Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xanthine oxidase, acting on acetaldehyde under aerobic conditions, produces a flux of O2- and H2O2 which attacks artificial liposomes and washed human erythrocytes. The liposomes were peroxidized and the erythrocytes suffered oxidation of hemoglobin followed by lysis. The oxidation of hemoglobin followed by lysis. The oxidation of hemoglobin, within the exposed erythrocytes, could be largely prevented by prior conversion to carbon monoxyhemoglobin, without preventing lysis. Hemolysis thus appeared to be a consequence of direct oxidative attack on the cell stroma. The enzyme-generated flux of O2- and of H2O2 also inactivated the xanthine oxidase. Superoxide dismutase or catalase, present in the suspending medium, protected the liposomes against peroxidation, the erythrocytes against lysis, and the xanthine oxidase against inactivation. Scavengers of O2('deltag), such as histidine or 2,5-dimethylfuran, which do not react with O2- or H2O2, also prevented peroxidation of liposomes and lysis of erythrocytes when present at low concentrations. In contrast a scavenger of OH-, such as mannitol was ineffective at low concentrations and provided significant protection only at much higher concentrations. It is proposed that O2- and H2O2 cooperated in producing OH- and O2('deltag), which were the proximate causes of lipid peroxidation and of hemolysis.
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PMID:Liposome oxidation and erythrocyte lysis by enzymically generated superoxide and hydrogen peroxide. 19 2

The role of endothelium-derived relaxing factor (EDRF) on the effect of oxygen-derived free radicals (generated by xanthine-xanthine oxidase system) on intrapulmonary arterial in chronic hypoxic rats was studied by a microbioassay method. Intrapulmonary artery rings with intact or denuded endothelium of hypoxic (5,000 m, 10 days) and normoxic rats were prepared for observation of oxygen-derived free radicals induced contraction. It was shown that oxygen-derived free radicals induced contractions of intrapulmonary arterial rings with intact endothelium were obviously augmented in hypoxic rats than in normoxic controls. The augmented responses could be further potentiated by the addition of EDRF inactivator reduced hemoglobin (RHb), but diminished or even abolished by applying superoxide dismutase (Cu-Zn SOD). However, no effect on denuded rings was observed when RHb or SOD was added. It is concluded that chronic hypoxia may attenuate the action of EDRF in the enhancement of the reactivity of intrapulmonary artery to oxygen-derived free radicals.
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PMID:[Role of endothelium-derived relaxing factor in the contractions of intrapulmonary artery induced by oxygen-derived free radicals in chronic hypoxic rat]. 145 57

We studied the effect of inhibition of oxyradical formation and of endogenous glutathione (GSH) depletion on lesion formation in the gastrointestinal tract in a modified rat hemorrhagic shock model (1 h hypotension and 1 h reperfusion). Allopurinol, an inhibitor of xanthine oxidase, did not protect against lesion formation. This suggests that oxygen radicals generated from xanthine oxidase may not be the major cause of injury under these conditions of prolonged 'ischemia'-reperfusion. Phorone (diisopropylideneacetone), a GSH depletor, decreased mucosal GSH levels in the corpus, duodenum and small intestine, and also significantly reduced lesion formation histologically in the corpus, antrum, duodenum and small intestine. However, there was no significant differences in mucosal blood flow (as estimated by changes in mucosal hemoglobin concentrations and oxygen saturation of mucosal hemoglobin) in the corpus, antrum, duodenum and small intestine between phorone-pretreated and control rats. We conclude that phorone decreased mucosal GSH concentrations and exerted a protective effect against hemorrhagic shock-induced gastrointestinal mucosal lesions. The protective effect appears to be independent of mucosal blood flow.
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PMID:Effect of phorone and allopurinol on ischemia-reperfusion injury in gastrointestinal mucosa of the rat. 150 63

Reperfusion injury occurs during open-heart surgery after prolonged cardioplegic arrest. Cardiopulmonary bypass also is known to cause hemolysis. Since reperfusion of ischemic myocardium is associated with the generation of oxygen free radicals, and since free radicals can attack a protein molecule, it seems reasonable to assume that hemolysis might be the consequence of free radical attack on hemoglobin protein. The results of this study demonstrated that reperfusion following ischemic arrest caused an increase in free hemoglobin and free heme concentrations, simultaneously releasing free iron and generating hydroxyl radicals. In vitro studies using pure hemoglobin indicated that superoxide anion generated by the action of xanthine oxidase on xanthine could release iron from the heme ring and cause deoxygenation of oxyhemoglobin into ferrihemoglobin. This study further demonstrated that before the release of iron from the heme nucleus, oxyhemoglobin underwent deoxygenation to ferrihemoglobin. The released iron can catalyze the Fenton reaction, leading to the formation of cytotoxic hydroxyl radical (OH.). In fact, the formation of OH. in conjunction with hemolysis occurs during cardiac surgery, and when viewed in the light of the in vitro results, it seems likely that oxygen-derived free radicals may cause hemolysis during cardiopulmonary bypass and simultaneously release iron from the heme ring, which can catalyze the formation of OH..
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PMID:Oxygen-derived free radicals and hemolysis during open heart surgery. 158 46

In the current study we evaluated effluent blood from extremities of human patients undergoing reconstructive surgical treatment which is routinely accompanied by upper extremity exsanguination and application of a tourniquet. Following tourniquet release (reperfusion), there were immediate increases in the plasma levels of xanthine oxidase activity, uric acid, and histamine. Xanthine dehydrogenase activity was not detectable. Plasma also contained products consistent with the formation of oxygen-derived free radicals, namely hemoglobin and fluorescent compounds. Our data indicate in humans that ischemia-reperfusion events are associated with the appearance of xanthine oxidase activity and its products in the plasma effluent.
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PMID:Role of oxygen radicals in tourniquet-related ischemia-reperfusion injury of human patients. 179 87

The main reason for an insufficient oxygenation of the arterial blood during acute lung injury should be an increased shunt fraction. The aim of this study was to check if in this connection the magnitude of hypoxic pulmonary vasoconstriction is reduced--a fact, which could be causal involved in the arising of increased shunt fraction. 21 male rats were anaesthetized (pentobarbitone) and ventilated artificially (F1O2 = 0.6). In 10-minute-intervals hypoxia (F1O2 = 0.06) was applied. After the first hypoxic exposure the animals were divided into 4 groups according to the application of 3 U xanthine oxidase (XO) or 0.5 ml physiological saline (NaCl) intratracheally (i.t.) or intravascularly (i.v.)--group A: XO i.t.; group B: XO i.v.; group C.: NaCl i.t.; group D: NaCl i.v. At the end of each hypoxic or hyperoxic period (steady state) mean blood pressure in the right ventricle (Prv) and in the A. carotis communis (Psa) were measured. Then blood samples (100 microliters each) were drawn from the artery and the right ventricle and pH, PO2, PCO2, SO2 and hemoglobin concentration were determined. During hyperoxic conditions from the latter values we calculated the shunt fraction. Additional the lung-thorax compliance before and after the application was measured body plethysmographically. As an indirect measure of the reagibility of the pulmonary vasculature the increase of Prv during hypoxic exposure was considered. In the groups B, C and D no significant changes between the measured parameters before and after the application procedure could be observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Hypoxic pulmonary vasoconstriction following lung damage by xanthine oxidase--studies in rats]. 208 Jun 31

Endothelium-derived relaxing factor (EDRF) has been suggested to be derived from the metabolism of arginine or an arginine-containing moiety. We have compared the vascular effects of arginine and some of its N-substituted derivatives on the perfusion pressure (Pp) of the isolated rat kidney preparation preconstricted with phenylephrine. Irrespective of the stereochemistry, high doses (10(-4) mol) of L- and D-arginine HCl produced a slight vasodilation. In contrast L- and D-arginine free base, at similar doses, further increased renal Pp. N-substituted L-arginine compounds, however, decreased Pp dose-dependently. Their order of potency (ED50) was as follows: N-alpha-benzoyl-L-arginine ethyl ester (BAEE, 3.8 x 10hm6 mol) greater than N-alpha-benzoyl-L-arginine methyl ester (2.5 x 10(-5) mol) greater than L-arginine ethyl ester (2.7 x 10(-5) mol) greater than L-arginine HCl (10(-4) mol). Methylene blue (10(-5) M), hemoglobin (10(-5) M) and NG-mono-methyl-L-arginine (5 mumol) antagonized the vasodilation elicited by infusion of BAEE. Similarly, injection of xanthine oxidase/xanthine (100 mU) reversed BAEE-induced renal vasodilation, but had no effect on dilation elicited by infusion of atrial natriuretic peptide. These data demonstrate that substituted arginine compounds are more potent renal vasodilators than L-arginine and their potency depends on the nature of the substitution. These compounds exert their effect, at least in part, via an endothelium-dependent mechanism. We conclude that exogenous L-arginine is a poor substrate for EDRF generation in the kidney, and that it may cause release of EDRF by another mechanism, possibly related to a change in the pH of the medium.
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PMID:Endothelium-mediated effects of N-substituted arginines on the isolated perfused rat kidney. 224 37

We evaluated effluent blood from extremities of human patients undergoing reconstructive surgical treatment, which is routinely accompanied by upper-extremity exsanguination and application of a tourniquet, resulting in total interruption of arterial blood flow to one upper extremity. After tourniquet release (reperfusion), there were immediate increases in the plasma levels of xanthine oxidase activity, uric acid, and histamine in the ipsilateral limb and much smaller increases, if any, in levels of the same materials in plasma obtained from the contralateral extremity. There was no detectable xanthine dehydrogenase activity in plasma from either limb. Plasma also contained evidence of products consistent with the formation of oxygen-derived free radicals, namely, the appearance predominantly in the reperfused limb of hemoglobin and fluorescent compounds. These data indicate for the first time in humans that ischemia-reperfusion events are associated with the appearance of xanthine oxidase activity and its products in the plasma effluent.
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PMID:Ischemia-reperfusion in humans. Appearance of xanthine oxidase activity. 231 21

The inhibitory effects of hydrolyzable tannins, condensed tannins and related polyphenols on the activity of xanthine oxidase (XOD), catalyzing uric acid formation from xanthine, were investigated. Marked differences in the strength of the inhibition were observed. Some of the differences among the monomeric hydrolyzable tannins were due to their molecular weights, reflecting the number of phenolic hydroxyl groups in the molecule. However, the inhibitory activity of several oligomeric hydrolyzable tannins seemed particularly low in spite of their large molecular size. It was also observed that differences in location of acyl groups on the carbohydrate cores caused differences in the inhibitory activity among monomeric and oligomeric hydrolyzable tannins. A caffeic acid derivative (caffeetannin), 3,5-di-O-caffeoylquinic acid (24), also inhibited this enzyme. Galloylation and the degree of polymerization in proanthocyanidins were also shown to affect remarkably the strength of the inhibition. Among the compounds tested in the present study, valoneic acid dilactone (29), isolated from Mallotus japonicus, inhibited the enzyme most effectively. A kinetic study showed that this dilactone inhibited XOD non-competitively. Comparison of the inhibitory effect on XOD, with the binding activity to hemoglobin, for each tannin, suggests that their inhibition of XOD is not based on non-specific binding to the protein. Similar comparison of the inhibitory effect on XOD with the inhibitory effect on the generation of superoxide anion radical (O2-.) from the hypoxanthine-XOD system revealed that the inhibition of O2-. generation by tannins is due to their radical-scavenging activity, and not due to their inhibitory activity upon the enzyme.
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PMID:Effects of interaction of tannins with co-existing substances. VII. Inhibitory effects of tannins and related polyphenols on xanthine oxidase. 239 48

When exposed to oxidative stress, by oxygen radicals or H2O2, E. coli exhibited decreased growth, decreased protein synthesis, and dose-dependent increases in protein degradation. The quinone menadione induced proteolysis when cells were incubated in air, but was not effective when cells were incubated without oxygen. Anaerobically grown cells also exhibited significantly lower proteolytic capacity than did cells that were grown aerobically. Xanthine plus xanthine oxidase (which generate O2- and H2O2) caused a stimulation of proteolysis which was inhibitable by catalase, but not by superoxide dismutase: Indicating that H2O2 was responsible for the increased protein degradation. Indeed, H2O2 alone was effective in inducing increased intracellular proteolysis. Two-dimensional polyacrylamide gel electrophoresis of [3H]leucine labeled E. coli revealed greater than 50% decreases in the concentrations of 10-15 cell proteins following H2O2 or menadione exposure, while several other proteins were less severely affected. To test for the presence of soluble proteases, we prepared cell-free extracts of E. coli and incubated them with radio-labeled protein substrates. E. coli extracts degraded casein and globin polypeptides at rapid rates but showed little activity with native proteins such as superoxide dismutase, hemoglobin, bovine serum albumin, or catalase. When these same proteins were denatured by exposure to oxygen radicals or H2O2, however, they became excellent substrates for degradation in E. coli extracts. Studies with albumin revealed correlations greater than 0.95 between the degree of oxidative denaturation and proteolytic susceptibility. Pretreatment of E. coli with menadione or H2O2 did not increase the proteolytic capacity of cell extracts; indicating that neither protease activation, nor protease induction were required.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Degradation of oxidatively denatured proteins in Escherichia coli. 290 82


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