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

Reactive oxygen metabolites have been reported to be important in the pathogenesis of ischemia/reperfusion-induced and alcohol- and drug-induced liver injuries. We investigated the role of superoxide dismutase, cellular and extracellular, in preventing reactive oxygen metabolite-induced cytotoxicity in cultured rate hepatocytes. Cells were exposed to reactive oxygen metabolites enzymatically generated by hypoxanthine-xanthine oxidase. Cytotoxicity was quantified by measuring 51Cr release from prelabeled cells and lactate dehydrogenase release. Reactive oxygen metabolites caused dose-dependent cytotoxicity. Good correlation was found between the values for 51Cr and lactate dehydrogenase release. Reactive oxygen metabolite-induced cell damage was reduced by catalase but not by superoxide dismutase. Cellular superoxide dismutase and catalase activities were not increased after incubation with exogenous superoxide dismutase and catalase for up to 5 hr. Pretreatment with diethyldithiocarbamate inhibited cellular superoxide dismutase activity without inhibiting other antioxidants such as catalase, glutathione, glutathione reductase and glutathione peroxidase and sensitized cells to reactive oxygen metabolite-induced cytotoxicity. We conclude that hydrogen peroxide is an important mediator in hypoxanthine-xanthine oxidase-induced cell damage and that superoxide dismutase plays a critical role in cellular antioxidant defenses against hypoxanthine-xanthine oxidase-induced cytotoxicity in cultured rat hepatocytes in vitro.
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PMID:Role of cellular superoxide dismutase against reactive oxygen metabolite-induced cell damage in cultured rat hepatocytes. 131 53

Hypoxic injury of rat astroglial cells in primary culture initiates several modifications of their functional integrity. A significant decrease of the cellular oxygen consumption was observed in astrocytes submitted to a 15 h low oxygen pressure. The addition of almitrine (dialylamino-4',6'-triazinyl 2')-1-(bis-parafluorobenzydryl)-4-piperazine, a chemoreceptor agonist, restored almost completely the respiratory activity of the hypoxia treated cells. In order to test the hypothesis that oxygen free radical formation may contribute to the cellular damage resulting from ischemia, the activities of the following antioxidant enzymatic systems have been determined in the cultured astrocytes: Cu,Zn- and Mn-superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), glutathione reductase (GSH-RED), and catalase (CAT). Only a significant and specific decrease of the Mn-SOD activity was observed after the hypoxia-normoxia exposure. The other oxygen radical scavenging systems were not modified. The addition of almitrine antagonized the decrease of the Mn-SOD activity observed in the low oxygen pressure treated cells, but results clearly point-out the importance of oxygen radical production in the astroglial response after hypoxic injury. A beneficial effect of almitrine toward the observed alteration has been underlined. It is suggested that some mitochondrial alterations could be related to some aspects of the astroglial hypoxic stress.
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PMID:Free radical scavenging systems of rat astroglial cells in primary culture: effects of anoxia and drug treatment. 140 63

This study was designed to clarify the effects of changes in liver tissue glutathione (GSH) concentration on postischemic liver injury together with the effects of gamma-glutamylcysteine ethyl ester (GCE), a prodrug of GSH, and GSH. Rats were pretreated with GSH (50 mg/kg, i.v.), or GCE (50 mg/kg, i.v.), or untreated. In each rat, liver was isolated, and liver mitochondria were prepared after 2 h of ischemia or 1 h of reperfusion following 2 h of ischemia. Mitochondrial function was measured polarographically. Liver adenine nucleotide concentrations were also determined using high-performance liquid chromatography. Liver tissue GSH, an oxidized form of glutathione (GSSG) concentrations, and activities of GSH peroxidase and GSSG reductase were determined enzymatically. Liver hypoxanthine and xanthine concentrations were determined by HPLC. Liver tissue concentration of lipid peroxide was measured. Leakages of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and adenine nucleotides into the hepatic vein after reperfusion were also measured. Administration of GCE improved the recovery of mitochondrial function and maintained tissue GSH concentration concomitantly. Increases in liver lipid peroxide concentration after reperfusion, and leakage of liver cell enzymes and adenine nucleotides were mitigated by administration of GCE. Administration of GSH itself failed to maintain tissue GSH concentration and had no protective effects. From these results, it is concluded that in the postischemic process, free radical formation might be enhanced, and the radical scavenging system deteriorated. To enhance the radical scavenging system is a possible maneuver to prevent radical-related cell damage associated with reperfusion, because pharmacological reduction of breakdown of ATP to hypoxanthine and xanthine seems to be difficult. GCE maintained liver GSH concentrations and mitigated postischemic liver injury, concomitantly. Clinical use of GCE might be recommended.
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PMID:The effects of gamma-glutamylcysteine ethyl ester, a prodrug of glutathione, on ischemia-reperfusion-induced liver injury in rats. 833 63

Activity of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase as well as content of diene conjugates and malonic dialdehyde were studied in blood serum and cerebrospinal fluid of patients with transitory ischemia, small ischemic insult, ischemic insult of middle severity and with severe ischemic insult without lethality within 1-2, 7-8 and 14-15 days of diseases. Content of lipid peroxidation products and activity of antioxidant enzymes were decreased in the biological fluids studied in all the forms of brain circulation impairments within early periods of pathology. These patterns tend to normalization within 14-15 days. The rate of biochemical alterations corresponded highly to severity of impairments developed and these patterns may be used for diagnostic and prognostic purposes.
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PMID:[Activity of antioxidant protection enzymes and content of lipid peroxidation products in blood serum and cerebrospinal fluid in patients with ischemic brain disease]. 141 27

Injury to the gastrointestinal tract by oxygen dependent processes is important in ischemia, inflammatory bowel disease, and necrotizing enterocolitis. The Caco-2 cell line is an important tool in assessing various gastrointestinal functions and offers a unique opportunity to assess gastrointestinal oxidant metabolism on a cellular level. However, some Caco-2 cell functions change with time after confluence. To determine if antioxidant enzyme activity changes during differentiation, Caco-2 cells were grown to confluence, and superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase activities and specific mRNA content were quantitated. With time after confluence the enzymes demonstrated a small, but statistically significant increase in activity. Neither superoxide dismutase nor glutathione peroxidase mRNA levels correlated with enzyme activity changes. Catalase mRNA levels increased as catalase activity increased. Thus, differentiated Caco-2 cells express superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase activities and the superoxide dismutase, glutathione peroxidase, and catalase genes. Superoxide dismutase activity and glutathione peroxidase activity do not correlate with mRNA levels, and suggest that regulation may be at a level other than transcription. The correlation between catalase activity and catalase mRNA suggests differentiation may occur at transcription. If Caco-2 cells are used to elucidate oxidative metabolism, changes in activities of antioxidant enzymes as a function of cell differentiation should be considered.
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PMID:Antioxidant enzymes in the differentiated Caco-2 cell line. 142 66

After 60 min of reperfusion following 60 min of ischemia, the ischemia-induced decrease in liver tissue adenosine triphosphate (ATP) concentration had recovered by 66%, and full recovery of mitochondrial function--that is, the respiratory control index (RCI) and the rate of oxygen consumption in state-III respiration (ST III O2)--was observed. In contrast, liver tissue ATP concentration had recovered by only 13%, and marked low RCI and ST III O2 were observed after 60 min of reperfusion following 180 min of ischemia. Intermediate results were observed in rats after 60 min of reperfusion following 120 min of ischemia. Liver tissue hypoxanthine and xanthine, substrates of xanthine oxidase, increased ischemic time dependently. Liver tissue concentrations of the reduced form of glutathione (GSH) and the oxidized form of glutathione (GSSG) and activities of glutathione peroxidase and glutathione reductase did not change after 60 min of reperfusion following 60 min of ischemia. In contrast, GSH concentration and glutathione peroxidase activity decreased significantly after 60 min of reperfusion following 180 min of ischemia. Since the glutathione redox system is an important contributor to the scavenging of free radicals after reperfusion following a long time of ischemia, the free radical scavenging ability might decrease in spite of enhancement of free radical generation, which might play an important role in the inhibition of the recovery of tissue ATP concentrations and mitochondrial function.
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PMID:Changes in the glutathione redox system during ischemia and reperfusion in rat liver. 143 57

Previous studies demonstrated that preconditioning of a heart by repeated stunning can reduce the cellular injury to the heart from subsequent acute ischemic insult. To examine the possible biochemical mechanism for such myocardial preservation afforded by preconditioning, swine heart was subjected to four episodes of 5 min. stunning by occluding the left anterior descending coronary artery (LAD), followed by 10 min. of reperfusion after each stunning. Heart was then made regionally ischemic for 60 min. by LAD occlusion, followed by 6 hrs. reperfusion. Control heart was perfused for 60 min., followed by 60 min. ischemia and 6 hrs. reperfusion. The results of our studies indicated the stimulation of a number of antioxidative enzymes, including Mn-superoxide dismutase (Mn-SOD), catalase, glutathione peroxidase, and glutathione reductase, after repeated stunning and reperfusion. In addition, a number of new proteins were expressed after preconditioning the heart, including some oxidative-stress related proteins and 72 kDa heat-shock protein. These results suggest that preconditioning of a heart by repeated stunning may lead to strengthening of the oxidative defense system of the heart, which is likely to play a role in myocardial preservation during subsequent ischemic and reperfusion injury.
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PMID:Preconditioning of heart by repeated stunning. Adaptive modification of antioxidative defense system. 147 1

Preconditioning the heart with 5 min of ischemia renders the heart very resistant to infarction from subsequent ischemia by an unknown mechanism. We investigated whether the protective effect of preconditioning might be related to an increase in rabbit heart antioxidant defenses. The antioxidant activities of catalase, glutathione peroxidase, Mn superoxide dismutase, Cu,Zn superoxide dismutase, glucose-6-phosphate dehydrogenase, glutathione reductase, and total glutathione were measured in ischemic and normal regions from both control and preconditioned rabbit hearts. All hearts experienced 30 min regional ischemia and 5 min reperfusion. None of the antioxidant enzymes changed in activity when comparing nonischemic and postischemic zones in either nonpreconditioned or preconditioned hearts. Total glutathione, however, was reduced in reperfused zones and showed better preservation in preconditioned hearts. To determine whether this preservation resulted from a higher value at the onset of reperfusion or slower washout during reperfusion, we analyzed a second group of nonreperfused hearts after 30 min ischemia. The hearts had normal glutathione content in both ischemic and nonischemic zones of either preconditioned or control hearts. The most likely explanation is that preconditioned hearts experienced less washout of glutathione simply because they were less injured. We therefore conclude that enhancement of antioxidant defenses is not the mechanism of preconditioning.
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PMID:Protection from reperfusion injury by preconditioning hearts does not involve increased antioxidant defenses. 153 19

The cardioprotective effects of a high dose of ascorbate on ischemia-reperfusion-induced myocardial damage were investigated using open chest anesthetized dogs. Two-hour occlusion of the left anterior descending coronary artery (LAD) induced mitochondrial dysfunction with a depletion of mitochondrial glutathione (GSH) concentration. Two-hour LAD occlusion followed by 1-h reperfusion worsened the ischemia-induced mitochondrial dysfunction together with a marked depletion of mitochondrial GSH concentration. Ascorbate reduced the mitochondrial dysfunction and prevented the depletion of mitochondrial GSH concentration after 2-h LAD occlusion and 1-h reperfusion. Activities of mitochondrial glutathione peroxidase and glutathione reductase did not change significantly in each group. Administration of ascorbate also prevented reperfusion arrhythmias without affecting blood pressure or heart rate. These results suggest that coronary reperfusion induces mitochondrial dysfunction and a depletion of mitochondrial GSH concentration, and that a high dose of ascorbate prevents reperfusion damage.
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PMID:The effects of a high dose of ascorbate on ischemia-reperfusion-induced mitochondrial dysfunction in canine hearts. 158 8

Rats were subjected to bilateral carotid artery occlusion for 30 min, followed by reperfusion for varying time periods. The concentration of reduced and oxidized glutathione, glutathione peroxidase and glutathione reductase were determined in whole brain after varying periods of reperfusion. Lipid peroxidation was also assessed by determining the levels of malondialdehyde (MDA) in the brain. Reperfusion for 1 hr following bilateral carotid artery occlusion resulted in significant decrease in total glutathione (GSH) concentration along with small but significant increase in oxidized glutathione (GSSG) levels. After 4 hr of reperfusion, GSH levels recovered, although GSSG levels remained elevated up to 12 hr of reperfusion. Increase in malondialdehyde levels was also detected in the brain up to 12 hr of reperfusion. Glutathione reductase activity remained significantly low up to 144 hr of reperfusion, while glutathione peroxidase activity remained unaffected. These results demonstrate that oxidative stress is generated in the brain during reperfusion following partial ischemia due to bilateral carotid artery occlusion.
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PMID:Glutathione homeostasis in brain during reperfusion following bilateral carotid artery occlusion in the rat. 158 35


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