Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence is presented that oxygen products generated from xanthine oxidase (XO) may also be involved in the pathogenesis of neutrophil-mediate lung injury following intravascular activation of complement with cobra venom factor (CVF). CVF injection in rats resulted in a rapid increase in plasma of both XO activity (but not xanthine dehydrogenase) and its reaction product, uric acid. These changes were greatly attenuated in allopurinol-treated animals. The appearance of XO activity was paralleled by a rise in plasma of histamine. Prevention of histamine release by pretreatment of rats with cromolyn abolished both the rise in plasma histamine and the increase in XO activity. Since we have previously shown that histamine can enhance XO activity in vitro and in vivo (Am. J. Pathol. 135:203, 1989), these observations suggest that the increase in plasma XO activity following CVF injection is related to the appearance in plasma of histamine. Accordingly, pretreatment of rats with xanthine oxidase inhibitors (allopurinol, lodoxamide) or prevention of histamine release by pretreatment with cromolyn significantly attenuated development of lung injury following injection of CVF. Our data support the concept that oxygen radicals derived from both neutrophils and XO are playing a role in the CVF-induced acute lung injury.
 ...
PMID:Lung injury and complement activation: role of neutrophils and xanthine oxidase. 189 64

Xanthine oxidase has been implicated in the production of reactive oxygen species and cell injury produced by various toxic compounds. Since allyl alcohol injuries the liver by an oxygen-dependent mechanism, we examined the actions of this hepatotoxicant on the conversion of xanthine dehydrogenase into xanthine oxidase in perfused livers. A microassay for NAD(+)-dependent xanthine dehydrogenase, based on measuring the production of NADH fluorometrically under anaerobic conditions, was developed and used to examine the actions of allyl alcohol on this activity in periportal and pericentral regions of the liver lobule. The oxygen-dependent activity, xanthine oxidase, was monitored in whole liver homogenates by uric acid formation at 302 nm under aerobic conditions. Perfusion of the liver with allyl alcohol (350 microM) increased xanthine oxidase and decreased xanthine dehydrogenase in whole liver consistent with the hypothesis that allyl alcohol enhanced calcium-dependent proteolytic conversion of the NAD(+)-dependent to the O2-dependent form. Xanthine dehydrogenase was higher in pericentral than in periportal regions of the liver lobule and tended to decrease selectively in periportal zones of livers exposed to allyl alcohol. O2 uptake was stimulated transiently by allyl alcohol followed by subsequent inhibition of respiration. These results are consistent with the idea that conversion of NAD(+)-dependent xanthine dehydrogenase to xanthine oxidase is involved in the zone-specific hepatotoxicity of allyl alcohol.
 ...
PMID:Effect of allyl alcohol on xanthine dehydrogenase activity in the perfused rat liver. 189 1

The effect of aurothiomalate in modulating the conversion of xanthine dehydrogenase to its superoxide producing oxidase form in rat and human liver cytosolic preparations has been investigated. Low concentrations (10(-8)-10(-5) mol.dm-3) of this second-line agent were found to inhibit the conversion of the dehydrogenase to its corresponding oxidase form. High concentrations (10(-4) mol.dm-3), however, accelerated this conversion. It is possible that the influence of aurothiomalate on the relative proportions of xanthine dehydrogenase and xanthine oxidase is a reflection of the gold(I) blockage of critical thiol(ate) or sulphido ligands present in this enzymatic system. These effects may form the basis of aurothiomalate's anti-proliferative action on endothelial cells.
 ...
PMID:Influence of disodium aurothiomalate on the activities of xanthine dehydrogenase and xanthine oxidase in endothelial cells. 190 38

Clinical evidence has suggested that mitomycin C (MMC) potentiates doxorubicin (DOX) induced cardiotoxicity. In this study a mouse model was used to examine the effect of DOX on the ability of cardiac tissue to bioactivate MMC to generate oxygen radicals. Cardiac damage was assessed by measuring serum CPK-MB isoenzyme levels and thiobarbituric acid reactive substances (TBARS) in the cardiac tissue. The exposure of animals to DOX or DOX and MMC over a three week period led to an increase in serum CPK-MB isoenzyme levels as well as TBARS. Treatment with DOX led to an increase in MMC-dependent, NADH-dependent, cyanide insensitive oxygen consumption, compared to control animals, thereby suggesting increased MMC-dependent oxygen radical generation. Levels of xanthine oxidase (XO; EC 1.1.3.22) and NADPH:cytochrome C reductase, two enzymes known to bioactivate MMC with subsequent oxygen radical generation, were measured in cardiac tissue with a 4.5 x increase in XO activity seen in DOX treated animals vs controls and no change in NADPH:cytochrome C reductase activity. Cardiac levels of xanthine dehydrogenase (XDH; EC 1.1.1.204) activity in DOX treated animals decreased while the XO/XDH ratio increased, suggesting a conversion of XDH to XO following DOX treatment.
 ...
PMID:Role of xanthine oxidase in the potentiation of doxorubicin-induced cardiotoxicity by mitomycin C. 191 Oct 46

The effect of repeated administration of allopurinol (50 mg.kg-1 48, 24, and 4 hours before analysis) on the activity of enzymes of degradation and resynthesis of adenine nucleotides was studied. The activity of xanthine dehydrogenase and xanthine oxidase was inhibited in the heart, liver and kidney and the activity of membrane-bound 5'-nucleotidase was particularly elevated in the heart and brain, suggesting that membrane transport processes may be affected. The increase in the activity of hypoxanthine guanine phosphoribosyl transferase in the liver is indicative of a potential mechanism of positive action of allopurinol upon restoring the purine nucleotide store. The authors present their hypothesis on the mechanism of allopurinol action upon the metabolism of adenine nucleotides. The suggested mechanisms might become operative in protecting tissues against ischemia and reperfusion induced damage.
 ...
PMID:[Mechanisms of the effect of allopurinol on the metabolism of adenine nucleotides]. 191 98

Interactions between rat pulmonary artery endothelial cells and hydrogen peroxide or toxic oxygen products from phorbol ester-activated human neutrophils result in endothelial cell killing defined by 51Cr release. It has been shown that this cytotoxic reaction can be blocked by the presence of catalase, iron chelators, or scavengers of the hydroxyl radical. Evidence shows that products from xanthine oxidase of endothelial cells are necessary for the toxic effects of hydrogen peroxide or phorbol ester-activated neutrophils. Addition of xanthine oxidase inhibitors protects against phorbol ester-mediated injury of endothelial cells. Preloading of endothelial cells with superoxide dismutase attenuates injury caused either by hydrogen peroxide or phorbol ester-activated neutrophils. Conversion of xanthine dehydrogenase to xanthine oxidase in endothelial cells occurs during contact of endothelial cells by activated neutrophils. This conversion is not related to oxygen products of neutrophils. Conversion of xanthine dehydrogenase to xanthine oxidase in endothelial cells is also induced by endothelial cell contact with C5a, N'-formyl-methionyl-leucyl-phenylalanine (fMLP), or tumor necrosis factor alpha (TNF alpha). Interaction of hydrogen peroxide with endothelial cells rapidly depletes adenosine triphosphate (ATP) and causes the extracellular appearance of xanthine and hypoxanthine. Agents that protect endothelial cells from the toxic effects of hydrogen peroxide do not prevent falls in cellular ATP caused by hydrogen peroxide, indicating that ATP levels do not necessarily correlate with cytotoxic events. A synergy between hydrogen peroxide and proteases in endothelial cell killing has been demonstrated. TNF alpha causes alterations in endothelial cells, the result of which is increased susceptibility to killing by PMA-activated neutrophils.
 ...
PMID:Mechanisms of endothelial cell killing by H2O2 or products of activated neutrophils. 192 18

The effects of hypoxia and reoxygenation on the conversion of xanthine dehydrogenase to the free radical-producing xanthine oxidase in Chinese hamster V79 cells have been investigated using a newly developed fluorimetric enzyme assay. Hypoxia caused an increase in xanthine oxidase activity from 25% to 80% of the total activity of xanthine oxidase and dehydrogenase. The ratio returned to normal levels within 24 h of aerobic incubation. Hypoxia caused the release of xanthine oxidase in the medium of V79 cells and an increase in total protein concentration in the medium. There was an early change induced in lipid peroxidation markers and this was inhibited by allopurinol. The effects of glucose deprivation and calcium blockers were also investigated. Fura-2 AM was found to interact with V79 cells, making it impossible to determine intracellular calcium levels in V79 cells by this reagent.
 ...
PMID:Effects of hypoxia and reoxygenation on the conversion of xanthine dehydrogenase to oxidase in Chinese hamster V79 cells. 193 36

It has been widely proposed that conversion of xanthine dehydrogenase (XDH) to its free radical-producing form, xanthine oxidase (XOD), underlies ischemic/reperfusion injury, although the relationship of this conversion to hypoxia and its physiologic control have not been defined. This study details the time course and control of this enzymatic interconversion. In a functionally intact, isolated perfused rat liver model, mean % XOD activity increased as a function of both the duration (25 to 45% in 3 h) and degree (r = 0.97) of hypoxia. This process was markedly accelerated in ischemic liver by an overnight fast (45 vs. 30% at 2 h), and by imposing a short period of in vivo ischemia (cardiopulmonary arrest 72%). Moreover, only under these conditions was there a significant rise in the XOD activity due to the conformationally altered XDH molecule (XODc, 18%), as well as concomitant morphologic injury. Neither circulating white blood cells nor thrombosis appeared to contribute to the effects of in vivo ischemia on enzyme conversion. Thus, it is apparent that conversion to the free radical-producing state, with high levels of XOD activity and concurrent cellular injury, can be achieved during a relatively short period of hypoxia under certain well-defined physiologic conditions, in a time course consistent with its purported role in modulating reperfusion injury. These data also suggest that the premorbid condition of organ donors (e.g., nutritional status and relative state of hypoxia) is important in achieving optimal organ preservation.
 ...
PMID:Enhanced activity of the free radical producing enzyme xanthine oxidase in hypoxic rat liver. Regulation and pathophysiologic significance. 199 28

Verapamil administered before treatment, but not after treatment, had a beneficial effect on a 90-minute warm ischemia-reperfusion rat liver injury model. The possible activation of proteases converting the xanthine dehydrogenase to xanthine oxidase, the significant mitochondrial calcium loading during the ischemic period, and the potentiation of calcium and oxygen-derived free radicals to promote injury to mitochondria are mechanisms supported by this study, based on both histologic observations and on the pattern of enzyme leak after the acute ischemic event.
 ...
PMID:The role of calcium ions and calcium channel entry blockers in experimental ischemia-reperfusion-induced liver injury. 199 40

Using a highly specific assay that minimizes enzyme inactivation in vitro, we found that rabbit myocardial tissue contained low levels of xanthine oxidase (XO) and xanthine dehydrogenase (XD) activity that were effectively inhibited by pretreatment of hearts with allopurinol. In parallel, allopurinol treatment also improved ventricular developed pressure, peak systolic pressure, and coronary flow in isolated hearts subjected to 30 min of normothermic global ischemia and 30 min of reperfusion. Although function was protected by allopurinol treatment, creatine kinase (CK) release was not altered by allopurinol. Inhibition of myocardial XO with allopurinol did not increase myocardial ATP or phosphocreatine. In addition, allopurinol did not scavenge superoxide anion or hydrogen peroxide in vitro. The results support the possibility that relatively low amounts of XO activity, similar to levels reported in human myocardium, may contribute to cardiac ischemia-reperfusion injury.
 ...
PMID:Existence and participation of xanthine oxidase in reperfusion injury of ischemic rabbit myocardium. 200 Sep 75


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>