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

1. The aim of this study was to clarify the role of lipid peroxidation in cellular injury as assessed by lactate dehydrogenase (LDH) release from cultured coronary artery endothelial cells of the pig. Cells exposed to H2O2 at concentrations of 0.1 to 20 mM or to a xanthine and xanthine oxidase (X/XO) reaction mixture released LDH into the medium. Significant release from X/XO-treated cells took place with a delay of 2 h. 2. Superoxide dismutase (SOD), catalase or dimethylthiourea attenuated the release of LDH from X/XO-treated cells. Similarly the putative inhibitor of lipid peroxidation, U78517F attenuated the release of LDH by X/XO with an IC50 of 0.08 microM. 3. H2O2 was continuously produced by the addition of X/XO to the medium alone. However, in the presence of endothelial cells, H2O2 was eliminated at 1 h. U78517F had no effect on either process. 4. The oxygen radical-induced release of LDH was associated with malondialdehyde (MDA) formation. U78517F inhibited the formation of MDA with an IC50 of 0.27 microM. 5. Reduction of the Ca2+ concentration in the incubation medium from 1.6 mM to 0.016 mM markedly attenuated the release of LDH from endothelial cells. Nifedipine (1 microM) did not attenuate the LDH release from the cells. 6. It is likely that porcine coronary artery endothelial cells can be thus injured by oxygen radicals presumably through hydroxyl radicals formed and consequent lipid peroxidation, and that the extracellular Ca2+ concentration plays an important role in the genesis of such endothelial cell damage.
 ...
PMID:Cellular mechanism of U78517F in the protection of porcine coronary artery endothelial cells from oxygen radical-induced damage. 848 19

The role of xanthine oxidase in paraquat toxicity was investigated using cultured bovine pulmonary artery endothelial cells. Exposure to paraquat 0.1 mM was done for 24 hr with or without tungsten pretreatment and in the presence or absence of xanthine oxidase inhibitors. Exposure to paraquat significantly increased O2- production and relative xanthine oxidase activity (xanthine oxidase activity divided by total xanthine dehydrogenase plus xanthine oxidase) while depressing cell growth. In contrast, tungsten and allopurinol inhibited the increase of xanthine oxidase activity and decreased O2- release. Cell injury was assessed by leakage of lactate dehydrogenase and by fluorescein diacetate staining; it was found that oxidase inhibitors (both allopurinol and tungsten) reduced paraquat cytotoxicity. Thus the toxicity of paraquat was at least partly due to intracellular O2- production mediated by xanthine oxidase and the subsequent formation of other free radicals.
 ...
PMID:Xanthine oxidase mediates paraquat-induced toxicity on cultured endothelial cell. 853 10

Cultured rat retinal neurons exposed to kainate produced free radicals, as demonstrated by electron spin resonance (ESR) spin trapping using the nitrone 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and the generation of DMPO hydroxyl adduct (DMPO-OH). This DMPO-OH production was abolished by EGTA, nitro-arginine and oxypurinol, suggesting that it was dependent on Ca2+ influx and subsequent activation of nitric oxide synthase and xanthine oxidase. Moreover, kainate induced a receptor-mediated Ca2+ influx and neuronal injury assessed by lactate dehydrogenase release. Neuroprotection afforded by nitro-arginine and oxypurinol shows that calcium-dependent free radical production plays a major role in kainate retinal toxicity.
 ...
PMID:Calcium-dependent free radical generation in cultured retinal neurons injured by kainate. 857 85

The scavenging effect of Chinonin on NO and oxygen free radicals and its protective effect on myocardium from the ischemia-reperfusion injury was studied with electron spin resonance (ESR) and chemiluminescence techniques. Chinonin can effectively inhibit the oxidative activity of ONOO-, (the IC50 = 7 x 10 (-5) mmol/L) and scavenge oxygen free radicals generated from the reaction of xanthine and xanthine oxidase (the IC50 = 2/5 x 10(-4) mmol/l). It is difficult to find another antioxidant which can scavenge so effectively both ONOO- and oxygen free radicals simultaneously. In the system of ischemia-reperfusion injury of myocardium, Chinonin can, in parallel, scavenge the NO and oxygen free radicals generated from the ischemia-reperfused myocardium, and decrease the activities of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary artery effluent of ischemia-reperfused heart and therefore protect the heart from ischemia-reperfusion injury. The protective effect of 0.1 mmol/l Chinonin is similar to that of 1500 U/ml SOD and catalase.
 ...
PMID:Scavenging effect of Chinonin on NO and oxygen free radicals and its protective effect on the myocardium from the injury of ischemia-reperfusion. 860 70

The protective effect of allopurinol, an inhibitor of the enzyme, xanthine oxidase, against the renal ischaemia-reperfusion of the rat was investigated. Rats were subjected to renal ischaemia by clamping of the left renal artery and vein for 45 min, and were then reperfused for 24 h; these animals were randomized to receive either saline (n = 10) or allopurinol (n = 10) at a dose of 50 mg/kg bolus intraperitoneally 5 min before reperfusion. The control group comprised seven healthy rats not exposed to ischaemia or reperfusion. The blood urea nitrogen and plasma creatinine levels were increased in the allopurinol group, but the increase was less than that in the placebo group, compared with the controls. The kidney glutathione level was significantly reduced in the placebo group but not in the allopurinol group compared with the controls. The glutathione peroxidase activity in the kidney tissues was reduced more than two-fold in the placebo group compared with the controls, but the reduction in glutathione peroxidase was considerably less in the allopurinol group. Renal tissue lactate dehydrogenase, aspartate amino-transferase, gamma-glutamyl transferase and alkaline phosphatase activities were reduced almost two-fold in the placebo group, but allopurinol treatment maintained these enzyme activities close to the control activities. These results provide evidence that allopurinol treatment may have beneficial effects on antioxidant defences against ischaemia-reperfusion injury of rat kidneys.
 ...
PMID:Beneficial effects of allopurinol on glutathione levels and glutathione peroxidase activity in rat ischaemic acute renal failure. 867 98

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.
 ...
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.
 ...
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'.
 ...
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.
 ...
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.
 ...
PMID:Modelling cortical cataractogenesis. XVIII. In vitro diabetic cataract reduction by venoruton. A flavonoid which prevents lens opacification. 888 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>