Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hepatotoxic effects of hyperthermia have been proposed to be related to lipid peroxidation as a consequence of oxidative stress. This can result from exposure of the cell to "radical oxygen" species such as the superoxide and hydrogen peroxide generated by the activity of the oxidase form (type O) of xanthine oxidase (XO), which is converted to that form by perfusion of the liver at hyperthermic temperatures. These radical species are not reactive enough in themselves to cause cell damage but require the presence of a catalyst such as low molecular weight chelated iron. In these studies, ferritin was shown to be a source of iron for the oxidative stress of hyperthermia. (a) Iron was released from ferritin in vitro by the activity of rat liver XO. The rate of iron release from ferritin in this incubation system was a function of the amount of type O XO present and the temperature. Inclusion of allopurinol or superoxide dismutase in the incubation resulted in significantly lower rates of iron release. (b) Livers from Sprague-Dawley rats were perfused at 42.5 degrees and 37 degrees C for 1 h. During the recirculating perfusion, loss of iron from the liver into the perfusate was significantly greater (P less than 0.05) at 42.5 degrees C than at 37 degrees C. Also, there was a pronounced increase in the lactate dehydrogenase and aspartate aminotransferase enzymes in the perfusate during perfusion at 42.5 degrees C. Furthermore, intrahepatic levels of low molecular weight chelated iron were significantly (P less than 0.05) increased following perfusion at 42.5 degrees C. All these responses were abrogated by the inclusion of allopurinol in the perfusate. (c) Oxidative stress, assessed by the efflux of glutathione and oxided glutathione from the liver at 42.5 degrees and 37 degrees C, was significantly (P less than 0.05) increased at the hyperthermic temperature. This oxidative stress was inhibited by iron chelation and allopurinol. These results demonstrate that there is a causal relationship between the generation of superoxide by type O XO produced by hyperthermic perfusion and mobilization of iron from ferritin to form a pool of low molecular weight chelated iron. This iron pool in combination with active oxygen species leads to oxidative stress and lipid peroxidation.
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PMID:Involvement of xanthine oxidase in oxidative stress and iron release during hyperthermic rat liver perfusion. 155 Oct 99

We have used phase-contrast microscopy to determine a necrotic end point of the order of minutes in primary hepatocytes exposed to oxyradicals generated with xanthine oxidase plus hypoxanthine. This study examines whether the morphologic end point thus determined agrees with other criteria of cell necrosis. When 95-100% of the cells were shown to be necrotic by our morphologic assay, transmission electron microscopy confirmed definitive subcellular evidence of cell death, trypan blue exclusion revealed a 92% loss in the ability of cells to exclude the dye, and there was a 47% specific release of 51Cr (versus a 50% theoretical value). In contrast, the appearance of extracellular aspartate aminotransferase activity was relatively slow and did not corroborate the morphologic end point. In summary, we have validated the morphologic end point in our cell-based assay of oxyradical damage.
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PMID:Validation of the morphologic end point of necrosis in rat hepatocytes subjected to oxyradical damage. 179 34

Reactive oxygen metabolites generated from the enzyme xanthine oxidase (XO) play an important role in the pathogenesis of ischemia-induced tissue injury. The observation that intracellular proteins such as aspartate transaminase (AST) and alcohol dehydrogenase (ADH) are released from the ischemic liver during reperfusion led us to postulate that XO could be released into the systemic circulation. Livers from fasted rats were extirpated, perfused with oxygenated Krebs-Henseleit buffer, and subjected to 2 h ischemia followed by 2 h reperfusion. Reperfusion increased AST in the perfusate from 1 +/- 1 to 830 +/- 280 U/l, whereas ADH increased from 0.3 +/- 0.1 to 95 +/- 26 U/l. Concomitantly, xanthine dehydrogenase (XDH) + XO activity in the perfusate increased from 0 to 4.1 +/- 1.0 mU/ml. A 64% decrease in endogenous tissue XDH + XO activity paralleled release of XDH + XO. The XDH + XO activity predicted to appear in the circulation after hepatic ischemia was sufficient, when supplied with substrate, to produce severe vascular endothelial injury in vitro, even in the presence of serum or whole blood. These results suggest that massive quantities of XDH and XO are released into the circulation after hepatic ischemia and that the resulting reactive oxygen metabolites could produce widespread tissue injury.
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PMID:Circulating xanthine oxidase: potential mediator of ischemic injury. 233 69

The hepatotoxic effects of hyperthermic liver perfusion were investigated in male Fischer 344 rat livers. Perfusions were carried out at 37, 41, 42, 42.5, and 43 degrees C for 2 hr. During the 2 hr, the perfusate was analyzed for activity of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), N-acetyl-beta-glucosaminidase (NAG), and glutathione (GSH), oxidized glutathione (GSSG), allantoin, and potassium. After perfusion, each liver was homogenized and analyzed for total xanthine oxidase (XO) activity, percentage type-D and type-O XO, and total GSH content. Perfusate AST, LDH, NAG, and potassium levels were increased significantly with time and were significantly different in all hyperthermic perfusions from the 37 degrees C perfusion values by the end of the perfusion. Perfusate GSH + GSSG levels were increased significantly in all hyperthermic perfusions after 60 min. Liver GSH levels were significantly lowered following perfusion at hyperthermic temperatures. There was a temperature-dependent increase in the percentage of XO in the type-O form following perfusion at hyperthermic temperatures, which was strongly and positively correlated with the loss of hepatic GSH. These data support the hypothesis that hyperthermic toxicity to the liver is the result of oxidative stress brought about by conversion of XO to the type-O form.
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PMID:Effects of hyperthermia on xanthine oxidase activity and glutathione levels in the perfused rat liver. 259 31

Rat livers were perfused at 37 degrees C, 41 degrees C, 42 degrees C, 42.5 degrees C, and 43 degrees C for 2 hr. Among perfusate constituents analyzed were urea, total amino acids, N-acetyl-beta-glucosaminidase (NAG), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malonaldehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), allantoin, potassium, phosphate, and glucose. After perfusion, livers were homogenized and analyzed for xanthine oxidase (XO) activity, GSH content, and lysosomal lability. Perfusate AST, LDH, NAG, potassium, glucose, and phosphate increased significantly with time, and there were significant differences in the final values between 37 degrees C and 42 degrees C, 42.5 degrees C and 43 degrees C (P less than .05). GSH levels increased significantly at all temperatures after 90 and 120 min, whereas GSSG levels differed significantly at 60, 90, and 120 min for 37 degrees C vs. 42 degrees C, 42.5 degrees C, and 43 degrees C (P less than .05). Mean MDA levels at 37 degrees C differed from those at 41 degrees C and 43 degrees C (P less than .05) at each temperature. Allantoin levels increased significantly with time of perfusion; mean levels at 37 degrees C were significantly different from mean levels at each temperature at 60, 90, and 120 min. GSH liver tissue levels decreased with perfusion at hyperthermic temperatures; mean values at 41 degrees C, 42 degrees C, and 42.5 degrees C, and 43 degrees C differed from 37 degrees C mean values (P less than .01). Type O XO increased after 120 min perfusion from 6.4% +/- 2.0% at 37 degrees C to 55% +/- 30%, 43% +/- 27%, and 63% +/- 29% at 42 degrees C, 42.5 degrees C, and 43 degrees C, respectively. Lysosomal lability increased after perfusion at 42.5 degrees C. There was a significant increase in nonsedimentable NAG activity at 42.5 degrees C (P less than .05). These data support the premise that hyperthermic toxicity to the liver may be a consequence of oxidative stress brought about by enhanced adenosine triphosphate (ATP) consumption and conversion of XO to type O. Such conversion results in superoxide formation and subsequent depletion of cellular GSH, labilization of the lysosomes, and plasma membrane damage.
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PMID:Hyperthermic liver toxicity: a role for oxidative stress. 279 43

Fractionation of cell organelles of nitrogen-fixing nodules of cowpea (Vigna unguiculata L. Walp) by discontinuous and continuous sucrose density centrifugation indicated that starch-containing plastids possessed the complete pathway for purine nucleotide synthesis together with significant activities of some other enzymes associated with the provision of substrates in purine synthesis; triosephosphate isomerase (EC 5.3.1.1), NADH-glutamate synthase (EC 2.6.1.53), aspartate aminotransferase (EC 2.6.1.1), phosphoglycerate oxidoreductase (EC 1.1.1.95), and methylene tetrahydrofolate oxidoreductase (EC 1.5.1.5). Enzymes of purine oxidation, xanthine oxidoreductase (EC 1.2.3.2), and urate oxidase (EC 1.7.3.3) were recovered in the soluble fraction; glutamine synthetase (EC 6.3.1.2) occurred in bacteroids and in the cytosol. Intact, infected (bacteroid-containing) and uninfected cells were prepared by enzymatic maceration of the central zone of the nodule and partially separated by centrifugation on discontinuous sucrose gradients. Glutamine synthetase was largely restricted to infected cells whereas plastid enzymes, de novo purine synthesis, and urate oxidase were present in both cell types. Although the levels of all enzymes assayed were higher in infected cells, both cell types possessed the necessary enzyme complement for ureide formation. A model for the cellular and subcellular organization of nitrogen metabolism and the transport of nitrogenous solutes in cowpea nodules is proposed.
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PMID:Cellular and subcellular organization of pathways of ammonia assimilation and ureide synthesis in nodules of cowpea (Vigna unguiculata L. Walp.). 687 Feb 68

Xanthine oxidase may contribute to oxygen free radical formation during reoxygenation after hypoxia, but in humans the enzyme is present in substantial amounts only in the liver and intestine. We developed a sensitive assay for xanthine oxidase using 14C-xanthine as substrate and investigated whether xanthine oxidase was released into the systemic circulation when 19 newborn pigs were resuscitated after severe hypoxemia. In five piglets plasma xanthine oxidase concentrations increased from undetectable levels to a median value of 8 (range 4-18) microU/ml after 30 min of reoxygenation. In these pigs serum aspartate aminotransferase increased from 45 to 148 U/l, while alanine aminotransferase was unchanged (28-31 U/l). The release of xanthine oxidase did not seem to correlate with the severity of the histological brain damage after 4 days. We conclude that only low levels of xanthine oxidase are released to the systemic circulation after severe hypoxemia in newborn pigs.
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PMID:Release of xanthine oxidase to the systemic circulation during resuscitation from severe hypoxemia in newborn pigs. 763 44

An investigation was made into the possible involvement of the enzyme xanthine oxidase (XO) (EC 1.1.3.22), both reversible (XOrev) and irreversible (XOirr), in damage observed after short-term in vivo hepatic ischaemia/reperfusion (60 or 120 min I and 15 min R) in fasted rats with: (i) a physiological content of XO (25%); and (ii) higher XO percentage (45%). In the latter the hepatic XO physiological percentage was increased by diethylmaleate treatment (300 mg kg-1) that depleted the cytosolic glutathione (GSH) to 14% of the controls. It was shown that, in animals with physiological content of XO, 60 and 120 min of hepatic ischaemia followed by 15 min reperfusion results in decreased GSH levels, and significantly increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum levels, without any modification of either the percentages of XO (XOirr and XOrev) or the hepatic thiobarbituric acid reactive substances (TBARS). Sixty minutes of ischaemia/reperfusion in rats with the higher XO level and lower hepatic GSH content led to further conversion of XDH to XOrev, with no increase in XOirr. In addition, the ALT and AST serum levels in these animals rose to the same extent as in normal rats after 120 min ischaemia and 15 min reperfusion, this extent being observed to be associated with a moderate increase in thiobarbituric acid reactive substances (TBARS). However, the administration of allopurinol, at a dose of 50 mg kg-1, which almost completely inhibits XO activity, did not lead to any decrease in liver damage or TBARS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:No documentable role for xanthine oxidase in the pathogenesis of hepatic in vivo ischaemia/reperfusion injury. 786 19

The acute administration of ethanol by gastric catheter significantly increases the plasma xanthine oxidase activity in both rats and hamsters without changing other enzyme activities--alanine aminotransferase and aspartate aminotransferase. The plasma xanthine oxidase level seems to be a sensitive marker of liver damage. Its higher activity due to the acute ethanol intoxication may have an impact on ethanol organ damage.
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PMID:Plasma xanthine oxidase level and alcohol administration. 814 77

Cardiopulmonary and other organ dysfunction often occurs after operation on the descending thoracic aorta. Though there are multiple causes of organ dysfunction in this setting, free radical injury may play a prominent role. Xanthine oxidoreductase, an enzyme that generates oxidants after exposure to ischemia, could be released from ischemic liver and intestine during reperfusion. To test this hypothesis, we created aortic occlusion in eight rabbits for 40 minutes by inflation of a 4F Fogarty balloon catheter in the descending thoracic aorta. Eight sham-operated rabbits served as a control group. Two hours of reperfusion followed removal of the balloon catheter. Hemodynamic and acid-base status were maintained near baseline values during reperfusion. Plasma samples were obtained for determination of the activity of the hepatocellular enzymes xanthine oxidoreductase, aspartate aminotransferase, alanine transferase, and lactate dehydrogenase. Plasma xanthine oxidoreductase activity increased significantly (p < 0.001) during reperfusion (729 +/- 140 microU/ml, mean +/- standard error of the mean) compared with baseline (132 +/- 18 microM/mL). The other enzymes followed a similar pattern of release. We report the release of xanthine oxidoreductase in an animal model that simulates the situation of human thoracic aorta operations. The oxidants produced by the circulating xanthine oxidoreductase observed during reperfusion would likely be toxic to vascular endothelium, potentially contributing to multiple organ dysfunction.
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PMID:Xanthine oxidoreductase release after descending thoracic aorta occlusion and reperfusion in rabbits. 817 64


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