), glutathione S-transferase (GST), and GPx were determined for both cell lines with and without treatment with GLA or DHA. Significant DOX accumulation occurred in both cell lines with GLA or DHA pretreatment, but without any change in p-gp expression in either cell line. Sensitivity to DOX cytotoxicity was improved by GLA or DHA pretreatment in P388/DOX in which only SOD activity was significantly increased, but not in the parental cell line P388 in which both SOD and CAT were significantly increased by the pretreatment. However, combined pretreatment of GLA or DHA with antioxidants, pyrrolidinedithiocarbamate (PDTC) or Vitamin C, could sensitize not only P388/DOX but also P388 cells to DOX. We conclude that the effects of c-UFA pretreatment on the sensitivity of cancer cells to DOX not only depend on the change in drug accumulation but also the change in the levels of antioxidant enzyme activities, and suggest that combined administration of c-UFAs, antioxidants, and DOX may be more effective in treating leukemia.
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PMID:Effects of cis-unsaturated fatty acids on doxorubicin sensitivity in P388/DOX resistant and P388 parental cell lines. 1095 54

Lipid peroxide levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione transferase (GST) activities were investigated in mitochondrial fractions obtained from tumorous and nontumorous colorectal tissues of fourteen patients with colon and rectum cancer. Histopathological evaluations, including type, stage, necrosis and lymphocyte infiltration were also performed for each patient. The activities of SOD, GSH-Px and GST were increased significantly, but lipid peroxide levels remained unchanged in mitochondria obtained from tumors compared to adjacent normal tissues of subjects with colorectal cancer. When the patients were grouped according to their histopathological evaluation, such as type, stage, necrosis and lymphocyte infiltration, no relationship was observed between the histopathological results and the mitochondrial lipid peroxidation or antioxidant enzyme activities.
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PMID:Mitochondrial lipid peroxides and antioxidant enzymes in colorectal adenocarcinoma tissues. 1112 24

This study aims to investigate the effects of the herbicide 2,4-D and the insecticide azinphosmethyl on hepatic antioxidant enzyme activities and lipid peroxidation in tilapia. Fish were exposed to 27 ppm 2,4-D, 0.03 ppm azinphosmethyl and to a mixture of both for 24, 48, 72 and 96 h. Activities of catalase (EC 1.11.1.6), glutathione-S-transferase (GST, EC 2.5.1.18) and the level of malondialdehyde (MDA) in the liver of Oreochromis niloticus exposed to 2,4-D and azinphosmethyl, both individually and in combination, were not affected by the pesticide exposures. However, glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) and glutathione reductase (GR, EC 1.6.4.2) activities in individual and combined treatments, increased significantly compared to controls. Furthermore, glutathione peroxidase (GPx, EC 1.11.1.9) activity increased in individual treatment, while the same enzyme activity decreased in combination. 2,4-D did not affect the activity of superoxide dismutase (SOD, EC 1.15.1.1), but the activity of this enzyme in azinphosmethyl treatment decreased, while its activity increased in combination. Combined treatment of the pesticides exerted synergistic effects in the activity of SOD, while antagonistic effects were found in the activities of G6PD, GPx, GR. The results indicate that O. niloticus resisted oxidative stress by antioxidant mechanisms and prevented increases in lipid peroxidation.
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PMID:Combined effects of 2,4-D and azinphosmethyl on antioxidant enzymes and lipid peroxidation in liver of Oreochromis niloticus. 1124

The apparent anticarcinogenic effect of cruciferous vegetables found in numerous epidemiological and experimental studies has been associated with their influence on phase I and phase II metabolising enzymes as well as on the antioxidant status. In the present study we investigated the effect of administration of a Brussels sprouts extract on the expression at the mRNA level and/or catalytic activity in rat liver of three phase I enzymes [cytochrome P450-1A2 (CYP1A2),-2B1/2 (CYP2B1/2) and-2E1 (CYP2E1)] and two phase II enzyme [NADPH:quinone reductase (QR) and glutathione S-transferase pi 7 (GSTpi)], all previously suggested to be induced by vegetables. We also examined the activity and/or expression of several important antioxidant enzymes: glutathione peroxidase (GPx), catalase and gamma-glutamyl-cysteine synthetase (GCS) and the activity of the repair enzyme 8-oxoguanine DNA glycosylase (OGG1). QR, GPx 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 in the liver. Oral administration of an aqueous Brussels sprouts extract for 4 days was found to induce the expression of GST 1.3-fold (P < 0.05) and the activity of QR 2.6-fold in rat liver (P < 0.05). No significant differences were seen in the expression of the phase I enzymes. No differences in antioxidant enzyme activity/expression or OGG1 activity were observed. In a second experiment, administration of the Brussels sprouts extract for 3 or 7 days was found to increase the level of 8-oxodG in rat liver from 0.75 to 0.97 per 10(5) dG and from 0.81 to 0.97 per 10(5) dG, respectively (P < 0.05). No effects 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 of cruciferous vegetables is beneficial.
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PMID:Effects of a Brussels sprouts extract on oxidative DNA damage and metabolising enzymes in rat liver. 1134 82


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