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)

Rat livers were orthotopically transplanted after 90-min cold ischemia (group 1) or after 20-min warm and 70-min cold ischemia without (group 2) or with (group 3) allopurinol treatment (AT) (50 mg/kg i.v. 10 min prior to warm ischemia into the donor, flush perfusates with 1 mmol/l). Recovery processes were followed up for 60 min of reperfusion. Liver tissue levels of ATP and total adenine nucleotides were restored in group 1 to almost preischemic ranges within 15-30 min, remained significantly reduced by 30 and 20%, respectively, in group 2, and recovered with AT within 60 min in group 3 to almost the same extent as in group 1. A massive increase in the tissue malondialdehyde concentration, indicative of lipid peroxidation, occurred in the beginning of reperfusion of warm-ischemically damaged donor livers, which in group 3 with AT tended to be less pronounced than in group 2 without AT. The GSSG/GSH ratio reflecting intracellular oxidant stress averaged 3.3 x 10(-3) in group 1 between 15 and 60 min reperfusion. In group 3 AT resulted in comparably low values averaging 3.8 x 10(-3), while in warm-ischemically damaged livers without AT of group 2 this ratio was significantly and continuously elevated averaging 5.8 x 10(-3).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Allopurinol effects in rat liver transplantation on recovery of energy metabolism and free radical-induced damage. 758 99

Deficiency of the amino acid taurine is implicated in various pathologic states of the heart. Besides other effects, taurine has been proposed to be an antioxidant. However, its benefit under conditions associated with the generation of reactive oxygen species in the heart has not been clearly demonstrated. To assess the potential of taurine to influence neutrophil-dependent reperfusion injury, a model was developed based on the isolated working guinea pig heart. After an initial work phase, hearts were subjected to 15 min of global ischemia. Reperfusion, in a nonworking mode, was carried out in the absence or presence of homologous neutrophils (PMN) and/or taurine. After 15 min, work was resumed and percentage recovery of function was determined another 20 min later. During the reperfusion phase, coronary venous effluent was collected to quantify release of lactate and glutathione, markers of ischemic challenge and redox-stress, respectively. Furthermore, direct effects of taurine on radical formation were investigated in a chemiluminescence assay. Control hearts without application of PMN or taurine had a postischemic recovery of external heart work (EHW) of 76%, in the presence of taurine (15 mM) recovery was 72%. The application of PMN for merely the first minute of reperfusion led to a significant decrease in recovery to 30%, PMN having no effect without a foregoing ischemia. When taurine was additionally applied during reperfusion, EHW recovered to 60%. Release of lactate and of oxidized glutathione (GSSG) did not differ between the groups. In contrast, effluent concentrations of reduced glutathione (GSH) were considerably elevated by the presence of PMN in the sample and remained high even after PMN-washout. Taurine tended to attenuate this PMN effect. At the 5th and 10th min of reperfusion, GSH release of individual hearts correlated inversely with postischemic recovery of EHW. Surprisingly, taurine, by itself, did not significantly alter glutathione release. However, taurine (15 mM) markedly reduced luminol-dependent chemiluminescence elicited by activated guinea pig PMN as well as by chemically generated hypochlorous acid and hydroxyl radicals, but not superoxide radicals. Our results demonstrate that taurine protects the heart from PMN-induced reperfusion injury and oxidative stress. Because respiratory burst activity of PMN was also significantly reduced in the presence of taurine, the beneficial effect appears to be mediated by antioxidative properties of taurine.
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PMID:Taurine protects the heart from neutrophil-induced reperfusion injury. 759 Mar 95

In control rabbits, a renal ischemia of 60 min followed by 10 min of reperfusion resulted in an enhanced free radical production in cortical tissue, as assessed by a significant decrease of free glutathione (42%), protein-bound GSH (17%), and vitamin E (49%). In contrast, catalase or glutathione peroxidase activities were not affected by these experimental conditions. Free radical production in this model was also measured directly using electron spin resonance (ESR) spectroscopy associated with a PBN (alpha-phenyl N-tert-butyl-nitrone) spin trap agent in the venous blood arising from the ischemic kidney. The signal consisted of a triplet of doublets. In contrast, no signal could be detected in control blood samples taken prior to inducing ischemia. The burst of free radical production occurred in the early phase after restoration of flow in the kidneys rendered ischemic, as evidenced by a signal of weak intensity which generally appeared within the third minute after reperfusion and progressively increased to form a well-defined asymmetric signal following 10 min of reperfusion. The precise nature of free radicals trapped by the PBN agent remains, however, to be elucidated, but analysis of the coupling constants (aN = 14.5-15 G; a beta H = 2.5-3 G) and asymmetry of the central doublets suggests that the ESR signal may arise from a nitorxy-radical adduct resulting from the spin trapping by PBN of both oxygen- or carbon-centered radicals of lipid origin. As evidenced by both direct and indirect measurements, exchange of rabbit blood immediately after inducing renal ischemia with 30 ml/kg of Diaspirin Crosslinked Hemoglobin (7.5 g/dl in lactated electrolyte) or human serum albumin (7.5 g/dl in lactated electrolyte) did not exacerbate free radical production mediated by an ischemia reperfusion phenomenon, a typical situation found in a resuscitation setting.
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PMID:Diaspirin crosslinked hemoglobin (DCLHb): absence of increased free radical generation following administration in a rabbit model of renal ischemia and reperfusion. 763 50

We investigated whether intraportal injection of 150 mg/kg N-acetylcysteine (NAC) into rats reduced hepatic ischemia-reperfusion injury after 48 hours of cold storage and 2 hours of reperfusion. The organ was isolated and perfused to evaluate liver function. The control group received an intraportal injection of 5% dextrose. NAC increased L-cysteine concentrations 15 minutes after injection (1.29 +/- 0.11 mumol/g vs. 2.68 +/- 0.4 mumol/g, P < .05). However, neither treatment modified glutathione liver concentrations relative to preinjection values. After 48 hours of cold storage and 2 hours of reperfusion, livers from NAC-treated rats produced larger amounts of bile than those in the control group (5.04 +/- 1.92 vs. 0.72 +/- 0.37 microL/g liver; P < .05), and showed a significant reduction in liver injury, as indicated by reduced release of lactate dehydrogenase (679.4 +/- 174.4 vs. 1891.3 +/- 268.3 IU/L/g; P < .01), aspartate transaminase (AST) (13.94 +/- 3.5 vs. 38.75 IU/L/g; P < .01), alanine transaminase ALT) (14.92 +/- 4.09 vs. 45.91 +/- 10.58 IU/L/g; P < .05), and acid phosphatase, a marker of Kupffer cell injury (344.4 +/- 89.6 vs. 927.3 +/- 150.8 IU/L/g; P < .01) in the perfusate. Reduced glutathione concentrations in the perfusate were similar in the two groups (805 +/- 69 vs. 798 +/- 252 nmol/L/g), whereas oxidized glutathione (GSSG) concentrations were higher in the control group (967 +/- 137 vs. 525 +/- 126 nmol/L/g; P < .05). Reduced glutathione (GSH) concentrations in liver tissue collected at the end of perfusion were significantly higher in the NAC group (7.3 +/- 0.9 vs. 4.1 +/- 1.0 mumol/g; P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protective effects of N-acetylcysteine on hypothermic ischemia-reperfusion injury of rat liver. 763 22

We investigated the cardioprotective effect of FK506, a newly developed immunosuppressive agent, on ischemia-reperfusion-induced myocardial damage and the inhibitory effect of FK506 on superoxide radical formation by neutrophils. Open-chest anesthetized dogs were divided into two groups: group 1, 2-h occlusion of the coronary artery followed by 1-h reperfusion; and group 2, 2-h occlusion followed by 1-h reperfusion with preadministration of FK506 (0.5 mg/kg). After reperfusion, heart mitochondria were prepared from the normal and reperfused areas and mitochondrial function and mitochondrial GSH (the reduced form of glutathione) and GSSG (the oxidized form of glutathione) concentrations were measured. In addition, neutrophils were collected from normal healthy dogs, and the inhibitory effect of FK506 on superoxide radical formation by neutrophils was also investigated. One-hour reperfusion after 2-h coronary occlusion induced significant mitochondrial dysfunction associated with a marked depletion of mitochondrial GSH concentration. FK506 reduced mitochondrial dysfunction, depletion of mitochondrial GSH concentration, and development of reperfusion arrhythmias. FK506 also reduced stimulant-induced superoxide radical formation by normal neutrophils dose dependently. Radical scavenging activity decreased in association with reperfusion, and FK506 reduced superoxide radical formation by neutrophils, which might contribute to lessening ischemia-reperfusion damage.
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PMID:Protective effect of FK506 on ischemia/reperfusion-induced myocardial damage in canine heart. 768 7

We investigated the cytoprotective effects of verapamil, a Ca channel blocker, and of iloprost (ZK 36374), a stable prostacyclin analogue, on ischemia/reperfusion (I/R) injury in Wistar albino rat kidneys that were subjected to 60 min of warm ischemia and reperfusion. The groups included sham, ischemia-untreated (ISCH), verapamil-treated (VER), iloprost-treated (ILO), and verapamil + iloprost (VER + ILO)-treated rats. The 7-day survival of all the treated groups was better than that of the ISCH group. The creatinine concentration on the 3rd day was significantly lower in the VER + ILO group than in the ISCH group. Serum creatinine on day 3 was also low in the VER + ILO groups compared to the ISCH group, although the differences were not significant. The creatinine values on day 7 were significantly lower in the VER and ILO group than in the control, VER, or ILO groups. The malondialdehyde (MDA) concentrations of the kidney cortex tissue after reperfusion in all groups were higher than normal. The tissue-reduced glutathione (GSH) concentrations of the kidneys sampled immediately after reperfusion were significantly lower in the ISCH group than in all of the other treated groups. These results indicate that although verapamil and iloprost have independent cytoprotective effects on 60-min warm ischemia/reperfusion injury of rat kidneys, the protection afforded when both drugs are combined is synergistic. The mechanism of cytoprotection is not limited to the suppression of lipid peroxidation, and a nearly complete protection of reperfusion injury can be obtained by such an intervention.
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PMID:The cytoprotective effects of verapamil and iloprost (ZK 36374) on ischemia/reperfusion injury of kidneys. 768 89

The role of the glutathione redox cycle in cellular protection form skin necrosis during the ischemic stress response (preconditioning) is unknown. In this series of experiments, we tested the hypothesis that oxidant stress reduces available total glutathione during injury and contributes to skin necrosis in flaps. Dorsal skin flaps (10 x 4 cm) were raised as acute flaps and skin grafts were obtained from the flaps at 0, 1, 4, 6, 12, or 24 hr. Some flaps were preconditioned as bipedicle flaps for 24, 48, 72, or 96 hr and the distal attachment divided before skin grafts were obtained 24 hr later. Flap survival was measured at 7 days. Total glutathione (GSH) and oxidized GSH (GSSG) were extracted and their levels determined enzymatically. Tissue GSH reductase (GR) activity was assayed with a spectrofluorometer and expressed as mumoles of NADPH oxidized/hr/g. Biochemical data were compared between the proximal and distal ends of the flaps using a two-tailed Student t test while differences between groups were compared using ANOVA. Skin necrosis was 5.4 +/- 0.12 cm in the distal ends at 7 days in acute flaps, while there was no skin necrosis in flaps preconditioned for 7 days. In acute flaps, total GSH levels fell precipitously in the distal end at 24 hr (P < 0.05). However, after 72 hr of preconditioning, the GSH levels in the distal end of the flap remained elevated while GSSG levels were undetectable. At 24 hr of ischemia, GR activity was 79 +/- 4 in the distal ends of acute flaps, while after preconditioning and 24 hr of ischemia, the GR activity increased to 172 +/- 13 in the distal ends (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidant stress: the role of the glutathione redox cycle in skin preconditioning. 772 18

Reduced glutathinone (tau-glutamylcysteinglycine, GSH) is a scavenger for oxygen radicals and plays in important role in protection of cells from ischemia and from the harmful effects of free oxygen radicals. Free oxygen radicals due to cerebral vasospasm increase in both vasospasm and proliferative vasculopathy. This experiment was performed to determine whether GSH plays a role in cerebral vasospasm after subarachnoid hemorrhage by preventing the harmful effects of free oxygen radicals. In this study, GSH was administered intraarterially and intracisternally following vasospasm of the canine basilar artery. Less vasospasm was observed in the group treated with GSH intraarterially following subarachnoid hemorrhage than in the one treated with GSH intracisternally and in the control group. The arterial wall was investigated ultrastructurally. We evaluated the effect of the anti-oxidating substance through the activity of superoxide dismutase in the arterial wall. We compared the effect of glutathione reductase in the two groups treated with GSH intraarterially and intracisternally. Arterial degeneration was more prominent in the group in which GSH was used intracisternally, while the superoxide dismutase levels were low. In contrast, arterial degeneration was less in the other group in which GSH was used intraarterially, while the superoxide dismutase levels were high.
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PMID:Effect of GSH on cerebral vasospasm in dogs. 775 17

Copper Fenton systems (Cu(II)/H2O2 and Cu(II)/Asc) inactivated the lipoamide reductase and enhanced the diaphorase activity of pig-heart lipoamide dehydrogenase (LADH). Cupric ions alone were less effective. As a result of Cu(II)/H2O2 treatment, the number of titrated thiols in LADH decreased from 6 to 1 per subunit. NADH and ADP (not NAD+ or ATP) enhanced LADH inactivation by Cu(II). NADH also enhanced the effect of Cu(II)/H2O2. Dihydrolipoamide, dihydrolipoic acid, Captopril, acetylcysteine, EDTA, DETAPAC, histidine, bathocuproine, GSSG and trypanothione prevented LADH inactivation. 100 microM GSH, DL-dithiothreitol, N-(2-mercaptopropionylglicine) and penicillamine protected LADH against Cu(II)/Asc and Cu(II), whereas 1.0 mm GSH and DL-dithiothreitol also protected LADH against Cu(II)/H2O2. Allopurinol provided partial protection against Cu(II)/H2O2. Ethanol, mannitol, Na benzoate and superoxide dismutase failed to prevent LADH inactivation by Cu(II)/H2O2 or Cu(II). Catalase (native or denaturated) and bovine serum albumin protected LADH but that protection should be due to Cu binding. LADH inhibited deoxyribose oxidation and benzoate hydroxylation by Cu(II)/H2O2. It is concluded that site-specifically generated HO, radicals were responsible for LADH inactivation by Cu(II) Fenton systems. The latter effect is discussed in the context of ischemia-reoxygenation myocardial injury.
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PMID:Inactivation of heart dihydrolipoamide dehydrogenase by copper Fenton systems. Effect of thiol compounds and metal chelators. 775

The objectives of this study were to determine 1) whether reactive oxygen species generated upon postischemic reperfusion lead to oxidative stress in rat hearts, and 2) whether an exogenous prooxidant present in the early phase of reperfusion causes additional injury. Isolated buffer-perfused rat hearts were subjected to 30 min of hypothermic no-flow ischemia followed by 30 min of reperfusion. Increased myocardial content of glutathione disulfide (GSSG) and increased active transport of GSSG were used as indices of oxidative stress. To impose a prooxidant load, cumene hydroperoxide (20 microM) was administered during the first 10 min of reperfusion to a separate group of postischemic hearts. Reperfusion after 30 min of hypothermic ischemia resulted in a recovery of myocardial ATP from 28% at end-ischemia to 50-60%, a release of 5% of total myocardial LDH, and an almost complete recovery of both coronary flow rate and left ventricular developed pressure. After 5 and 30 min of reperfusion, neither myocardial content of GSSG nor active transport of GSSG were increased. These indices were increased, however, if cumene hydroperoxide was administered during early reperfusion. After stopping the administration of cumene hydroperoxide, myocardial GSSG content returned to control values and GSH content increased, indicating an unimpaired glutathione reductase reaction. Despite the induction of oxidative stress, reperfusion with cumene hydroperoxide did not cause additional metabolic, structural, or functional injury when compared to reperfusion without cumene hydroperoxide. We conclude that reactive oxygen species generated upon postischemic reperfusion did not lead to oxidative stress in isolated rat hearts. Moreover, even a superimposed prooxidant load during early reperfusion did not cause additional injury.
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PMID:Glutathione disulfide as an index of oxidative stress during postischemic reperfusion in isolated rat hearts. 779 51


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