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)

Anisodamine, a Chinese traditional medicine herb, has been used for treatment of adult respiratory distress syndrome effectively, but little is known about its mechanism. We attempted to investigate if anisodamine could protect bovine pulmonary endothelial cell injury induced by exogenous oxygen-free radicals that were generated by xanthine/xanthine oxidase or opsonized zymosan-stimulated polymorphonuclear leukocytes. Results showed that with the addition of xanthine/xanthine oxidase into cultured bovine pulmonary endothelial cells, production of malondialdehyde and release of lactate dehydrogenase in supernatant increased, and synthesis of prostacyclin decreased. Damaged cellular membranes were revealed by scanning electron microscopy. The same was true for the addition of opsonized zymosan-stimulated polymorphonuclear leukocytes. While treatment with anisodamine greatly attenuated all of the above-mentioned parameters, results showed that (1) cultured bovine pulmonary endothelial cells could be damaged by oxygen-free radicals, (2) anisodamine had a protective effect on this injury as effective as that of superoxide dismutase and catalase, and (3) the membrane-stable action might contribute to the mechanism of protective effect against this injury.
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PMID:Protective effect of anisodamine on cultured bovine pulmonary endothelial cell injury induced by oxygen-free radicals. 141 86

In order to examine the possible contribution of the Kupffer cell to the generation of hypoxia/reoxygenation injury in the liver, primary cultures of hepatocytes, either alone or in coculture with Kupffer cells, were exposed to 90 min of sublethal hypoxia followed by 120 min of reoxygenation. Prolonged incubation of cocultured hepatocytes and Kupffer cells resulted in increased release of lactic dehydrogenase (LDH) indicating cell injury even under normoxic conditions. LDH release was further increased by the presence of Kupffer cells during hypoxia/reoxygenation. To determine whether or not this effect of Kupffer cells might be the result of oxygen-derived free radical production, we assessed the efficacy of the enzymatic scavengers superoxide dismutase (SOD) + catalase in ameliorating the Kupffer cell mediated injury. SOD + catalase was effective in preventing free radical injury generated by hypoxanthine + xanthine oxidase. However, SOD + catalase did not ameliorate hepatocyte injury caused by Kupffer cells. Thus, activation of Kupffer cells may be an important factor in the genesis of liver injury, but the mediator of Kupffer cell exacerbation of hepatocyte injury appears to be a mechanism other than free radicals released into the medium. These results indicate that chemical substances from the activated Kupffer cells may cause hepatocyte damage, which cannot be blocked by SOD + catalase, and suggest that these substances at reflow may be important for the genesis of reperfusion injury in vivo.
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PMID:Kupffer cell exacerbation of hepatocyte hypoxia/reoxygenation injury. 142 16

The effect of methionine or citrate on antioxidant defense system has been studied in urolithic rat. Liver weight and its protein concentration did not change in the rats fed with calculi producing diet (CPD) when compared to normal diet fed rats. Feeding rats along with citrate (c-CPD) or methionine (m-CPD) improved their body weight gain. Liver microsomes and mitochondria fractions of CPD and c-CPD fed groups showed increased susceptibility for lipid peroxidation in presence of ascorbate and t-butyl hydroperoxide when compared to either control or m-CPD fed groups. Increased superoxide dismutase and xanthine oxidase activities, decreased catalase, glutathione peroxidase and glucose-6-phosphate dehydrogenase activities, decreased concentrations of reduced glutathione, total thiols, ascorbic acid and vitamin-E and increased formation of hydroxyl radical, hydroperoxides and diene conjugates were observed in the liver of both CPD fed group as well as c-CPD fed group. Except SOD and xanthine oxidase, all other parameters were normalized in m-CPD fed group. This suggested that feeding methionine reduced the susceptibility for lipid peroxidation by restoration of the level of free radical scavengers.
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PMID:Restoration of antioxidants in liver by methionine feeding in experimental rat urolithiasis. 142 65

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

Previous studies have shown that washed human platelets attenuate oxidant oedema in isolated perfused rabbit lungs through mechanisms dependent on platelet glutathione. We hypothesized that the platelet glutathione redox cycle scavenges hydrogen peroxide in this model and thereby protects vascular endothelial cells from oxidant injury. This hypothesis was tested by asking two questions: (1) do glutathione-supplemented platelets demonstrate augmented lung protection compared with control platelets, and (2) does conjugation of platelet glutathione with 1-chloro-2,4-dinitrobenzene or inactivation of catalase with 3-amino-1,2,4-triazole decrease in vitro platelet metabolism of hydrogen peroxide? We incubated washed human platelets with reduced glutathione or glutathione monoester and observed platelet glutathione contents of 181% and 189%, respectively, compared with control values. Incubation of platelets with N-acetylcysteine did not alter platelet glutathione content. Infusion of glutathione-supplemented platelets into isolated lungs injured by purine and xanthine oxidase did not augment platelet protection compared with untreated platelets. We also found that conjugation of platelet glutathione and/or inactivation of platelet catalase did not decrease the rate constant for platelet metabolism of hydrogen peroxide. We conclude that platelets attenuate oxidant lung oedema through glutathione-dependent mechanisms other than direct scavenging of hydrogen peroxide.
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PMID:Platelet prevention of oxidant lung oedema is not mediated through scavenging of hydrogen peroxide. 145 Mar 19

Feeding calculi producing diet (CPD) to rats for 4 weeks produced calcium oxaltate stones. Supplementation of sodium citrate to CPD (c-CPD) prevented stone formation. Except oxalate, the excretion of calcium, phosphorus and magnesium was restored to normal in c-CPD fed rats. The CPD fed rats exhibited increase in glycolic acid oxidase (GAO) and lactate dehydrogenase (LDH) activities and only GAO activity was partially restored in c-CPD fed rats. Kidney sub-cellular fractions of calculi producing diet (CPD) fed rats showed increased susceptibility for lipid peroxidation in presence of promotors. Antioxidant enzyme activities of superoxide dismutase (SOD), catalase and glutathione peroxidase and antioxidant concentrations of reduced glutathione, total thiols, ascorbic acid and vitamin E were significantly decreased while the xanthine oxidase activity, and concentrations of hydroxyl radical, diene conjugates and hydroperoxides were significantly increased in CPD fed rats. The susceptibility to lipid peroxidation, activities of antioxidant enzymes, and the concentration of antioxidants were not normalized by feeding citrate.
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PMID:Effect of citrate feeding on free radical induced changes in experimental urolithiasis. 145 50

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

Rat ventricular myocytes have been isolated and cultured by two separate procedures. Using phase-contrast and electron microscopies, we illustrate that (a) definitive cell damage is produced when myocytes are exposed to xanthine oxidase--hypoxanthine and (b) purpurogallin between 0.25 and 1.0 mM prolongs survival of both myocyte preparations in a dose-dependent manner. The cytoprotection produced by 1 mM purpurogallin exceeds that given by 2 mM each of ascorbate, Trolox, and mannitol, or 24,200 IU superoxide dismutase/L and (or) 92,000 IU catalase/L. Furthermore, we noted, for the first time, that purpurogallin markedly protects rat aortic endothelial cells, a key target of free radical generation and attack. In contrast, Trolox has a negligible effect here. Mechanistically, we showed that purpurogallin inhibits urate formation by xanthine oxidase more potently than allopurinol. Also, the compound diminishes formation of superoxide-reduced cytochrome c. Therefore, purpurogallin is a potent protector of ventricular myocytes and aortic endothelial cells, both of which are important cells in the cardiovascular system.
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PMID:Purpurogallin protects both ventricular myocytes and aortic endothelial cells of rats against oxyradical damage. 148 57

The purpose of the present study was to determine the effects of chronic portal diversion on antioxidant levels in the rat liver. Male Sprague-Dawley rats (n = 32) were used for these studies. An end-to-side portacaval anastomosis was constructed in 17 of the rats. Sham-operated rats (n = 15) served as controls. Two weeks later, hepatic blood flow was measured by the radioactive microsphere technique and the liver was harvested for biochemical measurement of catalase, manganese superoxide dismutase, copper-zinc superoxide dismutase, selenium glutathione peroxidase, xanthine oxidase, xanthine dehydrogenase and reduced glutathione (acid soluble sulfhydryls). Total hepatic blood flow was approx. 40% lower in portacaval-shunted rats when compared to sham-operated control rats. Total superoxide dismutase (SOD) and xanthine dehydrogenase (XD) levels were significantly reduced in the liver of shunted rats when compared to controls. Xanthine oxidase activity was unaltered. The decreased superoxide dismutase levels were exclusively due to reductions in the cytosolic Ca/Zn SOD; Mn SOD levels were unaltered. These data are consistent with oxidant stress and suggest that the liver of subjects with conditions characterized by decreased portal blood flow may be more susceptible to oxidant-induced liver injury.
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PMID:Hepatic oxidant and antioxidant systems in portacaval-shunted rats. 150 Jun 90


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