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-derived oxidants and leukocytes have been implicated in the microvascular injury associated with reperfusion of ischemic intestine. The objective of this study was to determine whether xanthine oxidase-derived oxidants play a role in the leukocyte-microvascular interactions initiated by ischemia-reperfusion. Adherence and extravasation of leukocytes were monitored in cat mesenteric venules subjected to 1 h of ischemia (blood flow reduced to 20% of control) and reperfusion. Leukocyte rolling velocity, vessel diameter, and red cell velocity were also measured in control (untreated) animals and in animals pretreated with either allopurinol or superoxide dismutase. The responses of venular blood flow, wall shear rate, and leukocyte rolling velocity to ischemia and reperfusion did not differ between the three experimental groups. In control animals, 1 h of ischemia was associated with significant adherence and extravasation of leukocytes with reperfusion greatly enhancing these responses. Allopurinol treatment did not alter the responses to ischemia per se, yet it largely prevented the further increment in adherence and extravasation associated with reperfusion. Superoxide dismutase treatment attenuated the leukocyte responses elicited by both ischemia and reperfusion. Our observations that both allopurinol and superoxide dismutase attenuate reperfusion-induced leukocyte adherence and extravasation are consistent with the hypothesis that xanthine oxidase-derived oxidants initiate the leukocyte infiltration induced by reperfusion of ischemic intestine.
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PMID:Leukocyte adherence to venular endothelium during ischemia-reperfusion. 259 4

The potential role of the hypoxanthine-xanthine oxidase system in human chorionic gonadotropin-induced ovulation, nuclear maturation, and preimplantation development was investigated in the rabbit by use of the xanthine oxidase inhibitor allopurinol. Allopurinol (50 mg/kg) or vehicle was injected, followed by human chorionic gonadotropin (100 IU). Administration of inhibitor or vehicle was repeated 3 hours later. Ovaries and ovulated ova were inspected 12 or 24 hours after human chorionic gonadotropin administration for follicle rupture, cumulus dispersal, and nuclear maturation. Ova were inseminated in vitro and assessed for development to the blastocyst stage, up to 96 hours after insemination. Allopurinol significantly reduced ovulatory efficiency, defined as the percent of large follicles that ovulate, and decreased the percent of ova with cumulus dispersal. Allopurinol significantly inhibited morula and blastocyst formation. These data suggest that the xanthine oxidase system may play a role in ovulation and early embryonic development.
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PMID:In vivo administration of allopurinol affects ovulation and early embryonic development in rabbits. 260 30

Xanthine:acceptor oxidoreductase activities were assayed in free skin flaps following prolonged preservation. In normal rat skin, xanthine dehydrogenase transfers electrons to NAD+ and accounts for 73% of total oxidoreductase activity, and xanthine oxidase transfers electrons to molecular oxygen and accounts for the remaining 27%. Xanthine oxidase activity increased significantly in skin flaps during ischemia: approximately 30 and 100% increases after 6 and 24 hr of ischemia, respectively. Allopurinol inhibited xanthine oxidoreductase activity: free skin flaps obtained from allopurinol-treated animals exhibited a low level of xanthine oxidoreductase activity throughout the period of preservation. Systemic allopurinol significantly improved the survival rate from 32 to 75% of free flaps transferred after 24 hr of preservation at room temperature. These observations suggest that the xanthine oxidase system is a major source of oxygen free radicals following ischemia/reperfusion in skin. The increase in xanthine oxidase is attributable to the conversion of xanthine dehydrogenase to oxidase, a conversion which involves sulfhydryl oxidation in skin flaps.
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PMID:Xanthine:acceptor oxidoreductase activities in ischemic rat skin flaps. 264 73

The transfer of purines through the hematoencephalic barrier is poorly understood. Allopurinol inhibits the enzyme xanthine oxidase and increases xanthine and hypoxanthine plasma levels, but it should not increase the cerebrospinal fluid (CSF) levels of these purines owing to the absence of xanthine oxidase in the central nervous system (CNS). In the present study we evaluated the plasma and CSF concentrations of uric acid, hypoxanthine, xanthine and inosine in the baseline state and after 7 days of allopurinol administration (5-10 mg/kg/24 h) in 4 patients with hypoxanthine phosphoribosyltransferase (HPRT) deficiency. The CSF uric acid level was positively correlated with its plasma level (r = 0.93, p less than 0.01). The CSF hypoxanthine and xanthine concentrations were, as a mean, 5 and 2 times higher, respectively, in patients with HPRT deficiency than in 4 control individuals. As hypoxanthine basically comes from adenine nucleotides, while xanthine comes from guanine nucleotides, this finding suggests that in the CNS of patients with HPRT deficiency there is a higher degradation level of adenine nucleotides than of guanine nucleotides. Allopurinol increased plasma concentration of hypoxanthine, xanthine and inosine 4, 10 and 3 times, respectively, in relation to baseline values. In CSF, the mean increase of hypoxanthine and xanthine concentration was 17.5 mumol and 7.7 mumol, respectively, whereas inosine level was unchanged. These results suggest that in HPRT deficiency hypoxanthine and xanthine may be transferred to the brain.
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PMID:[Purine transport through the blood-brain barrier in hypoxanthine phosphoribosyltransferase deficiency]. 272 4

Oxypurines (hypoxanthine + xanthine, HX) were measured polarographically in the mixed umbilical cord blood plasma, the maternal venous blood plasma and in the anterior amniotic fluid of 104 deliveries. The HX increase was found in groups with clinical signs of perinatal hypoxia. The HX concentration in the mixed umbilical plasma above 15 umol/l (i.e., means +/- 2 S.D.) should be considered as pathological. The following results of experiments on animals suggested a possible pathogenic significance of xanthine oxidase (XOD) reaction on hypoxic injury: The higher the plasma XOD activity of different species (guinea pig, hamster, rat, mouse) the shorter was the survival time of the species in the interrupted hypoxia. Administration of hypoxanthine decreased the survival time of rats in the interrupted hypoxia, while the administration of allopurinol increased it. Allopurinol suppressed the post-hypoxic autoimmune response of the rats to brain tissue.
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PMID:Hypoxanthine in diagnosis, prognosis and pathogeny of hypoxic injury. 273 Jun 7

Experiments were conducted on 268 male albino rats with modeled acute pancreatitis to study the xanthine oxidase (XO) activity in the pancreatic tissue during intraperitoneal administration of stimulators of pancreatic exocrine function (pilocarpine) and inhibitors of enzyme activity (allopurinol). Pilocarpine (0.1 mg/kg) increased XO activity by 90-100% one-three hours after injection, which was due to increased synthesis of the enzyme. Allopurinol (500 mg/kg) inhibiting XO activity removes the XO activating effect of pilocarpine in the first two hours after injection. It was established that one of the tranquilizers of the 1,4-benzodiazepine series--seduxen (15 mg/kg) produces an inhibiting effect on XO activity and, like allopurinol, removes the XO activating effect of pilocarpine. Complete parallelism was also revealed between the dynamics of changes of XO activity in the pancreatic tissue and alpha-amylase in blood under the effect of the preparations studied.
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PMID:[Role of xanthine oxidase in the genesis of acute pancreatitis]. 275 30

It has been suggested that oxygen-derived free radicals play a decisive role in the pathogenesis of acute experimental pancreatitis in a model of edematous pancreatitis. Accordingly, allopurinol, a xanthine oxidase inhibitor, was shown to mitigate the development of nonfatal acute pancreatitis in ex vivo perfusion models using dogs. For further evaluation of allopurinol, its effect was studied in two forms of fatal necrotizing acute experimental pancreatitis: sodium taurocholate-induced pancreatitis in rats and choline-deficient ethionine-supplemented diet-induced pancreatitis in mice. Allopurinol did not affect the mortality rate, pancreatic enzyme elevation in serum and ascites, the enzyme content of the pancreas, or any parameter indicating histopathological damage in the pancreas. Although these experiments did not determine the role oxygen-derived free radicals play in the development of pancreatitis, they show, none the less, the absence of any beneficial therapeutic effect of a xanthine oxidase like allopurinol on the development of the disease once it has begun.
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PMID:Xanthine oxidase inhibitor in acute experimental pancreatitis in rats and mice. 276 73

Rabbit kidneys were subjected to 120 min of warm ischaemia or to 120 min of warm ischaemia followed by 60 min reperfusion with blood in vivo before being removed, homogenised and incubated at 37 degrees C for 90 min. Lipid extracts were obtained and monitored for Schiff base (fluorescence emission 400-450 nm, excited at 360 nm), thiobarbituric acid (TBA)-reactive material (emission 553 nm, excited at 515 nm) and diene conjugates (absorbance at 237 nm). Samples removed before incubation were assayed for reduced glutathione (GSH) and oxidised glutathione (GSSG) to provide an index of glutathione redox activity (GSH:GSSG). Allopurinol injected systemically i.v. (a) 15 mins before kidneys were clamped, (b) 15 mins before they were reperfused or (c) as two injections (before clamping and before reperfusion) significantly inhibited these biochemical markers of lipid peroxidation. Administration before reperfusion had a markedly more pronounced effect than when allopurinol was given before warm ischaemia only. It is concluded that allopurinol is probably effective because of its ability to inhibit xanthine oxidase and consequently lipid peroxidation during reperfusion rather than by preventing loss of purine nucleotides from hypoxic cells during ischaemia.
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PMID:Allopurinol inhibits lipid peroxidation in warm ischaemic and reperfused rabbit kidneys. 279 46

Oxygen-derived free radicals are believed to contribute to reperfusion injury based, in part, upon results conferred by the pharmacologic administration of allopurinol. Allopurinol inhibits xanthine oxidase (XO) activity in ischemic tissues. The possible role of XO as a pathologic mediator prompted examination of its effects on isolated peripheral canine neutrophils. In contrast to neutrophils alone, or following stimulation with phorbol myristate acetate (PMA), it was determined that XO affected both the membrane potential and the metabolism significantly. Membrane potential assay showed that at 5-10 min, PMA depolarized 89-96% of the canine neutrophils between 32-48%. Incubation with 0.5 U/ml XO involved fewer cells (54-86%), but at substantially increased cellular depolarization levels (76-90%). Metabolic assay showed that XO concentrations as low as 0.124 U induced significant cellular H2O2 production compared with temperature controls. At 0.25-0.5 U XO/10(6) cells, cytosolic H2O2 increases were almost three times those of PMA.
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PMID:Xanthine oxidase potentiation of reactive oxygen intermediates in isolated canine peripheral neutrophils. 279 91

The existence of uric acid in mammalian brain was recently reported, but it has not yet become a consensus. The mammalian brain has been thought to lack xanthine oxidase, which catalyzes hypoxanthine to xanthine and xanthine to uric acid as the last steps of ATP degradation in other tissue. Using high-performance liquid chromatography, we performed assays for hypoxanthine, xanthine, and uric acid in rat brain after cerebral ischemia. It was confirmed that all three substances showed significant augmentation in the removed brains and that the chronological order of those increases corresponded to the order in the metabolic pathway. Allopurinol, a specific inhibitor of xanthine oxidase, significantly suppressed the increases in uric acid and xanthine, and a compensatory accumulation of hypoxanthine was observed. From these results, it was concluded that uric acid does exist in the brain, increases after ischemia, and is possibly the end product of purine degradation in the brain. Furthermore, it is suggested that xanthine oxidase exists in the brain and catalyzes the reaction from hypoxanthine to xanthine and then to uric acid. These reactions catalyzed by xanthine oxidase are considered to be a source of free radicals and may play important roles in the pathogenesis of cerebral ischemic injury.
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PMID:Cerebral uric acid, xanthine, and hypoxanthine after ischemia: the effect of allopurinol. 279 98


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