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)

In exercise-induced muscle damage, oxidative stress derived from the liberation of reactive oxygen species (ROS) is assumed to be of etiological importance. Xanthine oxidase (XO) located in capillary endothelium is one of the possible sources for ROS, mainly investigated so far under conditions of ischemia/reperfusion. XO can be inhibited by allopurinol. To investigate the contribution of XO for the oxidative stress-induced development of muscle damage, mice were subjected to a single bout of exhaustive running exercise. Another exercised group received allopurinol. The reduced form of glutathione (GSH) was measured to estimate the amount of oxidative stress in soleus muscle, and the same muscle was examined in the light and electron microscope at different periods of time (0, 48, 96 h) after exercise. While exercise alone resulted in a marked reduction of GSH indicative for oxidative stress, which only recovered at 96 h, the administration of allopurinal to exercised animals induced a complete recovery already at 48 h after exercise. Muscle damage was more pronounced in the exercised animals which had not been treated with allopurinol. It is concluded that endothelium-derived ROS contribute reasonably to oxidative stress to exercised muscle and to fiber and capillary damage.
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PMID:Endothelium-derived oxidative stress may contribute to exercise-induced muscle damage. 830 Feb 69

The specific activity of seven enzymes involved in protecting tissue from oxidative stress was determined in rat kidneys subjected to 0, 2, 4, or 8 h of normothermic ischemia and in isolated rat livers during control perfusion, after 2 h ischemia, and after 2 h ischemia plus 1 h of reperfusion. In general, none of the antioxidant enzymes measured showed any consistent variation throughout the ischemic period even though mitochondrial function was significantly decreased, indicating substantial cell injury. Glutathione peroxidase (Se-GSH-Px) activity remained constant during 8 h of ischemia, although a small (29%) increase above control activity was noted at 4 h of ischemia. Se-independent GSH-Px activity (non-Se-GSH-Px) and glutathione reductase (GSSG-Red) remained constant up to 8 h of ischemia, when we measured an increase of 158% above controls in non-Se-GSH-Px and a decrease of 35% relative to controls in GSSG-Red. In perfused livers, the only change in enzyme activity after 2 h of ischemia was an increased GSSG-Red activity of 21% above control. This increase persisted into the reperfusion phase (35% above control activity) and was accompanied by decreases in both forms of GSH-Px (28% Se-GSH-Px and 44% non-Se-GSH-Px).
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PMID:Antioxidant enzyme status of ischemic and postischemic liver and ischemic kidney in rats. 837 97

Brain is a logical target of free radical damage, considering the large lipid content of myelin sheaths and the high rate of brain oxidative metabolism. Thus, the hypothesis that free radicals may be involved in the pathogenesis of certain CNS diseases has gained increasing popularity in recent years. In CNS ischemia-reperfusion injury, the role of free radicals appears to be well established, however, involvement of other factors, such as excitatory amino acids and prostaglandins, may also contribute to the production of neuronal necrosis following ischemia. Liberation of free iron appears to play a crucial role in the generation of reactive oxygen species in posttraumatic epilepsy. Although there is no direct evidence to indicate free radical involvement in the pathogenesis of Alzheimer's disease, brain trauma with release of iron, amyloid angiopathy and disturbances in blood-brain barrier function all appear to contribute to the development of ischemic episodes with free radical generation and neuronal degeneration. In Parkinson's disease, the substantia nigra appears to be under oxidative stress as evidenced by the findings of increased lipid peroxidation, reduced GSH levels, high concentration of iron and free radical generation via autocatalytic mechanisms within neuromelanin-containing catecholaminergic neurons. Regardless of the initial insult, a cascade of events involving both reactive oxygen radicals and mitochondrial metabolism is likely to contribute to cell injury.
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PMID:Oxygen, antioxidants and brain dysfunction. 837 80

The peroxidation of lipids and changes in the activities of related enzymes, such as xanthine-xanthine oxidase (XOD), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) in the gastric mucosa were studied in rat model of ischemia-reperfusion with pylorus ligation. Myeloperoxidase (MPO), a marker enzyme of leucocytes, was also studied. Thiobarbituric acid reactive substances (TBA RS) in gastric mucosa were significantly increased by clamping the celiac artery for 30 min and reperfusion for 60 min after 3 h of pylorus ligation. XOD activity in gastric mucosa increased with the development of gastric mucosal injury. Allopurinol significantly suppressed XOD activity but did not inhibit mucosal injury or the increase in TBA RS. MPO activity in the gastric mucosa was significantly increased by gastric mucosal injury. Famotidine significantly inhibited the increase in MPO activity in gastric mucosa, while allopurinol did not. SOD and GSH-px activities in the gastric mucosa were decreased significantly by gastric mucosal injury. SOD activity was normal following treatment with famotidine and allopurinol. Moreover, GSH-px activity recovered to the normal level with famotidine and allopurinol treatment. These findings suggest that oxygen radicals and lipid peroxidation can cause gastric mucosal injury by ischemia-reperfusion in the pylorus-ligated rat. The generation of oxygen free radicals may be derived mainly from activated polymorphonuclear leukocytes (PMN), and the decrease in SOD and GSH-px activity in gastric mucosa seems to aggravate mucosal injury by free radicals and lipid peroxidation.
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PMID:Role of lipid peroxidation in gastric mucosal lesions induced by ischemia-reperfusion in the pylorus-ligated rat. 839 87

The activation of microsomal glutathione (GSH) S-transferase in isolated rat liver by oxidative stress was investigated using both ischemia/reperfusion and perfusion with hydrogen peroxide. When the isolated liver was reperfused for 30 min and 60 min after 90 min ischemia, microsomal GSH S-transferase activity, but not cytosolic transferase activity, was increased 1.2-fold and 1.3-fold, respectively. In addition, microsomal GSH peroxidase activity was also significantly increased after 60 min reperfusion following ischemia. The increase in microsomal GSH S-transferase activity by ischemia/reperfusion was reversed by dithiothreitol. When N-ethylmaleimide, which activates microsomal GSH S-transferase by covalent binding to the cysteine residue of the enzyme, was incubated with microsomes, transferase activity was increased to 526% in control microsomes and to 399% in liver that underwent ischemia/reperfusion liver. These data indicate that microsomal GSH S-transferase is activated by ischemia/reperfusion of the liver by means of disulfide bond formation. When rats were pretreated with a catalase inhibitor 3-amino-1,2,4-triazole for 6 weeks, microsomal GSH S-transferase activity was increased 1.4-fold by ischemia/reperfusion, corresponding to a 1.8-fold increase as compared to the non-perfused liver of untreated rats. Perfusion of the isolated liver with hydrogen peroxide (1 mM, 15 min) also caused a significant increase in microsomal GSH S-transferase activity with a concomitant decrease in GSH content, confirming that liver microsomal GSH S-transferase in rats was activated in vivo by oxidative stress.
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PMID:Oxidative stress-induced activation of microsomal glutathione S-transferase in isolated rat liver. 842 21

Reperfusion injury following ischemia is thought to be the consequence of reactive oxygen species possibly generated either by xanthine oxidase activity or by processes associated with neutrophil activation in the affected organ or tissue. The conversion of xanthine dehydrogenase to the oxidase as well as the interactions between endothelium and neutrophils in the margination and activation of the latter are all considered to be results of conditions resulting from the ischemic episode. Determination of the redox status of glutathione in an ischemic/reperfused organ is frequently employed as an indicator of oxidative stress created by the production of oxygen free radicals during the reperfusion period. In this procedure, the ratio of oxidized glutathione (GSSG) to total glutathione (GSH + GSSG) is utilized to demonstrate the proportion of glutathione oxidized during reperfusion. We determined this ratio in the rat small intestine during ischemia and reperfusion and found that while the ratio of GSSG/(GSH + GSSG) does increase, this increase was the result of GSH disappearance rather than an increase in GSSG, and that essentially all of this loss occurred during the ischemic episode. We demonstrated that no oxidation of GSH occurred that was attributable to reperfusion per se; nor was there an increase of GSSG during this reoxygenation period.
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PMID:Evidence that the large loss of glutathione observed in ischemia/reperfusion of the small intestine is not due to oxidation to glutathione disulfide. 846 26

The mechanisms underlying cell damage in stroke or during experimental brain ischemia are not fully understood. L-Cysteine, an excitotoxic amino acid that could contribute to tissue damage, is normally found in relatively low levels in brain (ca. 0.05 mumol/g), compared to the cysteine-containing tripeptide, glutathione (GSH, ca. 1.5 mumol/g). We have observed that during brain ischemia in gerbils, levels of cysteine rise 10-13-fold over an 8 h period to 0.66 and 0.62 mumol/g, respectively, in the ischemic hippocampus and striatum. At the same time, levels of GSH fall by 0.84 and 0.94 mumol/g, respectively. The elevated free cysteine may be derived largely from GSH. The levels of cysteine found in ischemic brain are similar to those reported after parenteral administration of neurotoxic doses of L-cysteine to perinatal rats. The remarkable increase in cysteine during brain ischemia, coupled to its neurotoxic properties, may play a role in aspects of brain damage during or following brain ischemia.
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PMID:Brain ischemia markedly elevates levels of the neurotoxic amino acid, cysteine. 849 46

The effect of lowered brain glutathione content on the glutamate release following cerebral ischemia was investigated. Diethylmaleate (4 mmol/kg, i.p.), a commonly used chemical reagent for tissue glutathione depletion, significantly reduced the ischemia-induced glutamate release. The release of another excitatory amino acid aspartate was not affected by the diethylmaleate administration. These results suggested that part of the elevated glutamate content induced by ischemia might result from the cellular GSH.
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PMID:Lowered brain glutathione by diethylmaleate decreased the glutamate release induced by cerebral ischemia in anesthetized rats. 858 90

Nicorandil is a compound with hybrid properties of nitrates and adenosine triphosphate (ATP)-sensitive potassium channel (KATP) opening. The effects of nicorandil and isosorbide dinitrate (ISDN) were investigated in a model of 60-min coronary occlusion/180-min reperfusion in open chest pigs. Three groups of 10 pigs were randomly assessed to receive saline or equihypotensive doses of nicorandil or ISDN. Drug infusion was started at 30 min of ischemia and continued throughout reperfusion. Area at risk (AAR) and infarcted area (IA) were assessed by monastral blue dye-triphenyltetrazolium dual staining technique and calculated by planimetry. Myeloperoxidase concentration (MPO) in the non-ischemic area and in the IA was assessed as an index of presence of neutrophils. Measurements of reduced glutathione (GSH), oxidized glutathione (GSSG), lipofuscine, and malondialdehyde were performed on coronary vein blood as indexes of oxidative stress. IA, as a percentage of AAR, was 78 +/- 10% after saline, 61 +/- 12% after N (p < 0.05 vs. saline), and 69 +/- 14% after ISDN (not significant vs. saline). Cardiac output and left ventricular dP/dt were depressed during coronary occlusion in all groups and their recovery during reperfusion was earlier in the nicorandil group. In the saline group, MPO was increased in the IA compared to the nonischemic area (78 +/- 63 vs. 21 +/- 21 micrograms/mg prot, p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Limitation of myocardial infarct size by nicorandil after sustained ischemia in pigs. 858 91

Breakdown of membrane phospholipids is a causative event leading to irreversible cell injury after ischemia and reperfusion insults, which might be one mechanism leading to liver tumor cell death after repeated arterial ischemia as well. After 2 hr of hepatic dearterialization followed by 30 min of reperfusion tumor phospholipid was measured chromatographically, glutathione (GSH) analyzed by determining nonprotein sulfhydryl and activity of glutathione-S-transferase (GST) determined spectrophotometrically using 1-chloro-2,4-dinitrobenzene (CDNB) as the substrate. A transient, arterial ischemia for 2 hr induced a substantial decrease of phosphatidylserine (PS) and phosphatidylinosital (PI) compared with sham treatment (P < 0.01). Although phosphatidylcholine (PC) and phosphatidylethanolamine (PE) did not significantly decline after a single arterial ischemia for 2 hr, they dropped dramatically following repeated arterial ischemia for 2 hr during 5 days (P < 0.01 and P < 0.05 respectively). GSH was depleted in tumors after both a single (P < 0.01) and repeated arterial ischemia (P < 0.05) and GST was inactivated as well (P < 0.001). By contrast, neither liver phospholipid nor liver GSH or GST was significantly changed. Tumor growth was significantly retarded in rats subjected to repeated arterial ischemia compared with sham treatment (P < 0.01). Repeated arterial ischemia facilitated degradation of tumor membrane phospholipids and induced depletion of GSH and inactivation of GST without affecting the normal liver. Thus, ischemia/reperfusion induced depletion of membrane phospholipids and of GSH might represent two mechanisms by which repeated arterial ischemia led to tumor growth delay.
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PMID:Glutathione and phospholipid depletion of liver tumors after arterial ischemia. 862


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