Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Under normal conditions the intestinal mucosa is impermeable to potentially harmful materials from the intestinal lumen. Mucosal disruption promotes bacterial translocation, which is postulated to be a fuel source for sepsis and multiorgan failure. We have previously demonstrated that mesenteric ischemia-reperfusion (I/R) injury increases intestinal permeability (IP); however, the mechanism remains unclear. This study was designed to examine the hypothesis that changes in IP, after I/R injury, are mediated by xanthine oxidase-generated, oxygen-derived free radicals. Thirty-three Sprague-Dawley rats (weighing 300 to 400 g) were included in this study. Group 1 (n = 10) received enteral allopurinol, a xanthine oxidase inhibitor, 10 mg/kg daily for 1 week prior to mesenteric ischemia. Group 2 consisted of 11 untreated, ischemic animals. Groups 1 and 2 were subjected to superior mesenteric artery occlusion with interruption of collateral flow for 20 minutes to produce ischemic injury to the intestine. An additional 12 rats (group 3), served as nonischemic controls (sham). A loop of distal ileum was isolated and cannulated proximally and distally to allow luminal perfusion with warmed Ringer's lactate at 1 mL/min. IP was determined in all groups by quantitatively measuring the plasma-to-luminal clearance of chromium (51Cr)-labeled ethylenediaminetetraacetate (EDTA) at baseline, during ischemia and 20, 40, and 60 minutes after reperfusion. Complete ischemia produced significant increases in IP over baseline values in the untreated rats (group 2, baseline: 0.49 +/- 0.006, ischemia: 0.149 +/- 0.039) compared with sham rats (baseline: 0.41 +/- 0.006; ischemia: 0.047 +/- 0.009) or allopurinol-treated rats (baseline: 0.098 +/- 0.020, ischemia: 0.073 +/- 0.012, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Allopurinol prevents intestinal permeability changes after ischemia-reperfusion injury. 140 60

A vibration technique was used to dislocate the epithelium from the rat small intestine, in order to study the possible regulatory role of the epithelium on intestinal motility. Complete removal of the epithelium led to a slightly potentiated contraction of the longitudinal smooth muscle by the muscarinic agonist methacholine (pD2. 6.5 +/- 0.1 vs. 6.2 +/- 0.2). The maximal beta-adrenergic response expressed relative to the relaxation by 0.5 mM dibutyryl cyclic AMP increased from 55.9 +/- 9.0% to 72.6 +/- 9.1% by this treatment. Efforts were made to relate these observations to the endothelium-dependent relaxation in blood vessels, but no indication was found for a similar mechanism in the small intestine. Not only mechanical dislocation can be employed to affect the mucosal layer, but also intestinal ischemia has been reported to lead to mucosal damage. In this study we mimicked ischemia by applying in vitro anoxia and subsequent reoxygenation to isolated intestinal segments. When intestinal segments are isolated and kept in physiological buffer, xanthine dehydrogenase is converted slowly to xanthine oxidase, irrespective of whether the buffer is oxygenated or not. No evidence was found for oxygen radical damage after anoxia and reoxygenation. However, the intestinal mucosa was damaged both after normoxia, and after anoxia and reoxygenation. Anoxia and subsequent reoxygenation did not affect muscarinic contraction, but slightly increased the beta-adrenergic relaxation, which partly correlates with the effects of mechanical dislocation of the epithelium. The increased sensitivity of the smooth muscle after epithelial damage might be involved in motility changes during intestinal inflammatory diseases.
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PMID:Role of the epithelium in the control of intestinal motility: implications for intestinal damage after anoxia and reoxygenation. 141 84

A striking similarity exists between the pathogenetic properties of group A streptococci and those of activated mammalian professional phagocytes (neutrophils, macrophages). Both types of cells are endowed by the ability to adhere to target cells; to elaborate oxidants, hydrolases, and membrane-active agents (hemolysins, phospholipases); and to freely invade tissues and destroy cells. From the evolutionary point of view, streptococci might justifiably be considered the forefathers of "modern" leukocytes. Our earlier findings that synergy between a streptococcal hemolysin (streptolysin S, SLS) and a streptococcal thiol-dependent proteinase and between cytotoxic antibodies+complement and streptokinase-activated plasmin readily killed tumor cells, led us to hypothesize that by analogy to the pathogenetic mechanisms of streptococci, the mechanisms of tissue destruction initiated by activated leukocytes in inflammatory sites, as well as in tissues undergoing episodes of ischemia and reperfusion, might also be the result of the synergistic effects among leukocyte-derived oxidants, phospholipases, proteinases, cytokines, and cationic proteins. The current report extends our previous synergy studies with endothelial cells to two additional cell types--monkey kidney epithelial cells and rat beating heart cells. Monolayers of 51Cr-labeled cells that had been treated by combinations of sublytic amounts of hydrogen peroxide (generated either by glucose oxidase, xanthine-xanthine oxidase, or by paraquat) and with sublytic amounts of a variety of membrane-active agents (streptolysin S, phospholipases A2 and C, lysophosphatides, histone, chlorhexidine) were killed in a synergistic manner (double synergy). Crystalline trypsin markedly enhanced cell killing by combinations of oxidant and the membrane-active agents (triple synergy). Injury to the cells was characterized by the appearance of large membrane blebs that detached from the cells and floated freely in the media, looking like lipid droplets. Cytotoxicity induced by the various combinations of agonists was depressed, to a large extent, by scavengers of hydrogen peroxide (catalase, dimethyl thiourea, and by Mn2+) but not by SOD or by deferoxamine. When cationic agents were employed together with hydrogen peroxide, polyanions (heparin, polyanethole sulfonate) were also found to inhibit cell killing. It is proposed that in order to effectively combat the deleterious toxic effects of leukocyte-derived agonists on cells and tissues, antagonistic "cocktails" comprised of cationized catalase, cationized SOD, dimethylthiourea, Mn(2+)+glycine, proteinase inhibitors, putative inhibitors of phospholipases, and polyanions might be concocted. The current literature on synergistic phenomena pertaining to mechanisms of cell and tissue injury in inflammation is selectively reviewed.
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PMID:Synergism among oxidants, proteinases, phospholipases, microbial hemolysins, cationic proteins, and cytokines. 142 26

Intravenous administration of xanthine (X: 0.225 mg/kg, i.v.) plus xanthine oxidase (XO: 3.0 units/kg, i.v.) to anesthetized rats resulted in a rapid fall in the arterial pressure and a mortality rate of over 80% during 120 min observation period. Pretreatment of the rats with superoxide dismutase (SOD) or SOD plus catalase significantly enhanced survival rate to 60% confirming that the toxicity after [X + XO] administration is due to the generation of oxygen free radicals. Pretreatment of the rats with either felodipine, a dihydropyridine calcium antagonist or verapamil, a structurally different Ca(2+)-channel blocker was most effective in promoting survival rate to 90%; in contrast, hydralazine, an arteriolar dilator but not a calcium antagonist, was ineffective in significantly enhancing survival. In the vehicle treated groups, mortality of the rats after [X + XO] administration was associated with significant increases in serum creatine phosphokinase (CPK) levels; both the calcium antagonists as well as hydralazine prevented any significant changes in CPK levels. Since only the calcium antagonists but not hydralazine were effective in providing significant protection against mortality, the data suggests that CPK may not be a reliable indicator to predict prevention of lethal toxicity induced by free radicals. Hence, the observation that calcium antagonists can promote survival would suggest that calcium overload may be the ultimate mediator of tissue toxicity. These observations can account for the remarkable efficacy of various calcium antagonists in preventing ischemia-reperfusion induced damage to organs, such as heart and kidneys, in which a role for free radicals has been postulated.
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PMID:Evaluation of the effects of felodipine, verapamil and hydralazine on the survival rate of rats subjected to lethal effects of oxygen free radicals. 143 30

After 60 min of reperfusion following 60 min of ischemia, the ischemia-induced decrease in liver tissue adenosine triphosphate (ATP) concentration had recovered by 66%, and full recovery of mitochondrial function--that is, the respiratory control index (RCI) and the rate of oxygen consumption in state-III respiration (ST III O2)--was observed. In contrast, liver tissue ATP concentration had recovered by only 13%, and marked low RCI and ST III O2 were observed after 60 min of reperfusion following 180 min of ischemia. Intermediate results were observed in rats after 60 min of reperfusion following 120 min of ischemia. Liver tissue hypoxanthine and xanthine, substrates of xanthine oxidase, increased ischemic time dependently. Liver tissue concentrations of the reduced form of glutathione (GSH) and the oxidized form of glutathione (GSSG) and activities of glutathione peroxidase and glutathione reductase did not change after 60 min of reperfusion following 60 min of ischemia. In contrast, GSH concentration and glutathione peroxidase activity decreased significantly after 60 min of reperfusion following 180 min of ischemia. Since the glutathione redox system is an important contributor to the scavenging of free radicals after reperfusion following a long time of ischemia, the free radical scavenging ability might decrease in spite of enhancement of free radical generation, which might play an important role in the inhibition of the recovery of tissue ATP concentrations and mitochondrial function.
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PMID:Changes in the glutathione redox system during ischemia and reperfusion in rat liver. 143 57

The protective effect of a new potent protease inhibitor, ONO 3307, in combination with a xanthine oxidase inhibitor, allopurinol, was tested in pancreatico-biliary duct obstruction (PBDO) with temporary pancreatic ischemia in rats. After PBDO with ischemia, we observed hyperamylasemia, pancreatic edema, congestion of amylase and lysosomal enzyme cathepsin B as well as impaired output of amylase and cathepsin B into the pancreatic juice and a redistribution of lysosomal enzyme from the lysosomal fraction to the zymogen fraction. The administration of ONO 3307 plus allopurinol almost completely prevented the pancreatic injuries induced by PBDO with ischemia. These results indicate the important roles of temporary pancreatic ischemia in the pathogenesis of pancreatic damage and the usefulness of combination therapy with a new potent protease inhibitor and xanthine oxidase inhibitor in the protection against clinical acute pancreatitis.
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PMID:Protective effects of combined therapy with a protease inhibitor, ONO 3307, and a xanthine oxidase inhibitor, allopurinol on temporary ischaemic model of pancreatitis in rats. 144 2

The aim of this work was to assess the catalytic activity of xanthine oxidase, the level of lipid peroxides and enzymic antioxidant systems in isolated rat heart muscle subjected to a globally partial ischemia followed by varying durations of reperfusion. After 40 min of globally partial ischemia (residual perfusion flow rate: 0.1 ml/min), four different durations of reperfusion were investigated (0, 20, 40, and 60 min). After each experimental ischemia/reperfusion sequence, the heart was frozen in liquid nitrogen. Lipid peroxides were assayed in the cardiac homogenate and the catalytic activity of xanthine oxidase and enzymic antioxidant systems (glutathione peroxidase, superoxide dismutase and catalase) were determined in the centrifuged supernatant. In the different experimental protocols studied in this work, there was no significant increase in the activity of cardiac xanthine oxidase or in the level of lipid peroxides when compared to the non reperfused or to the continuously perfused hearts. Indeed, enzymic antioxidant systems were also not significantly modified in the different periods of reperfusion when compared to control hearts (continuously perfused hearts). These results suggest that xanthine oxidase is apparently not a major source of free radicals in the course of an ischemia-reperfusion sequence in heart muscle, in particular, if we consider the early phases of reperfusion. The process of lipid peroxidation, assessed by assaying thiobarbituric acid reactants, is not a predominant phenomenon of reperfusion-induced injury, at least in the experimental model used here. However, enzymic antioxidant systems investigated in this study do not seem modified. This could mean that the small quantity of oxygen free radicals produced does not overwhelm the enzymic antioxidant systems of myocardium which is in agreement with peroxidatized lipid results.
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PMID:Ischemia and reperfusion injury in isolated rat heart: effect of reperfusion duration on xanthine oxidase, lipid peroxidation, and enzyme antioxidant systems in myocardium. 146 31

The enzyme xanthine oxidase has been implicated in the tissue oxidative injury after ischemia-reperfusion. This enzyme, which is a source of oxygen free radicals, is formed from a dehydrogenase form during ischemia. The ratio dehydrogenase/oxidase of rat kidney homogenates decreases during the ischemia and the reperfusion. Two flavonoids, quercetin and silybin, characterized as free radical scavengers, exert a protective effect preventing the decrease in the dehydrogenase/oxidase ratio observed during ischemia-reperfusion. The mechanism of this effect and the role of flavonoids in the ischemia-reperfusion tissue damage is discussed.
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PMID:Changes in the xanthine dehydrogenase/xanthine oxidase ratio in the rat kidney subjected to ischemia-reperfusion stress: preventive effect of some flavonoids. 147 27

To investigate the pathophysiology of warm ischemia (WI) of the liver, the changes in hemodynamics and energy metabolism were studied during and after 60-min complete WI induced by total hepatic vascular exclusion (HVE) in the canine model. Hepatic arterial blood flow after WI was maintained at 76% of the pre-ischemic level, while portal blood flow was only 27% of the pre-ischemic level associated with increased portal vein pressure, which was twice the pre-ischemic level, resulting in a decrease of total hepatic blood flow to 46% of the pre-ischemic level. Concentration of tissue lipid peroxide increased after WI. Arterial blood ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state, could not recover to the pre-ischemic level after termination of WI. However, when 100 mg/kg of allopurinol (xanthine oxidase inhibitor) was administered intravenously 10 min prior to initiating WI, AKBR was restored to the pre-ischemic level at 30 min after WI in spite of the fact that allopurinol administration to one group produced no remarkable changes in the hepatic hemodynamics compared with the group without allopurinol treatment. Concentration of adenine nucleotides was significantly higher for the treated group at the end of and after WI than for the group without allopurinol treatment and was maintained at a higher level even after WI. Lipid peroxide production was suppressed. Electron microscopic examination revealed that allopurinol treatment could not prevent mitochondrial swelling. It is suggested that WI causes injury primarily to the portal sinusoidal circulation, resulting in portal congestion concomitant with high portal pressure after the release of WI. Allopurinol could prevent the deterioration of mitochondrial ATP metabolism, and was able to inhibit lipid peroxide production, resulting in the rapid recovery of mitochondrial redox state in spite of the fact that it produced no amelioration of hepatic hemodynamics and morphological alterations.
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PMID:Preserved mitochondrial function by allopurinol despite deteriorated hemodynamics in warm ischemia-damaged canine liver. 148 Aug 16

Recent research was shown that oxygen-derived free radicals are involved in the pathogenesis of various diseases, including ischemia-reperfusion injury. We have also reported that oxygen-derived free radicals and lipid peroxidation may play an important role in gastric mucosal injury induced by ischemia-reperfusion. The hypoxanthine-xanthine oxidase system and neutrophils are considered important sources of oxygen-derived free radicals in this process. In recent years, it also has been shown that serum platelet-activating factor (PAF) levels increased during ischemia-reperfusion, and that induction of superoxide generation by neutrophils is one of the important biological effects of PAF. In the present study, we examined the effect of CV-6209, a specific PAF receptor antagonist, on gastric mucosal injury induced by ischemia-reperfusion, to shed some light on the possible involvement of PAF in such lesions. CV-6209 significantly attenuated the gastric mucosal injury induced by ischemia-reperfusion, and inhibited both an increase of thiobarbituric acid reactive substances and a decrease of alpha-tocopherol in gastric mucosa after ischemia-reperfusion. However, CV-6209 had no effect on gastric mucosal blood flow during ischemia-reperfusion. These results suggest that endogenous PAF may play an important role in gastric mucosal injury induced by ischemia-reperfusion, and that CV-6209 exerts its beneficial effect mainly by inhibiting neutrophil superoxide production induced by PAF.
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PMID:Effects of a platelet-activating factor antagonist, CV-6209, on gastric mucosal lesions induced by ischemia-reperfusion. 148 54


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