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)

Effects of ethanol (EtOH), mannitol (Man), L-histidine (His) and glutathione (GSH) on the oxidation of 2'-deoxyguanosine (dG) to its 8-hydroxy derivative (8-OH-dG) with H2O2 plus L-ascorbic acid (Ascb) in the absence and presence of Ni(II) were investigated in order to unveil the nature of active oxygen species involved in that oxidation. In the absence of Ni(II), production of 8-OH-dG was inhibited by His much greater than GSH greater than or equal to GSSG (oxidized glutathione) much greater than EtOH, but not by Man. The latter tended to enhance the production of 8-OH-dG. In the presence of Ni(II), the inhibition by His, GSH and GSSG, but not EtOH, was prevented. The results indicate involvement of a 'crypto-hydroxyl' radical as the dG oxidizing species in both the absence and presence of Ni(II). Also, the results provide evidence that Ni(II) complexes with His, GSH and GSSG may lack antioxidant capacity. Moreover, the Ni(II) complex with His was found capable of enhancing 8-OH-dG production by the Ascb+H2O2 system to a greater extent than Ni(II) alone. Likewise, although to a lesser extent, the formation of 8-OH-dG was enhanced by the combination of Ni(II) and Man which do not form complexes at pH 7.4. Since His is a major Ni(II) carrier in animal tissues, the dG oxidation enhancing capacity of the Ni(II) complex with His may contribute to the toxic and carcinogenic effects of Ni(II).
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PMID:Reversal by nickel(II) of inhibitory effects of some scavengers of active oxygen species upon hydroxylation of 2'-deoxyguanosine in vitro. 132 52

To better understand the mechanisms of tissue injury during and after carbon monoxide (CO) hypoxia, we studied the generation of partially reduced oxygen species (PROS) in the brains of rats subjected to 1% CO for 30 min, and then reoxygenated on air for 0-180 min. By determining H2O2-dependent inactivation of catalase in the presence of 3-amino-1,2,4-triazole (ATZ), we found increased H2O2 production in the forebrain after reoxygenation. The localization of catalase to brain microperoxisomes indicated an intracellular site of H2O2 production; subsequent studies of forebrain mitochondria isolated during and after CO hypoxia implicated nearby mitochondria as the source of H2O2. In the mitochondria, two periods of PROS production were indicated by decreases in the ratio of reduced to oxidized glutathione (GSH/GSSG). These periods of oxidative stress occurred immediately after CO exposure and 120 min after reoxygenation, as indicated by 50 and 43% decreases in GSH/GSSG, respectively. The glutathione depletion data were supported by studies of hydroxyl radical generation using a salicylate probe. The salicylate hydroxylation products, 2,3 and 2,5-dihydroxybenzoic acid (DHBA), were detected in mitochondria from CO exposed rats in significantly increased amounts during the same time intervals as decreases in GSH/GSSG. The DHBA products were increased 3.4-fold immediately after CO exposure, and threefold after 120 min reoxygenation. Because these indications of oxidative stress were not prominent in the postmitochondrial fraction, we propose that PROS generated in the brain after CO hypoxia originate primarily from mitochondria. These PROS may contribute to CO-mediated neuronal damage during reoxygenation after severe CO intoxication.
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PMID:Mitochondrial oxidative stress after carbon monoxide hypoxia in the rat brain. 132 93

The existence of a Na+/H+ exchange mechanism and its role in the regulation of lens fiber cell intracellular pH, as well as the effect of oxidants and antioxidants, have been examined in vesicular preparations from spiny dogfish and bovine eyes. The fluorescent probes, SBFI (sodium-binding benzofuran isophthalate) for Na+ and SNARF-1 (seminaphthorhodafluor-1) for H+, were used to determine fluorescent ratios in a dual-wavelength spectrofluorimeter. The results show that: (1) the plasma membrane vesicles can be purified from lens fiber (52.5% of the vesicles were in the right-side out orientation for the fish eyes and 56.3% for the bovine eyes, show enrichment for the membrane marker activities and have an average size of 0.2-0.5 microns); (2) the influx of Na+ was dependent on an outwardly directed pH gradient with the uptake of Na+ sensitive to 500 microM amiloride but not affected by 50 microM valinomycin and 50 mM K gluconate; (3) when the pHo (extravesicular pH) of the vesicles was set at 8.1 and pHi (intravesicular pH) to 6.1, an inwardly directed Na+ gradient caused an increase in intravesicular pH by about 0.3 pH unit, and in bovine lens fiber vesicles the Na+ influx is highly dependent on the intravesicular pH (or on the pHo/pHi gradient); (4) 50 microM H2O2 increases the Na+/H+ exchange rate by 174% in the vesicles derived from fish lens fibers. Similarly, 100 microM H2O2 stimulates the Na+/H+ exchange rate by 194% in bovine eye fibers. This activation is prevented by preincubation with GSH (reduced glutathione) but not with GSSG (oxidizing glutathione). We conclude that a Na+/H+ exchange mechanism is present in the lens fiber membranes. This exchange possibly regulates intracellular pH and controls the intracellular Na+ concentration. The sensitivity of the Na+/H+ exchanger to the oxidant, hydrogen peroxide (H2O2) and the protection by the antioxidant GSH suggests a possible role for the Na+/H+ exchange mechanism in the formation of cataracts.
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PMID:A Na+/H+ exchanger and its relation to oxidative effects in plasma membrane vesicles from lens fibers. 133 Jun 62

Mitochondria extracted from Wistar rat hearts at 3, 14-18 and 24 months of age showed no change in state 3-mitochondrial respiration measured in the presence of glutamate or succinate. Again no changes were found in the SMP-O2- production at the level of the rotenone-inhibited region, whilst at the level of the antimycin-inhibited region there was a marked increase in O2- production in the group of 14-18-month-old rats. In the same age period, the production of mitochondrial H2O2 supported by glutamate or succinate and the level of GSSG increased in comparison to the young group, accompanied by a decrease in the GSH level. Mitochondrial TBARS levels did not change during a life span, while a progressive accumulation in the mitochondrial lipofuscin content with age was measured.
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PMID:Mitochondrial production of oxygen free radicals in the heart muscle during the life span of the rat: peak at middle age. 133 12

In order to investigate the mechanism by which H2O2 damages the epithelium, 8 x 10(5) rabbit lens epithelial cells were treated with TEMPOL or deferoxamine and exposed to a single sublethal dose of 0.5 mM H2O2. TEMPOL is a SOD mimic, has a characteristic EPR spectrum and is metal independent. EPR spectra indicated that TEMPOL was not destroyed by H2O2, catalyzed the destruction of the superoxide anion, and penetrated the cells. Cells treated with H2O2 showed membrane blebbing, growth inhibition, an increase in GSSG, a dose-dependent decrease in GSH, ATP, NAD+, and in the activity of G3PDH, and in lactate production. H2O2 stimulated the hexose mono-phosphate shunt and induced single strand breaks in DNA. Treatment with TEMPOL or deferoxamine prevented or curtailed H2O2-induced inhibition of growth, the decrease in NAD+, the induction of single strand breaks in DNA, and membrane blebbing, but not the other biochemical parameters investigated. Both TEMPOL and deferoxamine prevent Fe+2-mediated generation of the damaging hydroxyl radical. TEMPOL reacts with superoxide and thus prevents it from recycling Fe+3 to Fe+2. It also oxidizes DNA-Fe+2 to DNA-Fe+3. Deferoxamine chelates intracellular Fe+3 and prevents its reduction to Fe+2. These compounds which limit the availability of Fe+2 by different means indicate that transition metals (including those bound to DNA) mediate certain of the damaging effects of H2O2.
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PMID:Tempol and deferoxamine protect cultured rabbit lens epithelial cells from H2O2 insult: insight into the mechanism of H2O2-induced injury. 133 54

Administration of menadione (vitamin K3; 2-methyl-1,4-naphthoquinone) to cultured bovine pulmonary artery endothelial cells caused a dose- and time-dependent depletion of cellular ATP and depletion of intracellular glutathione (GSH). The toxicity of menadione was correlated with an increase of menadione-glutathione conjugate in the medium and with an increase in H2O2 generation. Recent studies have suggested that GSH may be useful as a pharmacological agent to prevent oxidant injury. In the present study, treatment with exogenous GSH prevented the loss of cellular GSH and ATP caused by menadione. Protection by extracellular GSH involved two mechanisms. In one mechanism, extracellular GSH was degraded by gamma-glutamyl transpeptidase, producing substrates for subsequent intracellular de novo GSH synthesis. We found that the protective effect of extracellular GSH was decreased by inhibiting gamma-glutamyl transpeptidase. In the other mechanism, GSH reacted in the medium with menadione to form a conjugate. Although formation of the menadione-glutathione conjugate within cells may contribute to menadione toxicity, addition of menadione-glutathione conjugate to the medium was found to be nontoxic to endothelial cells. Thus exogenous GSH protected endothelial cells by two mechanisms: maintenance of intracellular GSH and prevention of menadione entrance into cells.
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PMID:Exogenous glutathione protects endothelial cells from menadione toxicity. 135 Apr 24

The kinetic effects of hydrogen peroxide (H2O2) on cultured endothelial cells isolated from bovine carotid artery were studied. The cytoprotective effects of glutathione (GSH) on H2O2-induced cell injury were also investigated. H2O2-induced a dose- and time-dependent cell injury in cultured endothelial cells. H2O2-induced cell injury was blocked by simultaneous treatment by catalase, but not by superoxide dismutase. H2O2 also induced endogenous PGI2 biosynthesis, and the maximum PGI2 production was reached after 1 h treatment. Stimulation of PGI2 production was parallel with arachidonate release from H2O2-treated cells. However the prostaglandin biosynthesis enzyme activity in cells was inhibited by H2O2 treatment. When the cells were treated with GSH, the intracellular GSH reached a plateau after 3 h treatment. Both H2O2-induced cell injury and PGI2 production were significantly inhibited by the 3 h pretreatment with GSH. The cytoprotective effect of GSH was completely inhibited by buthionine sulfoximine which is a specific inhibitor of gamma-glutamylcysteine synthetase. The results indicate that the cytoprotective effect of GSH on H2O2-induced cell injury in cultured bovine carotid artery endothelial cells depends on the increase in intracellular GSH content.
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PMID:Cytoprotective effect of reduced glutathione in hydrogen peroxide-induced endothelial cell injury. 135 Dec 88

Pulsed field gel electrophoresis showed that caffeic acid induced DNA strand breaks in cultured human cells in the presence of Mn(II). With alkali treatment, DNA single-strand breaks were observed. The strand breakage was increased by the treatment of buthionine sulphoximine (a GSH synthesis inhibitor) and 3-aminotriazol (a catalase inhibitor) and decreased by catalase, indicating the involvement of H2O2. The DNA damage was decreased by o-phenanthroline, indicating the involvement of transition metal ion. Damage to isolated DNA from c-Ha-ras-1 protooncogene was investigated by a DNA sequencing technique. Caffeic acid caused DNA damage in the presence of Cu(II) but not in the presence of either Mn(II) or Fe(III). Caffeic acid plus Cu(II) induced piperidine-labile sites frequently at thymine residues, especially of the 5'-GTC-3' and 5'-CTG-3' sequences. Typical OH scavengers showed no inhibitory effects. The inhibitory effects of bathocuproine and catalase on Cu(II)-mediated DNA damage suggest that Cu(I) and H2O2 have important roles in the production of active species causing DNA damage. The Cu(II)-mediated DNA damage was enhanced by pre-incubation of caffeic acid with Mn(II). Mn(II)- or Cu(II)-catalyzed autoxidation of caffeic acid produced H2O2 with efficiency of Mn(II) greater than Cu(II). These results suggest that in the presence of Mn(II) or Cu(II), caffeic acid produces H2O2, which is activated by transition metals to cause damage to DNA in vitro and probably in cultured cells.
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PMID:Caffeic acid causes metal-dependent damage to cellular and isolated DNA through H2O2 formation. 139 30

In this work the resistance of peroxisome-proliferated hepatocytes to hydrogen peroxide (H2O2) has been studied. The question has been raised as to whether this resistance is a response to cytotoxicity. In an initial series of experiments, hepatocytes were isolated from rats that had been treated with nafenopin (NAF-hepatocytes). Isolated cells were exposed to a H2O2-generating system or to H2O2 in pulses. The ability to attach to collagen was used as a toxicological endpoint. Loss of attachment was found to be correlated to glutathione (GSH) depletion, and NAF-hepatocytes were more resistant to GSH depletion and to loss of attachment induced by H2O2 than were control hepatocytes. NAF-hepatocytes were not resistant to hydroquinone or to adriamycin. It was also indicated that this resistance was related to an altered metabolism of H2O2, less dependent on GSH. In a second series of experiments, hepatocytes from altered hepatic foci-bearing rats, treated with nafenopin or di(2-ethylhexyl)phthalate (DEHP), were used. This model was used in an attempt to monitor the development of resistance in different subpopulations of hepatocytes. It was found that the majority of hepatocytes developed resistance towards H2O2, and that, for example, foci marker-positive hepatocytes were as resistant as marker-negative cells. In control experiments with this model, it was found that marker-positive cells were more resistant towards diethyl maleate (DEM) or phorone than were marker-negative cells. In addition to demonstrating the validity of the model, these control experiments indicate an increased steady-state level of H2O2 in cells from peroxisome proliferator-treated rats. Other control experiments suggested that a low GSH-peroxidase activity protected from, rather than aggravated, the effect of peroxisome proliferation on marker-negative and GSH-depleted cells. It is concluded that H2O2 metabolism may affect the function of collagen receptors, but that a shift in H2O2 metabolism, so that it becomes less dependent on GSH, conferred resistance to this effect. The apparent non-focal induction of resistance to peroxisome proliferators, as opposed to the focal induction of resistance induced by most liver carcinogens, may explain the lack of development of gamma-glutamyltranspeptidase-positive foci in peroxisome proliferator-treated rats.
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PMID:Peroxisome proliferation and resistance to hydrogen peroxide in rat hepatocytes: is development of resistance an adaptation to cytotoxicity? 142 34

The chemical targets and mechanisms of iron-catalyzed oxidative injury in myocardium are poorly understood. Oxygen metabolites, in the presence of iron, can initiate free-radical chain reactions in unsaturated membrane lipids, generating lipid peroxides and causing membrane injury. We examined whether exposure to iron-catalyzed oxidative injury would increase myocardial lipid peroxide levels as injury evolved in the intact heart. Isolated, buffer perfused rabbit hearts were exposed for 30 min to 100 uM Fe2+/500 uM ADP and 10 uM H2O2 (IRON group, n = 5), saline vehicle (CON group, n = 6) or 500 uM ADP and 10 uM H2O2 without iron (ADP, n = 5). Lipid peroxides were measured in cytosol and membrane fractions by a new method, using the lipid peroxide-induced oxidation of exogenous GSH to GSSG, catalyzed by the enzyme glutathione peroxidase. The results indicated that iron-catalyzed lipid peroxidation occurs in the intact heart during chemically-mediated oxidative injury.
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PMID:Iron-catalyzed reactions cause lipid peroxidation in the intact heart. 143 19


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