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)

Two typical systems of lipid peroxidation in egg yolk phosphatidylcholine (egg PC) liposomes were compared: an enzymic system involving superoxide (O2) generated by xanthine (X), xanthine oxidase (XO) and Fe(3+)-chelates (Fe(3+)-ADP and Fe(3+)-EDTA), and a non-enzymic system involving ascorbic acid (ASA) and Fe2+. These two systems exhibited a different pH-dependence: the rate in the enzymic system was maximal at pH 8-8.5, whereas that in the non-enzymic system was high below pH 7.4 and low above pH 7.6. The rates of lipid peroxidation differed with the membrane charge, and this charge-dependent phenomenon differed in the two peroxidation systems: in the Fe(3+)-chelates/X-XO-system, the rate was slow in neutrally charged egg PC liposomes and rapid in egg PC liposomes containing negatively charged dicetylphosphate (DCP) or positively charged stearylamine (SA), whereas in the Fe2+/AsA-system, the rate was rapid in neutral egg PC liposomes but no lipid peroxidation occurred in egg PC liposomes charged with DCP or SA. The decomposition rate of the hydroperoxide of PC (PC-OOH) incorporated into dimyristoyl-phosphatidylcholine (DMPC) liposomes differed depending on the membrane charge in the two systems and this charge-dependence of the rates correlated well with that of the initiation rate of lipid peroxidation dependent on membrane charge. In the Fe2+/AsA-system, lipid peroxidation depended on the endogenous presence of PC-OOH, and the amounts of PC-OOH required for initiation of the reaction differed depending on the membrane charge. However, in the Fe(3+)-chelates/X-XO-system, lipid peroxidation occurred very slowly in the absence of PC-OOH, but rapidly in its presence.
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PMID:Lipid peroxidation in egg phosphatidylcholine liposomes: comparative studies on the induction systems Fe2+/ascorbate and Fe(3+)-chelates/xanthine-xanthine oxidase. 874 72

We investigated the hypothesis that xanthine oxidase (XO) mediates platelet aggregation and cyclic flow variations (CFVs) in stenosed canine coronary arteries. CFVs were produced by an external constrictor placed at the site of the coronary artery with the injured endothelium. The severity of CFVs was evaluated by a pulsed Doppler flow probe. If CFVs developed, dogs intravenously received allopurinol, a specific XO inhibitor. The transcardiac gradient (difference between coronary vein and left atrium) of purine metabolites was determined during CFVs and after allopurinol administration. Allopurinol significantly reduced CFVs (from 8 +/- 1 to 1 +/- 1 cycles/h, P < 0.01, n = 14), whereas saline did not (from 8 +/- 1 to 7 +/- 1 cycles/h, n = 7). In seven dogs with CFVs, the transcardiac gradient of xanthine and uric acid concentrations significantly increased after the establishment of CFVs and significantly decreased after the administration of allopurinol. In vitro platelet studies showed that XO enhanced (from 30.9 +/- 2.0 to 47.6 +/- 1.5%, P < 0.0001, n = 10) and allopurinol inhibited ADP-induced platelet aggregation (from 48.3 +/- 1.3 to 24.8 +/- 1.5%, P < 0.0001, n = 10). Our results indicate that allopurinol inhibits platelet aggregation in vitro and provides a protection against CFVs in vivo. Thus XO may be an important mediator in this model.
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PMID:Xanthine oxidase mediates cyclic flow variations in a canine model of coronary arterial thrombosis. 876 49

Experiments were designed to evaluate endothelium-dependent responses of pulmonary arteries following prolonged exposure to oxygen-derived free radicals. Rings of canine pulmonary arteries with and without endothelium were suspended for measurement of isometric force in organ chambers and incubated with xanthine (10(-4)M) plus xanthine oxidase (0.015 U/ml) for 1 h in the absence and presence of either superoxide dismutase (SOD, 150 U/ml), catalase (1,200 U/ml), deferoxamine (10(-3)M), or a combination of all three scavengers. Xanthine plus xanthine oxidase caused significantly greater contractions of rings without compared with those with endothelium. In rings with endothelium, contractions were reduced by SOD or catalase but not by deferoxamine. Following 1 h of exposure to xanthine plus xanthine oxidase, endothelium-dependent relaxations to ADP were reduced but not those to bradykinin or the calcium ionophore A-23187 (calcimycin). Relaxations to ADP were not corrected by incubation with the antioxidants used singly or in combination during the exposure to xanthine plus xanthine oxidase. These results suggest that oxygen-derived free radicals generated from exogenously applied xanthine plus xanthine oxidase cause contractions of canine pulmonary arteries. In addition, even when contractions of rings with endothelium were prevented by SOD and catalase, subsequent expression of some but not all endothelium-dependent relaxations were reduced. Therefore, scavenging of oxygen-derived free radicals may prevent some but not all of the vascular injury caused by oxygen-derived free radicals.
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PMID:Effects of prolonged exposure to oxygen-derived free radicals in canine pulmonary arteries. 876 72

We investigated the inhibition mechanism of lipid peroxidation by estrogens. Estradiol and 2-hydroxyestradiol showed strong inhibitory activities toward NADPH and ADP-Fe(3+)-dependent lipid peroxidations in the microsomes from rat livers only when the steroids were added to the reaction system before the start of the peroxidation reaction. These steroids also strongly inhibited oxygen uptake only when added before the start of the reaction. These results suggest that estradiol and 2-hydroxyestradiol inhibit the initial stage of microsomal lipid peroxidation. Lipid peroxidation of erythrocyte membranes induced by the systems of xanthine oxidase-hypoxanthine and ascorbate was strongly inhibited by 2-hydroxyestradiol, but not by estradiol. Lipid peroxidation of erythrocyte membranes induced by 2.2'-azobis- (amidinopropane) dihydrochloride was not markedly inhibited by estradiol and 2-hydroxyestradiol, suggesting that the steroids have low reactivity with lipid peroxyl radicals. However, lipid peroxidation induced by t-butyl hydroperoxide-Fe3+ was strongly inhibited only by 2-hydroxyestradiol. It seems that 2-hydroxyestradiol may interact with alkoxyl rather than with peroxyl radicals during lipid peroxidation.
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PMID:Inhibition of lipid peroxidation by estradiol and 2-hydroxyestradiol. 877 1

Treatment of rabbit synovial fibroblasts with active oxygen (AO) released by xanthine/xanthine oxidase resulted in an induction of procollagenase in these cells in concentrations ranging from 12.5 micrograms/ml xanthine plus 0.0025 U/ml xanthine oxidase to 50 micrograms/ml xanthine plus 0.01 U/ml xanthine oxidase. Preceding this there was an accumulation of poly(ADP-ribose) for the same concentration range of xanthine/xanthine oxidase. Furthermore, it was found that AO caused activation of the latent procollagenase to the active enzyme in concentrations ranging from 0.1 micrograms/ml xanthine plus 0.00002 U/ml xanthine oxidase to 1 microgram/ml xanthine plus 0.0002 U/ml xanthine oxidase. It is suggested that poly(ADP-ribosyl)ation participates in the induction of procollagenase by relaxing chromatin. Furthermore, it is proposed that AO activates latent procollagenase under physiological conditions.
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PMID:Induction and activation of procollagenase in rabbit synovial fibroblasts after treatment with active oxygen released by xanthine/xanthine oxidase. 883 93

The impact of in vivo ischaemia and ischaemia-reperfusion (I-R) on mitochondrial respiratory function was investigated in hypertrophied (HP) hearts with aortic constriction compared with control hearts using an open-chest rat surgical model. Moreover, mitochondrial susceptibility to superoxide radicals (O2-.) in vitro was examined in HP and control hearts with or without I-R. With the site I substrates pyruvate-malate, mitochondrial state 4 (basal) respiration and the respiratory control index (RCI) were not affected by either ischaemia alone or I-R in both HP and control hearts. State 3 (ADP-stimulated) respiration was increased with I-R in control hearts, but showed a reduction after I-R in the HP hearts. Exposure of mitochondria to O2-. (20 nM hypoxanthine in the presence of 0.13 unit mL-1 xanthine oxidase) significantly increased state 4 respiration, whereas state 3 respiration and RCI were decreased in all treatment groups. I-R hearts in both HP and control showed greater increases in state 4 respiration with O2-. than either sham or ischaemic hearts. HP hearts exhibited a significantly lesser extent of inhibition in state 3 respiration and RCI by O2-. compared with control hearts. These changes in mitochondrial respiratory properties were not observed with the site II substrate succinate. Myocardial reduced vs. oxidized glutathione ratio was significantly decreased after I-R in both control and HP hearts. Malondialdehyde content showed an increase with I-R, but the increase was significant only in control hearts. These data indicate that short-term in vivo I-R does not impair heart mitochondrial respiratory function, but renders the organelles more vulnerable to imposed oxidative stress. Mitochondria from the HP hearts are more resistant to free radical damage under normal and ischaemic conditions; however, this advantage is severely compromised after reperfusion.
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PMID:Ischaemia-reperfusion induced alterations of mitochondrial function in hypertrophied rat heart. 886 86

The acetone-H2O (9:1) extract from the stem of Cistanche deserticola showed a strong free radical scavenging activity. Nine major phenylethanoid compounds were isolated from this extract. They were identified by NMR as acteoside, isoacteoside, 2'-acetylacteoside, tubuloside B, echinacoside, tubuloside A, syringalide A 3'-alpha-rhamnopyranoside, cistanoside A and cistanoside F. All of these compounds showed stronger free radical scavenging activities than alpha-tocopherol on 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and xanthine/xanthine oxidase (XOD) generated superoxide anion radical (O2-.). Among the nine compounds, isoacteoside and tubuloside B, whose caffeoyl moiety is at 6'-position of the glucose, showed an inhibitory effect on XOD. We further studied the effects of these phenylethanoids on the lipid peroxidation in rat liver microsomes induced by enzymatic and non-enzymatic methods. As expected, each of them exhibited significant inhibition on both ascorbic acid/Fe2+ and ADP/NADPH/Fe3+ induced lipid peroxidation in rat liver microsomes, which were more potent than alpha-tocopherol of caffeic acid. The antioxidative effect was found to be potentiated by an increase in the number of phenolic hydroxyl groups in the molecule.
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PMID:Antioxidative effects of phenylethanoids from Cistanche deserticola. 899 43

Xanthine dehydrogenase (XDH) and xanthine oxidase (XO) are enzymes involved in the metabolism of purines in various organisms. XO produces superoxide radicals, suggesting that is responsible for tissue ischemia-reperfusion injury. To test this notion further studies were performed on rat kidneys and the time course of changes in purine nucleotides, oxypurines and XDH and XO activity was determined. At 24 hours after reperfusion subsequent to 30-minute ischemia, serum creatinine increased to 0.83 +/- 0.74 mg/dl from 0.28 +/- 0.06 mg/dl (the level prior to ischemia, the control). Renal ATP and ADP contents were reduced after ischemia lasting for 30 minutes and restored 10 minutes after reperfusion following 30 minutes of ischemia. The renal AMP content increased after 30 minutes of ischemia and recovered within 10 minutes after reperfusion. The total adenine nucleotide (TAN) content was reduced gradually during ischemia-reperfusion in the rat kidney. Although the energy charge was reduced following 30 minutes of ischemia, it was restored to the control level 10 minutes following reperfusion. Hypoxanthine (HX) and xanthine (X), which had accumulated at 30 minutes after ischemia, were reduced to the control levels 10 minutes after reperfusion. There were no significant changes in the pre-ischemia values of total XDH and XO activities or XDH/XO ratio during the period nor at various time intervals (up to 24 hours) during reperfusion. It was shown that HX and X accumulate without significant conversion of XDH to XO during ischemia. Therefore the putative role of XO in ischemia-reperfusion injury seems to more complex than initially predicted.
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PMID:[The role of xanthine dehydrogenase (xanthine oxidase) in ischemia-reperfusion injury in rat kidney]. 901 77

The effect of eugenol on xanthine oxidase (XO) xanthine(X)-Fe+3-ADP mediated lipid peroxidation was studied in liver microsomal lipid liposomes. Eugenol inhibited the lipid peroxidation in a dose dependent manner as assessed by formation of thiobarbituric acid reactive substances. When tested for its effect on XO activity per se, (by measuring uric acid formation) eugenol inhibited the enzyme to an extent of 85% at 10 microm concentration and hence formation of O2.- also. However, the concentration of eugenol required for XO inhibition was more in presence of metal chelators such as EDTA, EGTA and DETAPAC, but not in presence of deferoxamine, ADP and citrate. The antiperoxidative effect of eugenol was about 35 times more and inhibition of XO was about 5 times higher as compared to the effect of allopurinol. Eugenol did not scavenge O2.- generated by phenazine methosulfate and NAD but inhibited propagation of peroxidation catalyzed by Fe2+ EDTA and lipid hydroperoxide containing liposomes. Eugenol inhibits XO-X-Fe+3 ADP mediated peroxidation by inhibiting the XO activity per se in addition to quenching various radical species.
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PMID:Inhibition of xanthine oxidase-xanthine-iron mediated lipid peroxidation by eugenol in liposomes. 904 22

The effect of 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl(4-OH-TEMPO), a scavenger for free radicals, and 4-hydroxypyrazolo [3,4-d(pyrimidine)allopurinol], a xanthine oxidase inhibitor, on the hydrazine-induced changes of mitochondrial ultrastructure and those in the antioxidant system of the liver were investigated using rats as experimental animals. Animals were placed on a powdered diet containing 0.5% hydrazine for 7 d in the presence and absence of a combined treatment with 4-OH-TEMPO or allopurinol. Results obtained were as follows. 4-OH-TEMPO completely prevented the hydrazine-induced formation of megamitochondria in the liver, while it was partly prevented by allopurinol. The following changes observed in hydrazine-treated animals were improved almost completely by 4-OH-TEMPO:decreases in the body weight and liver weight; lowered rates of ADP-stimulated respiration and coupling efficiency of hepatic mitochondria; remarkable elevation of the level of lipid peroxidation. Improving effects of allopurinol were incomplete. The present results suggest that free radicals may play a key role in the mechanism of the hydrazine-induced formation of megamitochondria and that a part of free radicals generated during the hydrazine intoxication is ascribed to the degradation of purine nucleotides via xanthine oxidase. A general mechanism of the megamitochondria formation induced in various pathological conditions besides the case of hydrazine are discussed.
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PMID:Role of free radicals in the mechanism of the hydrazine-induced formation of megamitochondria. 919 91


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