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

The reversible and irreversible conversion of xanthine dehydrogenase to xanthine oxidase during ischemia/reperfusion and oxidative stress induced by hydrogen peroxide or diamide and its relationship with glutathione and protein SH groups were studied. The direct spectrophotometric measurement of the various forms of the xanthine-converting enzyme indicates that, in the fresh rat heart or after normoxic perfusion, there always is a basal level of 80% xanthine dehydrogenase and 20% of xanthine oxidase (15% irreversible and 5% reversible) that could contribute to the background production of free radicals. There is no significant increase of irreversible xanthine oxidase during ischemia nor during reperfusion. After global ischemia the reversible oxidase shows almost no increase while, when ischemia is followed by reperfusion, there is a limited increase (less then 9%) of the reversible xanthine oxidase. In the latter conditions there is a decrease of glutathione and of SH groups of about 70% and 25%, respectively. Perfusion for 1 h with oxidizing agents like hydrogen peroxide (60 microM) or diamide (100 microM) determines a marked conversion of xanthine dehydrogenase to reversible xanthine oxidase of about 40% and 60%, respectively; this oxidase activity partially reconverts to the dehydrogenase after withdrawing the oxidizing agents from the perfusion medium. The level of irreversible xanthine oxidase remains unchanged in all the conditions tested. Both hydrogen peroxide and diamide induce a strong decrease in SH groups and depletion of glutathione. The xanthine dehydrogenase----xanthine oxidase conversion thus appears to be sensitive to the redox state of thiol groups.
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PMID:Modification of the xanthine-converting enzyme of perfused rat heart during ischemia and oxidative stress. 316 24

Previous studies have proposed and supported a role for the proteolytic, irreversible conversion of xanthine dehydrogenase to xanthine oxidase (XO) in postischemic injury in a wide variety of organs. A second mechanism of conversion, due to sulfhydryl modification and reversible with dithiothreitol (DTT), is potentially important but has not been well investigated. In this study rat liver and kidney were found to produce significant amounts of DTT-reversible XO during normothermic global ischemia. Formation of reversible XO precedes that of irreversible XO by approximately 0.5 h with a strong correlation (r = 0.92) existing between the rate of irreversible XO formation and the concentration of reversible XO. The formation of reversible XO is preceded by a depletion of glutathione with concentrations of glutathione during ischemia correlating (r = 0.85) with the observed concentration of reversible XO. While a large increase in the extent of liver damage occurs concurrently with conversion in an in vivo liver model of liver ischemia, an ischemia-reperfusion regimen (1 h of ischemia plus 0.5 h of reperfusion) that resulted in no conversion caused significant elevations in serum glutamic pyruvic transaminase and serum glutamic-oxaloacetic transaminase. Rats depleted of XO by tungsten dieting release 65% less enzyme after the same insult, suggesting that endogenous XO may also participate in the damage process independent of any conversion.
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PMID:Mechanisms of conversion of xanthine dehydrogenase to xanthine oxidase in ischemic rat liver and kidney. 316 35

Oxygen radicals derived from xanthine oxidase (XO) are important mediators of the cellular injury associated with reperfusion of ischemic intestine, stomach, liver, kidney, and pancreas. XO exists in nonischemic tissue predominantly as xanthine dehydrogenase (XDH) and converts to oxygen radical-producing XO with ischemia. Grinding intestine under liquid nitrogen and placing the powder in phosphate buffer (pH 7.0) containing thiol reductants and protease inhibitors adequately preserved total XDH + XO activity and the percentage in the oxidase form (%XO) for 24 h. Total activity in nonischemic intestine ranged from 374 nmol.min-1.g-1 in duodenum to 138 nmol.min-1.g-1 in ileum, while XO activity was approximately 19% of total activity throughout the entire small intestine. The rate of XDH conversion to XO during normothermic ischemia varied only slightly throughout the intestine, increasing 13% per hour to 34, 46, and 61% XO after 1, 2, and 3 h of ischemia, respectively. Our results contrast with previous reports where XDH conversion to XO occurred within 60 s ischemia but are consistent with physiological and morphological evidence of ischemic injury and provide further support for involvement of XO in intestinal injury associated with ischemia.
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PMID:Conversion of xanthine dehydrogenase to oxidase in ischemic rat intestine: a reevaluation. 316 36

In response to global ischemia, tissue xanthine dehydrogenase was converted to xanthine oxidase in all tissues with half-times of conversion at 37 degrees C of approximately 3.6, 6, 7, and 14 h for the liver, kidney, heart, and lung, respectively. The time course of enzyme conversion at 4 degrees C was greatly extended with half-conversion times of 6, 5, 5, and 6 d for the respective tissues. Increases in xanthine oxidase activity were accompanied by the appearance of a distinct new protein species with greater electrophoretic mobility. The oxidase from ischemic rat liver was purified 781-fold and found to migrate with a higher mobility on native gels than the purified native dehydrogenase. Sodium dodecyl sulfate profiles revealed the presence of a single major band of 137 kD for the native dehydrogenase, whereas the oxidase had been partially cleaved generating polypeptides of 127, 91, and 57 kD. Polypeptide patterns for the oxidase resemble those seen following limited in vitro proteolysis of the native dehydrogenase supporting a proteolytic mechanism for the conversion of xanthine dehydrogenase to oxidase in ischemic rat liver.
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PMID:Conversion of xanthine dehydrogenase to oxidase in ischemic rat tissues. 329 98

The xanthine oxidase pathway has been proposed as a source of oxygen-derived free radicals in ischemic and reperfused myocardium. A spectrophotometric assay was employed to measure the xanthine oxidase activity of rat and rabbit hearts exposed to varying durations of global ischemia. In the rat 24.6 +/- 4.8 mIU/g wet wt of xanthine dehydrogenase + xanthine oxidase activity were detected in both ischemic and normally perfused myocardium. In the non-ischemic state only 6% of this activity was associated with the free radical-producing oxidase form. After 5 min of ischemia however about 25% of the enzyme was in the oxidase form, a value which remained unchanged over the following 25 min. Neither xanthine dehydrogenase nor xanthine oxidase could be detected in the rabbit heart. Failure of allopurinol, an inhibitor of xanthine oxidase, to limit infarct size in a rabbit model of ischemia/reperfusion provides further evidence that this species has insignificant amounts of xanthine oxidase in its heart. Anesthetized rabbits were subjected to coronary artery ligation for 45 min and 3 h of reperfusion. The volume of the zone of underperfusion was assessed with fluorescent microspheres and infarct size was assessed by tetrazolium staining. In control animals 67.5 +/- 3.8% of the zone of underperfusion became necrotic. In rabbits given superoxide dismutase (15000 IU/kg) + catalase (50,000 IU/kg) for 90 min starting 15 min before occlusion, infarct size was only 35.4 +/- 3.3% of the zone of underperfusion. However, in rabbits pretreated with allopurinol (75 mg p.o. 24 h before study + 30 mg/kg 5 min before occlusion) infarct size was 65.8 +/- 8.7%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Xanthine oxidase is not a source of free radicals in the ischemic rabbit heart. 348 2

In a feline model of regional intestinal ischemia, reoxygenation resulted in a rise in the concentration of oxidized glutathione, from 2.3 +/- 0.7 to 4.1 +/- 0.5% of the total glutathione. Also conjugated diene as an indirect measurement for lipid peroxidation increased after reperfusion from 2.5 +/- 0.5 mumol/g to 5.5 +/- 1.2 micrograms mol/g tissue. These results are in line with the hypothesis that ischemia results in an accumulation of hypoxanthine and a conversion of xanthine dehydrogenase into its O2-dependent form. Upon reoxygenation, hypoxanthine can be oxidized giving yield to a burst of O2-. and its interconversion products. These may initiate peroxidative tissue damage. Pretreatment of the cats with superoxide dismutase inhibited the biochemical alterations and protected the tissue from peroxidation damage.
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PMID:Inhibition of lipid peroxidation by superoxide dismutase following regional intestinal ischemia and reperfusion. 357 86

The pathogenic mechanisms responsible for heart damage following temporary coronary artery occlusion are unknown. Some damage may be mediated by a normal cellular enzyme, xanthine dehydrogenase, which converts to xanthine oxidase during myocardial ischemia. Reperfusion, with restoration of oxygen supply, may then lead to formation of superoxide by xanthine oxidase, possibly initiating a cascade of oxidative events. In support of this, reperfusion of transiently ischemic canine myocardium leads to a rapid loss of cellular glutathione and a decrease in catalase activity, both indicative of enhanced generation of activated oxygen. Allopurinol--an inhibitor of xanthine oxidase--ameliorates both biochemical damage and functional deficits ordinarily triggered by ischemia and reperfusion, suggesting one possible mode of pharmacologic intervention following acute myocardial infarction.
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PMID:Reactive oxygen species may cause myocardial reperfusion injury. 383 75

Recent evidence suggests that oxygen free radicals are largely responsible for the increased vascular permeability and early mucosal lesions associated with partial intestinal ischemia. It is postulated that oxygen radicals are produced by the reaction of the enzyme xanthine oxidase with hypoxanthine and molecular oxygen. In normal healthy cells, xanthine oxidase exists as a nicotinamide adenine dinucleotide-reducing dehydrogenase and not the oxygen radical-producing oxidase. In the intestine, dehydrogenase-to-oxidase conversion is nearly complete with less than 1 min of ischemia. Biochemical evidence from the intestine and liver indicate that ischemia-induced conversion of xanthine dehydrogenase to xanthine oxidase can be prevented by administration of protease inhibitors such as soybean trypsin inhibitor. In order to assess the role of proteases in oxygen radical-mediated ischemic injury to the small bowel, quantitative analyses of mucosal lesion development and vascular permeability were performed in autoperfused segments of cat ileum subjected to 1 or 3 h of ischemia and pretreated with 15 mg/kg (i.v.) soybean trypsin inhibitor. One hour of ischemia produced a significant increase in intestinal vascular permeability. The ischemia-induced increase in vascular permeability was significantly attenuated by soybean trypsin inhibitor pretreatment. Three hours of ischemia led to the development of mucosal lesions in untreated animals. Pretreatment with soybean trypsin inhibitor largely prevented the development of the mucosal lesions. The findings of our study are consistent with biochemical evidence that, during ischemia, proteases trigger the conversion of xanthine dehydrogenase to xanthine oxidase and thereby lead to oxygen radical production and subsequent tissue injury.
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PMID:Soybean trypsin inhibitor attenuates ischemic injury to the feline small intestine. 400 13

The superoxide radical plays major roles in the neutrophil-medicated acute inflammatory response and in postischemic tissue injury, although the sources and actions of the radical are quite different in these two pathological states. While neutrophils produce superoxide for the primary purpose of aiding in the killing of ingested microbes, a second useful function has evolved. The superoxide released from actively phagocytosing neutrophils serves to attract more neutrophils by reacting with, and activating, a latent chemotactic factor present in plasma. Superoxide dismutase, by preventing the activation of this superoxide-dependent chemotactic factor, exerts potent anti-inflammatory action. During ischemia, energy-starved tissues catabolize ATP to hypoxanthine. Calcium transients in these cells appear to activate a calmodulin regulated protease which attacks the enzyme xanthine dehydrogenase, converting it to a xanthine oxidase capable of superoxide generation. When the tissue is reperfused and reoxygenated, all the necessary components are present (xanthine oxidase, hypoxanthine, and oxygen) to produce a burst of superoxide which results in extensive tissue damage. Ischemic tissues are protected by superoxide dismutase or allupurinol, an inhibitor of xanthine oxidase.
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PMID:The pathophysiology of superoxide: roles in inflammation and ischemia. 629 73

Reactive oxygen species play an important role in pathogenesis of a variety of pathological processes, e.g., ischemia-reperfusion, acute viral infections, thermal injury, hepatic diseases, and acute lung injury. Xanthine oxidase (XO) may be a significant source of these cytotoxic oxygen species. We tested the hypothesis that hepatic ischemia-reperfusion releases xanthine dehydrogenase + XO (XDH + XO) into the circulation and that circulating XO damages isolated perfused lung. Isolated liver + lung preparation was perfused with Krebs-Henseleit buffer to minimize confounding effects of circulating neutrophils. In one group, livers were rendered globally ischemic for 2 h and then reperfused (I/R). In another group, livers were pretreated with allopurinol and perfused with buffer containing additional allopurinol (I/R + Allo). After 2 h of ischemia, an isolated lung was connected to liver, and liver + lung preparation was reperfused in series for 15 min. Liver reperfusion was terminated, and lung was recirculated with liver effluent for 45 min. Capillary filtration coefficient (ml.min-1.cmH2O-1.100 g lung dry wt-1) was 2.0 +/- 0.3 and 1.9 +/- 0.4 in control and I/R + Allo lungs, respectively, and 9.0 +/- 1.2 in I/R lungs (P < 0.001). Lung wet-to-dry weight ratio in control and I/R + Allo lungs was 8.6 +/- 0.3 and 9.1 +/- 0.5, respectively, and 14.9 +/- 1.1 in I/R lungs (P < 0.01). Control and I/R + Allo bronchoalveolar lavage protein content was < 1.0 mg/ml compared with 32.6 +/- 8.4 mg/ml in I/R group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Liver ischemia-reperfusion increases pulmonary permeability in rat: role of circulating xanthine oxidase. 761 20


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