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

It has been suggested that oxidative processes are involved in a variety of pathological conditions, notably ischemia-reperfusion injury. Moreover, anesthetics appear to exert differential effects on the severity of such injury, these being unlikely wholly attributable to their differential effects on cardiovascular or microcirculatory status. It is possible that these variable effects of anesthetics on this type of injury may be due, at least in part, to changes in the production of free radicals and/or in their detoxification by endogenous antioxidant enzymes. We have attempted to explore the latter possibility by measuring activities of catalase, superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione reductase in normal heart tissue and red cells obtained from rats anesthetized using a variety of agents (CO2, halothane, pentobarbital or ether). For comparison, analyses were also performed on tissues from unanesthetized animals rendered unconscious by stunning prior to sacrifice. Results indicated that myocardial SOD activity was significantly greater in halothane-anesthetized as compared with CO2-anesthetized animals. Red cell SOD activities did not show such differences. However, red cell GPX activity was found to be greater in halothane-anesthetized than in pentobarbital-anesthetized rats. In general, however, antioxidant enzyme activities measured ex vivo were minimally affected by the use of anesthetics prior to euthanasia. Our findings, therefore, do not support the proposal that the influence of anesthetics on the course of ischemia-reperfusion injury involves effects at the level of enzymatic antioxidant components.
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PMID:Effects of various anesthetic regimens on tissue antioxidant enzyme activities. 816 73

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

This study examined whether brief repeated myocardial ischemia altered free radical generating and scavenging activity in a dog model. In dogs preconditioned with four 5-min left anterior descending coronary artery (LAD) occlusions and reperfusions, we examined transcardiac changes in both the function of neutrophils, cells which are major free radical generators, and in myocardial antioxidant enzyme activity, as an indication of free radical scavenging. Neutrophil function was assessed by determining luminol-enhanced whole blood chemiluminescence (CL) induced by zymosan. Blood was taken simultaneously from the carotid artery and the cardiac vein running along the occluded LAD. Preconditioning with sublethal ischemia significantly reduced whole blood CL in the cardiac vein compared with the carotid artery after the first and fourth 5-min reperfusions, while there was no difference in neutrophil count between these sampling sites. Immediately after brief repeated ischemia and reperfusion, manganese-superoxide dismutase (SOD) activity was significantly enhanced, and glutathione reductase activity was markedly reduced in the ischemic, compared with the non-ischemic, myocardium. There were no differences in the myocardial activities of copper, zinc-SOD, glutathione peroxidase, and glutathione S-transferase between the ischemic and non-ischemic regions. Also, no difference was observed between the reduced myocardial glutathione levels in these regions, although the oxidized glutathione level was significantly higher in the ischemic regions of the subepicardial and subendocardial areas. We demonstrated that brief repeated ischemia affects free radical generating and scavenging systems in the ischemic myocardium.
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PMID:Brief myocardial ischemia affects free radical generating and scavenging systems in dogs. 840 20

In 31 male patients undergoing coronary bypass surgery who underwent different periods of cardioplegic hypothermic arrest, the activities of glutathione peroxidase, glutathione reductase, glutathione transferase, copper/zinc-containing and manganese-containing superoxide dismutases, and catalase were studied in the right atrial myocardium, before and 5 minutes after aortic cross-clamping. The levels of thiobarbituric acid reactive substances (TBARS) and nonproteic thiol compounds (NP-SH) were also assessed. Prolonged ischemia followed by reperfusion induced activation of the major myocardial antioxidant enzymes with marked NP-SH depression and TBARS increase, despite cold crystalloid cardioplegic protection. These changes were significantly related to the duration of the ischemic arrest, suggesting: (1) that reperfusion free radical generation is dependent on the severity of the previous ischemic period; and (2) the occurrence of myocardial oxidative stress during cardiopulmonary bypass.
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PMID:Myocardial antioxidant defenses during cardiopulmonary bypass. 846

Non-protein thiols (NP-SH) and the activities of the glutathione status-regulating enzymes gamma-glutamylcysteine synthetase (G-GCS), gamma-glutamyl transpeptidase (G-GT) and glutathione reductase (GR) were assessed in perfused rabbit hearts subjected to severe (60 min) or mild (7 min) total ischemia and 30 min reperfusion. Severe ischemia significantly decreased NP-SH, which were further depressed on reperfusion together with a significant decline in G-GCS activity; G-GT and GR activities were unchanged. Specific analytes were unaffected by mild ischemia-reperfusion. Thus, impaired enzymatic biosynthesis of GSH is operative in the reperfused rabbit myocardium after 60 min ischemia. This phenomenon may favour myocardial GSH depression and oxidative reperfusion injury after severe ischemia.
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PMID:Impaired glutathione biosynthesis in the ischemic-reperfused rabbit myocardium. 870 34

The biochemical adaptations of cellular antioxidant defenses that permit anoxia-tolerant animals to deal effectively with rapid and large changes in oxygen availability, and hence oxidative stress, during transitions from anoxia to normoxia provide insights into the strategies of antioxidant defense that could help to minimize reperfusion injuries to mammalian organs after anoxia/ischemia stress. The present study analyzes the effects of 30 h anoxia exposure followed by reoxygenation on the antioxidant defenses (activities of five enzymes, glutathione status) and lipid peroxidation damage to organs of the leopard frog Rana pipiens (5 degrees C-adapted autumn frogs). Exposure to 30 h anoxia resulted in significant increases in the activities of skeletal muscle and heart catalase (by 53 and 47%), heart and brain glutathione peroxidase (by 75 and 30%), and brain glutathione S-transferase (by 66%). In most cases, enzyme activities had returned to the control values after 40 h aerobic recovery. Activities of superoxide dismutase and glutathione reductase were unaltered in all of the organs, and anoxia/recovery had no effect on any of the enzymes in liver. Glutathione equivalents (GSH-eq) were maintained in four organs during anoxia but decreased by 32% in brain during anoxia. Brain GSH-eq had recovered after 90 min reoxygenation, and, in addition, hepatic GSH-eq rose by 71% after 90 min reoxygenation. The ratio of oxidized glutathione to GSH-eq was also affected by anoxia in an organ-specific way. Lipid peroxidation, assessed as the content of thiobarbituric acid-reactive substances (TBARS), was unaltered in skeletal muscle and liver after 30 h anoxia exposure or short (25 and 90 min)- or long-term (40 h) periods of reoxygenation, indicating that cycles of natural and survivable anoxia/reoxygenation occur without significant increase in TBARS in selected organs. Overall, the data demonstrate that elements of the antioxidant system of R. pipiens are induced during anoxia exposures as a possible preparation for dealing with potentially harmful oxygen reperfusion stress.
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PMID:Relationship between anoxia exposure and antioxidant status in the frog Rana pipiens. 889 82

Selenium induces several proteins, including glutathione and stress proteins. These proteins have been shown to be cardioprotective against oxidative injury. To determine whether ebselen, a seleno-organic compound, can also induce these proteins and exert cardioprotective action, we examined the effects of preconditioning with ebselen on glutathione metabolism and stress protein expression and on myocyte injury induced by oxidative stress. Treatment of cultured cardiac myocytes with ebselen (0.3-30 microM) for 24 hr increased the reduced glutathione content. Glutathione reductase activity, but not glutathione peroxidase activity, was significantly elevated in a dose-dependent manner. Pretreatment with ebselen increased the expression of such stress proteins as heat shock protein 70 and heme oxygenase-1 (heat shock protein 32) in cardiac myocytes, as assessed by Western blotting. Expression of heat shock protein 70 was increased only at a higher dose of ebselen (30 microM), whereas expression of heme oxygenase-1 was markedly increased at a lower dose of ebselen (3 microM). Under these conditions, the myocyte injury induced by hydrogen peroxide or simulated ischemia/reperfusion, assessed by the release of lactate dehydrogenase into the culture medium, was reduced by ebselen pretreatment in a dose-dependent manner. Results indicated that cardiac myocytes pharmacologically preconditioned with ebselen for 24 hr exhibited resistance to oxidative injury, possibly via the up-regulation of glutathione metabolism and the expression of stress proteins.
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PMID:Effects of preconditioning with ebselen on glutathione metabolism and stress protein expression. 919 Aug 85

Melatonin, the chief secretory product of the pineal gland, was recently found to be a free radical scavenger and antioxidant. This review briefly summarizes the published reports supporting this conclusion. Melatonin is believed to work via electron donation to directly detoxify free radicals such as the highly toxic hydroxyl radical. Additionally, in both in vitro and in vivo experiments, melatonin has been found to protect cells, tissues and organs against oxidative damage induced by a variety of free radical generating agents and processes, e.g., the carcinogen safrole, lipopolysaccharide, kainic acid, Fenton reagents, potassium cyanide, L-cysteine, excessive exercise, glutathione depletion, carbon tetrachloride, ischemia-reperfusion, MPTP, amyloid beta (25-35 amino acid residue) protein, and ionizing radiation. Melatonin as an antioxidant is effective in protecting nuclear DNA, membrane lipids and possibly cytosolic proteins from oxidative damage. Also, melatonin has been reported to alter the activities of enzymes which improve the total antioxidative defense capacity of the organism, i.e., superoxide dimutase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase, and nitric oxide synthase. Most studies have used pharmacological concentrations or doses of melatonin to protect against free radical damage; in a few studies physiological levels of the indole have been shown to be beneficial against oxidative stress. Melatonin's function as a free radical scavenger and antioxidant is likely assisted by the ease with which it crosses morphophysiological barriers, e.g., the blood-brain barrier, and enters cells and subcellular compartments. Whether the quantity of melatonin produced in vertebrate species is sufficient to significantly influence the total antioxidative defense capacity of the organism remains unknown, but its pharmacological benefits seem assured considering the low toxicity of the molecule.
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PMID:Pharmacological actions of melatonin in oxygen radical pathophysiology. 919 81

Melatonin's actions in organisms are more widespread than originally envisaged. Over three decades ago, the changing pattern of nocturnal melatonin production was found to be the signal for the annual cycle of reproduction in photoperiodic species. Since then, melatonin's actions also have been linked to circadian rhythms, immune function, sleep, retinal physiology and endocrine functions in general. In recent years, however, the sphere of influence of melatonin was further expanded when the indole was found to be an effective free radical scavenger and antioxidant. Free radicals are toxic molecules, many being derived from oxygen, which are persistently produced and incessantly attack and damage molecules within cells; most frequently this damage is measured as peroxidized lipid products, carbonyl proteins, and DNA breakage or fragmentation. Collectively, the process of free radical damage to molecules is referred to as oxidative stress. Melatonin reduces oxidative stress by several means. Thus, the indole is an effective scavenger of both the highly toxic hydroxyl radical, produced by the 3 electron reduction of oxygen, and the peroxyl radical, which is generated during the oxidation of unsaturated lipids and which is sufficiently toxic to propagate lipid peroxidation. Additionally, melatonin may stimulate some important antioxidative enzymes, i.e., superoxide dismutase, glutathione peroxidase and glutathione reductase. In in vivo tests, melatonin in pharmacological doses has been found effective in reducing macromolecular damage that is a consequence of a variety of toxic agents, xenobiotics and experimental paradigms which induce free radical generation. In these studies, melatonin was found to significantly inhibit oxidative damage that is a consequence of paraquat toxicity, potassium cyanide administration, lipopolysaccharide treatment, kainic acid injection, carcinogen administration, carbon tetrachloride poisoning, etc., as well as reducing the oxidation of macromolecules that occurs during strenuous exercise or ischemia-reperfusion. In experimental models which are used to study neurodegenerative changes associated with Alzheimer's and Parkinson disease, melatonin was found to be effective in reducing neuronal damage. Its lack of toxicity and the ease with which melatonin crosses morphophysiological barriers and enters subcellular compartments are essential features of this antioxidant. Thus far, most frequently pharmacological levels of melatonin have been used to combat oxygen toxicity. The role of physiological levels of melatonin, which are known to decrease with age, is being investigated as to their importance in the total antioxidative defense capacity of the organism.
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PMID:Melatonin in relation to cellular antioxidative defense mechanisms. 928 72

This study was designed to clarify the effects of pentoxifylline (PTX) and N-acetylcysteine (NAC) on hepatic reperfusion injury in rats. Rats were pretreated with NAC, or PTX, or combination of the drugs. In each rat, liver was isolated after twenty minutes reperfusion following thirty minutes ischemia. Plasma alanine amino transferase (ALT) activity, liver tissue glutathione (GSH) and malondialdehyde (MDA) levels, glutathione peroxidase (GPx), glutathione reductase (GSSGR), superoxide dismutase (SOD) and catalase (CAT) activities were determined. Plasma ALT activity was higher in ischemia/reperfusion groups than in control. It was decreased in the groups given NAC. Administration of NAC maintained tissue GSH levels, whereas the levels were decreased in both the ischemia/reperfusion groups treated (P < 0.05) and untreated with PTX (P < 0.01). Increases in liver MDA concentration in ischemia/reperfusion (P < 0.01) and PTX-treated groups (P < 0.05) were mitigated by administration of NAC. GPx and CAT activities were increased in the ischemia/reperfusion (P < 0.01, P < 0.05) and PTX-treated groups (P < 0.05, P < 0.001). GSSGR activities were increased in the NAC (P < 0.001) and NAC-PTX-treated groups (P < 0.01). SOD activities were higher in the ischemia/reperfusion (P < 0.01) and the PTX-treated (P < 0.01) and the NAC-PTX-treated groups (P < 0.01 ). In conclusion, short-term liver ischemia/reperfusion diminished GSH, increased MDA and induced some antioxidant enzymes. While we could not find any useful effects with PTX as we expected, our findings indicate that NAC might be useful to prevent tissue damage in hepatic ischemia/reperfusion injury.
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PMID:Pentoxifylline and N-acetylcysteine in hepatic ischemia/reperfusion injury. 972 Oct 71


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