Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since only little xanthine oxidase (XO) activity in mammalian brain was detected in earlier reports, the major end product of AMP degradation in the brain has been believed to be hypoxanthine. Our recent experimental study however, has indicated the presence of uric acid in the rat brain subjected to focal ischemia or cold injury. Allopurinol, a xanthine oxidoreductase inhibitor, has been found to markedly suppress the uric acid production in the same experimental settings. These results suggested that uric acid is generated from hypoxanthine by enzymatic reaction in injured brain tissue. The aim of this experiment is to prove the existence of xanthine oxidoreductase activity in brain tissue. Xanthine oxidoreductase activity in rat cerebral tissue was measured immediately or at 24-hour after decapitation. Under pentobarbital anesthesia, twenty Sprague-Dawley rats were killed by decapitation following washout of the blood by trans-cardiac perfusion with cold physiological saline. Immediately or after 24 hours of decapitation ischemia, the forebrain was removed and homogenized in 6 ml ice cold 0.05 M potassium phosphate buffer (pH 7.8) containing 1 mM phenylmethylsulfonyl fluoride, 0.3 mM EGTA, and 10 mM dithiothreitol. The homogenate was centrifuged at 100,000 g for 60 min and then the supernatant was dialyzed overnight against 0.05 M potassium phosphate buffer (pH 7.8). Aliquot of each dialyzed supernatant (sample) and standard xanthine solution with NAD was reacted at 37 degrees C for 15 min to measure the combined activity of xanthine dehydrogenase (XDH) and XO. For the measurement of XO, standard xanthine solution without NAD was used.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Xanthine oxidoreductase activity in rat brain tissue: the changes after decapitation]. 280 24

Uric acid (UA) in the rat brain was measured by HPLC with an electrochemical detector following focal ischemia. At 24 h after the operation, the UA level in the ischemic center was 105.47 +/- 8.39 nmol/g tissue, whereas it was 8.36 +/- 1.86 in the sham-operated group. Allopurinol, xanthine oxidase inhibitor, almost completely inhibited this UA accumulation. These data demonstrate that the UA increase in the ischemic brain is due to the xanthine oxidase reaction.
 ...
PMID:Allopurinol inhibits uric acid accumulation in the rat brain following focal cerebral ischemia. 280 84

This study was performed to clarify the relationship between hemodynamics, congestive damage, lipid peroxidation and intraluminal hemorrhage of the small intestine. Using 51Cr-red blood cells, with a temporary occlusion of the portal vein for 30 min. in rats, the hemodynamic, biochemical and histological changes were investigated. By occluding the portal vein, its pressure increased to a level eight times higher than normal, and destruction of the intestinal mucosa and an increase of TBA reactants were observed. The intraluminal hemorrhage of the intestine increased to a quantity 7.5 times higher than usual during portal vein occlusion, and it decreased gradually after reperfusion. At 120 min. after reperfusion, this amount remained high, but the administration of Allopurinol diminished its level. A technique of temporary simultaneous occlusion of the superior mesenteric artery or the bypass between the portal and jugular veins was effective in reducing the congestive damage on the intestine. During the occlusion of the portal vein, sudden and high pressure of the portal vein primarily causes congestive damage, and superoxide generated by a xanthine oxidase system during reperfusion may cause lipid peroxidation which induces reperfusion injury. Thus, the lipid peroxidation may accelerate the injury on the small intestine.
 ...
PMID:[Experimental study of injury on the small intestine in acute portal vein occlusion and the following restoration of portal vein flow in rats--hemodynamics and lipid peroxidation]. 281 42

We studied the cytotoxic effects of ferric nitrilotriacetate (Fe-NTA) on normal rat liver epithelial cells (RL34) cultured in medium containing 10% fetal calf serum. Marked cytolysis was present in cells exposed to greater than or equal to 25 micrograms/ml iron of Fe-NTA, but not all the cells exposed to 50 micrograms/ml iron were lethally injured. The remaining cells showed anomalous growth, namely cell pile-up and aggregation. Superoxide dismutase inhibited this iron-induced cytotoxicity, whereas catalase, mannitol, dimethyl sulfoxide, and 1,4-diazabicyclo-[2.2.2.] octane did not. RL34 cells exposed to Fe-NTA actually produced a large amount of superoxide radicals (O2-.), whereas unexposed control cells produced none. Allopurinol inhibited O2-. production and prevented cell injury by Fe-NTA. These results show that the injury to cells produced by Fe-NTA depends on the generation of O2-., the source of which may be xanthine oxidase.
 ...
PMID:Role of superoxide radicals in cytotoxic effects of Fe-NTA on cultured normal liver epithelial cells. 282 65

The role of oxygen radicals and lipid peroxidation in calcium-paradox injury in isolated perfused rat hearts was studied by examining the effects of mannitol and (or) allopurinol on this phenomenon. Myocardial changes due to calcium paradox were characterized by contractile failure, a rise in resting tension, and cell damage. These changes were also accompanied by increased lipid peroxidation, as indicated by an increase in malondialdehyde content. Mannitol (an effective quencher of hydroxyl radicals) treatment resulted in a dose-dependent decrease in lipid peroxidation but did not affect other changes due to calcium paradox. Allopurinol (an inhibitor of xanthine oxidase) neither affected lipid peroxidation nor modified any of the structure-function changes due to calcium paradox. These data demonstrate the occurrence of lipid peroxidation which, however, may not be involved in the observed structure-function changes due to calcium paradox. It is also suggested that in this experimental model, xanthine oxidase may not be the inducer of oxygen radicals or of lipid peroxidation.
 ...
PMID:Contracture and cell damage in calcium paradox is not caused by lipid peroxidation. 284 35

Allopurinol has been employed as a "specific" inhibitor of xanthine oxidase in studies of hypoxic/reoxygenation injury. Pulse radiolysis was used to establish rate constants for the reactions of allopurinol and its major metabolite oxypurinol with hydroxyl radicals: values were (1.45 +/- 0.24) x 10(9) M-1 s-1 for allopurinol and (4.95 +/- 0.84) x 10(9) M-1 s-1 for oxypurinol. These rate constants show that, in view of the amounts of allopurinol that have been used in animal studies, hydroxyl radical scavenging by this molecule could contribute to its biological actions, especially if animals are pre-treated with allopurinol, so allowing oxypurinol to form. The ability of allopurinol to protect tissues not containing xanthine oxidase against reoxygenation injury may be related to radical scavenging by allopurinol and oxypurinol.
 ...
PMID:On the specificity of allopurinol and oxypurinol as inhibitors of xanthine oxidase. A pulse radiolysis determination of rate constants for reaction of allopurinol and oxypurinol with hydroxyl radicals. 285 27

The release of D-[3H]aspartate, [3H]noradrenaline, and of endogenous glutamate and aspartate from rat hippocampal slices was significantly increased when the slices were incubated with xanthine oxidase plus xanthine to produce superoxide and hydroxyl free radicals locally. Allopurinol, a specific xanthine oxidase inhibitor, the hydroxyl-radical scavenger D-mannitol, or the superoxide-radical scavenger system formed by superoxide dismutase plus catalase prevented this release. These results suggest that endogenous excitatory amino acids are released consequent to the formation of free radicals. The excess of glutamate and aspartate released by this mechanism could be one of the factors contributing to the death of neurons after anoxic or ischemic injuries.
 ...
PMID:Excitatory amino acid release from rat hippocampal slices as a consequence of free-radical formation. 290 25

Paraxanthine (PX; 1,7-dimethylxanthine) is the major metabolite of caffeine in humans. Despite the continuous exposure of a large proportion of the population to PX, little is known about PX disposition in humans. The present study was performed to define the metabolic partial clearances of PX in humans and, by determining the effects of cimetidine and allopurinol pretreatments on PX disposition, assess the relative importance of cytochrome P-450 and xanthine oxidase in PX biotransformation. The combined formation of the 7-demethylated products 1-methylxanthine (1-MX), 1-methyluric acid (1-MU) and 5-acetyl-amino-6-formylamino-3-methyluracil (AFMU) accounted for 67% of PX clearance. Formation of 7-methylxanthine (7-MX) and 1,7-dimethyluric acid and renal excretion of unchanged PX comprised 6, 8 and 9% of PX clearance, respectively. Allopurinol pretreatment had no effect on PX plasma clearance but decreased 1-MU excretion and increased 1-MX excretion, with the combined excretion of these metabolites remaining constant. Cimetidine pretreatment decreased PX plasma clearance by 30%. Metabolic partial clearances to 1-MX + 1-MU and to AFMU were reduced to a similar extent (ca. 40%) in the cimetidine treatment phase, but other pathways were not significantly affected. These data are consistent with 1-MX and AFMU being derived from a common intermediate, the formation of which is mediated by cytochrome P-450. Xanthine oxidase catalyzes only the secondary conversion of 1-MX to 1-MU.
 ...
PMID:Paraxanthine metabolism in humans: determination of metabolic partial clearances and effects of allopurinol and cimetidine. 291 77

Recent studies examining the effect of allopurinol on bacterial killing by leukocytes [Tubaro et al., Biochem. Pharmac. 29, 3018 (1980); Tritsch and Neiswander, Life Sci. 32, 1359 (1983)] have been interpreted by those authors as proof that xanthine oxidase is the major superoxide producing enzyme in activated leukocytes. To test the assertion that xanthine oxidase is involved in the production of superoxide by activated human neutrophils, the xanthine oxidase content of neutrophils was measured, and the effect of allopurinol on neutrophil functions, including superoxide production, was studied. Neutrophils were found to contain a level of xanthine oxidase insufficient to account for the flux of superoxide associated with neutrophil activation. Allopurinol did not inhibit superoxide production induced by opsonized zymosan, phorbol myristic acetate, or formylmethionylleucylphenylalanine. Furthermore, neither chemotaxis nor degranulation was affected by allopurinol. Allopurinol was also found ineffective in blocking superoxide-mediated carrageenan-induced foot edema in the rat. These studies are interpreted as evidence that xanthine oxidase is not a major superoxide-generating system in activated neutrophils as has been suggested by others.
 ...
PMID:Effect of allopurinol on neutrophil superoxide production, chemotaxis, or degranulation. 299 56

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.
 ...
PMID:Inhibition of lipid peroxidation improves survival rate of endotoxemic rats. 302 69


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>