Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to test the hypothesis that the extracellular oxidation of glutathione (GSH) may represent an important mechanism to limit hepatic ischemia/reperfusion injury in male Fischer rats in vivo. Basal plasma levels of glutathione disulfide (GSSG: 1.5 +/- 0.2 microM GSH-equivalents), glutathione (GSH: 6.2 +/- 0.4 microM) and alanine aminotransferase activities (ALT: 12 +/- 2 U/l) were significantly increased during the 1 h reperfusion period following 1 h of partial hepatic no-flow ischemia (GSSG: 19.7 +/- 2.2 microM; GSH 36.9 +/- 7.4 microM; ALT: 2260 +/- 355 U/l). Pretreatment with 1,3-bis-(2-chloroethyl)-1-nitrosourea (40 mg BCNU/kg), which inhibited glutathione reductase activity in the liver by 60%, did not affect any of these parameters. Biliary GSSG and GSH efflux rates were reduced and the GSSG-to-GSH ratio was not altered in controls and BCNU-treated rats at any time during ischemia and reperfusion. A 90% depletion of the hepatic glutathione content by phorone treatment (300 mg/kg) reduced the increase of plasma GSSG levels by 54%, totally suppressed the rise of plasma GSH concentrations and increased plasma ALT to 4290 +/- 755 U/l during reperfusion. The data suggest that hepatic glutathione serves to limit ischemia/reperfusion injury as a source of extracellular glutathione, not as a cofactor for the intracellular enzymatic detoxification of reactive oxygen species.
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PMID:Vascular oxidant stress and hepatic ischemia/reperfusion injury. 206 Aug 45

We have investigated the relation between occurrence of myocardial oxidative stress and functional recovery during postischemic reperfusion in 20 selected patients subjected to aortocoronary bypass grafting. Patients were selected for having normal percent ejection fraction and left ventricular end-diastolic pressure before the operation. Occurrence of oxidative stress was assessed by measuring the formation and release of oxidized glutathione (GSSG) in the coronary sinus immediately before aortic cross-clamp, 1, 5, 10, and 20 minutes after removal of aortic cross-clamp, and 10 and 20 minutes after the end of cardiopulmonary bypass. Reduced glutathione (GSH), lactate, and creatine phosphokinase release were also monitored with the same timing. Standard hemodynamic measurements were recorded by means of a triple-lumen thermodilution pulmonary artery catheter before sternotomy, 15 minutes after the end of cardiopulmonary bypass, and during the 24 hours after termination of cardiopulmonary bypass. Reperfusion in patients after a short period of ischemia (less than 30 minutes; group 1) resulted in a small and transient release in the coronary sinus of GSSG and GSH and in a progressive improvement of hemodynamic parameters reaching a stable state 4 hours after the operation. In patients with a period of ischemia longer than 30 minutes (group 2), reperfusion induced a marked and sustained release of lactate, GSH, and GSSG; the arteriocoronary sinus difference for GSSG was still negative after the end of cardiopulmonary bypass. The arteriocoronary sinus difference for creatine phosphokinase also remained negative for as long as 20 minutes after cardiopulmonary bypass, and the rate of functional recovery was significantly delayed, reaching the values of group 1 only 12 hours after the operation. In these patients there was a positive correlation (r = 0.88, p less than 0.01) between the duration of ischemia and the myocardial arteriovenous difference for GSSG. In addition, there was a negative correlation between the arteriocoronary sinus difference for GSSG and cardiac index measured 2, 4, and 6 hours after the operation. These data suggest for the first time that, depending on the severity of the ischemic period, oxidative stress occurs during reperfusion of patients with coronary artery disease who are subjected to heart surgery and that it may be linked with a delay in postoperative recovery of cardiac function.
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PMID:Occurrence of oxidative stress during reperfusion of the human heart. 229 27

Neutrophil-related, oxidant-mediated injury to the pulmonary microvasculature appears to follow endotoxemia, cutaneous thermal injury, and ischemia-reperfusion injury to the liver or intestine. Glutathione is an important endogenous intracellular oxygen radical scavenger. Plasma concentrations of oxidized glutathione (GSSG) reflect oxidant injury resulting from an overdose of certain oxidatively metabolized drugs. The purpose of this investigation was to evaluate plasma GSSG as an indicator of oxidant stress resulting from activation of the endogenous inflammatory response. An established model of neutrophil- and oxidant-related acute lung injury following intestinal ischemia and reperfusion in rats was used. Intestinal ischemia was induced by clip occlusion of the superior mesenteric artery (SMA) for 120 min. Reperfusion resulted from SMA clip removal. Following reperfusion for 0, 15, or 120 min, plasma GSSG levels in portal vein, inferior vena cava (IVC), and aorta were obtained. Plasma GSSG was undetectable in sham animals and those with intestinal ischemia alone. Following reperfusion, all plasma samples had significant elevations in GSSG. Aortic plasma GSSG after 15 min of reperfusion was significantly elevated compared to both portal vein and IVC plasma GSSG. These data suggest that oxidant stress after intestinal reperfusion is reflected by elevations in plasma GSSG. The step up in plasma GSSG across the pulmonary vascular bed, a site of known oxidant injury, suggests that plasma GSSG may be a useful marker of oxidant stress in vivo, particularly with regard to the pulmonary microvasculature. This simple in vivo approach to assessing oxidant stress related to inflammatory tissue injury may have the potential to be of significant use in the clinical setting.
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PMID:Arterial levels of oxidized glutathione (GSSG) reflect oxidant stress in vivo. 233 13

Hearts isolated from rats treated 36 hr before with interleukin 1 (IL-1) had increased glucose-6-phosphate dehydrogenase (G6PD) activity and decreased hydrogen peroxide levels and injury after global ischemia (I, 20 min)/reperfusion (R, 40 min) compared with hearts from untreated rats. Hearts isolated from rats treated 6 hr earlier with IL-1 also had increased polymorphonuclear leukocytes (PMN), H2O2 levels, and oxidized glutathione (GSSG) contents compared with hearts from untreated rats. Depletion of circulating blood PMN by prior treatment with vinblastine prevented both early (from treatment 6 hr before study) IL-1-induced increases in myocardial PMN accumulation, H2O2 levels, and GSSG contents and late (from treatment 36 hr before study) increases in myocardial G6PD activity and protection against I/R. Our results indicate that IL-1 pretreatment causes an early (6 hr after IL-1 treatment) myocardial PMN accumulation and most likely an H2O2-dependent oxidative stress, which contributes to late (36 hr after IL-1 treatment) increases in myocardial G6PD activity and decreases in I/R injury.
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PMID:Interleukin 1 pretreatment decreases ischemia/reperfusion injury. 236 21

Oxidative loading during the reperfusion of the proximal jejunum of rats following a one hour-period of complete ischemia was demonstrated in in vivo-experiments by the increases of the GSSG: total glutathione ratio and the concentration of TBA-RS. The pretreatment of the animals with the xanthine oxidoreductase inhibitor allopurinol diminished the accumulation of GSSG and of TBA-RS. It was concluded that the purine nucleotide degradation is an important source of oxygen reduction products in reoxygenated small intestine. The tissue concentrations of nucleotides, nucleosides and nucleobases were measured by an ion-pair reversed-phase HPLC separation. There occurred fast declines of ATP and GTP concentrations during ischaemia leading to temporary increases of nucleoside mono- and diphosphate pools. The hypoxanthine concentration is increased about twentyfold during oxygen deficiency. The ATP and GTP restoration during the reperfusion was accelerated in presence of allopurinol. The shares of the beneficial allopurinol effects are not yet clarified.
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PMID:Radical formation in the rat small intestine during and following ischemia. 258 51

There is evidence that oxygen free radicals play a role in myocardial ischemic and reperfusion injury. We investigated the effect of ischemia and reperfusion on glutathione status. Reperfusion after prolonged ischemia (60 min) induced an important release of reduced (GSH) and oxidized (GSSG) glutathione, concomitant with an increase of tissue GSSG and no recovery of mechanical function, indicating that reperfusion results in oxidative stress. These alterations are associated with tissue and mitochondrial calcium accumulation, loss of mitochondrial function, and membrane damage. We also determined the arteriocoronary sinus difference for GSH and GSSG of 16 CAD patients undergoing coronary artery bypass. Patients were divided in two groups according to the length of clamping period: 25 +/- 2 min (group 1), and 55 +/- 6 min (group 2). In group 1, reperfusion resulted in a transient release of GSH, GSSG, CPK, and lactate, with return to preclamping values in 10 minutes. In group 2, reperfusion determined a sustained and pronounced release of GSH, GSSG, CPK, and lactate during declamping, suggesting the occurrence of an oxidative stress. Using an in vitro model, administration of alpha-tocopherol bound with albumin showed protection of mitochondrial function, improved recovery of contraction, and reduced oxidative stress during reperfusion.
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PMID:Oxygen free radical-mediated heart injury in animal models and during bypass surgery in humans. Effects of alpha-tocopherol. 269 6

Peroxidative loading during the reoxygenation of the rat small intestine following a complete ischemia was demonstrated in in vivo-experiments by the increases of the glutathione disulphide (GSSG): total glutathione ratio and the concentration of thiobarbituric acid-reactive substances (TBA-RS). The pretreatment of the rats with allopurinol diminished the accumulation of GSSG and of TBA-RS. From these effects was concluded that the purine nucleotide degradation is an important source of oxygen reduction products leading to peroxidations. The concentrations of nucleotides, nucleosides and nucleobases were measured by an ion-pair reversed-phase HPLC. The restoration of ATP and GTP concentrations during the reoxygenation period was accelerated by the application of allopurinol.
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PMID:Nucleotide degradation and radical formation in ischemic and reperfused small intestine. 273 Jun 3

The content of glutathione disulfide (GSSG) in tissue, coronary sinus blood plasma, and in cardiac lymph was measured in a well-characterized model of regional cardiac ischemia and reflow in dogs in vivo in order to assess the magnitude of the oxidant stress produced. No increase in GSSG content was observed during 60 min of occlusion of the circumflex or left anterior descending arteries, or during up to 70 min of reflow. The contents of 11-, 12-, and 15-hydroxyeicosatetraenoates (HETEs) in total lipids also were not increased following 60 min of regional ischemia and up to 60 min of reflow. In addition, global ischemia produced by aortic crossclamping and cardiopulmonary bypass did not increase HETE content. In contrast, infusion of tertiary butyl hydroperoxide (tBHP) into the left atrium produced readily measurable increases in GSSG content with or without prior induction of myocardial ischemia. Infusion of tBHP also increased tissue contents of the HETEs. These findings indicate that the canine myocardium subjected to ischemia-reflow conditions does not generate large amounts of reactive oxygen and does not form significant amounts lipid peroxidation products.
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PMID:Glutathione disulfide formation and lipid peroxidation during cardiac ischemia and reflow in the dog in vivo. 281 85

Reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver might in part be responsible for ischemic organ injury. Therefore, the effect of allopurinol, an inhibitor of xanthine oxidase, on the oxidant stress associated with reperfusion and on hepatic function 24 h after ischemia was assessed in a model of partial hepatic ischemia in rats. The increase in circulating glutathione disulfide (GSSG) was used as an index of oxidant stress. Hepatic function was assessed using a breath test to quantitative the demethylation of aminopyrine in vivo. In control animals the plasma concentration of GSSG 1 h after onset of reperfusion increased from 0.9 mumol/l in sham-operated controls to 4.2, 5.5, and 8.0 mumol/l following 45, 90 and 120 min of ischemia, respectively. The percent of the administered dose of (dimethylamine-14C)-aminopyrine appearing in breath as 14CO2 was not significantly different from sham-operated controls (40.2%) 24 h after 45 min of ischemia (34.1%), but decreased progressively to 26.0% (p less than 0.05) and 20.6% (p less than 0.05) after 90 and 120 min of ischemia, respectively. Allopurinol, administered at a dose of 50 mg/kg 18 h and 1 h prior to ischemia, did not prevent the rise in plasma GSSG, did not alleviate the release of transaminases, and did not improve the demethylation of aminopyrine 24 h after ischemia, suggesting that reactive oxygen species generated by xanthine oxidase during reperfusion of ischemic liver do not contribute significantly to ischemic injury.
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PMID:Effect of allopurinol on oxidant stress and hepatic function following ischemia and reperfusion in the rat. 321 73

The hypothesis that intracellular generation of reactive oxygen species in hepatocytes or reticuloendothelial cells may cause ischemia-reperfusion injury was tested in isolated perfused livers of male Fischer rats. GSSG was measured in perfusate, bile, and tissue as a sensitive index of oxidative stress. After a preperfusion phase of 30 min, the perfusion was stopped (global ischemia) for various times (30, 120 min) and the liver was reperfused for another 60 min. The bile flow (1.48 +/- 0.17 microliters/min X gram liver weight), the biliary efflux of total glutathione (6.54 +/- 0.94 nmol GSH eq/min X g), and GSSG (1.59 +/- 0.23 nmol GSH eq/min X g) recovered to 69-86% after short-term ischemia and to 36-72% after 2 h of ischemia when compared with values obtained from control livers perfused for the same period of time. During reperfusion, the sinusoidal efflux of total glutathione (16.4 +/- 2.1 nmol GSH eq/min X g) and GSSG (0.13 +/- 0.05 nmol GSH eq/min X g) did not change except for an initial 10-30-s increase during reperfusion washout. No increased GSSG secretion into bile was detectable at any time during reperfusion. The liver content of total glutathione (32.5 +/- 3.5 nmol GSH eq/mg protein) and GSSG (0.27 +/- 0.09 nmol GSH eq/mg protein) did not change significantly during any period of ischemia or reperfusion. We conclude, therefore, that at most only a minor amount of reactive oxygen species were generated during reperfusion. Thus, reactive oxygen species are unlikely to cause ischemia/reperfusion injury in rat liver by lipid peroxidation or tissue thiol oxidation.
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PMID:Reactive oxygen species during ischemia-reflow injury in isolated perfused rat liver. 335 Sep 71


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