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

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.
 ...
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)
 ...
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)
 ...
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.
 ...
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.
 ...
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.
 ...
PMID:Oxygen-mediated myocardial damage during ischaemia and reperfusion: role of the cellular defences against oxygen toxicity. 406 39

Dog experiments were performed to describe the time course of lipid peroxidation after various ischemic influences of the heart measured by formation of malondialdehyde (MDA), and the scavenger action determined by reduced glutathione (GSH) content and superoxide dismutase (SOD) activity. Experimental groups consisted of control dogs having intact hearts and dogs with acute ramus descendens anterior ligature (LAD) having ischemic areas through 15, 30, 45 minutes and 1, 2, 3, 24 hours. Heart tissue for biochemical assays was excised from both the ischemic areas and from nonischemic left ventricle. The acute ischemia caused characteristic alterations in the biochemical parameters: MDA level gradually increased with its peak value being found at the end of 3 hours ligature. GSH levels decreased moderately, whereas SOD levels reduced sharply. As increased MDA formation indicates breakdown of the polyunsaturated fatty acids (PUFA) in the membranes and decreased GSH and SOD levels indicate impairment of the natural scavengering, the observed changes clearly outline the extent of disintegration of membrane structure and function.
 ...
PMID:Lipid peroxidation and scavenger mechanism in experimentally induced heart infarcts. 407 87

The present study was undertaken to determine whether hepatic ischemia and the subsequent reflow of blood had any effect on the levels of endogenous coenzyme Q homologs, alpha-tocopherol, and glutathione, and whether coenzyme Q10 (6 mg/kg of body weight) altered these levels. Ischemia of the rat liver for 90 min resulted in decreases of 19.1 and 19.6% of endogenous alpha-tocopherol and total glutathione (GSH + GSSG) without significant changes in the levels of endogenous total coenzyme Q homologs (oxidized and reduced). Restoration of the blood flow resulted in marked decreases in endogenous coenzyme Q homologs, alpha-tocopherol, and total glutathione in the control group. In coenzyme Q10-treated animals, however, there were no changes in the levels of endogenous total coenzyme Q9, alpha-tocopherol, or total glutathione as well as in the level of the enhanced total coenzyme Q10 during the reperfusion period. On the other hand, decreases in alpha-tocopherol and total glutathione during the period of ischemia remained unchanged. These results are compatible with the assumption that cellular damage caused by hepatic ischemia can be explained by free radical reaction processes during ischemia and especially, reperfusion and suggest that exogenous coenzyme Q10 functions as an antioxidant with endogenous coenzyme Q homologs, alpha-tocopherol, and glutathione in lipid peroxidation during reperfusion.
 ...
PMID:Changes in the levels of endogenous coenzyme Q homologs, alpha-tocopherol, and glutathione in rat liver after hepatic ischemia and reperfusion, and the effect of pretreatment with coenzyme Q10. 669 4

The effect of the free radical scavenger glutathione (GSH) on the early post-ischemic liver cell death was studied on liver tissue of the rat. Animals with different pre-ischemic liver GSH contents were subjected to a 90 min period of ischemia, followed by a 3 h period of reperfusion. Cell death was evaluated morphologically by estimating intracellular calcium, using the stain Alizarin red S (ARS), and by dye-exclusion test using Evans blue. The extent of post-ischemic injury was also assessed by registration of the membrane potential (MP) in liver cells. Four groups of animals were studied: 1) fed rats. 2) fed rats pretreated with diethylmaleate. 3) rats fasted for 48 h. 4) fasted rats pretreated with cobalt-chloride. It was found that the early post-ischemic cell death was more extensive in rats with low initial GSH content (group 2 and 3), than in rats with high GSH content (group 1 and 4). It is suggested that GSH is protective against post-ischemic injury, probably by reducing lipid peroxidation.
 ...
PMID:Possible influence of glutathione on postischemic liver injury. 670 58

Thirty minutes of total cerebral ischemia (decapitation) decreased total glutathione (GSH + GSSG) by 7% but had no detectable effect on the concentration of oxidized glutathione (GSSG), reduced ascorbate, or total ascorbate, In a model of reversible, bilateral hemispheric ischemia (four-vessel occlusion) no changes in glutathione or ascorbate were detected after 30 min of ischemia. During 24 h of reperfusion following such an insult no detectable change in total ascorbate, reduced ascorbate, or oxidized glutathione was noted: however, total brain glutathione declined by 25%. The findings are discussed in relation to the hypothesis that the deleterious effects of ischemia are due to an increase in free radical production which in turn leads to increased lipid peroxidation.
 ...
PMID:Glutathione and ascorbate during ischemia and postischemic reperfusion in rat brain. 745 15


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>