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)

Cytotoxicity indicated by increased release of prelabeled 51chromium (51Cr) and lactate dehydrogenase (LDH) was studied in human prostate cancer and melanoma cells in cell culture following irradiation or exposure to several injurious substances. These changes were compared to those observed in bovine aortic endothelial cells (BAEC) subjected to identical treatments. Further, the effect of irradiation on plasminogen activator (PA) secretion from prostate cancer cells, and the effect of glycine on radiation-induced cytotoxicity in BAEC were also investigated. Radiation, lipopolysaccharide and xanthine/xanthine oxidase stimulated no release of 51Cr or LDH from tumor cells, while these treatments induced a dose- and time-related loss of those cytotoxic indicators from BAEC. Protease, elastase and Triton X-100 incited loss of 51Cr and LDH from all three cell types. Radiation, lipopolysaccharide and xanthine/xanthine oxidase have been shown to cause cell injury via a common pathogenic pathway of oxidant generation. Tumor cells appear quite resistant to oxidant stress. Cell damage precipitated by protease, elastase and Triton probably involves hydrolysis of proteins and phospholipids in the cell membrane, leading to an increased leakage of intracellular proteins such as LDH and those bound with 51Cr. Radiation caused a dose- and time-related reduction in the secretion of PA from prostate cancer cells. PA is alleged to play a role in tumor metastasis; the reduced secretion could be another beneficial effect of radiation, in addition to interruption of cell proliferation, in the impediment of tumor growth and spread. Glycine diminished cytotoxic injury of BAEC inflicted by radiation. This amino acid may prove useful in offering a degree of protection of normal tissue against radiation associated side-effects.
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PMID:Injury-specific cytotoxic response of tumor cells and endothelial cells. 868 34

Dopamine can oxidize to form reactive oxygen species and quinones, and we have previously shown that dopamine quinones bind covalently to cysteinyl residues on striatal proteins. The dopamine transporter is one of the proteins at risk for this modification, because it has a high affinity for dopamine and contains several cysteinyl residues. Therefore, we tested whether dopamine transport in rat striatal synaptosomes could be affected by generators of reactive oxygen species, including dopamine. Uptake of [3H]dopamine (250 nM) was inhibited by ascorbate (0.85 mM; -44%), and this inhibition was prevented by the iron chelator diethylenetriaminepentaacetic acid (1 mM), suggesting that ascorbate was acting as a prooxidant in the presence of iron. Preincubation with xanthine (500 microM) and xanthine oxidase (50 mU/ml) also reduced [3H]dopamine uptake (-76%). Preincubation with dopamine (100 microM) caused a 60% inhibition of subsequent [3H]dopamine uptake. This dopamine-induced inhibition was attenuated by diethylenetriaminepentaacetic acid (1 mM), which can prevent iron-catalyzed oxidation of dopamine during the preincubation, but was unaffected by the monoamine oxidase inhibitor pargyline (10 microM). None of these incubations caused a loss of membrane integrity as indicated by lactate dehydrogenase release. These findings suggest that reactive oxygen species and possibly dopamine quinones can modify dopamine transport function.
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PMID:Modification of dopamine transporter function: effect of reactive oxygen species and dopamine. 876 84

Na,K-ATPase activity, membrane lipid peroxidation (TBARM), and membrane 'leakiness' for small molecules were examined in rat cerebromicrovascular endothelial cells (RCEC) following exposure to hydrogen peroxide and xanthine/xanthine oxidase. Whereas short-term (15-30 min) exposure to either oxidant decreased ouabain-sensitive 86Rb uptake and increased TBARM in a concentration-dependent fashion, significant release of 51Cr (30-40%) from cells was observed only after one hour exposure to the oxidants. By comparison, much longer exposure times (i.e., 4 hours) were needed to induce significant lactate dehydrogenase release from oxidant-treated cells. The oxidant-evoked decrease in Na,K-ATPase activity and increases in TBARM and RCEC 'permeability' were abolished in the presence of the steroid antioxidants U-74500A and U-74389G (5-20 microM). Reduced glutathione (4 mM) partially attenuated oxidant-induced changes, whereas ascorbic acid (2 mM) and the disulfide bond-protecting agent, dithiothreitol (1 mM), were ineffective. These results suggest that the oxidant-induced loss of Na,K-ATPase activity in RCEC results primarily from changes in membrane lipids, and implicate both the inhibition of Na,K-ATPase and membrane lipid peroxidation in the mechanism responsible for the delayed free radical-induced increase in RCEC membrane 'permeability'.
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PMID:Free radical-induced endothelial membrane dysfunction at the site of blood-brain barrier: relationship between lipid peroxidation, Na,K-ATPase activity, and 51Cr release. 878 3

The possibility that verapamil (CAS 52-53-9) may intensify the efficacy of vitamin E in preventing the ischemia-reperfusion-caused biochemical dearrangement in rat cerebral cortex was investigated. A daily injection of vitamin E at i.m. dose of 175 mg/kg b.wt. for 7 days prior to subjecting the rats to 1 h bilateral occlusion of the common carotid arteries followed by reperfusion for another 1 h, moderately diminished the ischemia-reperfusion-induced increase in the activity of lactate dehydrogenase and in formation of conjugated dienes as well as in the conversion of xanthine dehydrogenase-->xanthine oxidase in cerebral cortex of rats. However, concomitant injection of verapamil at i.m. dose of 0.68 mg/kg b.wt. 15 min prior to ischemia-reperfusion together with vitamin E pretreatment afforded an elegant combined therapy that effectively abolished the dearrangement caused by ischemia-reperfusion in the above parameters. These results indicated that the protective efficacy of vitamin E against ischemia/reperfusion-induced biochemical dearrangement in cerebral cortex was intensified by concomitant use of verapamil.
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PMID:Influence of verapamil on the efficacy of vitamin E in preventing the ischemia-reperfusion-induced biochemical dearrangement in cerebral cortex of rat. 884 34

The effect of a novel flavonoid, venoruton (a mixture of mono-, di-, tri- and tetrahydroxyethylrutosides) has been investigated in healthy rat lenses and compared with diabetic cataract modelled in vitro. One mM venoruton was added to medium simulating healthy and diabetic conditions for the incubated lenses; damage was followed by either stereoscopic photography of the lenses under a Cooperative Cataract Research Group operating microscope or with our recently developed method: the leakage of lactate dehydrogenase (LDH) into the lens culture media. The increased LDH activity in the medium and observable development of the opacity were correlated with cell damage, which has been found to be associated with globular degeneration and cataract formation. The extent of opacification and LDH release is reduced if 1 mM venoruton is included in the medium. The protective effect may be related to antioxidant activity against reactive oxygen species: decreased luminol luminescence was shown after venoruton addition to either superoxide-generating hypoxanthine plus xanthine oxidase, or hydrogen peroxide.
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PMID:Modelling cortical cataractogenesis. XVIII. In vitro diabetic cataract reduction by venoruton. A flavonoid which prevents lens opacification. 888 54

Oxidant stress plays a major role in the pathophysiologic processes associated with ischemia-reperfusion injury. Xanthine oxidase (XO) is often implicated as a significant source of oxidants and increases in the circulation after hepatoenteric ischemia-reperfusion. We hypothesized that pulmonary injury is associated with hepatic ischemia-reperfusion resulting from descending thoracic aorta occlusion-reperfusion (AoOR). We also proposed that this remote pulmonary injury is attenuated through inactivation of circulating and tissue XO by tungstate, implicating an XO-dependent mechanism. Aortic occlusion was established in rabbits (standard or tungstate diet) for 40 min by 2 h reperfusion. Sham operated rabbits (standard or tungstate diet) served as controls. Hepatic reperfusion injury, as manifested by release of the hepatocellular enzyme alanine aminotransferase (ALT), was markedly increased after AoOR. Suprarenal-infrahepatic occlusion failed to increase ALT release. Tungstate pretreatment significantly (p < 0.05) reduced XO activity and ameliorated liver and intestinal injury (p < 0.05). Lung injury, manifested by increased bronchoalveolar lavage (BAL) protein concentration, BAL lactate dehydrogenase (LDH) activity and increased lung edema was significantly associated with liver injury (p < 0.05) and circulating XO activity (p < 0.001). XO inactivation significantly decreased BAL protein concentration, BAL LDH activity, and lung edema (p < 0.05). We conclude that remote pulmonary injury is significantly influenced by the extent of liver injury and circulating XO activity.
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PMID:Lung injury after hepatoenteric ischemia-reperfusion: role of xanthine oxidase. 891 49

Brain ischemia reperfusion causes increased formation of reactive oxygen species (ROS). Activity of the mitochondrial enzyme pyruvate dehydrogenase (PDH) has been shown to undergo a significant decrease following reperfusion of the ischemic tissue. We have examined the effect of a superoxide radical-generating system (xanthine oxidase/hypoxanthine, XO/HX) on the activity of this enzyme. Incubation of PDH in the presence of XO/HX resulted in its inactivation. The degree of the inactivation was dependent on the amount of XO present, which correlated linearly with the concentration of superoxide radical generated by this system. The activity of lactate dehydrogenase, an enzyme resistant to inactivation by ischemia reperfusion, was not affected by this system. Superoxide dismutase partially prevented and catalase exerted a nearly complete protective effect against the inactivation of PDH. Deferoxamine was partially protective. The sulfhydryl protective reagents, dithiothreitol and glutathione, prevented the inactivation of PDH, even though to varying degrees, which implicates sulfhydryl oxidation. A hydroxyl radical-generating system (hydrogen peroxide irradiated with ultraviolet radiation) effectively inactivated PDH. These results demonstrate that PDH is susceptible to damage and inactivation by ROS and point to the involvement of Fenton chemistry and hydroxyl radicals formed through it in PDH inactivation by XO/HX. A similar mechanism may be responsible for the PDH inactivation during ischemia/reperfusion.
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PMID:Reactive oxygen species-mediated inactivation of pyruvate dehydrogenase. 895 77

Apoptosis is a distinct form of cell death that is observed under various physiologic and pathologic conditions, and it is thought to be important in regulating the number of glomerular cells. This study investigated the possible role of reactive oxygen species in the induction of apoptosis in cultured human mesangial cells. Fragmented nuclei with condensed chromatin, a morphologic characteristic of apoptosis, were observed by electron microscopy in mesangial cells exposed to 0.02 mM hydrogen peroxide for 4 h. Nuclear DNA extracted from mesangial cells that had been incubated with hydrogen peroxide (2 to 20 mM) or with xanthine (0.05 mM) and xanthine oxidase (5 to 100 mU/mL) showed the ladder pattern on electrophoresis that is a biochemical marker for apoptosis. Hydrogen peroxide (0.02 to 20 mM) decreased the number of viable cells, as determined by trypan blue exclusion, in a dose-dependent manner. Hydrogen peroxide or xanthine and xanthine oxidase increased the lactate dehydrogenase release from mesangial cells in a dose- and time-dependent manners. The release of lactate dehydrogenase was prevented by treatment with a free radical scavenger, catalase. Hydrogen peroxide (2 mM) also significantly increased the number of mesangial cells with fragmented DNA as detected by in situ nick end-labeling Results indicate that reactive oxygen species induce apoptosis in cultured human mesangial cells. Furthermore, apoptosis of mesangial cells induced by reactive oxygen species may contribute to the loss of such cells observed in glomerular disease.
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PMID:Reactive oxygen species induce apoptosis in cultured human mesangial cells. 895 25

The effects of hypoxia of different durations (8, 12 or 15 min) and of subsequent reoxygenation were studied in rat hippocampal slices by measuring enzyme activities related to oxidative stress: superoxide dismutase (SOD), cytochrome c oxidase and lactate dehydrogenase (LDH). Simultaneously the degree of lipid peroxidation was estimated by measuring conjugated dienes (CD). Reoxygenation after 8-min of hypoxia induced general cell injury indicated by increased LDH activity. Reoxygenation after 12-min of hypoxia started lipid peroxidation assessed by an increase in CD, and after 15-min of hypoxia followed by reoxygenation CD were found to be significantly decreased, suggesting lipid degradation. The injury induced by a hypoxia of 12 min and reoxygenation was reduced by SOD and catalase, indicating that oxygen radicals were involved in this process. The oxygen radicals originating from the xanthine/xanthine oxidase system, from the synthesis of prostaglandins, as well as from the mitochondrial respiratory chain, since allopurinol, indomethacin and rotenone decreased while antimycin increased reoxygenation injury. An increase in ATP may also have been involved as cyanide, an inhibitor of ATP synthesis, decreased the reoxygenation injury. The chain-breaking antioxidants trolox, alpha tocopherol and the pyridoindole stobadine were effective in preventing reoxygenation injury, indicating the involvement of lipid peroxidation in this process.
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PMID:Mechanisms of hippocampal reoxygenation injury. Treatment with antioxidants. 914 55

Human spermatozoa possess a specialized capacity to generate reactive oxygen species (ROS) that is thought to be of significance in the redox regulation of sperm capacitation (De Lamirande and Gagnon, 1993; Aitken et al., 1995). However, the mechanisms by which ROS are generated by these cells are not understood. In this study we have examined the possible significance of NADPH as a substrate for ROS production by human spermatozoa. Addition of NADPH to viable populations of motile spermatozoa induced a sudden dose-dependent increase in the rate of superoxide generation via mechanisms that could not be disrupted by inhibitors of the mitochondrial electron transport chain (antimycin A, rotenone, carbonyl cyanide m-chlorophenylhydrazone [CCCP], and sodium azide), diaphorase (dicoumarol) xanthine oxidase (allopurinol), or lactic acid dehydrogenase (sodium oxamate). However, NADPH-induced ROS generation could be stimulated by permeabilization and was negatively correlated with sperm function. Both NADH and NADPH were active electron donors in this system, while NAD+ and NADP+ exhibited little activity. Stereo-specificity was evident in the response in that only the beta-isomer of NADPH supported superoxide production. The involvement of a flavoprotein in the electron transfer process was indicated by the high sensitivity of the oxidase to inhibition by diphenylene iodonium and quinacrine. These results indicate that NAD(P)H can serve as an electron donor for superoxide generation by human spermatozoa and present a simple strategy for the production of motile populations of free radical generating cells with which to study the significance of these molecules in the control of normal and pathological sperm function.
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PMID:Reactive oxygen species generation by human spermatozoa is induced by exogenous NADPH and inhibited by the flavoprotein inhibitors diphenylene iodonium and quinacrine. 921 32


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