UMLS:C1260386 - FACTA Search

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Query: UMLS:C1260386 (GSH)
38,102 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Liver microsomal enzyme activities and glutathione (GSH) contents of fasted male rats pretreated with phenobarbital (PBT) or vehicle controls were measured during and after exposure to trichloroethylene (TRI) (1% x 2 hr). TRI caused morphologic liver injury only in the pbt animals. Cytochrome P-450 and b5 contents were diminished by the end of the first hr of TRI exposure and NADH-cytochrome c reduction increased three-fold by eight hr in the PBT animals. The only change in vehicle animals exposed to TRI was a decrease in NADPH-cytochrome c reductase activity by eight hr. Hepatic GSH contents of vehicle animals, constant during TRI exposure, rose with time. In contrast, in PBT animals, hepatic GSH contents decreased during TRI exposure and then rebounded. Decreases in GSH were most profound in the microsomal fraction. When fed animals with approximately two-fold higher hepatic GSH levels than fasted animals were exposed to TRI, they had shorter anesthesia recovery times and less liver injury, although excreting similar or slightly more trichlorinated metabolite into their urine in 24 hr than their fasted counterparts. We suggest that the hepatoxic effects of trichloroethylene are caused by inadequate detoxification of its reactive intermediates.
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PMID:Trichloroethylene-induced deactivation of cytochrome P-450 and loss of liver glutathione in vivo. 84 Nov 73

Selenocystamine (RSe-SeR) was shown to catalyze the oxygen-mediated oxidation of excess GSH to glutathione disulfide, at neutral pH and ambient PO2. This glutathione oxidase activity required the heterolytic reduction of the diselenide bond, which produced two equivalents of the selenolate derivative selenocysteamine (RSe-), via the transient formation of a selenenylsulfide intermediate (RSe-SG). Formation of RSe- was the only reaction observed in anaerobic conditions. At ambient PO2, the kinetics and stoichiometry of GSSG production as well as that of GSH and oxygen consumptions demonstrated that RSe- performed a three-step reduction of oxygen to water. The first step was a one-electron transfer from RSe- to dioxygen, yielding superoxide and a putative selenyl radical RSe., which decayed very rapidly to RSe-SeR. In the second step, RSe- reduced superoxide to hydrogen peroxide through a much faster one-electron transfer, also associated with the decay of RSe. to RSe-SeR. The third step was a two-electron transfer from RSe- to hydrogen peroxide, again much faster than oxygen reduction, which resulted in the production of RSe-SG, presumably via a selenenic acid intermediate (RSeOH) which was trapped by excess GSH. This third step was studied on exogenous hydroperoxide in anaerobic conditions, and it could be eliminated from the glutathione oxidase cycle in the presence of excess catalase. The role of RSe- as a one- and two-electron reductant was confirmed by competitive carboxymethylation with iodoacetate. RSe- was able to rapidly reduce ferric cytochrome c to its ferrous derivative. The overall rate of catalytic glutathione oxidation was GSH concentration dependent and oxygen concentration independent. Excess glutathione reductase and NADPH increased the catalytic oxidation of GSH, probably by switching the rate-limiting step from selenylsulfide to diselenide cleavage. When GSH was substituted for dithiothreitol, it was shown to reduce RSe-SeR to RSe- in a fast and quantitative reaction, and selenocystamine behaved as a dithiothreitol oxidase, whose catalytic cycle was dependent on oxygen concentration. The oxidase cycle of glutathione was inhibited by mercaptosuccinate, while that of dithiothreitol was not affected. When mercaptosuccinate was substituted for GSH, a stable selenenylsulfide was formed. These observations suggest that electrostatic interactions affect the reductive cleavage of diselenide and selenenylsulfide linkages. This study illustrates the ease of one-electron transfers from RSe- to a variety of reducible substrates. Such free radical mechanisms may explain much of the cytotoxicity of alkylselenols, and they demonstrate that selenocystamine is a poor catalytic model of the enzyme glutathione peroxidase.
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PMID:Glutathione oxidase activity of selenocystamine: a mechanistic study. 160 42

Xenobiotics metabolized in rat pulmonary tissue are often selectively cytotoxic to individual lung cell populations. A non-homogeneous distribution of xenobiotic biotransformation enzymes, e.g., cytochrome P-450 (P-450)- and glutathione (GSH)-associated enzymes, in rat lung tissue may underlie this observed cell-selective pneumotoxicity. To evaluate this hypothesis, the relative activities of P-450- and GSH-associated enzymes were measured in sonicated, freshly isolated preparations containing enriched complements of individual toxicant-sensitive lung cell types, including non-ciliated bronchiolar epithelial (Clara) cells (24% pure), alveolar type II cells (86% pure) and pulmonary endothelial cells (identified by membrane-associated angiotensin converting enzyme activity). Lung cell fractions were isolated by centrifugal elutriation from male F344 rats that 48 h earlier received a single i.p. injection of either P-450-inducer beta-naphthoflavone (50 mg beta-NF/kg body weight) or corn oil vehicle. The enriched Clara cell fraction possessed (per 10(6) cells) greater P-450 and reduced GSH contents and higher enzyme activities (i.e., NADPH- and NADH cytochrome c reductases, benzyloxy (BROD)-, pentoxy (PROD)- and etoxyresorufin (EROD)-O-dealkylases, GSH transferase, GSH peroxidase, GSH reductase and NADPH quinone oxidoreductase) than either the enriched type II cell or endothelial cell preparations. However, the relative biochemical activities for the enriched fractions (Clara greater than type II greater than endothelial) generally reflected respective sonicate cellular protein content. Treatment of rats with beta-NF resulted in: (a) an induction in EROD activity in the enriched preparations of type II cells, Clara cells and endothelial cells (125-, 89- and 35-fold, respectively); (b) higher NADPH quinone oxidoreductase activities, which were increased to the greatest degree (3-fold) in the enriched type II cell fraction and (c) a small elevation in GSH transferase activity measured in the enriched Clara cell fraction. Although the enriched rat lung cell preparations possessed unique biochemical profiles for constitutive and beta-NF-inducible P-450- and GSH-associated enzymes, additional studies with higher purity preparations (e.g., Clara cells) will be required to more fully evaluate the relationship between relative cellular complements of xenobiotic biotransformation enzymes and pneumotoxicant susceptibility.
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PMID:Cytochrome P-450- and glutathione-associated enzyme activities in freshly isolated enriched lung cell fractions from beta-naphthoflavone-treated male F344 rats. 160 25

The biochemical characteristics of the electron transfer chain are evaluated in purified non-synaptic ("free") mitochondria from the forebrain of 60-week-old rats weekly subjected to peroxidative stress (once, twice, or three times) by the electrophilic prooxidant 2-cyclohexene-1-one. The following parameters are evaluated: (a) content of respiratory components, namely ubiquinone, cytochrome b, cytochrome c1, cytochrome c; (b) specific activity of enzymes, namely citrate synthase, succinate dehydrogenase, rotenone-sensitive NADH: cytochrome c reductase, cytochrome oxidase; (c) concentration of reduced glutathione (GSH). Before the first peroxidative stress induction, the rats are administered for 8 weeks by intraperitoneal injection of vehicle, papaverine, delta-yohimbine, almitrine or hopanthenate. The rats are treated also during the week(s) before the second or third peroxidative stress. The cerebral peroxidative stress induces: (a) initially, a decrease in brain GSH concentration concomitant with a decrease in the mitochondrial activity of cytochrome oxidase of aa3-type (complex IV), without changes in ubiquinone and cytochrome b populations; (b) subsequently, an alteration in the transfer molecule cytochrome c and, finally, in rotenone-sensitive NADH-cytochrome c reductase (complex I) and succinate dehydrogenase (complex II). The selective sensitivity of the chain components to peroxidative stress is supported by the effects of the concomitant subchronic treatment with agents acting at different biochemical steps. In fact, almitrine sets limits to its effects at cytochrome c content and aa3-type cytochrome oxidase activity, while delta-yohimbine sets limits to its effects at the level of tricarboxylic acid cycle (citrate synthase) and/or of intermediary between tricarboxylic acid cycle and complex II (succinate dehydrogenase).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Sequential damage in mitochondrial complexes by peroxidative stress. 166 94

The toxicity of some metabolic products pertinent to 4-ethoxyaniline in isolated hepatocytes were investigated. The compounds investigated were 4-ethoxynitrosobenzene (1), 4-ethoxy-4'-nitrosodiphenylamine (2), 3,6-bis(4-ethoxy-phenylimino)-4-ethoxy-1,4-cyclohexadienylamine (3), 4-(4-ethoxyphenylimino)-2,3-dimethyl-2,5-cyclohexadiene-1-one (4) and 4-(4-ethoxyphenylimino)-2,6-dimethyl-2,5-cyclohexadiene-1-one (5). Of these, 1, 2 and 3 are oxidation products of 4-ethoxyaniline. Compounds 4 and 5 are dimethyl analogues of previously investigated oxidation product 4-(4-ethoxyphenylimino(-2,5-cyclohexadiene-1-one (NEPBQI). Among the investigated compounds, 1 and 2 were the most toxic towards isolated hepatocytes. In hepatocytes treated with compounds 1, 2 and 4, loss of cell viability was also accompanied by surface bleb formation. All compounds except 3 reacted with GSH resulting in depletion of cellular GSH. No formation of GSSG was observed, however. Thus, the GSH depletion was apparently due to conjugate formation rather than oxidation. No superoxide dismutase inhibitable reduction of acetylated cytochrome c was observed, thus none of the compounds undergoes measurable redox cycling.
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PMID:Cellular effects of some metabolic oxidation products pertinent to 4-ethoxyaniline. 177 31

The ability of selenium (Se) to act as a redox catalyst is an important factor in understanding the biological function of selenoproteins in addition to that of GSH peroxidase. Selenocystine at micromolar levels exhibited pseudothiotransferase activity by enhancing the reduction of 5,5-dithiobis-(2-nitrobenzoic acid) (DTNB) by thiols. In contrast, selenite inhibited the reduction of DTNB by thiols. Selenite was more catalytic than selenocystine in the reduction of cytochrome c by GSH, whereas GSH peroxidase was a weak catalyst. Tissues from Se-deficient and Se-supplemented rats were assayed for activities of GSH-thiotransferase, NADPH cytochrome c reductase, formaldehyde dehydrogenase, and a hypothesized GSH cytochrome c reductase. GSH-thiotransferase activity was significantly increased in the liver of Se-deficient rats. No appreciable activity of this enzyme was found in the kidney of rats from either dietary group. No enzymatic activity for cytochrome c reduction by GSH was detected in cytosols, mitochondria, or microsomes from liver and kidney of Se-deficient or Se-supplemented rats. Formaldehyde dehydrogenase was significantly higher in liver cytosols from Se-supplemented rats than from Se-deficient rats. The higher activity was not attributed to Se-containing proteins, but to an unknown small molecular-weight factor. This study did not support the hypothesis that physiological levels of Se may be involved in sulfhydryl-disulfide exchange reactions in vivo, or that selenium may enhance cytochrome c reduction by GSH in vivo.
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PMID:Selenium as a sulfhydryl redox catalyst and survey of potential selenium-dependent enzymes. 282 Nov 93

The ability of intact human red cells to scavenge extracellularly generated H2O2 and O2-, and to prevent formation of hydroxyl radicals and hypochlorous acid has been examined. Red cells inhibited oxidation of ferrocytochrome c by H2O2. Cells treated with aminotriazole no longer inhibited, indicating that protection was almost entirely due to intracellular catalase. Contribution by the GSH system was slight, and apparent only with low H2O2 concentrations when catalase was inhibited by aminotriazole. The cells were about a quarter as efficient at inhibiting cytochrome c oxidation as an equivalent concentration of purified catalase. No inhibition of O2(-)-dependent reduction of ferricytochrome c or nitroblue tetrazolium was observed, although extracted red cell superoxide dismutase inhibited nitroblue tetrazolium reduction at one fortieth the concentration of that in the cells. Red cells efficiently inhibited deoxyribose oxidation by hydroxyl radicals generated from H2O2, O2- and Fe(EDTA), and myeloperoxidase-dependent oxidation of methionine to methionine sulfoxide by stimulated neutrophils. Most of the red cell inhibition of hydroxyl radical production, and all the inhibition of methionine oxidation, was prevented by blocking intracellular catalase with aminotriazole. Thus red cells are able to efficiently scavenge H2O2, but not O2-, produced in their environment, and to inhibit formation of hydroxyl radicals and hypochlorous acid. They may therefore have an important role in extracellular antioxidant defense.
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PMID:Human red cells scavenge extracellular hydrogen peroxide and inhibit formation of hypochlorous acid and hydroxyl radical. 282 62

Methanol dissimilatory enzymes detected in the methanol autotroph Xanthobacter H4-14 were a typical phenazine methosulphate-linked methanol dehydrogenase, a NAD+-linked formate dehydrogenase, and a dye-linked formaldehyde dehydrogenase that could be assayed only by activity stains of polyacrylamide gels. This same methanol dehydrogenase activity was found in ethanol-grown cells and was apparently utilized for ethanol oxidation. Formaldehyde dehydrogenase activities were investigated in Paracoccus denitrificans, Xanthobacter H4-14, and Pseudomonas AM1. P. denitrificans contained a previously reported NAD+-linked, GSH-dependent activity, but both Xanthobacter H4-14 and Pseudomonas AM1 contained numerous activities detected by activity stains of polyacrylamide gels. Induction studies showed that in Xanthobacter H4-14, a 10 kDal polypeptide, probably a dehydrogenase-associated cytochrome c, was co-induced with methanol dehydrogenase, but the formaldehyde and formate dehydrogenases were not co-regulated. Analogous induction experiments revealed similar patterns in P. denitrificans, but no evidence for co-regulation of dissimilatory activities in Pseudomonas AM1.
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PMID:Methanol dissimilation in Xanthobacter H4-14: activities, induction and comparison to Pseudomonas AM1 and Paracoccus denitrificans. 293 86

Diethyldithiocarbamate (DDC) exhibits a variety of pharmacologic activities, including both radioprotective and sensitizing properties. Since the glutathione/glutathione peroxidase system may be a significant factor in determining radiation sensitivity, the potential mechanisms of action of DDC in relation to this system were examined in vitro. The interaction of DDC with reduced glutathione (GSH) was tested using a simple system based on the reduction of cytochrome c. When DDC (0.005 mM) was incubated with GSH (0.5 mM), the reduction of cytochrome c was eightfold greater than that expected from an additive effect of DDC and GSH. GSH could be replaced by oxidized glutathione and glutathione reductase. Cytochrome c reduced by DDC was oxidized by mitochondria. The interaction of DDC with both the hexosemonophosphate shunt pathway and the mitochondrial respiratory chain suggests the possibility of linking these two pathways through DDC. Oxidation of DDC by peroxide and reversal by GSH indicated that the drug can engage in a cyclic reaction with peroxide and GSH. This was confirmed when DDC was used in the assay system for glutathione peroxidase (GSHPx) without GSHPx. DDC at a concentration of 0.25 mM was more active than 0.01 unit of pure GSHPx in eliminating peroxide, and much more active than the other sulfhydryl compounds tested. These studies indicate that DDC can supplement GSHPx activity or substitute for it in detoxifying peroxides, and suggests a unique role in the chemical modification of radiation sensitivity.
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PMID:A novel interaction of diethyldithiocarbamate with the glutathione/glutathione peroxidase system. 301 61

1. The oxidation of NADH and NADPH catalysed by the soluble supernatant from the hepatopancreas of Octopus vulgaris is due to a single enzyme, which has been purified approximately 100-fold. The enzyme reacts rapidly with potassium ferricyanide, and more slowly with 2,6-dichlorophenol-indophenol. No activity is obtained with oxygen, cytochrome c, lipoic acid, vitamin K(1), vitamin K(3), ubiquinone-30, p-benzoquinone, 2-p-iodophenyl-3-p-nitrophenyl-5-phenyltetrazolium chloride or methylene blue. 2. GSH, cysteine and mercaptoethanol stimulate the enzymic activity up to fivefold. GSSG is without any apparent effect. When stimulated by GSH the enzyme becomes sensitive to dicoumarol, which produces an inhibition competitive with respect to the activator. 3. The purified enzyme contains an acid-removable flavine component, which has been identified as FMN by spectrofluorimetry and chromatography in three solvent systems. After acid ammonium sulphate treatment the enzymic activity is lost, but it can be almost fully restored by incubation with FMN. FAD produces only a partial reactivation.
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PMID:Purification and properties of a soluble reduced nicotinamide-adenine dinucleotide (phosphate) dehydrogenase from the hepatopancreas of Octopus vulgaris. 417 22

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