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)

The effectiveness of superoxide dismutase (SOD), catalase (CAT), dimethyl sulphoxide (DMSO) and allopurinol in prevention of peritoneal adhesion formation induced by complete vascular obstruction and reperfusion of an ileal segment was investigated in rats. The ischaemic period was 30 min. Group A (n = 20) were controls, group B (n = 15) received SOD 15,000 U/kg i.v. and group C (n = 17) the same dose of CAT immediately before induction of ischaemia. In group D (n = 20) DMSO 20 mg/kg was given i.v. 5 min before ischaemia, and group E (n = 20) received allopurinol orally 50 mg/kg daily for 2 days and also 2 hours before ischaemia. Ten days later adhesions had developed in 80% of group A, 40% of group B, 47% of group C and 45% of groups D and E (p less than 0.05). The severity of the adhesions was significantly less in the pretreated groups than in the controls. Oxygen-derived free radicals may be pathogenetically important for such adhesion formation. Xanthine oxidase is the principal source of oxygen radicals after a 30-min period of complete regional intestinal ischaemia.
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PMID:The role of oxygen-derived free radicals in peritoneal adhesion formation induced by ileal ischaemia/reperfusion. 274 25

A major impediment to the confirmation of free radical mechanisms in pathogenesis is a lack of direct, chemical evidence that oxygen centered free radicals actually arise in living tissues in quantities sufficient to cause serious damage. This investigation was conducted to validate the use of dimethyl sulfoxide (DMSO) as a quantitative molecular probe for the generation of hydroxyl radicals (HO.) under physiologic conditions. Reaction of HO. with DMSO produces methane sulfinic acid (MSA) as a primary product, which can be detected by a simple colorimetric assay. To develop a method for estimating total HO. production, we studied two model systems: the superoxide driven Fenton reaction in vitro, using xanthine oxidase as the source of superoxide, and a computer model of Fenton chemistry. Measured MSA production both in vitro and in the computer model was a predictable function of the concentrations of DMSO and competing scavengers of HO., according to the principle of competition kinetics. Both experimental results and model calculations showed that Scatchard analysis may be used to infer total HO. generation, despite the presence of scavengers other than DMSO, such as mannitol. Thus, methane sulfinic acid production from DMSO holds promise as an easily measured marker for HO. formation in biologic systems pretreated with DMSO, and Scatchard analysis of repeated experiments with varying DMSO concentrations can yield an estimate of total HO. generation.
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PMID:Scatchard analysis of methane sulfinic acid production from dimethyl sulfoxide: a method to quantify hydroxyl radical formation in physiologic systems. 274 82

Spin-trapping of superoxide ion, O2-, which is produced from two different sources (OH(-)-DMSO and xanthine-xanthine oxidase systems), was investigated by use of a water-soluble, notroso-aromatic spin trap, sodium 3,5-dibromo-4-nitrosobenzene-sulfonate (DBNBS). It was found that O2- from all sources was easily trapped by DBNBS to yield the stable O2- adduct showing the ESR spectrum consisting of a triplet of a triplet [aN (1) = 12.63 G and aH (2) = 0.71 G]. Hydroperoxy radical (HO2.), which can be generated from the oxidation of hydrogen peroxide with Ce4+ ion, was not trapped by DBNBS. These results indicate that the trapped radical is O2-, but not HO2..
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PMID:Spin-trapping of superoxide ion by a water-soluble, nitroso-aromatic spin-trap. 301 Sep 90

When dehydration, infection, and mechanical trauma are prevented, procedures (such as cooling and/or oral antithromboxane) designed to diminish ischemia in experimental zone-of-stasis burns have been associated with no or only minor improvement in wound healing. To test the hypothesis that ongoing skin damage occurring postburn (PB) may in part be due to release of oxygen-derived free radicals during the 16-hour through 4-day PB period of reperfusion in such burns, beginning immediately and for a period of 5 days PB, equal numbers of guinea pigs received: allopurinol 150 mg/kg PO q 6 h vs. placebo, dimethylsulfoxide (DMSO) 75% applied topically q 12 h vs. placebo, or yeast-derived superoxide dismutase coupled with polyethylene glycol (PEG-SOD, Pharmacia) 10,000 U (Fridovich) given IV q 8 h producing a concentration of 16 U/cc of plasma 8 hr after injection vs. placebo. Gross and histologic examination of wounds by a 'blinded' investigator at 1 week and 3 weeks PB revealed no difference between treatment and control groups when rates of re-epithelialization and frequencies of hair-follicle retention were compared. Using the dosages, routes, and model described, treatment of a zone-of-stasis burn with PO allopurinol (a xanthine oxidase inhibitor), topical DMSO (a scavenger of the hydroxyl radical), or IV PEG-SOD (a scavenger of the superoxide radical) during the first 5 days PB was associated with no increase in the rate of re-epithelialization or frequency of hair follicle retention at 1 and 3 weeks PB when compared with controls.
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PMID:Oxygen-derived free radical inhibition in the healing of experimental zone-of-stasis burns. 302 94

The effect of scavengers of oxygen radicals on canine cardiac sarcoplasmic reticulum (SR) Ca2+ uptake velocity was investigated at pH 6.4, the intracellular pH of the ischemic myocardium. With the generation of oxygen radicals from a xanthine-xanthine oxidase reaction, there was a significant depression of SR Ca2+ uptake velocity. Xanthine alone or xanthine plus denatured xanthine oxidase had no effect on this system. Superoxide dismutase (SOD), a scavenger of .O2-, or denatured SOD had no effect on the depression of Ca2+ uptake velocity induced by the xanthine-xanthine oxidase reaction. However, catalase, which can impair hydroxyl radical (.OH) formation by destroying the precursor H2O2, significantly inhibited the effect of the xanthine-xanthine oxidase reaction. This effect of catalase was enhanced by SOD, but not by denatured SOD. Dimethyl sulfoxide (Me2SO), a known .OH scavenger, completely inhibited the effect of the xanthine-xanthine oxidase reaction. The observed effect of oxygen radicals and radical scavengers was not seen in the calmodulin-depleted SR vesicles. Addition of exogenous calmodulin, however, reproduced the effect of oxygen radicals and the scavengers. The effect of oxygen radicals was enhanced by the calmodulin antagonists (compounds 48/80 and W-7) at concentrations which showed no effect alone on Ca2+ uptake velocity. Taken together, these findings strongly suggest that .OH, but not .O2-, is involved in a mechanism that may cause SR dysfunction, and that the effect of oxygen radicals is calmodulin dependent.
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PMID:Calmodulin participation in oxygen radical-induced cardiac sarcoplasmic reticulum calcium uptake reduction. 303 9

Reactive oxygen species have been found to be responsible for the tissue injury caused in experimental pyelonephritis in mice. The extent of lipid peroxidation (as assayed by malondialdehyde formation) was found to be increased significantly (p less than .001) in the infected group as compared to the normal mice. Superoxide dismutase and catalase (oxygen free radical scavengers) showed a significant decrease (p less than .001) in the extent of lipid peroxidation even in the presence of infection. Dimethyl sulfoxide, a hydroxyl ion scavenger, was however found to be effective only at 4 and 7 days postinfection (p less than .001). Allopurinol, an inhibitor of xanthine oxidase, did not significantly (p greater than .05) inhibit the formation of lipid peroxides, even upto 7 days postinfection. There was a significant decrease (p less than .05) in the activities of renal brush border membrane enzymes used as markers of renal tissue damage (i.e. alkaline phosphatase, leucine amino-peptidase and gamma-glutamyl transpeptidase) in the infected group as compared to the normal group. In the presence of superoxide dismutase, dimethylsulfoxide and catalase except allopurinol, the activities of all the enzymes but maltase were found to be increased significantly (p less than .05) as compared to the infected group. There was a significant increase (p less than .01) in the bacterial count in the presence of superoxide dismutase and DMSO in infected mice as compared to the infected control mice. However, no significant difference was observed in the catalase and allopurinol treated groups.
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PMID:Effect of various oxygen free radical scavengers in preventing tissue injury caused by Escherichia coli in pyelonephritic mice. 305 56

Lesion formation due to oral administration of absolute ethanol could be prevented by parenteral pretreatment with antiperoxidative drugs such as butylated hydroxytoluene (BHT), quercetin and quinacrine. Also effective were allopurinol and oxypurinol, inhibitors of xanthine oxidase, but not superoxide dismutase (SOD) and hydroxyl radical scavengers, such as sodium benzoate and dimethyl sulfoxide (DMSO). BHT, quercetin, quinacrine and sulfhydryl compounds such as reduced glutathione and cysteamine which offer gastroprotection in vivo against ethanol inhibited lipid peroxidation induced in vitro by ferrous ion in porcine gastric mucosal homogenate, but SOD, sodium benzoate, DMSO, allopurinol and oxypurinol did not. These results suggest the possibility that an active species, probably derived from free iron mobilized by the xanthine oxidase system, other than oxygen radicals such as hydroxyl radicals, contributes to lipid peroxidation and lesion formation in the gastric mucosa after absolute ethanol administration.
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PMID:Effect of antiperoxidative drugs on gastric damage induced by ethanol in rats. 361 39

Endotoxin injures bovine pulmonary endothelial cells in culture but the cytotoxicity is unaffected by a host of antiinflammatory drugs. We hypothesized that agents which could decrease intracellular concentrations of toxic metabolites of O2 would prevent endotoxin effects on cultured pulmonary artery endothelial cells. We measured endotoxin-induced release of lactate dehydrogenase (LDH) from and production of prostanoids by cultured bovine pulmonary endothelial cells in the presence and absence of dimethyl sulfoxide (DMSO) and the xanthine oxidase inhibitor allopurinol. Escherichia coli endotoxin (0.001-10 micrograms/ml) caused a dose-related release of LDH and stimulated production of both prostacyclin [measured as 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha)] and prostaglandin E2 (PGE2). Both DMSO and allopurinol decreased endotoxin-induced LDH release; this effect was related to concentration of the drugs (0-2% for DMSO and 0-0.3 mg/ml for allopurinol). Both drugs also prevented endotoxin-induced changes in endothelial morphology. Endotoxin increased intracellular reduction of the redox dye nitro blue tetrazolium, caused intracellular oxidation of 2',7'-dichlorofluorescein diacetate and caused release of conjugated dienes from endothelial cells; both DMSO and allopurinol inhibited those responses. DMSO, but not allopurinol, prevented endotoxin-induced production of prostacyclin and PGE2 by endothelium. Direct injury of pulmonary endothelium by endotoxin is inhibited by two chemically dissimilar drugs which have a common potential for decreasing intracellular concentrations of toxic metabolites of O2; indirect evidence suggests that potential as a mechanism for the protective effects of the drugs.
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PMID:Antioxidants protect cultured bovine lung endothelial cells from injury by endotoxin. 365 44

Polymorphonuclear leukocytes undergo the respiratory burst when exposed to a variety of stimuli. This is associated with the production of superoxide anion radical (O-2). Dismutation of O-2 can occur spontaneously to produce hydrogen peroxide (H2O2) and in the presence of metal catalysts O-2 and H2O2 can react to form hydroxyl radical (OH.). Some of these reactive species are released into the interstitium and may cause lipid peroxidation and depolymerization of macromolecules. We have studied the effect of free radicals on vascular permeability. Hypoxanthine and xanthine oxidase were applied topically on the hamster cheek pouch microcirculation model, injected intravenously with FITC-dextran 150 (Mw 150,000) to visualize permeability changes. This caused a flux of O-2 and a significant increase in macromolecular leakage. An attempt was made to elucidate the roles of different radicals by addition of superoxide dismutase (SOD), catalase (CAT), dimethyl sulfoxide (DMSO) and L-methionine to the reaction mixture. A significant decrease in leakage was found with all these substances, indicating OH. or possibly singlet oxygen damage. These results indicate that a free radical flux can cause permeability changes, and we suggest that part of the permeability change seen during inflammation may be related to free radical flux produced by activated leukocytes.
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PMID:Evidence for participation of hydroxyl radical in increased microvascular permeability. 616 80

DMSO is a hydroxyl radical scavenger that inhibits platelet aggregation in vivo in injured microvessels, and that also inhibits the dilation displayed by pial arterioles following a local injury. The injurious stimulus is a result of local excitation of circulating sodium fluorescein by an appropriate light source. It is likely that this excitation results in the generation of hydroxyl radicals, which are the immediately injurious agent. This postulate is supported not only by the inhibitory effect of DMSO but also by the inhibitory effect of glycerol, another hydroxyl scavenger. Both the hypothesis that DMSO inhibits hydroxyl-mediated dilation, and the hypothesis that free radicals can dilate pial arterioles, are further supported by direct evidence from studies employing local application of xanthine oxidase plus acetaldehyde. This well established radical-generating system dilated pial arterioles. The dilation was inhibited by the local application of superoxide dismutase and also by local application of catalase, as well as by intraperitoneal administration of DMSO. Since DMSO failed to inhibit the dilation produced by increases of inspired CO2, we believe that the inhibitory effect of DMSO on the other dilating stimuli in these studies was due to the hydroxyl scavenging properties of this drug, rather than to other nonspecific effects.
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PMID:Dimethyl sulfoxide effects on platelet aggregation and vascular reactivity in pial microcirculation. 641 Sep 63


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