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)

We have assessed whether oxygen-derived free radicals produced by xanthine oxidase may be an important trigger mechanism in the genesis of reperfusion-induced arrhythmias. We have examined (i) the effects of inhibition of xanthine oxidase by both folic acid solution and amflutizole; (ii) the effects of the inhibitor of xanthine dehydrogenase to xanthine oxidase conversion, soybean trypsin inhibitor; (iii) the effects of administration of superoxide dismutase and catalase, both singly and in combination and (iv) in an isolated rat heart preparation we have investigated the ability of free radical scavengers to reduce reperfusion arrhythmias caused by the infusion of xanthine oxidase and hypoxanthine. The prior administration of folic acid solution, amflutizole, superoxide dismutase, catalase, and superoxide dismutase plus catalase all reduced the incidence of reperfusion-induced arrhythmias and resultant mortality, caused by reperfusion after a transient period of coronary artery occlusion in the anaesthetised rat. Prior administration of soybean trypsin inhibitor significantly reduced mortality. In an isolated, perfused rat heart preparation with temporary coronary artery occlusion, addition of xanthine oxidase-hypoxanthine to the perfusion medium increased the incidence of reperfusion arrhythmias and decreased the total duration of sinus rhythm during reperfusion. Further addition of superoxide dismutase or L-methionine increased significantly the total duration of sinus rhythm. These results suggest that in the rat heart xanthine oxidase may be involved in the genesis of reperfusion-induced arrhythmias.
J Mol Cell Cardiol 1988 Jan
PMID:Reperfusion-induced arrhythmias: a study of the role of xanthine oxidase-derived free radicals in the rat heart. 336 77

Free radicals such as superoxide (.O2-) produced by xanthine oxidase might cause cell death during reperfusion after myocardial ischemia. The effect of the xanthine oxidase inhibitor allopurinol on infarct size in ischemia-reperfusion models has been variable, possibly because of differences in treatment duration. Adequate inhibition of xanthine oxidase may require a sufficient pretreatment period to permit conversion of allopurinol to oxypurinol, the actual inhibitor of superoxide production. To test more definitively whether xanthine oxidase-derived free radicals cause cell death during reperfusion, the effect of oxypurinol on infarct size was evaluated in an ischemia-reperfusion model. Open chest dogs underwent 40 min of circumflex coronary artery occlusion followed by reperfusion for 4 days. Twelve dogs were treated with oxypurinol (10 mg/kg body weight intravenously 10 min before occlusion and 10 mg/kg intravenously 10 min before reperfusion) and 11 control dogs received drug vehicle alone (pH 10 normal saline solution). Nine control dogs from a concurrent study also were included. Infarct size was measured histologically and analyzed with respect to its major baseline predictors, including anatomic area at risk and collateral blood flow (measured with radioactive microspheres). Infarct size as a percent of the area at risk averaged 23.8 +/- 2.7% (mean +/- SEM) in the oxypurinol group (n = 10) and 23.1 +/- 4.2% in the control group (n = 17) (p = NS). Collateral blood flow to the inner two thirds of the ischemic wall averaged 0.08 +/- 0.01 ml/min per g in the oxypurinol group and 0.09 +/- 0.02 ml/min per g in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
J Am Coll Cardiol 1988 Jul
PMID:The xanthine oxidase inhibitor oxypurinol does not limit infarct size in a canine model of 40 minutes of ischemia with reperfusion. 337 7

We isolated and purified xanthine oxidase by Sephadex gel filtration and assayed the activity of the enzyme by urate production which we measured by HPLC and UV absorption at 290 nm. We applied this method to extracts of liver and heart of rats, guinea pigs, rabbits, and pigs and to heart of dogs and humans. We found that pig hearts do not exhibit xanthine oxidase activity and that human and rabbit hearts produced small amounts of urate only after hours of incubation. We conclude that xanthine oxidase does probably not play an important part in the mechanisms leading to myocardial infarction using the free radical generating pathway, because it is absent in one species (pig) and barely detectable in two others (rabbit and man) that are known for their rapid and complete infarction following acute coronary occlusion.
Basic Res Cardiol
PMID:The activity of xanthine oxidase in heart of pigs, guinea pigs, rabbits, rats, and humans. 342 27

Xanthine oxidase activities of pig myocardium and blood during and following myocardial ischemia were measured using HPLC, and electrochemical detection of hypoxanthine, xanthine and uric acid. Myocardial ischemia was produced by occluding the anterior descending coronary artery two-thirds of the way from its origin. There was no accumulation of either xanthine or urate in the ischemic pig myocardium during occlusion periods of 90 min, but there was a substantial accumulation of hypoxanthine. Similarly, there was no increase in myocardial xanthine or urate during the 30 min reperfusion following coronary artery occlusion periods of 15, 30, 60 or 90 min. Following in vitro incubation at pH 8 of myocardial homogenates or blood with either hypoxanthine or xanthine and NAD, no urate production was detectable. In contrast, significant amounts of xanthine and/or urate were produced, following addition of xanthine oxidase to the reaction mixtures. Additional in vitro experiments showed that the following pig tissues were lacking xanthine oxidase activity: left and right atrial appendage, left and right ventricle, interventricular septum, anterior descending and circumflex coronary arteries, ascending aorta, lung, and blood. Large amounts of xanthine oxidase (9.3 +/- 1.8 SEM mU/g wet weight, n = 7) were found in pig liver. In the ischemic pig heart, transmural infarction developed within 60 min of ischemia. Ventricular arrhythmias and fibrillation occurred most frequently within 45 min of ischemia and within seconds after reperfusion. These results showed that the pig heart and blood were xanthine oxidase deficient, suggesting that xanthine oxidase-derived free oxygen radicals were not involved in the cytotoxic and arrhythmogenic effects brought about by myocardial ischemia and/or reperfusion in the pig.
Basic Res Cardiol
PMID:Arrhythmias and infarction in the ischemic pig heart are not mediated by xanthine oxidase-derived free oxygen radicals. 342 28

We used isolated, buffer-perfused rabbit hearts to evaluate whether global, normothermic ischemia altered mitochondrial hydrogen peroxide (H2O2) generation and mitochondrial activities of the major enzymes responsible for degrading H2O2 and superoxide anion (O2-.): glutathione peroxidase (GPD) and superoxide dismutase (SOD), respectively. This preparation lacks exogenous neutrophils and endogenous xanthine oxidase, which are other potential sources of oxygen metabolites. Ischemia depressed mitochondrial oxidative phosphorylation parameters, State 4 succinate-supported H2O2 generation rates, and the relative flux of State 4 oxygen consumption that was diverted to H2O2 formation. The production of H2O2 was not abolished. Ischemia and reperfusion significantly reduced the activities of SOD (by 43%) and GPD (by 39%) in the mitochondrial fraction. Cytosolic GPD activity was also depressed. The results suggest that the myocardial cell's ability to enzymatically degrade H2O2 and O2-. is compromised, particularly in the mitochondrion. Although mitochondrial H2O2 production is decreased, the mitochondria may persist as a source of this oxygen metabolite following ischemia. Collectively, the data may help explain why mitochondria are vulnerable targets of free radical-mediated damage due to ischemia.
J Mol Cell Cardiol 1987 Dec
PMID:Mitochondrial hydrogen peroxide generation and activities of glutathione peroxidase and superoxide dismutase following global ischemia. 344 86

The xanthine oxidase pathway has been proposed as a source of oxygen-derived free radicals in ischemic and reperfused myocardium. A spectrophotometric assay was employed to measure the xanthine oxidase activity of rat and rabbit hearts exposed to varying durations of global ischemia. In the rat 24.6 +/- 4.8 mIU/g wet wt of xanthine dehydrogenase + xanthine oxidase activity were detected in both ischemic and normally perfused myocardium. In the non-ischemic state only 6% of this activity was associated with the free radical-producing oxidase form. After 5 min of ischemia however about 25% of the enzyme was in the oxidase form, a value which remained unchanged over the following 25 min. Neither xanthine dehydrogenase nor xanthine oxidase could be detected in the rabbit heart. Failure of allopurinol, an inhibitor of xanthine oxidase, to limit infarct size in a rabbit model of ischemia/reperfusion provides further evidence that this species has insignificant amounts of xanthine oxidase in its heart. Anesthetized rabbits were subjected to coronary artery ligation for 45 min and 3 h of reperfusion. The volume of the zone of underperfusion was assessed with fluorescent microspheres and infarct size was assessed by tetrazolium staining. In control animals 67.5 +/- 3.8% of the zone of underperfusion became necrotic. In rabbits given superoxide dismutase (15000 IU/kg) + catalase (50,000 IU/kg) for 90 min starting 15 min before occlusion, infarct size was only 35.4 +/- 3.3% of the zone of underperfusion. However, in rabbits pretreated with allopurinol (75 mg p.o. 24 h before study + 30 mg/kg 5 min before occlusion) infarct size was 65.8 +/- 8.7%.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1987 Nov
PMID:Xanthine oxidase is not a source of free radicals in the ischemic rabbit heart. 348 2

This study describes the effect of oxygen radicals on the ultrastructure of the isolated Langendorff-perfused rat heart. Oxygen radicals were enzymatically generated by xanthine oxidase (0.025 U/ml) and hypoxanthine (0.96 mM). Hearts were perfusion-fixed for electron microscopy and stereological technique was performed to obtain estimates of volume fractions (Vv) of different tissue components. Perfusion with oxygen radicals resulted in areas with severely damaged myocardial cells. These changes included swelling and cristolysis of mitochondria, disruption of filaments, development of intracellular edema and focal disruption of the sarcolemma. Stereological examination revealed few alterations after 5 min perfusion with oxygen radicals. After 10 min perfusion with oxygen radicals, however, the Vv (myocyte/myocardium) increased from 0.542 +/- 0.042 (mean +/- S.D.) to 0.663 +/- 0.144, and this paralleled the development of Vv (cellular edema/myocyte) being 0.047 +/- 0.028. Vv (capillary wall/capillary) increased from 0.215 +/- 0.046 to 0.411 +/- 0.123 indicating endothelial swelling. Although the mitochondria appeared swollen, Vv (mitochondria/myocyte) remained constant. The effect of a 35 min recovery period on the ultrastructure was minor. The application of SOD and catalase together with xanthine oxidase and hypoxanthine reduced the observed changes significantly, thus proving the participation of oxygen radicals. This study confirms that oxygen radicals can induce major alterations in myocardial ultrastructure.
J Mol Cell Cardiol 1987 Apr
PMID:Ultrastructural changes induced in the isolated rat heart by enzymatically generated oxygen radicals. 361 20

Evidence is presented that, as in cardiomyocytes, vascular endothelial cells use fatty acids, in addition to glucose, as a respiratory fuel. Attention is focused on the cardiac interstitium, lined by vascular cells and cardiomyocytes, which may be enriched with metabolic products from these cells. Also, certain proteins are present in the interstitial fluid (Qi) such as plasma proteins and fatty acid binding protein (FABP). However, the concentration of FABP is so low in Qi that albumin is more important to shuttle long chain fatty acids in the interstitial fluid between cardiomyocytes and the vascular compartment. Under hypoxic conditions (hypo)xanthine, lactate and fatty acids may be expected to accumulate in the interstitium, as well as proteins from adjacent cells, such as xanthine oxidase from endothelial cells. This enzyme, acting upon the elevated level of (hypo)xanthine, giving rise to O2-., may be involved in the damage of the ischaemic heart. The significance of the interstitium in ischaemia and in fibrosis following long standing cardiac lipidosis is briefly discussed, as well as the possible mechanisms involved in fatty acid transport in the heart.
Basic Res Cardiol 1987
PMID:Substrates for energy metabolism in the heart: the role of the interstitial compartment. 366 8

Little is known about postnatal changes in myocardial purine metabolism. We therefore studied how ATP catabolism was affected by hypothermia and ischaemia in neonatal and adult hearts. Hypothermia during ischaemia protected isolated adult and newborn hearts against ATP decline. Reperfusion after normothermic ischaemia resulted in higher ATP levels in newborn hearts with less release of ATP-catabolites. During normoxia adult hearts released mainly urate (80% of total purine release), while newborns released mainly hypoxanthine (64%). During early reperfusion adult and newborn hearts released mainly inosine (50-60%). The very low xanthine oxidase activity in the neonatal heart could be an important factor in the observed ATP preservation during reperfusion.
Basic Res Cardiol 1987
PMID:Developmental differences in myocardial ATP metabolism. 366 14

Experiments were performed to determine if xanthine oxidase is a source of free radicals during myocardial ischemia. Open chest dogs were subjected to 1 h of total occlusion of the left anterior descending coronary artery followed by 4 h of reperfusion. Directly after coronary artery occlusion, Ce141 microspheres were injected into the left atrium to mark the ischemic bed. At the end of reperfusion, the hearts were removed and sectioned. Autoradiography determined the ischemic myocardium at risk, and the necrotic zone was determined by triphenyl-tetrazolium staining. Animals were divided into three groups: control, allopurinol (24-h oral pretreatment 400 mg, then 50 mg/kg IV bolus on occlusion); and superoxide dismutase starting with occlusion (15 000 U/kg). The size of the infarct as a percentage of the tissue at risk was: 23.1 +/- 4.1 for the control; 8.7 +/- 1.2 for the allopurinol group; and 5.4 +/- 1.2 for the superoxide dismutase group. The infarcts in the allopurinol and superoxide dismutase groups were significantly smaller than those in the control groups. In a second series of experiments we determined the xanthine oxidase/xanthine dehydrogenase content of dog myocardium. The left anterior descending branch was ligated for 30 min and then biopsies were removed from both the normal and the ischemic regions. Total enzyme content did not differ between the two regions averaging 0.259 U/g protein for the ischemic tissue and 0.225 U/g protein for the normal region. Only 9.8% of the enzyme was in the oxidase form in the normal region while 32.8% was in the oxidase form in the ischemic zone.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Cardiol 1985 Feb
PMID:Xanthine oxidase as a source of free radical damage in myocardial ischemia. 383 24


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