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)

Oxygen free radical scavengers protect against ischemia/reperfusion injury of the kidney in vivo and against hypoxia/reoxygenation (H/R) injury of renal cells in several in vitro systems. In an attempt to maximize renal protection we tested several antioxidants in combination; the individual components had previously reduced reoxygenation injury of hypoxic renal epithelial cells. Both glutathione (GSH; 1 mM) and Cu,Zn-SOD provided significant protection against posthypoxic injury. Surprisingly, the combination of Cu,Zn-SOD plus GSH eliminated protection entirely and was highly toxic to normoxic cells. The toxicity of Cu,Zn-SOD+GSH was not prevented by the iron chelator deferoxamine and was only slightly reduced by the hydroxyl scavenger DMTU. Catalase reversed the toxicity of Cu,Zn-SOD+GSH and provided net protection. Direct measurement of intracellular peroxides using 2,7-dichlorofluorescein quantitated by laser cytometry also revealed enhanced generation of peroxides by cells during H/R when Cu,Zn-SOD+GSH was present. GSSG was less toxic than GSH when combined with Cu,Zn-SOD. Importantly, the combination of Mn-SOD+GSH provided superior protection to either agent alone. In the presence of added GSH, heated or autoclaved Cu,Zn-SOD was still toxic, whereas SOD free of chelatable Cu++ was benign. In the presence of GSH, Cu++ derived from SOD may promote the formation of toxic thionyl radicals, metal-centered radicals, and/or H2O2, thereby causing cell injury. Great care should be used in designing and interpreting studies employing combinations of antioxidants.
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PMID:Hazards of antioxidant combinations containing superoxide dismutase. 779 96

Antioxidative effects of the nitrovasodilator nicorandil (SG-75) and denitrated SG-75 (SG-86) were examined in vivo and in vitro. When the isolated rat liver was reperfused with Krebs-Henseleit solution after a 90-min ischemia, microsomal GSH S-transferase activity was increased significantly by oxidative modification of the sulfhydryl group of the enzyme. The increase in the transferase activity after ischemia/reperfusion was depressed by SG-75 but not by SG-86. Furthermore, only SG-75 significantly inhibited lipid peroxidation and the activation of microsomal GSH S-transferase induced by hydrogen peroxide treatment of liver microsomes. These data indicate that SG-75 has an antioxidative action and the nitro group of SG-75 may play a critical role for this action.
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PMID:Antioxidative action of the nitrovasodilator nicorandil: inhibition of oxidative activation of liver microsomal glutathione S-transferase and lipid peroxidation. 779 21

Creatine kinase is a sulfhydryl containing enzyme that is particularly susceptible to oxidative inactivation. This enzyme is potentially vulnerable to inactivation under conditions when it would be used as a diagnostic marker of tissue damage such as during cardiac ischemia/reperfusion or other oxidative tissue injury. Oxidative stress in tissues can induce the release of iron from its storage proteins, making it an available catalyst for free radical reactions. Although creatinine kinase inactivation in a heart reperfusion model has been documented, the mechanism has not been fully described, particularly with regard to the role of iron. We have investigated the inactivation of rabbit muscle creatine kinase by hydrogen peroxide and by xanthine oxidase generated superoxide or Adriamycin radicals in the presence of iron catalysts. As shown previously, creatine kinase was inactivated by hydrogen peroxide. Ferrous iron enhanced the inactivation. In addition, micromolar levels of iron and iron chelates that were reduced and recycled by superoxide or Adriamycin radicals were effective catalysts of creatinine kinase inactivation. Of the physiological iron chelates studied, Fe(ATP) was an especially effective catalyst of inactivation by what appeared to be a site-localized reaction. Fe(ICRF-198), a non-physiological chelate of interest because of its putative role in alleviating Adriamycin-induced cardiotoxicity, also catalyzed the inactivation. Scavenger studies implicated hydroxyl radical as the oxidant involved in iron-dependent creatine kinase inactivation. Loss of protein thiols accompanied loss of creatine kinase activity. Reduced glutathione (GSH) provided marked protection from oxidative inactivation, suggesting that enzyme inactivation under physiological conditions would occur only after GSH depletion.
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PMID:Free radical inactivation of rabbit muscle creatinine kinase: catalysis by physiological and hydrolyzed ICRF-187 (ICRF-198) iron chelates. 783 53

The potential beneficial effect of hepatocellular glutathione against inflammatory liver damage was investigated in a model of endotoxin-enhanced ischemia-reperfusion injury. Animals were subjected to 20 min of hepatic ischemia, followed by 4 hr of reperfusion. The injection of 0.5 mg/kg Salmonella enteritidis endotoxin potentiated liver injury and the postischemic oxidant stress, as indicated by increased plasma levels of glutathione disulfide. Depletion of hepatic glutathione levels by > 90% with phorone and inhibition of glutathione synthesis with buthionine sulfoximine further increased liver injury in this model, as indicated by enhancement of plasma alanine aminotransferase activities from 2,234 +/- 122 U/L to 4,024 +/- 282 U/L. Continuous infusion of a glutathione (GSH) solution in GSH-depleted animals (22 mumol/kg/hr) attenuated reperfusion injury by 55%. In vitro experiments demonstrated the capability of GSH to react rapidly with reactive oxygen species, such as hydrogen peroxide (H2O2) and hypochlorous acid (HOCl). Only H2O2 oxidized GSH quantitatively to its disulfide; HOCl oxidized GSH to higher oxidation states. These data support the hypothesis that the enhanced release of hepatocellular GSH functions as a defense mechanism against reactive oxygen species generated by inflammatory cells during endotoxemia and reperfusion. This internal defense system of the liver may be of general importance in preventing, or at least limiting, liver damage by reactive oxygen generated in particular by Kupffer cells during their physiological function to remove gut-derived endotoxin and bacteria.
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PMID:Beneficial effects of extracellular glutathione against endotoxin-induced liver injury during ischemia and reperfusion. 783 22

Glutathione is important in cellular defense against oxidative stress. We postulated that administration of N-acetylcysteine (NAC), a glutathione precursor, might help maintain or replenish hepatic glutathione stores, thereby reducing reperfusion injury in liver grafts after warm ischemia. Eighteen pigs were subjected to 2 hr of warm hepatic ischemia and divided into a control group (group A, n = 6), a preischemia treatment group (group B, n = 6: NAC, 150 mg/kg, continuous i.v. infusion 1 hr before ischemia), and a postischemia treatment group (group C, n = 6: NAC, 150 mg/kg continuous i.v., begun 20 min before reperfusion and continued for 1 hr). At initiation of laparotomy, we measured hepatic levels of reduced glutathione (GSH), its oxidized form (GSSG), ATP, aspartate aminotransferase (AST), and lactate dehydrogenase (LDH). Before reperfusion, after 2 hr of warm ischemia, GSH, GSSG, and ATP were measured. One hour after reperfusion, we measured GSH, GSSG, ATP, AST, and LDH. Bile output was recorded every 10 min. Postoperfusion AST and LDH were significantly lower in both treatment groups than in controls. In group B, hepatic glutathione was maintained at significantly higher levels than in controls, even after ischemia (P < 0.05). In group C, although hepatic GSH levels fell until reperfusion, after administration of NAC, hepatic GSH reached the level of the preischemia treatment group. In both treatment groups, GSH 1 hr after reperfusion was significantly higher than in the controls (P < 0.01): regeneration of glutathione was seen in all 6 animals in group C, compared with 2/6 in group B and none in the control group. ATP recovery, bile output, and survival were all better in the treatment groups than in the control group. Pretreatment with NAC helps maintain hepatic glutathione during warm ischemia; given after ischemia, NAC is effective in replenishing depleted glutathione stores. Adjunctive use of NAC was associated with improved glutathione homeostasis, improved bile output and ATP regeneration, and increased survival.
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PMID:N-acetylcysteine ameliorates reperfusion injury after warm hepatic ischemia. 856 May 64

Oxidized glutathione (GSSG) but not its reduced form (GSH) is taken up by intact myocardial cells, and is rapidly converted into GSH. Reduced glutathione is an important intracellular defense against oxygen-derived free radicals and has been found to enhance calcium sensitivity in skinned cardiac fibers. We have investigated the effects of intravenous GSSG on left ventricular systolic pressure, maximal rate of rise of pressure and regional segment-shortening in dogs subjected to occlusion of the left anterior descending artery for 30 minutes, followed by 45 minutes reperfusion. Starting 10 minutes before reperfusion, the dogs were randomly treated with either GSSG (100 mM, 5 ml/min, n = 5) or Ringer's solution (5 ml/min, n = 5) until 30 minutes of reperfusion. Myocardial blood flow was measured by radioactive microspheres. Infusion of GSSG increased total glutathione content in both ischemic (47 +/- 16 mumol/g protein) and nonischemic myocardium (71 +/- 17 mumol/g protein) as compared to controls (23 +/- 2 mumol/g protein, p < 0.05). In both groups paradoxical wall motion occurred in the ischemic region during occlusion. On reperfusion, regional dyskinesia persisted in controls; while, in glutathione-treated dogs, systolic segment-shortening reached half the baseline values (p < 0.05, treated vs controls, at 15, 30, 45 minutes reperfusion). During ischemia the area of pressure-length loops, obtained from simultaneous recordings of left ventricular pressure and regional segment length, decreased to 30 +/- 7% of baseline in controls and to 40 +/- 18% of baseline in GSSG-treated animals. After 45 minutes reperfusion it was restored to 78 +/- 22% baseline in treated hearts but was still 36 +/- 16 of baseline in controls (p < 0.05). We conclude that infusion of GSSG increases the intracellular stores of glutathione and improves the contractile state of postischemic myocardium.
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PMID:Infusion of oxidized glutathione enhances postischemic segment-shortening in dog hearts. 791 48

Adult T cell leukemia-derived factor (ADF) is a human homologue of thioredoxin (TRX) with many biological functions and is induced by various stimuli and stress. In the central nervous system (CNS), expression of ADF/TRX occurs in glial cells during ischemia and reperfusion. We showed that ADF/TRX was actively released from U251 astrocytoma cells upon exposure to a low concentration of H2O2. The addition of conditioned medium from H2O2-stimulated U251 cells or recombinant ADF (rADF) to the culture medium promoted the survival of neurons from embryonic mouse cortex and striatum, but the addition of mutant ADF (mADF), which has no reducing activity, did not. In addition to rADF, incubation with two other thiol compounds, 2-mercaptoethanol (2-ME) and N-acetyl-L-cysteine (NAC), also increased the neuronal cell survival rate. In contrast, L-buthionine-(S,R)-sulfoximine (BSO), which inhibited the synthesis of glutathione (GSH), decreased the neuronal cell survival rate. Intracellular GSH was increased by incubation with rADF for 24 h, as it is with 2-ME and NAC. Redox active molecules such as thiol compounds may be survival factors for central neurons in vitro, and this capacity may be supplied by endogenous molecules, such as ADF/TRX and glutathione, under certain pathologic conditions in vivo.
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PMID:Neuroprotection by glial cells through adult T cell leukemia-derived factor/human thioredoxin (ADF/TRX). 795 44

Changes in hepatic and biliary glutathione levels were studied in rat liver treated with tert-butyl hydroperoxide (t-BuOOH) and subjected to ischemia-reperfusion. Immediately after t-BuOOH administration, the oxidized glutathione (GSSG) values and reduced glutathione (GSSG/GSH) ratio in the bile increased dose-dependently and then returned to control level within 10 min, whereas the hepatic ATP level and bile flow rate were not affected by t-BuOOH at doses of up to 1.0 mmol/kg. These data suggested that the liver remains viable on treatment with up to 1.0 mmole/kg t-BuOOH, and that hepatocytes can rapidly dismute t-BuOOH at up to this dose. The hepatic GSH and GSSG levels did not vary appreciably during ischemia for 10 or 30 min or during subsequent reperfusion, but the GSSG/GSH ratio increased after ischemia for 30 min. The rate of bile flow and the biliary level of GSH decreased after ischemia for 30 min in proportion to the decrease in the hepatic ATP level. However, the biliary GSSG concentration did not vary on reperfusion, although GSSG secretion into the bile is also related to the hepatic ATP level. As a result, the GSSG/GSH ratio in the bile increased during reperfusion after ischemia for 30 min. This increased ratio is thought to reflect oxidation of hepatic GSH by hydroperoxide produced during reperfusion. The GSSG/GSH ratio in the bile after 30 min ischemia corresponded to that observed after a small dose (0.07 mmole/kg body wt) of t-BuOOH, which hepatocytes could dismute rapidly without loss of their viability.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in biliary glutathione level during ischemia-reperfusion of rat liver. 796 94

The protective effects of cyproheptadine (Cyp), an antiserotonin-antihistaminic agent with calcium channel blocker activity, on myocardial reperfusion injury in isolated Langendorff heart of rats were studied. After a low perfusion [0.17 ml.min-1, standard Krebs-Henseleit (K-H) buffer without glucose, gassed with 95% O2 + 5% CO2] of 60 min followed by a normal K-H buffer perfusion of 20 min, an extensive and severe myocardial injury appeared: a release of lactate dehydrogenase (LDH) and creatine kinase (CK), a decrease of superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) activities, and an increase of malondialdehyde (MDA) content. Serious inhibition of cardiac functions and appearance of arrhythmia, even asystole, were also elicited in the injured hearts. Cyp (2.5 and 5 mumol.L-1) effectively antagonized the damage. The results suggested that the protective effects of Cyp on the ischemia-reperfusion injury may be related to its actions of blocking the calcium channel, scavenging the oxygen free radicals, protecting the antioxygen free radical enzymes, and inhibiting the lipid peroxidation in the myocardium.
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PMID:[Protective effects of cyproheptadine on myocardial reperfusion injury in isolated rat hearts]. 797 81

The impact of cardiac hypertrophy on myocardial biochemical and physiological responses to ischaemia-reperfusion (I-R) was investigated in vivo. Hypertrophy was produced by aortic constriction (PH) or swimming training (TH). Open-chest rat hearts in PH, TH and a sedentary control group (SC) were subjected: (1) to ischaemia, by surgical occlusion of the main descending branch of the left coronary artery for 30 min; (2) to I-R, by releasing the occluded blood vessel for 15 min; or (3) to a sham operation. Ischaemia per se had little effect on heart oxidative and antioxidant status, or lipid peroxidation. However, I-R significantly decreased glutathione (GSH) content, increased glutathione disulfide (GSSG) content, and reduced GSH/GSSG ratio in the SC hearts. These alterations were associated with decreased activities of GSH peroxidase and GSSG reductase, and an increase in lipid peroxidation. Myocardial ATP, total adenine nucleotide content and energy charge in SC were significantly decreased after ischaemia, whereas levels of purine nucleotide derivatives, particularly adenosine, were elevated. No significant alteration of GSH status of adenine nucleotide metabolism occurred after ischaemia or I-R in hypertrophied hearts. In both PH and TH, glutathione content was significantly higher than in SC, whereas activities of GSH peroxidase and GSSG reductases were lower. TH rats maintained a higher heart rate (HR), peak systolic pressure, and energy charge during I-R. These data indicate that hypertrophied but well-functioned hearts may be more resistant to I-R induced disturbances of myocardial oxidative and antioxidant functions.
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PMID:Cardiac hypertrophy alters myocardial response to ischaemia and reperfusion in vivo. 797 1


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