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)

Using the isolated perfused rat liver, we investigated the relationship of glutathione (GSH) with reactive oxygen species (ROS) generation and liver cell damage during ischemia/reperfusion in normal and GSH-depleted conditions. Lucigenin-enhanced chemiluminescence was used as a sensitive index of tissue ROS generation. After 30 minutes of equilibration, livers were subjected to global ischemia for various times (60 or 90 minutes) and then reperfused for another 120 minutes. Intracellular ROS levels increased sharply at the onset of reperfusion and then declined slowly. After 30 to 60 minutes of reperfusion, ROS levels started to increase progressively in a linear fashion. However, sinusoidal glutathione disulfide release did not increase during reperfusion in the same livers, suggesting that intracellular ROS generation is too low to cause a significant increase in GSH oxidation. Pretreatment with phorone (300 mg/kg intrapentoneally [ip]), which reduced hepatic GSH by 90%, did not cause any difference in intracellular ROS generation compared with the control livers. There were also no significant differences in lactate dehydrogenase and thiobarbituric acid reactive substances (TBARS) release between the control and phorone-treated livers during reperfusion after various times of ischemia. These data indicate that ROS generation in the normal isolated perfused liver during ischemia/reperfusion is extremely low and intracellular GSH does not serve as a major intracellular defense system against such a low oxidative stress.
 ...
PMID:Glutathione and ischemia-reperfusion injury in the perfused rat liver. 157 30

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.
 ...
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.
 ...
PMID:Glutathione homeostasis in brain during reperfusion following bilateral carotid artery occlusion in the rat. 158 35

Renal levels of glutathione are markedly decreased during periods of renal ischemia due to catabolism to cysteine. We previously demonstrated that cysteine accumulates in the tissue as the thiol during ischemia, and resumption of blood flow causes a transient elevation of cysteine levels in the renal venous effluent and return of tissue cysteine levels to control values. In this study, the oxidation state of renal venous cyst(e)ine was determined. Although cysteine accumulated as the reduced thiol during ischemia, cysteine released into the renal vein upon blood reflow was found to be almost entirely in the disulfide form. To distinguish between oxidation of arterial cysteine and renal cysteine formed from ischemia-induced reduced glutathione (GSH) catabolism, a labeling procedure was developed to label kidney GSH with 35S without significant labeling of arterial plasma cyst(e)ine. With this procedure, the source of oxidized cysteine that appeared in the renal venous plasma after ischemia was identified as resulting from renal GSH catabolism. The data indicate that a rapid oxidative process occurs during the initial period of blood reflow to the postischemic kidney. After 35 min of ischemia, 3 mumol cysteine/g dry wt were released from the kidney and oxidized. Cysteine oxidation is also expected to generate oxygen-centered free radicals. Pretreatment of animals with deferoxamine, a iron chelator, was without effect on the relative amount of venous cysteine in the oxidized form, arguing against a role for free iron in this oxidative process.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cysteine oxidation by the postischemic rat kidney. 159 Apr 23

The urinary activities of N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl transpeptidase (gamma-GTP) and alanine aminopeptidase (AAP) are known to elevate markedly in initial phase of clinical acute renal failure (ARF). This study was performed to clarify the pathophysiological mechanism of the activation of these enzymes using experimental postischemic reperfusion ARF in rats. The relation between the levels of the lysosomal enzymes and lipid peroxidation induced by oxidant stress in these animal models was the main focus of this study. Renal ischemia was made by clamping renal artery for 30 minutes to create a complete ischemia and reflow. Catheterized urine was collected to measure changes of the activities of NAG. gamma-GTP and AAP from 60 to 480 minutes after reperfusion of the kidney. The activities of renal tissue glutathione peroxidase (GSH-Px), NAG and gamma-GTP, and the values of renal contents of glutathione (GSH) and malondialdehyde (MDA) were measured in each sample. It is already known that GSH redox cycle plays an important role in removing various hydroperoxides induced by oxidant stress, generating oxidated GSH from GSH in scavenging process. In order to confirm if GSH plays an important role in intrinsic anti-oxidant system in this model, buthionine sulfoximine (BSO) which is gamma-glutamylcysteine synthetase inhibitor, was administered intraperitoneally to decrease renal GSH contents before the procedure renal ischemia. The following results were obtained; 1) urinary activities of NAG, gamma-GTP and AAP were elevated markedly in GSH depleted rats compared with controls, 2) renal tissue activities of NAG were higher in BSO administered rats than controls.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Experimental studies on the elevation of urinary enzyme activities and its pathogenesis in acute renal failure]. 167 93

In a previous study, we tested the hypothesis that an elevated level of renal glutathione (GSH) would protect the kidney from ischemic injury. However, prior elevation of GSH with GSH monoethylester enhanced then injury induced by 35 min of ischemia and blood reflow [Scaduto RC Jr, Gattone VH, Grotyohann LW, et al; Effect of an altered glutathione content on renal ischemic injury. Am J Physiol 1988;255:F911-F921]. Additionally, GSH monoethylester produced morphologic alterations in the absence of ischemia. Thus the greater ischemic injury observed after GSH ester pretreatment could have been due to a synergistic effect between the events caused by ischemia and the pretreatment. The present study was conducted to evaluate the utility of elevating renal GSH levels by administration of GSH. Administration of GSH (1 mmol/kg body weight) caused a 3-fold elevation of renal GSH levels and a 6-fold elevation of renal cysteine levels after 60 min without causing changes in renal morphology or GFR. After 35 min of renal artery occlusion and 90 min of blood reflow, animals pretreated with GSH had a much greater decline in GFR than untreated control animals. This enhancement of renal ischemic injury in GSH-treated animals was similar to that observed following administration of GSH monoethylester. We conclude that administration of GSH is the method of choice for elevation of renal GSH and that elevation of renal GSH leads to an enhanced ischemia-induced injury which is independent of the method employed to elevate renal GSH.
 ...
PMID:Elevation of renal glutathione enhances ischemic injury. 172 Feb 57

Oxidative stress may affect cardiac function and metabolism. Oxidants are normally inactivated by reacting with reduced glutathione (GSH), with resulting formation and release of oxidized glutathione (GSSG). However, ischemia might affect glutathione metabolism. This might render ischemic hearts less resistant against subsequent oxidant injury during reperfusion, and it might also affect the reliability of GSSG measurements as a means to investigate oxidative stress in reperfused hearts. We compared the metabolic and functional consequences of an oxidant load in control rabbit hearts and in hearts reperfused after 30 min of normothermic total ischemia. In controls, H2O2 infusion (H2O2; 5-30 microM) induced a dose-dependent stimulation of GSSG release and a progressive impairment of cardiac function. At these doses, H2O2 challenge of postischemic hearts resulted in biochemical and functional changes identical to those observed in controls. Release of lactate dehydrogenase (LDH) and of GSH was negligible, similar in both groups. In additional experiments, infusion of H2O2 at a much higher dose (200 microM) elicited a further increase in GSSG release from both groups, although GSSG concentrations were lower in postischemic hearts. The functional effects of the 200 microM H2O2 infusion were similar in both groups, all hearts showing rapid and irreversible deterioration of function. Occurrence of irreversible cell injury was also manifested by a large release of LDH and GSH to a similar extent in both groups. These data demonstrate that cardiac tolerance toward oxidants is largely unaffected by a relatively brief episode of severe ischemia and indicate that GSSG release can be reliably used to investigate oxidative stress in reperfused hearts.
 ...
PMID:Effects of ischemia and reperfusion on cardiac tolerance to oxidative stress. 173 14

Oxygen-derived free radicals have been implicated in the pathogenesis of vasogenic edema and infarction caused by ischemia and reperfusion injury. In earlier studies, exogenously supplied liposome-entrapped CuZn superoxide dismutase (CuZn-SOD) ameliorated ischemic brain edema and infarction in rats following focal cerebral ischemia. To ascertain directly the role of SOD in the protection against superoxide radical-induced injury, we measured infarct size and water content 24 hr following focal cerebral ischemia in nontransgenic mice and in transgenic mice bearing the human SOD1 gene. These transgenic mice have 3.1-fold higher cellular CuZn-SOD activity in the brain than do their nontransgenic littermates. We also measured antioxidant levels (reduced glutathione and reduced ascorbate) of contralateral cortex, infarct cortex, surrounding cortex, and striatum. Infarct size and brain edema were significantly decreased in transgenic mice compared with nontransgenic mice. Reduced glutathione and reduced ascorbate levels decreased in the ischemic hemisphere, but levels in surrounding cortex and striatum were significantly higher in transgenic mice than in nontransgenic mice. These results indicate that increased endogenous SOD activity in brain reduces the level of ischemic damage and support the concept that superoxide radicals play an important role in the pathogenesis of infarction and edema following focal cerebral ischemia.
 ...
PMID:Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase. 176 30

Lipid peroxidation disrupts membrane integrity and causes structural and functional alterations in ischemic tissues. Taurine and ketamine are putative ischemic protectants that affect Ca2+ influx. Here we report the influence of these compounds on lipid peroxidation in subcellular fractions, isolated cells and intact tissue from bovine retinas. P2 membrane fractions and isolated cells were exposed to the lipid peroxidation inducers cadmium chloride (200 microM) or L-ascorbic acid (1 mM) in the presence of 0-50 mM taurine, 0-10 mM ketamine, 1 mM kynurenic acid or 1 mM dextromethorphan. The latter compounds are N-methyl-D-aspartate receptor antagonists. Lipid peroxidation in isolated eyes reperfused after 1 h of ischemia either with or without protectants was determined by thiobarbituric acid assay. Glutathione was measured in isolated retinas subjected in vitro to simulated ischemia (no glucose or oxygenation) for 60 min either alone or in the presence of taurine or ketamine. Ketamine inhibited chemical- or ischemia-induced lipid peroxidation as well as ischemic glutathione depletion. Under the same conditions, taurine failed to affect lipid peroxidation or glutathione. The data show a direct effect of ketamine on lipid peroxidation and point to separate mechanisms of action for ketamine and taurine.
 ...
PMID:Effects of taurine and ketamine on bovine retinal membrane lipid peroxidation. 183 70

To assess the value of myocardial substrate in the occurrence of ischemic-reperfusion damage, isolated, electrically paced rabbit hearts were perfused for 60 min under aerobic condition (25 ml/min with oxygenated Krebs-Henseleit solution containing glucose 11 mM). Thereafter the hearts were made ischemic for 30 min by reducing coronary flow to 3 ml/min. During ischemia, 3 different substrates were used glucose 11 mM (Group I), palmitate 1.2 mM (Group II) and palmitate 1.2 mM + glucose 11 mM (Group III). The hearts were then reperfused (25 ml/min) for 30 min under aerobic condition using glucose 11 mM as the only substrate. In the presence of glucose with or without palmitate (Group I and III) ischemic damage was mild. Recovery of the developed pressure was 95% and there was no contracture during ischemia and or reperfusion. During ischemia and reperfusion there was a small release of CPK, GSSG and GSH. In the presence of palmitate (Group II) ischemic and reperfusion damage was profound. Recovery of developed pressure was reduced (25%) and diastolic pressure significantly increased (68 +/- 5.1 vs 3 +/- 1.5, 5 +/- 1.8 mmHg). These mechanical data were concomitant with an important release of CPK (580 +/- 50 vs 180 +/- 35, 210 +/- 48 mU/min/gww) and oxidised glutathione (0.38 +/- 0.3 vs 0.05 +/- 0.001, 0.09 +/- 0.003 nmoles/min/gww). In addition the redox state of the cells of the Group II was significantly shifted through the oxidative state at the end of ischemia and of reperfusion. These results indicate that palmitate as substrate increases the deleterious effects of ischemia; glucose is able to overcome the negative effects of palmitate.
 ...
PMID:[Toxicity of fatty acids during myocardial reperfusion: a new possible mechanism of action]. 191 18


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