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)

Trolox, a hydrophilic analogue of alpha-tocopherol, was reported to scavenge peroxyl radicals better than vitamin E in sodium dodecyl sulfate micelles and in liposomes. However, it was not known if Trolox protects human cells against oxyradical damage or if it acts as an antioxidant there. Here we demonstrate that Trolox prolonged substantially the survival of human ventricular myocytes and hepatocyte against oxyradicals generated with xanthine oxidase plus hypoxanthine, and prevented lysis of red cells exposed to an azo-initiator (2,2'-azo-bis(2-amidinopropane) HCl). Note that Trolox did not inhibit xanthine oxidase. In each cell type, the protection by Trolox was dose dependent and surpassed those given by such water-soluble antioxidants as ascorbic acid, superoxide dismutase, and (or) catalase, each examined at or near its optimal level in the same system. Using hepatocytes as a model, we further observed that Trolox reduced markedly the quantity of phospholipid conjugated dienes (a chemical imprint of oxyradical damage) in cells despite their exposure to oxyradicals. These data suggested that Trolox behaves as an antioxidant in cells as illustrated in hepatocytes.
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PMID:The cytoprotective effect of Trolox demonstrated with three types of human cells. 226 14

The antioxidant properties of tryptophan and some of its oxidative metabolites were examined by measuring how efficiently they inhibited peroxyl radical-mediated oxidation of phosphatidylcholine liposomes and B-phycoerythrin. Low micromolar concentrations of 5-hydroxytryptophan, 3-hydroxykynurenine, xanthurenic acid, or 3-hydroxyanthranilic acid, but not their corresponding nonhydroxylated metabolic precursors, scavenged peroxyl radicals with high efficiency. In particular, 3-hydroxykynurenine and 3-hydroxyanthranilic acid protected B-phycoerythrin from peroxyl radical-mediated oxidative damage more effectively than equimolar amounts of either ascorbate or Trolox (a water-soluble analog of vitamin E). Enzyme activities involved or related to oxidative tryptophan metabolism, as well as endogenous concentrations of tryptophan and its metabolites, were determined within tissues of mice suffering from acute viral pneumonia. Infection resulted in a 100-fold induction of pulmonary indoleamine 2,3-dioxygenase (EC 1.13.11.17) as reported [Yoshida, R., Urade, Y., Tokuda, M. & Hayaishi, O. (1979) Proc. Natl. Acad. Sci. USA 76, 4084-4086]. This was accompanied by a 16- and 3-fold increase in the levels of lung kynurenine and 3-hydroxykynurenine, respectively. In contrast, endogenous concentrations of tryptophan and xanthurenic acid did not increase and 3-hydroxyanthranilic acid could not be detected. The activity of the superoxide anion (O2-.)-producing enzyme xanthine oxidase increased 3.5-fold during infection while that of the O2-.-removing superoxide dismutase decreased to 50% of control levels. These results plus the known requirement of indoleamine 2,3-dioxygenase for superoxide anion for catalytic activity suggest that viral pneumonia is accompanied by oxidative stress and that induction of indoleamine 2,3-dioxygenase may represent a local antioxidant defence against this and possibly other types of inflammatory diseases.
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PMID:Antioxidant activities of some tryptophan metabolites: possible implication for inflammatory diseases. 232 May 71

Mesenteric arteries supplying an intestinal segment were occluded for 5 minutes and then released. During reperfusion, two series of measurements were made with various substances topically applied to the extraluminal surface. In the first series, reduced nitro blue tetrazolium (NBT) was extracted from tissue and measured spectrophotometrically, as an index of oxidative damage. In the second series, mucosal and serosal surface pH was measured as an index of the functional ability to maintain ion gradients. In control conditions, NBT deposition averaged 55-63 micrograms/g tissue. After 60 and 120 minutes of reperfusion, NBT was elevated to 446-479 micrograms/g, which was approximately half as large as the NBT increment (846 micrograms/g) produced by a 15-minute application of xanthine plus xanthine oxidase to well-perfused tissue. As expected, NBT levels were significantly lower (299 micrograms/g) in tissue that was continuously suffused with superoxide dismutase (SOD) plus catalase (CAT) before occlusion and during reperfusion. Similar NBT levels (274 micrograms/g) were observed after reperfusion in animals that were fed a diet supplemented with the antioxidant vitamin E for 4-6 weeks. These observations affirm that some, but not all, NBT deposition after reperfusion can be attributed to oxyradicals. However, with exogenous adenosine (ADO) applied for the first 30 minutes after occlusion, NBT was elevated to 174 micrograms/g after 60 minutes, which was only half as large as the increment with SOD plus CAT, even though those substances were continuously applied. The opposite effect was produced by an ADO receptor antagonist, 8-phenyltheophylline; NBT was increased to 516 micrograms/g.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Actions of adenosine on nitro blue tetrazolium deposition and surface pH during intestinal reperfusion injury. 234 69

The exact mechanism whereby hypoxic pulmonary vasoconstriction (HPV) is elicited is still unsettled. We have evaluated a possible role for toxic oxygen metabolites (TOM), employing a set-up of blood-perfused isolated rat lungs. HPV reflected as pulmonary arterial pressor responses, was evoked by alternately challenging the airways with a hypoxic- and a normoxic gas mixture, resulting in gradually increasing responses until a maximum was obtained. In a sequence of responses (mean +/- s.e. mean) increasing from 2.5 +/- 0.2 kPa to 3.2 +/- 0.1 kPa, administration to the perfusate of the inhibitor of xanthine oxidase (XO), allopurinol (AP) reduced the subsequent response to 2.5 +/- 0.2 kPa (P less than 0.001). By contrast, AP did not affect vasoconstriction induced by serotonin or bradykinin. In control experiments responses continued to increase after administration of hypoxanthine (substrate of XO). Neither pretreatment with daily injections of the antioxidant vitamin E for 3 days in advance, nor addition to the perfusate of the scavenger enzymes superoxide dismutase and catalase, or dimethylsulfoxide had any impact on HPV; the subsequent responses rose at the same rate and in the same way as before. Thus, the present study has shown that AP inhibition of XO depresses HPV. This could be due either to reduced production of TOM or to accumulation of purine metabolites. The absence of inhibitory effects of quenchers of TOM refutes a role for these metabolites in the elicitation of HPV. More likely, AP inhibits HPV by interfering with the purine metabolism.
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PMID:Allopurinol inhibits hypoxic pulmonary vasoconstriction. Role of toxic oxygen metabolites. 238 53

We examined the role of superoxide in the increase in intracellular pH (pHi) of human histiocytic leukemia U937 cells treated with 4 beta-phorbol-12,13-didecanoate (4 beta-PDD) or serum. 4 beta-PDD or serum induced a rapid increase in pHi, and antioxidants such as superoxide dismutase (SOD), vitamin E, and butylated hydroxyanisole (BHA) were found to inhibit the amiloride-sensitive increase in pHi induced by 4 beta-PDD. SOD inhibited the increase in pHi caused by serum, and essentially the same was found in concanavalin A-stimulated mouse thymocytes. Also, a superoxide-generating system, xanthine-xanthine oxidase (X-XOD), increased pHi of U937 cells as much as 4 beta-PDD or serum. From these findings, it appears that superoxide is the basis for the modulation of pHi.
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PMID:Superoxide as a signal for increase in intracellular pH. 284 50

Lipid peroxidation of microsomal membranes isolated from rat liver, and Morris hepatomas 9618A (slow-growing) and 3924A (fast-growing) was induced by superoxide radicals generated by the action of xanthine oxidase on xanthine. The peroxidation, measured as malondialdehyde and lipid hydroperoxide formation, was optimized with regard to iron concentration and chelation of iron by ADP. In such conditions hepatoma microsomes catalyze lower rates of lipid peroxidation than the normal counterpart. However, while microsomes from hepatoma 3924A show a marked decrease in both the malondialdehyde and hydroperoxide production rates, microsomes from hepatoma 9618A differ moderately from the control, mainly in the long-term production of hydroperoxides. It is also reported here that the 9618A microsomes partially lack cytochrome P-450 (about 40% deficiency), but they have a fatty acid composition similar to that of control. No differences were found in the content of vitamin E between normal and hepatoma 3924A microsomes. Moreover, induction of vitamin E deficiency in hepatoma 3924A microsomes does not influence the rate of either malondialdehyde or lipid hydroperoxide production. On the basis of these results and previous data on the lipid composition of hepatoma 3924A microsomes it is proposed that the high resistance to superoxide-dependent lipid peroxidation of hepatoma 3924A microsomes is related to the low substrate availability rather than the content of membrane antioxidants; and a limitation only in the propagation phase characterizes the hepatoma 9618A microsomal lipid peroxidation and would be due to the partial deficiency of the endogenous propagating agent, cytochrome P-450.
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PMID:Superoxide-dependent lipid peroxidation and vitamin E content of microsomes from hepatomas with different growth rates. 298 56

A procedure to induce hemolysis by the hypoxanthine-xanthine oxidase reaction was developed and applied to vitamin E deficient red blood cells (RBCs) in rats. The reaction system was as follows: 0.16 mM hypoxanthine, 0.05 U/ml xanthine oxidase in 2.5% RBC suspensions with an isotonic buffer (pH 7.4) containing 10 mM phosphate buffer and 125 mM saline (277 mOsm). Hemolysis was observed to depend on the vitamin E concentrations in the RBCs. Hemolysis was inhibited by catalase but not by SOD. After the reaction with vitamin E deficient RBCs, an increase in TBARS in the aqueous phase of the reaction mixture was observed. This accompanied the increase in fluorescent substances in the lipid extracts, in association with a significant decrease in the PE and PS of the RBCs, and a decrease in arachidonic acid in membrane lipids. The above changes were almost completely inhibited by tocopherol incorporated into vitamin E deficient RBCs.
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PMID:Hemolysis and membrane lipid changes induced by xanthine oxidase in vitamin E deficient red cells. 302 41

The role of O2 free radicals in the reduction of sarcolemmal Na+-K+-ATPase, which occurs during reperfusion of ischemic heart, was examined in isolated guinea pig heart using exogenous scavengers of O2 radicals and an inhibitor of xanthine oxidase. Ischemia and reperfusion reduced Na+-K+-ATPase activity and specific [3H]ouabain binding to the enzyme in ventricular muscle homogenates and also markedly lowered sodium pump activity estimated from ouabain-sensitive 86Rb+ uptake by ventricular muscle slices. These effects of ischemia and reperfusion were prevented to various degrees by O2-radical scavengers, such as superoxide dismutase, catalase, dimethyl-sulfoxide, histidine, or vitamin E or by the xanthine oxidase inhibitor, allopurinol. The degree of protection afforded by these agents paralleled that of reduction in enhanced lipid peroxidation of myocardial tissue as estimated from malondialdehyde production. These results strongly suggest that O2 radicals play a crucial role in the injury to sarcolemmal Na+-K+-ATPase during reperfusion of ischemic heart.
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PMID:O2 free radicals: cause of ischemia-reperfusion injury to cardiac Na+-K+-ATPase. 302 76

The accumulation of lipoperoxide (LPO) is reported to occur in the organs of animals with endotoxemia, where it is accompanied by an activation of xanthine oxidase (XOD) and a depletion of superoxide dismutase (SOD). In the present study, three measures of preventing LPO accumulation, ie, prior treatment with a XOD inhibitor, exogenous supply of enzymatic scavengers, and supplementation with chemical quenchers, were investigated to determine how to improve the survival rate of rats with lethal endotoxemia. Thirty minutes after treatment with various doses of allopurinol, SOD, catalase (CAT), vitamin E (VE), and reduced glutathione (GSH), adult male Wistar rats were subjected to endotoxemia by an intraperitoneal injection of 0.4 mg/100 g of Escherichia coli endotoxin. Allopurinol did not improve survival rates, denoting a lower level of XOD and an almost normal level of SOD in the liver. SOD (9,000 U/100 g) with or without CAT (4,000 U/100 g) markedly increased the survival rate of rats, with complete inhibition of hepatic LPO accumulation and suppression of XOD activity. CAT alone had no salutary effects on survival rate or hepatic LPO. Large amounts of VE (100 mg/100 g) or GSH (50 mg/100 g) slightly suppressed the accumulation of LPO in the liver but had no effect on survival rate. In that exogenous SOD has been considered not to penetrate the cellular membrane because of its high molecular weight, the results suggest that the extracellular spaces are the site of SOD action. Lipid peroxidation of the biomembrane initiated by oxygen free radicals released into extra-cellular space from phagocytes may play an important role in the development of lethality in experimental endotoxemia.
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PMID:Inhibition of lipid peroxidation improves survival rate of endotoxemic rats. 302 69

Occlusion of the pulmonary arterial circulation to a lung for prolonged periods has been reported to result in only minimal alterations in lung morphology. We studied the effects of 48 h of pulmonary arterial occlusion followed by 4 h of reperfusion in 18 awake dogs. Because of evidence in other organ systems of O2 radical generation, during reperfusion, nine of the animals were randomly assigned to receive allopurinol, a xanthine oxidase inhibitor, and vitamin E, an antioxidant. Reperfusion resulted in marked edema and inflammatory infiltrates in the reperfused lung but also caused mild edema and inflammation in the contralateral continuously perfused lung. Electron microscopy demonstrated lysis of both capillary endothelial and alveolar epithelial cells bilaterally, with the frequency of cell injury greater on the reperfused side. During reperfusion, body temperatures rose dramatically from 39.4 +/- 0.1 to 40.6 +/- 0.2 degrees C (P less than 0.05) and marked leukopenia developed. There were no differences in any hemodynamic, gas exchange, or morphometric measurements between allopurinol-treated dogs and untreated animals. We conclude that reperfusion causes local and distant injury which does not appear to be mediated by xanthine oxidase-produced O2 radicals.
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PMID:Lung reperfusion in dogs causes bilateral lung injury. 311 55


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