UMLS:C0022116 - FACTA Search

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

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 conversion from xanthine dehydrogenase (XD) to xanthine oxidase (XO) and the effect of trifluoperazine (TFP), a calmodulin inhibitor, on the conversion were examined during the normothermic ischemia of the rat small intestine. Rat jejunums were stored in lactated Ringer's solution (LR) at 37 degrees C for various hours after intravascular flushing with LR. The extents of the conversion from XD to XO (%XO) constituted 21.1% +/- 3.0%, 36.2% +/- 7.0%, 63.2% +/- 8.1%, and 88.2% +/- 8.6% after 0, 2, 4, and 6 hours of the preservation, respectively (control group). The preservation without the intravascular flushing showed significant increase in the %XO (99.5% +/- 6.0%) only after 6 hours compared with those in the control group (P < .05). When the intestines were stored in LR containing 50 mg/L of TFP at 37 degrees C, or stored in LR at 37 degrees C after the intraperitoneal pretreatment with 10 mg/kg of TFP 1 hour before laparotomy showed significant decrease in the extents of the conversion after 4 hours (P < .005) and 6 hours (P < .025) of the preservation, compared with those in the control group. When the dose of TFP for the pretreatment was increased to 50 mg/kg, the suppressive effect on the conversion was found even after 2 hours (P < .025) as well as after 4 hours (P < .005) and 6 hours (P < .025) of the preservation. These results suggest that TFP could be effective on reducing the XO-mediated postischemic reperfusion injury by means of inhibiting the conversion during ischemia of the rat small intestine.
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PMID:Conversion of xanthine dehydrogenase to xanthine oxidase during ischemia of the rat small intestine and the effect of trifluoperazine on the conversion. 848 75

The possibility that verapamil (CAS 52-53-9) may intensify the efficacy of vitamin E in preventing the ischemia-reperfusion-caused biochemical dearrangement in rat cerebral cortex was investigated. A daily injection of vitamin E at i.m. dose of 175 mg/kg b.wt. for 7 days prior to subjecting the rats to 1 h bilateral occlusion of the common carotid arteries followed by reperfusion for another 1 h, moderately diminished the ischemia-reperfusion-induced increase in the activity of lactate dehydrogenase and in formation of conjugated dienes as well as in the conversion of xanthine dehydrogenase-->xanthine oxidase in cerebral cortex of rats. However, concomitant injection of verapamil at i.m. dose of 0.68 mg/kg b.wt. 15 min prior to ischemia-reperfusion together with vitamin E pretreatment afforded an elegant combined therapy that effectively abolished the dearrangement caused by ischemia-reperfusion in the above parameters. These results indicated that the protective efficacy of vitamin E against ischemia/reperfusion-induced biochemical dearrangement in cerebral cortex was intensified by concomitant use of verapamil.
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PMID:Influence of verapamil on the efficacy of vitamin E in preventing the ischemia-reperfusion-induced biochemical dearrangement in cerebral cortex of rat. 884 34

The time course of the energy metabolism after reperfusion, the relationship between the conversion of xanthine dehydrogenase to xanthine oxidase (D-to-O conversion) during ischemia, and the changes of the energy metabolism after reperfusion were studied using an ischemia-reperfusion model in the small intestine of the rat. The rat jejunum underwent an occlusion of the superior mesenteric artery and vein for either 30 minutes (group 1, n = 6) or 90 minutes (group 2, n = 6) with collateral interruption, and then it was reperfused. The contents of the adenine nucleotides in the small intestine of the rat were measured by high-performance liquid chromatography (HPLC) before ischemia, and 30, 60, and 90 minutes of ischemia, as well as 30, 60, 120, and 180 minutes after reperfusion. The recovery level of adenosine triphosphate (ATP) in group 1 (6.05 +/- 0.80 mumol/g dry weight) 30 minutes after reperfusion was significantly higher than that in group 2 (2.28 +/- 1.12 mumol/g dry weight) (P < .001). In addition, the ATP content after reperfusion in group 2 did not change from 30 to 180 minutes after reperfusion. The D-to-O conversion during ischemia in group 1 was not significantly greater than that before ischemia; however, that of group 2 did increase significantly during ischemia (P < .005). These results suggest that the tissue damage from ischemia-reperfusion injury after reperfusion under 90 minutes' ischemia is accomplished within the first 30 minutes after reperfusion. Therefore, the ATP level at 30 minutes after reperfusion may be useful for the evaluation of intestinal viability. Thus, the conversion of the xanthine oxidase enzyme system might play an important role in the expression of ischemia-reperfusion injury.
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PMID:The relationship between the adenine nucleotide metabolism and the conversion of the xanthine oxidase enzyme system in ischemia-reperfusion of the rat small intestine. 888 83

Activity of xanthine oxidoreductase (total xanthine dehydrogenase plus xanthine oxidase) and xanthine oxidase was determined cytophotometrically in periportal and pericentral areas of livers of rats under various (patho)physiological conditions that are known to affect the content of reduced glutathione. For this purpose, rats were either normally fed or fasted for 24 hours, fasted for 24 hours, and treated with diethylmaleate that depleted glutathione or treated by in vivo ischemia for 2 hours in the livers. Xanthine oxidoreductase activity was shown histochemically with the use of a tetrazolium salt procedure, and xanthine oxidase activity was localized with a cerium-diaminobenzidine-cobalt-hydrogen peroxide technique in unfixed cryostat sections of the livers. Cytophotometric measurements showed that total xanthine oxidoreductase activity was decreased after fasting and ischemia, whereas only ischemia caused reduced xanthine oxidase activity. Moreover, the percentage of xanthine oxidase of total xanthine oxidoreductase activity was constant in both periportal and pericentral areas at the level of approximately 4% in normally fed and 24-hour fasted and diethylmaleate-treated rats. Ischemia reduced this percentage in both areas of the liver to 2%. It was concluded that the amount of endogenous reduced glutathione did not affect the percentage of xanthine oxidase. The low percentage of xanthine oxidase as determined in the present in situ histochemical study indicates that in vivo the percentage oxidase in rat liver is lower than is assumed on the basis of biochemical assays in liver homogenates even after strictly controlled homogenization procedures. Apparently, conversion of xanthine dehydrogenase into xanthine oxidase may occur in vitro to yield percentages of xanthine oxidase of 10%-20% as are reported in the literature. The latter increase in the percentage of xanthine oxidase may be caused by changes in the local environment of the enzymes, which is left completely intact in histochemical assays. The finding of this low percentage of xanthine oxidase further stresses that the main function of xanthine oxidoreductase in the liver is not the production of superoxide anion radicals and/or hydrogen peroxide but rather the metabolism of xanthine to uric acid, which can act as a potent antioxidant.
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PMID:The proportion of xanthine oxidase activity of total xanthine oxidoreductase activity in situ remains constant in rat liver under various (patho)physiological conditions. 890 95

Upon reperfusion of ischemic tissues, reactive oxygen metabolites are generated and are responsible for much of the organ damage. Experimental studies have revealed two main sources of these metabolites: 1) the oxidation of hypoxanthine to xanthine and on to uric acid by the oxidase form of xanthine oxidoreductase and 2) neutrophils accumulating in ischemic and reperfused tissue. Blocking either source will reduce reperfusion damage in a number of experimental situations. Although xanthine oxidoreductase activity may be unmeasurably low in organs other than liver and intestine, it may be involved in reperfusion injury elsewhere because of its localization in capillary endothelial cells. Time course considerations suggest that substrate accumulation and NADH inhibition of dehydrogenase activity may be more important in the pathogenesis than conversion of xanthine dehydrogenase into the oxidase form. Neutrophil accumulation may be partly due to oxidants in the first place, suggesting a link between the two sources of reactive oxygen metabolites. In the clinical context, many of the sequelae of perinatal asphyxia may be accounted for by reperfusion damage to organs such as brain, kidney, heart, liver, and lungs. During asphyxia, substrates of xanthine oxidase accumulate, upon resuscitation the cosubstrate oxygen is introduced, and evidence for oxidant production and effects has been obtained. In the pathogenesis of brain damage after asphyxia, both microvascular injury and parenchymal cell damage are important. Oxygen metabolites are involved in the former, but in the latter process their role is less clear because ischemia-reperfusion triggers not only oxidant production but many other phenomena, including gene activation, ATP depletion, glutamate accumulation, and increase of intracellular calcium. A severe insult results in cell necrosis, but more moderate asphyxia may cause delayed neuronal death through apoptosis. The time course of the changes in high energy phosphates as well as of selective neuronal death suggest that in the first hours of life there is a "therapeutic window," with future possibilities for prevention of permanent damage.
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PMID:Reperfusion injury as the mechanism of brain damage after perinatal asphyxia. 912 79

The effects of anoxic submergence (20 h at 5 degrees C) and subsequent 24 h aerobic recovery on the antioxidant systems of six organs were examined in freshwater turtles, Trachemys scripta elegans. Both xanthine oxidase and xanthine dehydrogenase were detected in turtle tissues with xanthine oxidase composing 36-75% of the total activity. Turtle organs displayed high constitutive activities of catalase (CAT), superoxide dismutase (SOD), and alkyl hydroperoxide reductase (AHR). Measurements of lipid peroxidation damage products (conjugated dienes, lipid hydroperoxides, thiobarbituric acid reactive substances) showed minimal changes during anoxia or recovery suggesting that natural anoxic-aerobic transitions occur without the free radical damage that is seen during ischemia-reperfusion in mammals. Anoxia exposure led to selected decreases in enzyme activities in organs, consistent with a reduced potential for oxidative damage during anoxia: SOD decreased in liver by 30%, CAT decreased in heart by 31%, CAT and total glutathione peroxidase (GPOX) decreased in kidney (by 68 and 41%), and CAT and SOD decreased in brain (by 80 and 15%). AHR, however, increased 2 and 3.5 fold during anoxia in heart and kidney respectively. Most anoxia-induced changes were reversed during aerobic recovery although brain enzyme activities remained suppressed. Some specific changes occurred during the recovery period: SOD increased from controls in heart by 45%, AHR increased to 200 and 168% of control values in red and white muscle respectively, and total GPOX decreased from controls in heart and white muscle by 75 and 77% respectively. The results show that biochemical adaptation for natural anoxia tolerance in turtles includes well-developed antioxidant defenses that minimize or prevent damage by reactive oxygen species during the reoxygenation of organs after anoxic submergence.
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PMID:Antioxidant systems and anoxia tolerance in a freshwater turtle Trachemys scripta elegans. 914 33

Previous studies have demonstrated that intestinal preconditioning protects the organ from ischemia reperfusion damage. Xanthine oxidase mediating free radical generation contributes to the development of injury associated to ischemia reperfusion. Thus, any process able to modulate the oxygen free radical generation system could attenuate the injury. Also, it is known that nitric oxide is implicated in the preconditioning response. The aim of this work is to determine: (1) the effect of intestinal preconditioning on the xanthine oxidase system, (2) the relevance of this system in the development of injury, and (3) its relationship with nitric oxide. For this purpose, we have determined the activity of the xanthine dehydrogenase/xanthine oxidase system, the levels of its substrate (xanthine), and end-product (uric acid) and oxidant stress status in rat small intestine subjected to ischemic pre-conditioning. The effects of nitric oxide inhibition have also been evaluated. Results show that the percentage of xanthine dehydrogenase to xanthine oxidase conversion, xanthine, uric acid concentration, lipoperoxides, and reduced glutathione were significantly reduced in preconditioned rats irrespectively of nitric oxide inhibition. In summary, this work shows that oxidative stress in intestinal preconditioning is reduced as consequence of the diminished conversion of xanthine dehydrogenase to xanthine oxidase, and also as a consequence of the reduced availability of xanthine.
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PMID:Modification of oxidative stress in response to intestinal preconditioning. 1075 24

Xanthine oxidoreductase (XD: xanthine dehydrogenase + xanthine oxidase) is a complex enzyme that catalyzes oxidation of hypoxathine to xanthine, subsequently producing uric acid. The enzyme complex exists in separate but interconvertible forms, xanthine dehydrogenase (XDH) and xanthine oxidase (XOD). XOD is one of the major cellular sources of superoxide production and is well known as a causative factor in ischemia/reperfusion damage. At present, almost no information on the conversion status is available with respect to aging. In the present study, we investigated the effect of age on the XOD/XDH status and gene expression in the kidney. In addition, we assessed XOD-induced reactive oxygen species (ROS) using the dichlorofluoroscein (DCF) method. Our results show that XD activity gradually up to 18 months of age and then a slight decrease at 24 months of age. XDH activity showed increases up to 18 months of age, then decreased at 24 months of age. The conversion of XDH to XOD, assessed by changes in the ratios of XOD/(XOD+XDH), showed an age-related increase, which peaked at 24 months. Levels of XD protein and its mRNA paralleled to overall XD activity. ROS generation has tendency to increase with age. Our results suggest that the increased conversion of XDH to XOD observed with age may be an important contributing factor to the increased renal oxidative stress during aging.
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PMID:Modulation of renal xanthine oxidoreductase in aging: gene expression and reactive oxygen species generation. 1088 79

We have shown previously that rats subjected to tourniquet shock develop an acute form of remote organ injury of the liver that is both Kupffer cell (KC) and polymorphonuclear (PMN) leukocyte dependent. Circulating plasma xanthine oxidase (XO) has been shown to be responsible for the development of endothelial dysfunction and for remote organ injury of the lung and intestine after ischemia-reperfusion protocols. We now hypothesize that XO is released from rat hind limbs upon reperfusion and that it is responsible for KC and PMN leukocyte activation in this shock model. Our results show that about 30% of rat gastrocnemius muscle xanthine dehydrogenase (XD) is converted to XO during the 5-h tourniquet period and that it is released into the femoral vein within 10 min of reperfusion. Total muscle xanthine oxidoreductase activity (XO + XD) decreases within 30 min of reperfusion and is paralleled by a corresponding increase in femoral vein lactic dehydrogenase. In addition, liver tissue XO increases significantly within 30 min of reperfusion without a corresponding conversion of endogenous XD. Conversion of hepatic XD becomes evident 60 min after reperfusion is initiated, as does XO, and alanine aminotransferase (ALT) release into the hepatic vein, presumably from damaged hepatocytes as a consequence of oxidative stress. Tissue myeloperoxidase activity also increases significantly after the 60-min reperfusion period. That XO mediates KC and PMN activation is supported by the following observations: a) the close relationships between plasma XO and the time courses of tumor necrosis factor-alpha TNFalpha release into the hepatic vein and colloidal carbon clearance by KCs; b) that colloidal carbon clearance, TNFalpha and ALT release, loss of tissue free thiols, lipid peroxidation (TBARS), and liver infiltration by PMN neutrophils can also be induced by the administration of exogenous XO to normal rats; and c) pretreatment of rats with allopurinol inhibits KC activation and liver leukocyte infiltration. These results suggest that XO, released from the ischemic limb on reperfusion, is taken up by the liver were it mediates KC and PMN neutrophil activation and thus contributes to the development of multiple system organ failure after hind limb reperfusion.
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PMID:Xanthine oxidase released from reperfused hind limbs mediate kupffer cell activation, neutrophil sequestration, and hepatic oxidative stress in rats subjected to tourniquet shock. 1109 91

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