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)

It is well known that reperfusion damage of ischemic myocardium may be attributed to alterations in the antioxidant defense system against free radical aggression. In addition, the degree of myocardial damage may depend on the duration and severity of ischemia that precedes reperfusion. We carried out serial ischemic experiments (10, 30, 60 and 120 min) in ex-vivo rat hearts followed by 30 min reperfusion and we assayed the glutathione-dependent enzymatic activities (selenium-dependent glutathione-peroxidase: GSH-Px; selenium-independent glutathione peroxidase: GST-Px; glutathione-transferase: GST and glutathione-reductase: GS-SG-Red), Catalase activity (CAT) and non-proteic thiol compounds (NP-SH) at the end of reperfusion. We found a significant reduction of NP-SH, GSH-Px and CAT in ischemic/reperfused hearts from 30 min on, while GST activity was increased. In addition, we observed the appearance of a selenium-independent glutathione peroxidase activity (GST-Px) belonging to the GST system. In conclusion, we found the longer the duration of ischemia the greater the inbalance between the myocardial antioxidant system especially the GST activation, suggesting in particular for GST-Px, a role in the control of the damage against oxygen toxicity during ischemia/reperfusion.
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PMID:Myocardial antioxidant defense mechanisms: time related changes after reperfusion of the ischemic rat heart. 801 40

Acute renal failure induced by the administration of gentamicin (GM) was studied enzymochemically in comparison with that in rats with tubular disorder resulting from postischemic reperfusion. Renal ischemia was caused by clamping the renal artery for 30 minutes to create complete ischemia and reflow. The activities of renal tissue glutathione peroxidase (GSH-Px) and the values to the renal contents of glutathione (GSH) and malondialdehyde (MDA) were measured in each sample. In order to confirm whether GSH plays an important role in the intrinsic anti-oxidant system in this model, buthionine sulfoximine (BSO), which is a gamma-glutamylcysteine synthetase inhibitor, was administered intraperitoneally to decrease the renal GSH content before the procedure in renal ischemia. On the other hand, the GM-induced ARF model was made by injection with GM 100 mg/kg during a period of 5 days. In the GM group, a significant increase in MDA and a reduction in the sphigomyelin (SPH)/phosphatidylcholine (PC) ratio and inactivation of PLA2 were observed. In the kidney tissue obtained 15 min. after reperfusion, the renal content of MDA was elevated markedly in the BSO-preadministered group. A reduction of SPH/PC ratio was also observed in the reperfusion model. PAL2 hydrolyzes the acyl group at the 2-position containing much of the highly unsaturated fatty acids that are easily oxidized. Further, PLA2 is considered to act directly on one of PC or phosphatidylinositol. Phospholipidosis thesauruses, noted in acute renal failure induced by GM, is considered to be caused by reduced liberation of lysosomal intramembranous phospholipid into the cytoplasm and accelerated peroxidation of intramembranous lipid.
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PMID:[Lipid peroxidation and tubular disorder in experimental acute renal failure-enzymochemical study in the rat kidney]. 807 17

The prevention of oxidant-induced damage following reperfusion was experimentally evaluated. Two pharmacological regimens containing different combinations of antioxidant factors and membrane-stabilizing compounds, such as alpha-tocopherol (vitamin E), methionine, dexamethasone, mannitol and cysteine, were administered. The reduced/oxidized glutathione (GSH/GSSG) ratio in muscle was used to evaluate oxidative stress. Ischaemia was induced by occluding the aorta and the inferior vena cava with an irrigation-occlusion catheter. After 4 h of ischaemia, five sheep were reperfused without any treatment (control group) and five treated with an endoaortic bolus administered at declamping (treatment 1). In five other sheep, treatment started during ischaemia (treatment 2). Ischaemia and, in particular, reperfusion significantly reduced the muscle GSH content, compared with the basal value in the control group; thus the GSH/GSSG ratio decreased significantly in the control group from 10.5(2.2) (mean(s.e.) basal value) to 0.687(0.3) at reperfusion (P < 0.009). Both treatments 1 and 2 significantly prevented a reduction in GSH content induced by reperfusion following ischaemia; the GSH/GSSG ratio (10.5(2.2) basal value) increased to 19.67(4.6) with reperfusion in the treatment group 1, mainly because of a lower decrease of GSH and a lower level of GSSG while it did not change in treatment group 2 (10.7(5.0)). Levels of creatine phosphokinase did not change in the treated groups, although they increased significantly in the control group (P < 0.006). Although oxidative stress is not the only cause of damage in revascularization, this study confirms the protective ability of treatment with free radical scavengers and membrane-stabilizing compounds.
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PMID:Prevention of reperfusion syndrome in acute muscular ischaemia with free radical scavengers and membrane-protecting compounds: an experimental study. 807 54

Evidence is presented that the radical observed upon reaction of myoglobin with hydrogen peroxide is a peroxyl radical. Simulation of this spectrum gives principal values for the g tensor of gx = 2.0357, gy = 2.0082, and gz = 2.0016, which are consistent with those of a peroxyl radical. Use of molecular oxygen isotopically labeled with 17O confirmed that the radical observed was a peroxyl radical. Removal of oxygen from the incubation by use of glucose and glucose oxidase revealed two radicals, one at giso = 2.0028 and the other at giso = 2.0073. Addition of various amounts of the spin trap 5,5-dimethyl-1-pyrroline N-oxide revealed that the spin trap and oxygen compete for the same radical site. Four model substrates, glutathione, styrene, arachidonic acid and linoleic acid, were individually added to both the aerobic and anoxic systems. Glutathione reacted with the peroxyl radical, reducing its intensity by 98%, and entirely eliminated the giso = 2.0028 line from the spectrum of the anoxic incubation. Styrene, arachidonic acid and linoleic acid reacted with the peroxyl radical, reducing its amplitude by 84, 57, and 35%, respectively, but did not decrease the amplitude of either radical species in the anoxic incubation. The giso = 2.0028 species detected in the anoxic incubation appears to be the original radical site to which molecular oxygen binds to form the peroxyl radical. This myoglobin-derived peroxyl radical species is responsible for the advent of lipid peroxidation as proposed in ischemia/reperfusion injury, as well as other reactions, as exemplified by the O2-dependent epoxidation of styrene.
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PMID:Reaction of myoglobin with hydrogen peroxide forms a peroxyl radical which oxidizes substrates. 812 65

Intestinal ischemia/reperfusion (I/R) causes formation of reactive oxygen intermediates (ROI) which lead to mucosal cell injury. Glutathione (GSH), an ROI scavenger, protects tissues from ROI-mediated cell injury. Since GSH biosynthesis is partially dependent on glutamine (Gln) levels, we tested the hypothesis that intravenous Gln infusion will assist in maintaining mucosal cell GSH levels and decrease membrane lipid peroxidation during intestinal I/R. The external jugular vein of male Sprague-Dawley rats was cannulated and infused with normal saline (NS) at 2 cc/hr. After 3 days, matched pairs of rats received either NS alone or NS+ 3% Gln for an additional 24 hr. Next, mucosal GSH levels were measured after a sham I/R in 6 rats and after either 30 or 60 min of ischemia/60 min of reperfusion in a group of 8 and 12 rats, respectively. Finally, conjugated diene (CD), a byproduct of membrane lipid peroxidation, was measured following 60 min of ischemia/60 min of reperfusion in a separate group of 12 rats. Control rats had the highest GSH levels and there was no difference between NS vs NS + 3% Gln rats (2.50 +/- 0.48 vs 2.50 +/- 0.43, P = NS). With 30 and 60 min of ischemia/60 min of reperfusion, GSH levels were significantly lower in NS-infused rats compared to those in NS + 3% Gln-infused rats (30 min: 1.54 +/- 0.14 vs 1.80 +/- 0.16, P < 0.05; 60 min: 1.27 +/- 0.15 vs 1.52 +/- 0.20, P < 0.04). In addition, CD levels were lower in NS + 3% Gln-infused rats compared to those in NS alone-infused rats (5.58 +/- 0.87 vs 7.94 +/- 0.55, P < 0.04). In conclusion, Gln supplementation partially maintains gut GSH levels during bowel I/R, which in turn lessens I/R-induced cell membrane lipid peroxidation.
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PMID:Glutamine preserves gut glutathione levels during intestinal ischemia/reperfusion. 815 29

This study was performed to observe the effect of myocardial ischemia on the patients undergoing cardiopulmonary bypass (CPB) operation. For this aim, superoxide dismutase (SOD) activities, reduced glutathione (GSH) and lipid peroxide (LP) levels were determined in blood samples which were obtained from the coronary sinus. Sampling times were as follows: (1) Before CPB. (2) Immediately after CPB. (3) Fifteen minutes after the second specimen. (4) Thirty minutes after the second specimen. SOD activities of these groups were 5135.10 +/- 278.51 U/g Hb, 3505.64 +/- 302.09 U/g Hb, 4206.55 +/- 272.25 U/g Hb, 4707.20 +/- 270.91 U/g Hb respectively. Also the LP levels were 1.90 +/- 0.29 nmol MDA/ml, 4.37 +/- 0.52 nmol MDA/ml, 4.09 +/- 0.39 nmol MDA/ml, 2.74 +/- 0.30 nmol MDA/ml respectively. GSH levels were slightly increased during ischemia and reperfusion; 103.27 +/- 5.18 mg/dl, 125.00 +/- 10.36 mg/dl, 125.00 +/- 6.61 mg/dl, 111.18 +/- 8.22 mg/dl respectively. SOD activities were reduced significantly in second group (p < 0.001), in third and fourth groups (p < 0.01) as compared with control group. Also LP levels were increased significantly in all groups (p < 0.001) as compared with controls. Our results confirm the generation of oxygen free radicals from ischemia and reperfusion of heart during CPB. Also it appears that oxygen free radical generation exceeds the capacity of intracellular SOD, which is the most important scavenger of free radical in the cell.
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PMID:Oxygen free radicals in erythrocytes during open heart operation. 819 75

The GSH level in myocardial tissue represents an important defense mechanism against oxygen toxicity. Since the ischemia-induced depletion of GSH might favour the cytotoxicity of oxygen-derived free radicals produced during reperfusion, we assessed the effects of the GSH donor, glutathione monoethylester, in anaesthetized pigs subjected to 90 minutes of coronary occlusion followed by 30 minutes reperfusion. The drug was infused intracoronarily at a dose of 1 mg/ml (0.5 ml/min) throughout the experimental period. After coronary occlusion and reperfusion, we found a decrease in GSH, ADP, ATP and phosphocreatine levels in reperfused compared with non-ischemic tissue. Less evident were the differences in mitochondrial function, there being only a reduction in the reperfused tissue of the respiratory control index and state 3 respiration values when pyruvate was used as substrate. The infusion with glutathione monoethylester decreased the depletion of tissue GSH and improved the GSH/GSSG ratio, particularly in the non-ischemic tissue. Moreover, the drug decreased the mitochondrial dysfunction at the level of pyruvate utilization and partially prevented the fall in ATP in the reperfused tissue. This study confirms a possible protective effect of glutathione monoethylester in the prevention of reperfusion-induced myocardial damage.
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PMID:Effect of glutathione monoethyl ester on glutathione level and cardiac energetics in reperfused pig heart. 821 Jun 88

In the present study the influence of pretreatment with various GSH depletors such as buthionine sulfoximine (BSO) and diethylmaleate (DEM) was investigated in rats following cerebral post-ischemic reperfusion. Moreover, the effect of diethyldithiocarbamic acid (DDC), inhibitor of endogenous Cu,Zn-SOD, was evaluated. A significant depletion (40% of control value) of GSH levels was observed 24 h after DEM administration; after 48 h the value reached control levels. BSO showed maximal GSH depletion (59%) 24 h after administration and it was constant for almost 48 h. DDC administration caused a marked decrease (60%) of Cu,Zn-SOD activity 4 h after the injection and induced a marked decrease in percentage of survival with respect to control (untreated, ischemic) rats, when administered 4 h before ischemia. BSO and DEM prolonged the survival time of animals when administered 24 h before ischemia. This last paradoxical effect is unclear at present, but it might be due to an influence on glutamate cascade.
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PMID:Free radical scavenger depletion in post-ischemic reperfusion brain damage. 827 98

We have examined the direct effects of oxidant metabolites on cardiac sarcolemmal phosphoinositide phospholipase C which transduces signals from various receptors for the modulation of intracellular Ca2+ levels. The enzyme activity in rat cardiac sarcolemmal membranes that had been preincubated (10 min; 37 degrees C) with xanthine-xanthine oxidase, a superoxide anion generating system, was not significantly affected. The addition to this system of superoxide dismutase, which converts superoxide anion to hydrogen peroxide (H2O2), resulted in a significant decrease of the enzyme activity in comparison with control values. Such decrease was fully prevented by catalase. Preincubation of sarcolemma with hypochlorous acid also gave a significant inhibition of phospholipase C, which was counteracted by the synthetic thiol reducer dithiothreitol. H2O2-pretreatment induced a concentration-dependent inhibition of the enzyme which was prevented by catalase but not by the iron chelator deferoxamine. Dithiothreitol was able to protect against, as well as to recover the enzyme activity from the H2O2 effects. These data suggest that superoxide anions and hydroxyl radicals did not interfere with phospholipase C activity, and that the nonradical oxidants, H2O2 and hypochlorous acid, may have acted through oxidation of thiol (SH) groups. The existence of reactive SH groups associated with the enzyme was confirmed by the inhibitory effects of SH modifiers (p-chloromercuriphenylsulfonic acid, 5'5'-dithio-bis(2-nitrobenzoic acid), N-ethylmaleimide and methyl methanethiosulfonate), which were prevented and in some cases also reversed by dithiothreitol. The biological reducer glutathione (GSH) was not able to recover the H2O2-induced inhibition of phospholipase C, whereas its oxidized form (GSSG) decreased the enzyme activity both in control and H2O2-pretreated membranes. The enzyme was active in a wide range of GSH/GSSG redox states, but H2O2 pretreatment narrowed this range. The results showed that oxidative stress changed the redox state of sarcolemmal phospholipase C, and this deactivated the enzyme. The oxidants' concentrations that significantly impaired phospholipase C in this study were compatible with those occurring in vivo during ischemia-reperfusion [Am. J. Med. 91(Suppl. 3C):235, 1991]. This supports the possibility that alteration of the receptor-associated phospholipase C may be a factor in the oxidant-related dysfunction of the ischemic-reperfused heart.
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PMID:Oxidative stress modifies the activity of cardiac sarcolemmal phospholipase C. 828 Jul 55

Reactive oxygen metabolites have an important role in ischemia-reperfusion injury. One of the sources of reactive oxygen metabolites is xanthine oxidase, which is present in several tissues but is also released into the circulation after ischemia. We studied the effect of several potentially protective compounds on adenine nucleotide depletion induced by extracellular xanthine oxidase and hypoxanthine, in concentrations relevant to human pathophysiology. In umbilical vein endothelial cells prelabeled with 14C-adenine, cellular adenine nucleotides retained 64 +/- 9% of the initial radioactivity over a 4-h incubation with culture medium (controls), whereas in the presence of xanthine oxidase (80 mU/mL) and hypoxanthine (100 microM), only 3 +/- 4% of radioactivity remained in cellular nucleotides, the rest appearing in catabolic products in the medium. Glutathione and 3-aminobenzamide, an inhibitor of poly-ADP-ribose polymerase, partly prevented the nucleotide depletion (adenine nucleotide radioactivity 15 +/- 6% to 33 +/- 13% of total), but scavengers of the hydroxyl radical, dimethylthiourea and DMSO, as well as vitamins E and C, were without effect. Superoxide dismutase prevented the leakage of nucleotides into the culture medium but not intracellular nucleotide catabolism, whereas the latter process was decreased by catalase, consistent with predominant effects of superoxide and hydrogen peroxide at the cell membrane and interior, respectively.
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PMID:Nucleotide depletion due to reactive oxygen metabolites in endothelial cells: effects of antioxidants and 3-aminobenzamide. 828 91


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