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)

Creatine kinase is a sulfhydryl containing enzyme that is particularly susceptible to oxidative inactivation. This enzyme is potentially vulnerable to inactivation under conditions when it would be used as a diagnostic marker of tissue damage such as during cardiac ischemia/reperfusion or other oxidative tissue injury. Oxidative stress in tissues can induce the release of iron from its storage proteins, making it an available catalyst for free radical reactions. Although creatinine kinase inactivation in a heart reperfusion model has been documented, the mechanism has not been fully described, particularly with regard to the role of iron. We have investigated the inactivation of rabbit muscle creatine kinase by hydrogen peroxide and by xanthine oxidase generated superoxide or Adriamycin radicals in the presence of iron catalysts. As shown previously, creatine kinase was inactivated by hydrogen peroxide. Ferrous iron enhanced the inactivation. In addition, micromolar levels of iron and iron chelates that were reduced and recycled by superoxide or Adriamycin radicals were effective catalysts of creatinine kinase inactivation. Of the physiological iron chelates studied, Fe(ATP) was an especially effective catalyst of inactivation by what appeared to be a site-localized reaction. Fe(ICRF-198), a non-physiological chelate of interest because of its putative role in alleviating Adriamycin-induced cardiotoxicity, also catalyzed the inactivation. Scavenger studies implicated hydroxyl radical as the oxidant involved in iron-dependent creatine kinase inactivation. Loss of protein thiols accompanied loss of creatine kinase activity. Reduced glutathione (GSH) provided marked protection from oxidative inactivation, suggesting that enzyme inactivation under physiological conditions would occur only after GSH depletion.
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PMID:Free radical inactivation of rabbit muscle creatinine kinase: catalysis by physiological and hydrolyzed ICRF-187 (ICRF-198) iron chelates. 783 53

An investigation was made into the possible involvement of the enzyme xanthine oxidase (XO) (EC 1.1.3.22), both reversible (XOrev) and irreversible (XOirr), in damage observed after short-term in vivo hepatic ischaemia/reperfusion (60 or 120 min I and 15 min R) in fasted rats with: (i) a physiological content of XO (25%); and (ii) higher XO percentage (45%). In the latter the hepatic XO physiological percentage was increased by diethylmaleate treatment (300 mg kg-1) that depleted the cytosolic glutathione (GSH) to 14% of the controls. It was shown that, in animals with physiological content of XO, 60 and 120 min of hepatic ischaemia followed by 15 min reperfusion results in decreased GSH levels, and significantly increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum levels, without any modification of either the percentages of XO (XOirr and XOrev) or the hepatic thiobarbituric acid reactive substances (TBARS). Sixty minutes of ischaemia/reperfusion in rats with the higher XO level and lower hepatic GSH content led to further conversion of XDH to XOrev, with no increase in XOirr. In addition, the ALT and AST serum levels in these animals rose to the same extent as in normal rats after 120 min ischaemia and 15 min reperfusion, this extent being observed to be associated with a moderate increase in thiobarbituric acid reactive substances (TBARS). However, the administration of allopurinol, at a dose of 50 mg kg-1, which almost completely inhibits XO activity, did not lead to any decrease in liver damage or TBARS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:No documentable role for xanthine oxidase in the pathogenesis of hepatic in vivo ischaemia/reperfusion injury. 786 19

In 6-month-old male Wistar rats, levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA), dehydroascorbic acid (DHAA), uric acid, glutathione (GSH) and 1-methyl-4-phenylpyridinium ion (MPP+) were determined by HPLC in the crude striatal synaptosomal fraction after single injections of MPTP 35 mg/kg i.p. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced a 32.5% death rate within 15 min to 10 h. Groups of surviving rats were sacrificed 1, 3, 8 and 24 h after MPTP. MPTP significantly increased levels of DHAA and uric acid and decreased levels of DOPAC and GSH. Individual synaptosomal levels of MPP+ were correlated inversely with DOPAC (r = -0.601, P < 0.002) and GSH levels (r = -0.496, P < 0.02) and directly with levels of uric acid (r = +0.627, P < 0.001); these latter, in turn, were correlated with DHAA (r = +0.418, P < 0.05) and GSH levels (r = -0.357, P = 0.07). In conclusion, the response of the endogenous antioxidant system (increase in AA oxidation, decrease in GSH levels) correlates well with the MPTP-induced increase in uric acid levels and provides further evidence for a mechanism of MPTP neurotoxicity involving oxidative stress produced by xanthine oxidase.
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PMID:Correlation between 1-methyl-4-phenylpyridinium ion (MPP+) levels, ascorbic acid oxidation and glutathione levels in the striatal synaptosomes of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated rat. 790 98

Incubation of phorbol-myristate acetate-stimulated human polymorphonuclear leukocytes (PMNs) with phenylalanine and salicylate induced significant levels of formation of o- and m-tyrosines, and 2,3- and 2,5-dihydroxybenzoates (DHBAs), respectively, dependent on reaction time. Aromatic hydroxylation reactions were not inhibited by desferrioxamine, nor were they affected by the removal of trace ion contamination from the buffer solution used by treatment with conalbumin. Hydroxylation reactions were largely blocked by superoxide dismutase and hydroxyl radical (OH.) scavengers. The results of the present study suggest that the generation of OH. by human PMNs occurs during the respiratory burst. Hydroxylation of both phenylalanine and salicylate by stimulated human PMNs were significantly accelerated by incubation in the presence of the reduced form of glutathione (GSH). Hydroxylation of phenylalanine by stimulated guinea pig PMNs in the presence of GSH was significantly inhibited by desferrioxamine, although the same hydroxylation in the absence of GSH was not affected. Hydroxylation of phenylalanine by the hypoxanthine (HX)-xanthine oxidase (XO) system by intact PMNs was significantly accelerated by the addition of GSH, although that in the absence of PMNs was largely inhibited. Desferrioxamine showed an inhibitory effect on hydroxylation by the HX-XO system in the presence, but not in the absence, of intact PMNs. The results suggest that the formation of OH. by stimulated PMNs is accelerated by GSH, based on the occurrence of the Harber-Weiss reaction catalyzed by transition metal ions liberated and reduced by GSH from PMNs, and by the effective accumulation of H2O2 by the GSH-induced inhibition of catalase.
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PMID:Hydroxylation of phenylalanine and salicylate by stimulated polymorphonuclear leukocytes and the accelerating effect of glutathione on their hydroxylation. 795 Nov 35

In the present study, it was observed that somatostatin could significantly protect rat gastric mucosa from injury induced by cold-restraint stress and inhibit the stress induced increase of malonaldehyde (MDA) content. In the gastric mucosa of stress rats, the xanthine oxidase (XO) activity were increased and the glutathione peroxidase (GSH-Px) activity were decreased respectively, while the superoxide dismutase (SOD) activity showed no change. After pretreatment with somatostatin, the decrease of GSH-Px activity was significantly reversed, whereas XO and SOD activities were not significantly affected. The above results show that the protective effect of somatostatin against the stress-induced injury of gastric mucosa may be related to an enhancement of the ability of gastric mucosa to scavenge oxygen-derived free radicals.
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PMID:[Protective effect of somatostatin against stress injury of gastric mucosa may be related to the scavenge of free radicals]. 797 28

Superoxide, generated by a xanthine oxidase/hypoxanthine system, reacts with reduced glutathione (GSH) to cause an increase in oxygen consumption and oxidized glutathione (GSSG) formation, both of which are fully inhibited by superoxide dismutase. In this study we have shown that little, if any, of the additional oxygen consumed is converted to hydrogen peroxide. We have confirmed that approximately 90% of the GSH is oxidized to GSSG, the remainder being converted to the sulfonic acid. Approximately 1.2 mol of GSSG was formed for each additional mole of oxygen consumed in the presence of GSH. The efficiency of the reaction increased with increasing GSH concentration (1-8 mM), pH, and pO2 and with decreasing superoxide generation rate. The results are consistent with a superoxide-dependent chain that does not produce hydrogen peroxide and that is terminated primarily by superoxide dismutation. We propose that this occurs via an initial reaction of superoxide with GSH to produce a sulfinyl radical rather than hydrogen transfer to give the thiyl radical. Our data suggest a rate constant for the superoxide/GSH reaction in the 10(2)-10(3) M-1s-1 range. GSH at the millimolar concentrations found intracellular should react with superoxide, but because superoxide is regenerated, it will not be an effective scavenger. Physiologically, superoxide dismutase is required to prevent chain oxidation of GSH.
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PMID:The reaction of superoxide with reduced glutathione. 797 67

In 6-month-old male Wistar rats, levels of dopamine (DA), dihydroxyphenylacetic acid (DOPAC), ascorbic acid (AA), dehydroascorbic acid (DHAA), uric acid and glutathione (GSH) were determined by HPLC in the striatum and striatal synaptosomes after subchronic oral exposure to MnCl2 50-100-150 mg/kg. Mn significantly decreased levels of DA and GSH and increased levels of DHAA and uric acid both in the striatum and synaptosomes. In synaptosomes, individual total Mn doses/rat were directly correlated with individual DOPAC/DA ratio values (r = +0.647), uric acid (r = +0.532) and DHAA levels (r = +0.889) and inversely correlated with DA (r = -0.757) and GSH levels (r = -0.608). In turn, GSH levels were inversely correlated with uric acid (r = -0.451) and DHAA levels (r = -0.460). In conclusion, the response of striatal cellular defense mechanisms (increase in AA oxidation, decrease in GSH levels) correlated well with changes in markers of dopaminergic system activity and increase in uric acid levels. The latter provides evidence of an Mn-induced oxidative stress mediated by xanthine oxidase.
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PMID:Dopaminergic system activity and cellular defense mechanisms in the striatum and striatal synaptosomes of the rat subchronically exposed to manganese. 799 23

Pathobiological effects of eugenol (4-allyl-2-methoxyphenol), a major constituent of betel quid (BQ), were studied on oral mucosal fibroblasts. At a concentration higher than 3 mmol/L, eugenol was cytotoxic to oral mucosal fibroblasts in a concentration- and time-dependent manner. Cell death was associated with intracellular depletion of glutathione (GSH). Most of the GSH was depleted prior to the onset of cell death. At concentrations of 3 mmol/L and 4 mmol/L, eugenol depleted about 45% and 77% of GSH after one-hour incubation. In addition, eugenol decreased cellular ATP level in a concentration- and time-dependent manner. Eugenol also inhibited lipid peroxidation. Inhibition of lipid peroxidation was partially explained by its dose-dependent inhibition of xanthine oxidase activity. The IC50 of eugenol on xanthine oxidase activity was about 0.3 mmol/L. No DNA strand break activity for eugenol was found at concentrations between 0.5 and 3 mmol/L. Taken together, frequent exposure of oral mucosa to a high concentration of eugenol during the chewing of BQ might be involved in the pathogenesis of oral submucous fibrosis and oral cancer via its cytotoxicity. In contrast, eugenol at a concentration less than 1 mmol/L might protect cells from the genetic attack of reactive oxygen species via inhibition of xanthine oxidase activity and lipid peroxidation.
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PMID:Eugenol triggers different pathobiological effects on human oral mucosal fibroblasts. 800 31

The effect of protoporphyrin (PP) administration on the activities of enzymes related to and/or involved in lipid peroxidation and on the content of reduced glutathione (GSH) was investigated in rat liver. PP, at an intravenous dose of 20 mg/kg, increased GSH content, caused a weak suppression of NADPH-cytochrome c reductase activity and a slight increase of gamma-glutamyl transpeptidase activity 24 h after dosing, but had no effect on the activities of other enzymes such as xanthine oxidase, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase, gamma-glutamylcysteine synthetase or glutathione synthetase. Treatment of rats with diethyl maleate following PP injection resulted in the disappearance of antioxidative action of PP. Furthermore, sinusoidal, but not canalicular, efflux of hepatic GSH was decreased by the PP treatment. The increase of liver GSH content by PP treatment due to the decrease of sinusoidal efflux of GSH from the liver, thus would be involved in the exertion of antioxidative action of PP.
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PMID:Antioxidative effect of protoporphyrin and increase of glutathione in protoporphyrin-administered rat liver. 810 76

Isolated rat hepatocytes were used for the evaluation of nucleotide depletion and oxidative stress as two causal components of postischemic injury following oxygen deficiency. The ATP and GTP loss during anoxia was accompanied by temporary increases of nucleotide degradation products. The critical duration of anoxia for a complete ATP restoration during reoxygenation was between 30 and 60 min. The oxidative stress during reoxygenation was demonstrated by decrease of GSH concentration and increase of TBA-RS level. The tremendous GSH loss could not be balanced by the slight GSSG increase during reoxygenation. Prevention of GSH decrease and TBA-RS increase in parallel to prevention of viability loss in presence of oxipurinol in contrast to lacking improvement of ATP and GTP restoration by this drug speak in favor for the oxidative stress as major causal component for postischemic injury of hepatocytes in comparison with depletion of energy-rich purine nucleotides. The inhibition of formation of reactive oxygen species via xanthine oxidase reactions was found to be the dominant protective effect of oxipurinol against postischemic injury of hepatocytes in comparison with lacking influence on nucleotide salvage and ATP/GTP regeneration and with radical scavenging.
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PMID:Reoxygenation injury of rat hepatocytes: evaluation of nucleotide depletion and oxidative stress as causal components. 822 73


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