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)

Isolated, isovolumic rat hearts, perfused by Krebs-Henseleit buffer at constant coronary flow rate, were used to explore the hypothesis that endogenous cardiac glutathione provides protection against myocardial dysfunction associated with short periods of ischemia. Experimental animals were depleted of cardiac glutathione to 35% of control levels by intraperitoneal injections of diethylmaleate (DEM). Left ventricular pressure, coronary perfusion pressure, and glutathione levels were measured in control and experimental hearts after 60 minutes of oxygenated perfusion and after 20 minutes of global, no-flow ischemia and 30 minutes of reperfusion. With each protocol, both control and glutathione-depleted hearts received either standard buffer or one supplemented with 2 mM glutathione. Recovery of systolic function after ischemia-reperfusion was impaired in DEM-treated hearts compared with controls. In addition, the rise in perfusion pressure and chamber stiffness was also greater in DEM-treated hearts compared with controls. Recovery in glutathione-depleted hearts was improved when the reperfusate was supplemented with glutathione. In addition, the supplemented reperfusate prevented the decrease in compliance and the increase in coronary perfusion pressure in the glutathione-depleted hearts. Ischemia-reperfusion alone were not associated with a significant alteration in myocardial glutathione levels. Prewashout myocardial levels of glutathione were elevated after reperfusion with glutathione-supplemented buffer but fell to baseline levels after a short washout period. These studies demonstrate that endogenous glutathione is important in protection of myocardium from injury after ischemia-reperfusion, presumably by modifying levels of active oxygen intermediates. The smaller changes in left ventricular pressure and coronary resistance after administration of GSH probably reflects an extracellular mechanism because benefit is seen soon after reperfusion.
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PMID:Myocardial glutathione depletion impairs recovery after short periods of ischemia. 280 76

This investigation was focussed on the gravity of tissue injury caused by complete ischemia (for five min) and hypoxia (for three weeks) in the cerebral cortex (homogenate) and the erythrocyte lysate or the erythrocyte membrane of the rat in order to investigate if the changes that occur in brain tissue are reflected in the erythrocyte. To this end, glutathione (GSH), superoxide dismutase (SOD) and catalase were measured, also alterations in beta-adrenoceptor density under these two conditions were examined. It was found that in ischemia partial parallelism in changes that occur in the central nervous system (cerebral cortex) and the erythrocyte exists. The SOD activity became higher and the beta-adrenoceptor density (measured as specific (-)-[125I] iodocyanopindolol binding) was decreased in both tissues. However after the hypoxic condition we established a decrease in the number of beta-adrenoceptors in the cerebral cortex but an increase in beta-adrenoceptor density in the erythrocyte.
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PMID:The effect of ischemia and recirculation, hypoxia and recovery on anti-oxidant factors and beta-adrenoceptor density. Is the damage in the erythrocytes a reflection of brain damage caused by complete cerebral ischemia and by hypoxia? 282 46

To monitor free radical scavenging properties of drugs, the 'stable' radical 2,2,6,6-tetramethylpiperidino-1-oxyl (TEMPO) was used. The sydnonimine molsidomine (SIN-1) effectively reduced the ESR signal whereas the nitrate isosorbidemononitrate (ISMN) did not. Thiol reagents like 2-mercaptopropionylglycine (MPG) or glutathione (GSH) only were effective in the presence of Fe2+ or Fe3+. Protein-bound iron in hemoglobin proved about four times more effective in reducing ESR signal height by thiols. It is suggested that the decrease in thiol content adds to the lack in protein bound iron of hemoglobin to induce the burst of free radicals in hypoxia (ischemia) and reperfusion.
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PMID:Free radical scavenging drugs, assessed by ESR studies: influence of hemoglobin. 285 30

A growing body of experimental data indicates that reactive oxygen metabolites such as superoxide, hydrogen peroxide, and hydroxyl radicals may mediate the microvascular and parenchymal injury produced by reperfusion of ischemic skeletal muscle. One potential source of these reactive oxygen metabolites is the inflammatory neutrophil. To assess neutrophil accumulation in postischemic skeletal muscle, we measured tissue myeloperoxidase (MPO) activity in skeletal muscle biopsies taken during control, after 4 h of ischemia, and after 1 h of reperfusion. Tissue levels of reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were measured in the same samples to identify alterations in tissue free radical defense mechanisms due to ischemia-reperfusion. Reperfusion of ischemic skeletal muscle was associated with a dramatic increase in tissue neutrophil content (as reflected by a 26-fold increase over control in tissue MPO activity after 1 h of reperfusion) and a concurrent 50% decrease in GSH content. Tissue CAT and SOD activities were unaffected by ischemia-reperfusion. These results suggest a possible relationship between ischemia-reperfusion-induced injury, neutrophil infiltration, and the reduction in tissue GSH.
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PMID:Free radical defense mechanisms and neutrophil infiltration in postischemic skeletal muscle. 292 39

The effects of several concentrations of amines and reducing agents on the activity of creatine (CK) and adenylate (AK) kinases were determined in homogenates of the brain of the rat at 0 and 37 degrees C. The order of decreasing irreversible inhibition of the enzymes was peroxide, 6-hydroxydopamine, dopamine, norepinephrine, 5-hydroxytryptamine. At 37 degrees C, approx. 50% of the activity of creatine kinase was lost in 30 min in the presence of 20 microM dopamine. 5-Hydroxytryptamine was several orders of magnitude less toxic. The action of dopamine was not prevented by inhibition of monoamine oxidase, chelation of metals or the addition of a catalase, indicating that formation of peroxide by monoamine oxidase was not the primary cause of the loss of enzyme. Although auto-oxidation of dopamine to a toxic quinone was considered, the degree of inhibition of creatine kinase was not affected when auto-oxidation was prevented under anaerobic conditions. Glutathione (GSH), present during the incubation, protected the enzymes but could not restore activity after exposure to amine. Concentrations of glutathione above 5 mM and of oxidized glutathione as low as 10 microM inhibited creatine kinase. Ascorbate protected the enzymes even when present at a concentration much less than that of the amine, but ascorbate was itself toxic. The findings indicate that dopamine, at concentrations attained after drug-induced release or ischemia, can be toxic to a metabolic enzyme present in the synaptosomal membrane.
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PMID:Amine-mediated toxicity. The effects of dopamine, norepinephrine, 5-hydroxytryptamine, 6-hydroxydopamine, ascorbate, glutathione and peroxide on the in vitro activities of creatine and adenylate kinases in the brain of the rat. 300 2

Oxygen-derived free radicals play an important role in the myocardial injury associated with ischemia and reperfusion. This study was designed to assess whether the protection afforded by a K+ rich, Mg2+ rich cardioplegic solution could be enhanced by the addition of free radical scavengers acting at different levels of the radical generating pathway. Forty isolated isovolumic rat hearts were divided into five groups (n = 8). Four groups of hearts were subjected to 90 minutes of normothermic cardioplegic arrest followed by 45 minutes of reperfusion. Hearts were given an initial bolus of either unmodified cardioplegic solution or cardioplegic solution enriched with superoxide dismutase (200,000 U/L) reduced glutathione (0.1 mmol/L), or peroxidase (6,000 U/L). One group of hearts was aerobically perfused throughout the experimental protocol and served as nonischemic controls. Based on comparisons of postreperfusion ventricular pressure development, maximal ventricular dP/dt, left ventricular compliance and coronary flow, peroxidase-containing cardioplegic solution afforded the best myocardial protection, with values of these indicators not significantly different from those of nonischemic perfused control heart. Glutathione afforded protection slightly inferior to that of peroxidase but still markedly better than in groups receiving superoxide dismutase or unmodified cardioplegic solution. This study confirms that cardioplegic protection can be enhanced by the addition of free radical scavengers, in particular peroxidase.
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PMID:A comparative study of free radical scavengers in cardioplegic solutions. Improved protection with peroxidase. 301 15

Renal ischemia and reperfusion have been shown to be associated with an enhanced renal lipid peroxidation. Because glutathione (GSH) serves to protect cells from oxidative stress, the role of GSH in renal ischemia was investigated. The content of renal GSH in the rat declined to 40% of control values during 35 min of renal artery occlusion. Renal GSH levels only partially recovered after 120 min of blood reflow. To assess the significance of this effect, renal GSH levels were altered before occlusion of the renal artery. Rats were treated with either buthionine sulfoximine (BSO) or glutathione monoethylester (GSH-ester) to lower or elevate, respectively, renal GSH levels. The ischemia-induced changes in renal ATP, ADP, and AMP after 35 min of ischemia and 90 min of blood reflow were not affected by prior alteration of renal GSH levels. The ischemia-induced decrease in the respiratory control of isolated cortex mitochondria was also unaffected. In control animals, ischemia of 35 min increased urine flow rate 3.2-fold and decreased GFR to 29% of normal values during the reflow period. Similar changes occurred in kidneys with a depleted GSH level. In kidneys with an elevated GSH, however, both urine flow rate and GFR were decreased to values 50 and 3% of normal, respectively. Morphological analysis demonstrated that ischemia produced an enhanced degree of damage with an increase in cast formation in kidneys pretreated with GSH-ester; however, the ester also produced morphological changes in nonischemic kidneys. The severity of ischemic damage was similar in kidneys with a lower GSH content when compared with controls. We conclude that renal GSH is depleted by ischemia but depletion of renal GSH with BSO before ischemia has no effect on ischemic-induced damage to the kidney. However, ischemic-induced renal dysfunction is enhanced when GSH is elevated with glutathione monoethylester before ischemia.
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PMID:Effect of an altered glutathione content on renal ischemic injury. 318 64

The relation between adenine nucleotide liver concentrations and the viability of liver allografts after cold preservation and warm ischemia was studied. A rat model was used with storage times defined in terms of allograft viability. Livers were excised and stored for 4 hr at 4 degrees C or 1 hr at 37 degrees C (viable if transplanted) or for 8 hr at 4 degrees C or 2 hr at 37 degrees C (not viable if transplanted) in a solution containing 0.9% NaCl and 2 mM CaCl2. Adenine nucleotide, malondialdehyde, and glutathione concentrations were measured in liver biopsies at the end of the storage periods and in control livers. During cold preservation, ATP concentrations decline, but degradation is largely halted at AMP, and this is independent of the length of storage or viability of the allograft. Graft failure is not due to lack of availability of intramitochondrial substrate (AMP) for rephosphorylation to adenosine triphosphate (ATP), nor is it likely that provision of such substrate will be helpful. On the other hand, with warm ischemia, degradation to inosine, hypoxanthine and xanthine occurs and nonviable livers develop higher levels of xanthine than viable ones; in fact, xanthine concentrations provide 100% discrimination between viable and nonviable warm preserved livers. Malondialdehyde concentrations were also significantly greater in the warm preserved nonviable livers, indicating that some lipid peroxidation may occur even before reperfusion of allografts. Glutathione concentrations were similar in all experimental groups.
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PMID:Adenine nucleotide tissue concentrations and liver allograft viability after cold preservation and warm ischemia. 328 45

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

Effects of complete ischemia on levels of antioxidative enzymes including copper-zinc (CuZn) superoxide dismutase (SOD), manganese (Mn)-SOD, and glutathione peroxidase (GSH-Px) were studied in rat brain regions at 30 and 60 min following decapitation. CuZn-SOD activities were significantly decreased in cerebral cortex and hippocampus at both time points whereas the enzyme activities were decreased at 60 min in cerebellum and caudate areas. The reduction of Mn-SOD activities followed the same pattern of CuZn-SOD in various brain regions. However, GSH-Px activities in these brain regions were not affected by decapitation ischemia. These data suggest that the reduction of CuZn-SOD and Mn-SOD activities during ischemia, in conjunction with the significant decrease in the contents of alpha-tocopherol and other endogenous antioxidants, may compromise the brain's ability to defend against the toxic effects of superoxide radicals formed by ischemia and by subsequent reoxygenation.
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PMID:Reduction of activities of superoxide dismutase but not of glutathione peroxidase in rat brain regions following decapitation ischemia. 335 97


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