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)

Oxidative DNA damage, as expressed by 8-hydroxydeoxyguanosine (8-OHdG), was investigated in calf thymus DNA exposed to either ultraviolet radiation or to FeCl2/H2O2 in a Fenton-like reaction. The influence of iron (absent in the UV system and present in the FeCl2/H2O2 system) and pH (7.4 and 4.0) on the effect of glutathione (GSH), ascorbate, and 5-aminosalicylic acid (5-ASA, a drug used in the treatment of chronic inflammatory bowel diseases) was examined in these systems. Without iron, all three compounds considerably reduced 8-OHdG formation (i.e., acted as scavengers), while in the presence of iron salts, 8-OHdG formation was accelerated (except for GSH at pH 7.4), i.e., the compounds acted as prooxidants. This effect was augmented at low pH. The prooxidant property of 5-ASA may have implications for its clinical use. Maximum scavenging effect for all the compounds investigated was obtained at much lower doses than the maximum enhancing effect. This demonstrates that to the end of oxy-radical scavenging, the concentration of the GSH, ascorbate, and 5-ASA, respectively, should be chosen to obtain maximum antioxidant effect and minimum prooxidant effects. The significance of this finding for the selection of antioxidant dose is important but remains to be investigated further.
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PMID:8-Hydroxydeoxyguanosine in vitro: effects of glutathione, ascorbate, and 5-aminosalicylic acid. 151 38

The roles of glutathione (GSH), cysteine, vitamin C, liposome-encapsulated superoxide dismutase (L-SOD) and vitamin E in preventing oxidative DNA damage and cytotoxicity in the rat kidney after administration of potassium bromate (KBrO3) to male F344 rats were investigated by measuring 8-hydroxydeoxyguanosine (8-OH-dG), an oxidative DNA product, lipid peroxidation (LPO) levels and relative kidney weight (RKW). Combined pre- and posttreatment of animals with 2 x 800 mg/kg GSH i.p. inhibited the increase of 8-OH-dG, LPO levels and RKW caused by 80 mg/kg KBrO3 i.p. administration. In contrast, pretreatment with 0.3 ml/kg diethylmaleate (DEM) i.p., a depletor of tissue GSH, was associated with elevation of 8-OH-dG, LPO levels and RKW after a 20 mg/kg KBrO3 i.p. treatment, which itself caused no change. Administration of KBrO3 itself reduced renal non-protein thiol levels, but this was inhibited by the two doses of exogenous GSH. Combined treatment with DEM and KBrO3 lowered the non-protein thiol level in the kidney more than did DEM treatment alone. Protective effects against the oxidative damage caused by KBrO3 were also observed for pre- and posttreatment with 400 mg/kg cysteine i.p., another sulfhydryl compound, and daily i.g. application of 200 mg/kg vitamin C for 5 days. However, no influence was evident after pre- and posttreatment with 18,000 U/kg L-SOD i.p. or daily i.g. 100 mg/kg of vitamin E for 5 days. The results suggest that intracellular GSH plays an essential protective role against renal oxidative DNA damage and nephrotoxicity caused by KBrO3.
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PMID:The protective role of glutathione, cysteine and vitamin C against oxidative DNA damage induced in rat kidney by potassium bromate. 154 73

Changes in kidney levels of 8-hydroxydeoxyguanosine (8-OH-dG), lipid peroxidation (LPO), glutathione (GSH) and relative organ weight were examined 6, 24, 48, 72 and 96 h after a single i.p. administration of potassium bromate (KBrO3) at a dose of 70 mg/kg to male F344 rats. The 8-OH-dG level was significantly increased 24 h after the treatment at this dose and thereafter gradually decreased. On the other hand, significant elevation in LPO level was observed from 6 h after the treatment with a continuous increase up to a plateau at 48 h and no subsequent drop. GSH level was significantly raised from 6 to 72 h, and relative kidney weight varied in almost the same manner as the 8-OH-dG level. Investigation of the dose-response relation revealed the 8-OH-dG and LPO levels to be significantly increased from a dose of 40 mg/kg KBrO3 in a dose-dependent manner. The results suggest that enhanced formation of 8-OH-dG in kidney DNA due to KBrO3 is closely related to the increase in LPO levels.
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PMID:Relation of 8-hydroxydeoxyguanosine formation in rat kidney to lipid peroxidation, glutathione level and relative organ weight after a single administration of potassium bromate. 190 Aug 20

The effects of the antioxidants, glutathione (GSH) and its precursor cysteine (Cys) on oxidative damage induced by ferric nitrilotriacetate (Fe-NTA) were examined. Fe-NTA-associated oxidative stress caused the depletion of renal cellular GSH content. Administration of exogenous GSH and Cys suppressed 8-hydroxydeoxyguanosine (8-OH-dG) formation, an indicator of oxidative DNA damage and nephrotoxicity following Fe-NTA treatment. This suggests that generation of free radicals may be causally involved in oxidative lesion generation. Since lipid peroxidation was found to be inhibited only by GSH and not Cys treatment, this suggests that this effect and the DNA damage might be mediated by different pathways. Fe-NTA-associated oxidative stress in renal tubular cells might thus operate via both intracellular and external space modes.
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PMID:The effects of exogenous glutathione and cysteine on oxidative stress induced by ferric nitrilotriacetate. 204 81

The effects of glutathione (GSH) on the generation of radicals and the oxidation of DNA by Fenton reagent were studied. Hydroxyl radicals and thiyl radicals were detected by electron spin resonance spin trapping when GSH-Fe(II) reacted with H2O2; however, the mixture was ineffective at promoting the hydroxylation of 2'-deoxyguanosine in calf thymus DNA. When the concentrations of ferrous iron and hydrogen peroxide were both 100 microM, the concentration of GSH required to inhibit 8-hydroxy-2'-deoxyguanosine (8-OHdG) production by 92% was 1 mM. Other thiol compounds were also effective at inhibiting 8-OHdG formation; however, mannitol and benzoate were ineffective at inhibiting 8-OHdG formation when present at the same concentration. Single strand breaks were detected in phi X174 plasmid DNA treated with 2 microM Fe(II) and 2 microM H2O2; furthermore, the addition of 50 microM GSH to this system inhibited single strand break formation by 95%. In conclusion, GSH protected DNA from oxidation by Fe(II) and H2O2 even though it did not completely inhibit the production of radicals by the Fenton reaction.
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PMID:Effects of glutathione on Fenton reagent-dependent radical production and DNA oxidation. 750 44

Oxidation of mitochondrial DNA might be responsible for the persistence of structural and functional abnormalities of mitochondria in alcoholics after cessation of ethanol intake. Ethanol (4g/kg) was administered to mice, and DNA was isolated 3 h later from liver homogenates and mitochondria. Ethanol resulted in a 25% decrease of GSH in liver homogenates without increase in GSSG, oxidized proteins and 8-OHdG, respectively. In contrast, the content of carbonyls (23 +/- 1 vs 9 +/- 1 nmol/mg protein) and the extent of oxidation of DNA (49 +/- 8 vs 17 +/- 3 8-OHdG/10(5) dG) were significantly increased in mitochondria. Depletion of GSH with diethyl maleate also resulted in a 2-3 fold increase in the oxidation of proteins and DNA in mitochondria exclusively. Oxidation of DNA and low GSH together with the lack of DNA repair enzymes may result in permanent damage to the mitochondria of alcoholic subjects.
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PMID:Oxidation of mitochondrial proteins and DNA following administration of ethanol. 765 42

DNA was incubated with glutathione (GSH) and copper and then assayed for 8-hydroxydeoxyguanosine (8-OHdG) in order to better understand the antioxidant and prooxidant characteristics of GSH in copper-dependent DNA damage. Ratios of GSH to Cu(II) less than 3 resulted in 8-OHdG production; however, higher ratios did not generate 8-OHdG. A combination of GSH and Cu(I) (10:1) was used to determine if DNA oxidation occurred upon the addition of H2O2. No increase in 8-OHdG was noted until the concentration of H2O2 was almost half that of GSH, and then a substantial increase of 8-OHdG was detected. The stoichiometry of thiol oxidation by H2O2 was 2 mol GSH oxidized per 1 mol H2O2. Oxidation of Cu(I) was not detected until most of the thiol had been oxidized. When cysteine and Cu(I) was used instead of GSH and Cu(I), there was considerable hydroxylation of deoxyguanosine. The glycyl carboxyl, the gamma-glutamate carboxyl, and the amine of GSH were altered to determine their role in the peptide's ability to inhibit Cu-dependent damage. In the presence of Cu(I), H2O2, and DNA, these GSH analogs behaved similarly to GSH. However, when S-methylglutathione was used in this system, it was very effective at promoting oxidative damage to DNA. This indicated that the thiol ligand of GSH was essential for inhibition of Cu-dependent damage, while the carboxyl groups and the amine were not essential ligands. In conclusion, GSH can catalyze the in vitro hydroxylation of deoxyguanosine when the ratio of GSH to Cu is low, however, when the ratio is high GSH is an effective antioxidant.
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PMID:Hydroxylation of deoxyguanosine in DNA by copper and thiols. 787 76

Reactive oxygen species (ROS) induce 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation, which has been proposed as a key biomarker relevant to carcinogenesis. 8-OHdG has been induced in a number of different ways, most often without knowledge of the specific type and amount of ROS generated. We have measured 8-OHdG formation in calf thymus DNA exposed to ionizing radiation under conditions generating either hydroxyl radicals (OH.), superoxide anions (O2-) or both. Additionally, we investigated the relationship between the scavenger effect of the drug 5-aminosalicylic acid (5-ASA) and increasing OH. exposure toward 8-OHdG formation. The effect of this drug was compared to those of the physiological scavengers ascorbate and reduced glutathione (GSH). We found that OH. generated 8-OHdG in a dose-dependent manner, whereas O2- did not cause 8-OHdG formation. 5-ASA, ascorbate and GSH all acted as hydroxyl radical scavengers, although with different concentration-effect curves, emphasizing the importance of using relevant pharmaco-/physiological concentrations in studies focusing on therapeutic applications of scavengers. The scavenger effect of 5-ASA at concentrations > or = 0.1 mM was similar at 30 and 100 Gy radiation, i.e. within a wide range of OH. exposure, which is useful information considering clinical applications where the exact amount of ROS formed is unknown. Both 5-ASA and ascorbate at low concentrations (< or = 0.1 mM) were less efficient in preventing 8-OHdG formation from X-ray generated OH. than was shown in a previous comparable study using light as the source of ROS. This differentiation probably reflects variations in both number and type of ROS formed in the two systems.
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PMID:Radiation-induced formation of 8-hydroxy-2'-deoxyguanosine and its prevention by scavengers. 805 39

Occupational exposure to silica has often been associated with the development of pulmonary fibrosis and, occasionally, lung cancer. Their development may be mediated by oxidant-induced cellular injury. The short- and long-term effects of a single intratracheal instillation of silica in rats (10 mg/200 microliters/saline per rat) was assessed by measuring 8-hydroxy-2'-deoxyguanosine (oh8dG) levels in lung tissue and peripheral blood leukocytes. Cell differentials, reduced glutathione (GSH), and superoxide dismutase (SOD), lipid peroxide, and total phospholipids in peripheral blood and/or bronchoalveolar lavage fluid (BALF) were also measured. The pulmonary oh8dG levels increased approximately 2.24- 2.86-fold from 1 to 5 days after exposure to silica. It was still elevated 1 and 4 weeks after installation, but the difference was no longer statistically significant. The oh8dG levels in peripheral blood leukocytes were never significantly different, but they were generally higher than in the controls. The low SOD levels in the BALF of exposed rats in the early stage and the higher GSH levels in the late stage may represent protective reactions against the generation of oxygen species. A significant increase in oh8dG levels in lung tissue suggested the possible carcinogenicity of silica.
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PMID:Oxidative DNA damage induced by silica in vivo. 860 69

Treatment of isolated DNA with crocidolite and man-made vitreous fibre-21 (MMVF-21) significantly increased the concentration of 8-hydroxydeoxyguanosine (8-OHdG) in isolated DNA above background levels and co-treatment with glutathione (GSH) eliminated this effect. Crocidolite, MMVF-21 and chrysotile fibres increased the number of revertants in Salmonella typhimurium TA100 and GSH-deficient strains, TA100/NG-54 and TA100/NG-57, over background levels. This increase was small in TA100 but was greater in the GSH-deficient strains. When these bacterial strains were further depleted of GSH by co-culture with buthionine sulfoximine, all fibres tested caused a significant increase in the number of revertants over the parent strains. Pre-treatment with the GSH precursor N-acetyl-L-cysteine reduced the number of revertants to below that of the parent strain. Previous studies have shown a mechanistic role for iron-catalyzed production of oxygen radicals in the mutagenicity of fibres and this study suggests a protective role for GSH against such oxidative damage possibly by acting as a radical scavenger.
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PMID:Glutathione modulates the formation of 8-hydroxydeoxyguanosine in isolated DNA and mutagenicity in Salmonella typhimurium TA100 induced by mineral fibres. 889 1


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