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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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 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

In this study we sought to define the role of oxygen-derived free radicals during ischemia and reperfusion in the production of acute damage to the gastric mucosa of baboons. The protective effect of the xanthine oxidase inhibitor, allopurinol, the superoxide scavenger, superoxide dismutase (SOD), and a long-acting SOD-albumin was determined. Mucosal damage was evaluated using light and scanning electron microscopy. Evidence for oxidative insult to the gastric mucosa was sought by measuring tissue concentrations of reduced (GSH) and oxidized (GSSG) glutathione. Gastric mucosal blood flow was estimated using the microsphere technique. A similar pattern of tissue damage was found at the end of ischemia in all three groups. Thirty minutes after reperfusion, severe mucosal damage (grade 3) increased only in the untreated control. In the two treated groups, grade 3 damage remained unchanged during reperfusion and a decrease in the percentage of moderate damage (grade 2) was seen. Both GSH and GSSG tissue concentrations were lower in the untreated controls as compared to the scavenger-treated groups, making it questionable whether GSH/GSSG tissue levels adequately reflect oxidative stress. We conclude that in our ischemia-reperfusion model the generation of oxygen-derived free radicals produces mucosal damage and prevents the restitution of moderate mucosal damage during reperfusion. In ischemia, factors other than free radicals seem to be responsible for mucosal damage. The protective effect of allopurinol and SOD was not mediated by changes in gastric mucosal blood flow.
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PMID:Gastric mucosal lesions induced by hemorrhagic shock in baboons. Role of oxygen-derived free radicals. 337 79

Pretreatment of animals with certain antioxidant enzymes and substances decreases renal damage following ischemia and reperfusion. The hypothesis that reoxygenation imposes an oxidant stress has been used to explain this. The present study has directly assessed oxidant stress under these conditions by measuring the glutathione redox ratio ([GSSG/(GSH + GSSG)] x 100) in freeze-clamped kidney. The glutathione peroxidase system plays a role in removing peroxides which result from oxidant stress, generating GSSG from GSH in the process. The selenium-dependent glutathione peroxidase can metabolize H2O2 and other hydroperoxides. A non-selenium-dependent glutathione peroxidase activity is present and can metabolize organic hydroperoxides, but it cannot metabolize H2O2. Under anesthesia, the left renal artery was occluded for 40 minutes and then reflow was allowed. Kidneys were freeze clamped before reflow and after 5, 10, and 15 minutes of reflow. The contralateral kidney was freeze clamped and used as a control. The control value for the glutathione redox ratio was 1.09 +/- 0.05. This fell during ischemia to 0.67 +/- 0.22 and increased significantly to 1.66 +/- 0.29 after five minutes of reperfusion. By 15 minutes it had returned to 1.09 +/- 0.22. Treatment of rats with diquat, which causes a severe oxidant stress, raised the glutathione redox ratio from 0.88 +/- 0.12 to 1.89 +/- 0.15. Thus, reperfusion was concluded to cause a large but transient oxidant stress. Selenium-deficient rats were used to examine the nature of the oxidant stress. Activity of the selenoenzyme glutathione peroxidase was depressed to 2% of control in the kidneys of these rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidant stress following renal ischemia: changes in the glutathione redox ratio. 338 35

Studies were performed to determine whether renal glutathione (GSH) is an important free-radical scavenger following ischemia and reperfusion, whether alterations in renal transport work affect renal GSH levels, and whether a decrease in renal work decreases susceptibility to postischemic renal injury via the first two effects. Following administration of either intravenous GSH to increase renal GSH or intraperitoneal diethylmaleate to decrease renal GSH, Sprague-Dawley rats underwent 60 minutes of renal ischemia. In animals with high renal GSH following GSH infusion, GFR 24 hours after ischemia was 0.43 +/- 0.08 ml/min compared to 0.15 +/- 0.02 ml/min in saline-infused control animals (P less than 0.01). When renal GSH was decreased by the administration of diethylmaleate postischemic renal dysfunction was accentuated. Twenty-four hours after ischemia GFR was 0.05 +/- 0.02 ml/min in diethylmaleate-treated animals and 0.28 +/- 0.06 ml/min in control animals (P less than 0.005). To test whether a decrease in renal transport work alters renal GSH the filtered load of sodium was reduced by producing unilateral renal artery stenosis. Alternatively, renal work was lessened when sodium reabsorption was interfered with by the infusion of a combination of natriuretic agents. Renal artery stenosis produced a 37% decrease in GFR. Renal GSH was 0.435 +/- 0.089 nmol/mg protein in intact kidneys and 0.804 +/- 0.239 nmol/mg protein in stenotic kidneys (P less than 0.05). The infusion of natriuretic agents produced no change in GFR or renal plasma flow but resulted in a striking elevation in renal GSH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal work, glutathione and susceptibility to free radical-mediated postischemic injury. 338 36

Toxicity of t-butylhydroperoxide (t-BuOOH) was studied at different steady state O2 concentrations under conditions at which O2 deficiency alone did not cause cell death. t-BuOOH-induced cell death was more rapid in hypoxic than normoxic cells; the maximal rate of cell death occurred in anoxic cells. t-BuOOH elimination was independent of O2 concentration and was complete within 15 min; t-Butanol was produced at the same rate and was the only product detected by gas chromatography. Measurement of radical production by formation of adducts of the spin-trapping agent N-tert-butylphenylnitrone showed that the amount of radicals trapped was 0.02% of the amount of peroxide added and was the same under anoxic and oxygenated (214 microM O2) conditions. These results show that the O2 dependence of t-BuOOH-induced toxicity is not related to quantitative alterations in its metabolism. Lipid peroxidation was lowest in anoxic cells and increased as the O2 concentration was increased to 1.07 mM O2, showing that enhanced toxicity during hypoxia and anoxia was not due to enhanced lipid peroxidation. In contrast, O2 deficiency impaired the ability of cells to maintain and recovery GSH and NADPH pools after addition of t-BuOOH. GSH was decreased to a greater extent in anoxic cells than in normoxic cells, and the GSH content remained lower in these cells for up to 30 min. This decrease was due both to a decrease in the rate of synthesis and to decreased supply of the NADPH needed for the reduction of GSSG. Taken together, these results show that O2 deficiency has little effect on metabolism of t-BuOOH but impairs the ability of cells to maintain cellular GSH and renders them more susceptible to injury from oxidizing agents. This suggests that oxidative injury under hypoxia or following ischemia may not require a marked stimulation in generation of oxidative species but may occur as a consequence of the impaired ability to tolerate or repair oxidative injury.
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PMID:Effect of hypoxia on tert-butylhydroperoxide-induced oxidative injury in hepatocytes. 341 29

In the isolated and perfused rabbit heart ischemia induced a rapid decline of contractility, associated with a reduction of the content of tissue GSH with no significant changes in GSSG. Reperfusion induced a small recovery of contractility, a substantial release of total glutathione and a further decrease in the content of tissue GSH with a significant increase of tissue GSSG. Glutathione reductase and glutathione peroxidase activities were not affected by ischemia and reperfusion. This study suggests a possible role for glutathione in the determination of functional damage induced by myocardial ischemia and reperfusion.
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PMID:Changes in the cardiac glutathione status after ischemia and reperfusion. 396 36

The possibility that myocardial ischaemia alters the defence mechanisms against oxygen toxicity has been investigated. Ischaemia was induced in isolated, perfused rabbit hearts by reducing coronary flow from 25 ml/min to 1 ml/min for 90 min. Two different degrees of ischaemic damage have been achieved using either spontaneously beating or electrically stimulated hearts. The effects of post-ischaemic reperfusion were also followed for 30 min. Tissue activity of superoxide dismutase (SOD), glutathione peroxidase and reductase (GPD and GRD) have been determined together with tissue content of reduced and oxidized glutathione (GSH and GSSG) and of protein SH groups. The changes in myocardial ATP and CP content and release of CPK and of GSH and GSSG were also determined. Systolic and diastolic pressures were continuously monitored. In the spontaneously beating hearts ischaemia induced a reduction of tissue GSH and protein SH groups. On reperfusion there was a recovery of mechanical function, a transient release of GSH into the coronary effluent and an increase of tissue GSH. In the paced hearts, ischaemia resulted in 50% reduction of mitochondrial SOD activity together with a reduction of tissue GSH and protein SH groups. Reperfusion induced a massive release of CPK and of GSH and GSSG, a further reduction of tissue GSH concomitant with an increase of GSSG and no recovery of mechanical function. GPD and GRD activity were not affected by ischaemia and reperfusion. These data indicate that severe ischaemia induces a reduction of the protective mechanisms against oxygen toxicity.
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PMID:Oxygen-mediated myocardial damage during ischaemia and reperfusion: role of the cellular defences against oxygen toxicity. 406 39


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