Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Free radicals may arise from a number of sources as a result of a variety of cellular mechanisms; they are generated under both normal and pathological circumstances. The xanthine oxidase pathway, the arachidonic acid pathway, invading leucocytes, catecholamine oxidation, and mitochondrial activity can all lead to the production of a variety of reactive oxygen intermediates including superoxide, hydrogen peroxide, and the hydroxyl radical. Whatever their source, free radicals can be extremely toxic to the cell and they are capable of causing major membrane injury by initiating lipid peroxidation or by altering the activity of membrane-bound enzyme systems which control ionic movement. The cell possesses highly efficient protective mechanisms, including antioxidants such as vitamins C and E and the enzymes superoxide dismutase and catalase, all of which are designed to prevent the occurrence of free radical-induced injury under normal conditions. However, during ischaemia and reperfusion, these protective mechanisms may be overwhelmed and severe free radical-mediated injury may occur. Ischaemia may prime the myocardium for free radical-induced injury. The great majority of the evidence that manipulation of free radicals may protect against such injury is, however, circumstantial.
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PMID:Free radicals and the heart. 202 51

From in vitro studies involving multilamellar liposomes or other artificial systems, several groups of workers have deduced that Trolox (a water-soluble analogue of vitamin E) and ascorbate are synergistic antioxidants. Here, we demonstrate that while Trolox and ascorbate individually protect cultured hepatocytes against oxyradicals generated either with xanthine oxidase plus hypoxanthine or with hydrogen peroxide, the two antioxidants do not appear to be synergistic when used in equimolar combinations. Also, in a rat model of hepatic ischemia-reperfusion, we observed that infusion of Trolox or ascorbate (7.5-10 mumol/kg body weight) into the postischemic liver reduced the reperfusion injury by 76 or 67%, respectively. However, when both compounds were used together (each at the same dose as used separately), the organ salvage amounted to only 79%. Therefore, there is no evidence of synergism between Trolox and ascorbate in our in vitro and especially in vivo systems.
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PMID:Trolox and ascorbate: are they synergistic in protecting liver cells in vitro and in vivo? 203 21

Washed human platelets prevent edema formation in isolated rabbit lungs infused with xanthine oxidase, an enzyme that injures endothelial membranes by generating extracellular oxidants. We hypothesized that platelets would similarly preserve membrane permeability in isolated lungs exposed to ischemia-reperfusion injury, a model that perturbs endothelial cells by the generation of intracellular oxidants. Isolated perfused rabbit lungs (IPL) were exposed to warm ischemia-reperfusion to cause lung edema. The infusion of washed human platelets (1.05 +/- 0.02 x 10(10) cells) prevented edema formation as measured by lung weight gain, wet-to-dry lung weight ratios, histological edema, and preservation of paraendothelial cell tight junctions. Inhibition of the platelet glutathione redox cycle with 1,3-bis(2-chloroethyl)-1-nitrosourea, dehydroepiandrosterone, or 1-chloro-2,4-dinitrobenzene interfered with platelet protective effects. In contrast, inhibition of platelet catalase with aminotriazole and H2O2 had no effect on platelet protection. Lung tissue malonyldialdehyde concentrations were similar in isolated lungs exposed to ischemia-reperfusion with or without the infusion of platelets. These results indicate that platelet attenuation of ischemia-reperfusion lung edema depends on platelet glutathione redox cycle antioxidants but not platelet catalase.
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PMID:Washed human platelets prevent ischemia-reperfusion edema in isolated rabbit lungs. 203 73

Oxygen derived free radicals have been shown to be generated during reperfusion of ischemic myocardium by a variety of approaches including spin trap probes. Three levels of injury have been described for the reperfused heart. Periods of ischemia of only several minutes can trigger lethal arrhythmias on reperfusion. Anti-oxidants including SOD and or catalase, as well as iron chelators reduce the incidence of these arrhythmias in both dog and rat. Xanthine oxidase inhibitors are equipotent with SOD in this model suggesting that xanthine oxidase is the source of the radicals. Periods of occlusion lasting 10-15 minutes produce a recoverable defect in contractility termed "stunning". SOD plus catalase has been shown to reduce the incidence of stunning in a variety of models including the xanthine oxidase deficient rabbit. Neither agent on its own seemed to be effective against stunning in either the rabbit or the dog. Stunning is more difficult to demonstrate in the rabbit heart, presumably due to its lack of xanthine oxidase. Periods of ischemia in excess of 20 minutes will result in some irreversible cell death (infarction) with reperfusion. While studies using histochemical methods suggesting that SOD plus catalase given at the time of reperfusion could limit necrosis in the dog model, histological studies reveal that infarct size was not modified but rather, SOD appears to interfere with the ability of tetrazolium to histochemically discriminate between living and dead cells. While PEG SOD with its extended plasma half life was reported to reduce infarct size in the dog, it was unable to protect the reperfused rabbit heart. To date, none of the scavengers have been proven to limit infarction suggesting that free radicals contribute to arrhythmias and stunning, but do not kill cells in the reperfused heart.
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PMID:Superoxide dismutase therapy for myocardial ischemia. 206 Aug 42

This study was undertaken to evaluate the usefulness of a canine ischemic heart model achieved by coronary retrograde flow (RF) diversion, and to examine the effect of allopurinol on the myocardial infarction. The left anterior descending coronary artery (LAD) was occluded for 90 min followed by 4h reperfusion. Group 1 (n = 9) was a simple LAD occlusion group. In group 2 (n = 8), retrograde flowing blood from the distal of the occluded LAD was simultaneously diverted during LAD occlusion. In group 3 (n = 8), allopurinol was administered 60 min before ischemia with RF diversion followed by its continuous infusion. Infarcted myocardium was determined by triphenyl tetrazolium chloride staining and myocardium at risk by the dye double perfusion technique. RF diversion significantly reduced not only regional myocardial blood flow (RBF) (0.21 +/- 0.05 ml/min/g in group 1 vs 0.05 +/- 0.01 ml/min/g in group 2; p less than 0.05) but also its variance (p less than 0.01). Furthermore, the infarct size (infarct/risk ratio) in the allopurinol treated group was significantly reduced without any significant difference in rate pressure product, risk size or RBF (89.4 +/- 4.0% in group 2 vs 48.9 +/- 4.5% in group 3; p less than 0.01). We conclude that the canine RF diversion model is useful for myocardial infarct study because of the minimizing of the difference of collateral flow, and that canine myocardial xanthine oxidase may produce free radicals which take part in myocardial injury after reperfusion.
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PMID:A useful canine model of ischemic myocardium with coronary retrograde flow diversion, and its application for the study of allopurinol on myocardial infarct size. 206

Bacterial translocation (BT) occurs transiently after thermal injury and may result from an ischemic intestinal insult. To evaluate continued intestinal ischemia in the ongoing BT associated with sepsis after injury, rats were randomized to (1) 30% burn injury with Pseudomonas wound infection (BI), (2) BI + fluid resuscitation (BI + Fluid), (3) BI after allopurinol pretreatment to inhibit xanthine oxidase (BI + Allo), or (4) BI after azapropazone pretreatment to inhibit neutrophil degranulation (BI + Aza). On postburn days (PBD) 1, 4, and 7, animals were studied for evidence of BT and intestinal lipid peroxidation. BI + Fluid, BI + Allo, and BI + Aza significantly (p less than 0.05) reduced rates of BT and ileal lipid peroxidation acutely after thermal injury (PBD 1) compared to BI. All four groups had equally high rates of BT associated with the onset of sepsis (PBDs 4 and 7), without evidence of further intestinal lipid peroxidation. These data indicate that the chronic gut barrier failure associated with sepsis after injury occurs independently of continued intestinal ischemia.
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PMID:Differential pathophysiology of bacterial translocation after thermal injury and sepsis. 206 68

This study evaluated the effect of ischemia-reperfusion (I-R) on pulmonary capillary permeability in isolated rabbit lungs and the roles of xanthine oxidase (XO), aldehyde oxidase (AO), and neutrophils (PMN) in producing this lung injury. Effects of XO and AO were studied by inactivation with a tungsten-enriched diet (0.7 g/kg) and inhibition of XO by allopurinol (100 microM) or AO by menadione (3.5 microM). PMN effects were studied by preventing endothelial adhesion with the monoclonal antibody IB4 (10 microM). Vascular permeability was evaluated by determining the capillary filtration coefficient (Kf,c) measured before and after I-R in all experimental conditions. Reperfusion after 2 h of ischemia significantly increased pulmonary capillary permeability (Kf,c changed from 0.096 +/- 0.014 to 0.213 +/- 0.025 ml.min-1. cmH2O-1.100 g-1), and this increase was blocked by the addition of catalase (50,000 U) at reperfusion (baseline Kf,c was 0.125 +/- 0.023 and 0.116 +/- 0.014 ml.min-1.cmH2O-1.100 g-1). XO inactivation with the tungsten-supplemented diet and XO inhibition with allopurinol prevented the Kf,c increase observed after I-R (0.183 +/- 0.030 to 0.185 +/- 0.033 and 0.126 +/- 0.018 to 0.103 +/- 0.005 ml.min-1.cmH2O-1.100 g-1). Inhibition of AO had no effect on I-R injury (Kf,c 0.108 +/- 0.011 to 0.167 +/- 0.014 ml.min-1.cmH2O-1.100 g-1). Preventing PMN adhesion resulted in significant attenuation of the change in Kf,c associated with I-R (0.112 +/- 0.032 to 0.090 +/- 0.065 ml.min-1.cmH2O-1.100 g-1). We conclude that XO and PMN adherence, but not AO, are involved in the increased capillary permeability associated with I-R.
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PMID:Role of xanthine oxidase and neutrophils in ischemia-reperfusion injury in rabbit lung. 207 95

The effect of organ flushing with the calcium entry blocker verapamil on the conversion of innocent enzyme xanthine dehydrogenase (XDH) to superoxide generating enzyme xanthine oxidase (XOD) in ischemic rat livers was studied. This enzyme conversion progressed over time in warm or cold ischemia. In non-flushed livers, the activities of XOD as percentages of XDH plus XOD after 6 h at 37 degrees C and 6 days at 4 degrees C were 80.3 +/- 5.2 and 31.6 +/- 2.1, respectively. In the livers flushed with Euro-Collins solution, the conversion was inhibited to 37.0 +/- 3.9% (P less than 0.001) after 6 h of warm ischemia, while this inhibitory effect was not found in cold ischemia. Verapamil given through the portal vein on flushing further suppressed the conversion in both warm and cold ischemia (with 5.0 microM of verapamil, 21.2 +/- 5.8% (P less than 0.001) after 6 h of warm ischemia and 25.2 +/- 3.3% (P less than 0.01) after 6 days of cold ischemia). A similar effect was also obtained with the addition of 10 or 30 mM of EGTA instead of verapamil. In contrast, no inhibitory effect on conversion was obtained in livers flushed and homogenized with 10.0 microM of verapamil followed by incubation for 6 h at 37 degrees C. In the livers that were flushed and stored at a warm temperature for 6 h, verapamil reduced the increase of tissue lipid peroxidation product (P less than 0.02) after 15 min of reperfusion. Although the precise mechanisms of these inhibitory effects of verapamil on the enzyme conversion are still uncertain, it is thought that organ flushing with verapamil might reduce the XOD-mediated postischemic reperfusion injury in livers subjected to prolonged ischemia.
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PMID:Effect of verapamil on conversion of xanthine dehydrogenase to oxidase in ischemic rat liver. 208 35

Although the specific cause(s) of inflammatory bowel diseases (IBD) has not been identified, one theory suggests ischemia as the early event that occurs in IBD and reperfusion causes sustained release of oxyradicals, leading to inflammation and ulceration. In this study, we have confirmed that H2O2 in the concentration seen during ischemia/reperfusion is primarily responsible for cellular membrane damage in the rat colonic fragments in vitro. Hydrogen peroxide caused a time and dose-dependent increase in 6-keto-PGF1 alpha and TXB2 release. Hydrogen peroxide-stimulated 6-keto-PGF1 alpha release was blocked (50%) by phospholipase A2 (PLA2) inhibitors quinacrine and dimethyleicosadienoic acid at 5 min. Hydrogen peroxide-stimulated 6-keto-PGF1 alpha release was completely blocked by indomethacin, significantly blocked (69%) by nordihydroguiaretic acid, and completely blocked by catalase. Superoxide dismutase and uric acid failed to inhibit H2O2-stimulated 6-keto-PGF1 alpha release. Endogenous catalase inhibitors 3-aminotriazole and sodium azide further enhanced the release of 6-keto-PGF1 alpha stimulated by H2O2 by 29% and 73%, respectively. Xanthine-xanthine oxidase also increased 6-keto-PGF1 alpha release from the fragments by 110%. This release was not inhibited by superoxide dismutase and uric acid, but was completely inhibited by catalase. These studies suggest a direct effect of H2O2 on colonic fragments leading to submicroscopic cellular membrane damage and excess prostanoid production utilizing a PLA2/cyclooxygenase and catalase-sensitive pathway without the formation of toxic hydroxyl ions. The quick release of 6-keto-PGF1 alpha also suggests an early manifestation of H2O2-induced damage in rat colonic fragments.
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PMID:Hydrogen peroxide-induced alterations in prostaglandin secretion in the rat colon in vitro. 209 May 84

Our previous studies demonstrated that the bilateral hindlimb ischemia/reperfusion stimulates thromboxane A2 (TXA2) production. The present study tests the role of xanthine oxidase-derived oxygen free radicals in mediating this event. In twelve anesthetized dogs, the abdominal aorta and the inferior vena cava were clamped for 150 min, declamped and reperfused for 30 min. Two groups were studied: untreated control group and pretreated group with xanthine oxidase inhibitor, allopurinol 100 mg.kg-1 orally 24 hr before clamping plus 25 mg.kg-1 intravenously 15 min before clamping. In the control group, plasma TXB2 levels increased markedly after reperfusion. On the other hand, prior treatment with allopurinol attenuated the increase in plasma TXB2 levels at 30 min after reperfusion. This model revealed partial ischemia, because the femoral arterial blood flow was approximately 15% of baseline during clamping. However, the present study suggests that ischemia/reperfusion stimulates TXA2 production, which may be partly affected by hypoxanthine-xanthine oxidase-derived oxygen free radicals and may be an important mechanism responsible for reperfusion injury.
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PMID:[The effect of xanthine oxidase inhibitor on hindlimb ischemia-induced thromboxane A2 release]. 209 92


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