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)

The mono-electronic reduction of oxygen in the hypoxanthine-xanthine oxidase system led to the formation of active species eliciting an evident and highly reproducible mutagenic response in strain TA104 of S. typhimurium. Similar effects were observed by generating oxy radicals either extracellularly or inside bacterial cells. Mutagenicity was selectively detected in TA104 and not in other Salmonella strains, which points out the importance of the hisG428 mutation and of the deletion excising the uvrB gene, as far as sensitivity to oxy radicals is concerned. The mutagenicity of the system was further enhanced in the presence of superoxide dismutase. Catalase did not affect the mutagenicity of hypoxanthine plus xanthine oxidase, whereas it inhibited the mutagenicity induced by the mixture of hypoxanthine with xanthine oxidase and superoxide dismutase. This demonstrates that not only hydrogen peroxide but also the superoxide radical anion is positive in this system. Glutathione and 2 synthetic thiols, i.e., N-acetylcysteine and alpha-mercaptopropionylglycine, besides decreasing the high spontaneous mutagenicity of TA104, efficiently prevented the mutagenicity of active oxygen species.
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PMID:Mutagenicity of active oxygen species in bacteria and its enzymatic or chemical inhibition. 267 96

The amounts of different factors, which are involved in oxygen free radical production or in protection against oxygen radicals, were determined in different parts of the gastrointestinal tract (GI-tract). Glutathione and superoxide dismutase were present in lower amounts within the small intestine compared with the stomach and the large intestine. In the small intestine glutathione peroxidase and catalase both prevailed in the intestinal muscle compared to the mucosa, whereas in the large intestine both enzymes are equally distributed among the mucosa and muscle. Xanthine oxidase was mainly present in the small intestinal mucosa. Taken together, these results suggest that the large intestine is better provided with protective enzymic and non-enzymic factors against oxidative stress than the small intestine. The protective capacity of different intestinal preparations against lipid peroxidation in liver microsomes was assessed, and particularly the mucosal fractions from the small intestine showed a marked protection against lipid peroxidation, which is not easily explained with the presence of the enzymes measured in this study. Pretreatment of intestinal segments with hydrogen peroxide or cumene hydroperoxide resulted in a damaged contractile response of the longitudinal smooth muscle to methacholine in all parts of the GI-tract, expressed in a lower pD2 value and a decreased maximal response. Pretreatment with these peroxides also decreased contractions after depolarization with K+. The large intestine is more sensitive to hydrogen peroxide and cumene hydroperoxide than the small intestine, which parallels with the sensitivity to lipid peroxidation. The results obtained with hydrogen peroxide also correlate well with the catalase activity in the various segments of the intestine. In conclusion, oxidative stress in the GI-tract alters intestinal motility, especially in the large intestine. Probably this does not occur at the level of muscarinic receptors.
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PMID:Modulation of oxidative stress in the gastrointestinal tract and effect on rat intestinal motility. 267 48

The pathogenesis of neonatal necrotizing enterocolitis is unknown, but a possible role for reactive oxygen metabolites has been postulated. We evaluated whether developmental differences exist in the levels of 1) the free radical-generating enzyme xanthine oxidase, 2) granulocyte peroxidase, an index of the resident granulocyte population, 3) free radical-scavenging enzymes (superoxide dismutase, catalase, and glutathione peroxidase), and 4) reduced glutathione, an endogenous antioxidant, in the ileal and colonic mucosa of 1-d-old, 3-d-old, 2-wk-old, and 1-mo-old piglets. We found no xanthine dehydrogenase/oxidase activity in 1-d to 1-mo-old piglets. Mucosal granulocyte peroxidase activity was higher in older animals, indicating that there was an age-dependent infiltration of granulocytes (eosinophils, neutrophils) in the distal bowel. The peroxidase activity per circulating granulocyte, however, did not vary with age. Superoxide dismutase activity was significantly higher in 1-d-old piglets than in all older age groups; glutathione peroxidase activity was significantly lower in 1-d-old animals than that of older age groups. There was no detectable catalase activity in the mucosa when tissue was corrected for catalase activity of blood. Finally, ileal GSH levels were significantly lower in 1-d-old than in 2-wk-old and 1-mo-old animals, whereas colonic reduced glutathione activity did not differ among age groups. In conclusion, the distal bowel of the neonatal piglet appears to have a limited capacity to generate oxidants via xanthine oxidase and resident granulocytes. However, the neonatal piglet intestine has a lower capacity to detoxify hydrogen peroxide than that of older animals.
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PMID:Developmental biology of oxidant-producing enzymes and antioxidants in the piglet intestine. 274 Jan 52

Rabbit kidneys were subjected to 120 min of warm ischaemia or to 120 min of warm ischaemia followed by 60 min reperfusion with blood in vivo before being removed, homogenised and incubated at 37 degrees C for 90 min. Lipid extracts were obtained and monitored for Schiff base (fluorescence emission 400-450 nm, excited at 360 nm), thiobarbituric acid (TBA)-reactive material (emission 553 nm, excited at 515 nm) and diene conjugates (absorbance at 237 nm). Samples removed before incubation were assayed for reduced glutathione (GSH) and oxidised glutathione (GSSG) to provide an index of glutathione redox activity (GSH:GSSG). Allopurinol injected systemically i.v. (a) 15 mins before kidneys were clamped, (b) 15 mins before they were reperfused or (c) as two injections (before clamping and before reperfusion) significantly inhibited these biochemical markers of lipid peroxidation. Administration before reperfusion had a markedly more pronounced effect than when allopurinol was given before warm ischaemia only. It is concluded that allopurinol is probably effective because of its ability to inhibit xanthine oxidase and consequently lipid peroxidation during reperfusion rather than by preventing loss of purine nucleotides from hypoxic cells during ischaemia.
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PMID:Allopurinol inhibits lipid peroxidation in warm ischaemic and reperfused rabbit kidneys. 279 46

Rat livers were perfused at 37 degrees C, 41 degrees C, 42 degrees C, 42.5 degrees C, and 43 degrees C for 2 hr. Among perfusate constituents analyzed were urea, total amino acids, N-acetyl-beta-glucosaminidase (NAG), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), malonaldehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG), allantoin, potassium, phosphate, and glucose. After perfusion, livers were homogenized and analyzed for xanthine oxidase (XO) activity, GSH content, and lysosomal lability. Perfusate AST, LDH, NAG, potassium, glucose, and phosphate increased significantly with time, and there were significant differences in the final values between 37 degrees C and 42 degrees C, 42.5 degrees C and 43 degrees C (P less than .05). GSH levels increased significantly at all temperatures after 90 and 120 min, whereas GSSG levels differed significantly at 60, 90, and 120 min for 37 degrees C vs. 42 degrees C, 42.5 degrees C, and 43 degrees C (P less than .05). Mean MDA levels at 37 degrees C differed from those at 41 degrees C and 43 degrees C (P less than .05) at each temperature. Allantoin levels increased significantly with time of perfusion; mean levels at 37 degrees C were significantly different from mean levels at each temperature at 60, 90, and 120 min. GSH liver tissue levels decreased with perfusion at hyperthermic temperatures; mean values at 41 degrees C, 42 degrees C, and 42.5 degrees C, and 43 degrees C differed from 37 degrees C mean values (P less than .01). Type O XO increased after 120 min perfusion from 6.4% +/- 2.0% at 37 degrees C to 55% +/- 30%, 43% +/- 27%, and 63% +/- 29% at 42 degrees C, 42.5 degrees C, and 43 degrees C, respectively. Lysosomal lability increased after perfusion at 42.5 degrees C. There was a significant increase in nonsedimentable NAG activity at 42.5 degrees C (P less than .05). These data support the premise that hyperthermic toxicity to the liver may be a consequence of oxidative stress brought about by enhanced adenosine triphosphate (ATP) consumption and conversion of XO to type O. Such conversion results in superoxide formation and subsequent depletion of cellular GSH, labilization of the lysosomes, and plasma membrane damage.
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PMID:Hyperthermic liver toxicity: a role for oxidative stress. 279 43

Evidence has been obtained that implicates the generation of reactive oxygen species as an early and critical event in the promotion of neoplastic transformation in mouse JB6 cells. The time courses for specific inhibition by CuZn-superoxide dismutase (CuZn-SOD) of the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced promotion of neoplastic transformation in JB6 cells and for changes in antioxidant enzyme activities associated with TPA-exposure were examined. The antipromoting effect of CuZn-SOD was found to be critically dependent on the time of addition of CuZn-SOD relative to the start of a 14-day exposure of cells to TPA. Treatment of JB6 P+ Clone 22 and Clone 41 cells with CuZn-SOD for 18 h before, simultaneously with or up to 1 h after exposure to TPA, all inhibited promotion of transformation maximally. Delay of addition of CuZn-SOD by 2 h or more after the start of TPA treatment resulted in a marked decrease in the promotion inhibitory effect. CuZn-SOD added 24 or 48 h after TPA had no effect on promotion of transformation. Exposure of JB6 cells to 0.2- (superoxide anion radical) generated exogenously by the aerobic xanthine oxidase reaction resulted in promotion of neoplastic transformation that was prevented by concurrent addition of CuZn-SOD. Taken together these studies provide evidence that increased superoxide anion generation within the first 2 h following TPA exposure is an essential event in promotion of transformation in JB6 cells. Upon TPA exposure, JB6 Clone 41 cells exhibited time-specific activity changes in the cellular SOD, glutathione peroxidase (GSH-Px), and catalase. SOD and GSH-Px activities were reduced to 54% and 26% respectively of basal levels within 2 h of TPA treatment. GSH-Px activity recovered to basal levels within 4 h and CuZn-SOD within 48 h. Catalase activity was maximally reduced to 50% of basal within 1 h after TPA treatment and rebounded to greater than basal levels within 4 h. It is postulated that a c-kinase-dependent event induces rapid elevation of superoxide anion following TPA exposure and that this leads to reduced activity of antioxidant enzymes. Since antipromotion by exogenous CuZn-SOD is effective only during the first 2 h following TPA exposure, this suggests that the promotion-relevant 0.2- elevation is transient.
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PMID:Early superoxide dismutase-sensitive event promotes neoplastic transformation in mouse epidermal JB6 cells. 282 3

The protective effects of various tannins on ocular lens against the induced oxidative damage were examined. Oxidative damage on mouse lenses was induced by incubating them with xanthine-xanthine oxidase, ADP and Fe3+ (X.XOD system). X.XOD system caused an increase in lipid peroxide of lens membrane and decreases in Na,K-ATPase and GSH reductase activities in the lenses. After pretreatment of lenses with X.XOD system, the lenses were incubated with tannins in the medium containing no X.XOD system and the effects of tannins on biochemical parameters in the lenses were determined. Higher molecular tannins (penta-O-galloyl-beta-D-glucopyranose and geraniin) decreased the lipid peroxide in the lens and restored GSH content, Na,K-ATPase and GSH reductase activities in the lens to the level comparable to control. However, all of tannins tested restored much insufficiently the cation level (ratio of Na+/K+) in the lens regardless of extents of restoration of Na,K-ATPase level by them. Because it was supposed that tannins might act primarily on the plasma membrane, the effect of tannins on lens plasma membrane was examined using cell free system. Lens was homogenated and separated into membrane pellet and supernatant. When the pellet was treated with X.XOD system, the lipid peroxide in the pellet increased and its Na,K-ATPase activity decreased. In addition, the treated pellet decreased the GSH level and GSH reductase activity in the supernatant, when the pellet was combined with the supernatant. Higher molecular tannins reduced lipid peroxide content in the X.XOD-treated pellet to control level and the pellet in which lipid peroxide content was reduced by tannins caused much less decreases of GSH level and GSH reductase activity in the supernatant. These results suggest that, in intact lens, higher molecular tannins act on plasma membrane to eliminate lipid peroxide produced by the X.XOD system and consequently suppress the decreases in both Na,K-ATPase and GSH reductase activities without their entering inside the cell.
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PMID:Effects of tannins on the oxidative damage of mouse ocular lens. I. Using the oxidative damage model induced by the xanthine-xanthine oxidase system. 284 23

Day 9.5 rat embryos were exposed in culture to xanthine/xanthine oxidase generated active oxygen species. Growth and development were assessed after 46 hr of culture. The treatment induced abnormalities of the neural suture, the severity of which increased in a dose-related manner with the concentration of substrate or enzyme. Glutathione (10 mM) or catalase (50 micrograms/ml) either partially or completely abolished the effects of xanthine/xanthine oxidase, whereas the addition of superoxide dismutase (50 micrograms/ml) or desferrioxamine (1mM) did not reduce the number of malformed embryos. These findings suggest that hydrogen peroxide and/or hydroxyl radicals are responsible for the effects of xanthine and xanthine oxidase.
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PMID:Malformations induced in cultured rat embryos by enzymically generated active oxygen species. 288 69

The selenium-containing glutathione peroxidase, when in its active reduced form, was inactivated during exposure to the xanthine oxidase reaction. Superoxide dismutase completely prevented this inactivation, whereas catalase, hydroxyl radical scavengers, or chelators did not, indicating that O2 was the responsible agent. Conversion of GSH peroxidase to its oxidized form, by exposure to hydroperoxides, rendered it insensitive toward O2. The oxidized enzyme regained susceptibility toward inactivation by O2 when reduced with GSH. The inactivation by O2 could be reversed by GSH; however, sequential exposure to O2 and then hydroperoxides caused irreversible inactivation. Reactivity toward CN- has been used as a measure of the oxidized form of GSH peroxidase, whereas reactivity toward iodoacetate has been taken as an indicator of the reduced form. By these criteria both O2 and hydroperoxides convert the reduced form to oxidized forms. A mechanism involving oxidation of the selenocysteine residue at the active site has been proposed to account for these observations.
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PMID:Inactivation of glutathione peroxidase by superoxide radical. 299 78

Na-Ca exchange activity in bovine cardiac sarcolemmal vesicles was stimulated up to 10-fold by preincubating the vesicles with 1 microM FeSO4 plus 1 mM dithiothreitol (DTT) in a NaCl medium. The increase in activity was not reversed upon removing the Fe and DTT. Stimulation of exchange activity under these conditions was completely blocked by 0.1 mM EDTA or o-phenanthroline; this suggests that the production of reduced oxygen species (H2O2, O2-.,.OH) during Fecatalyzed DTT oxidation might be involved in stimulating exchange activity. In agreement with this hypothesis, the increase in exchange activity in the presence of Fe-DTT was inhibited 80% by anaerobiosis and 60% by catalase. H2O2 (0.1 mM) potentiated the stimulation of Na-Ca exchange by Fe-DTT under both aerobic and anaerobic conditions; H2O2 also produced an increase in activity in the presence of either FeSO4 (1 microM) or DTT (1 mM), but it had no effect on activity by itself. Superoxide dismutase did not block the effects of Fe-DTT on exchange activity; however, the generation of O2-. by xanthine oxidase in the presence of an oxidizable substrate stimulated activity more than 2-fold. Hydroxyl radical scavenging agents (mannitol, sodium formate, sodium benzoate) did not attenuate the stimulation of activity observed with Fe-H2O2. Exchange activity was also stimulated by the simultaneous presence of glutathione (GSH; 1-2 mM) and glutathione disulfide (GSSG; 1-2 mM). Neither GSH nor GSSG was effective by itself and either 0.1 mM EDTA or o-phenanthroline blocked the effects on transport activity of the combination of GSH + GSSG. Treatment of the GSH and GSSG solutions with Chelex ion-exchange resin to remove contaminating transition metal ions reduced (by 40%) the degree of stimulation observed with GSH + GSSG. Full stimulating activity was restored to the Chelex-treated GSH and GSSG solutions by the addition of 1 microM Fe2+; Cu2+ was less effective than Fe2+ whereas Co2+ and Mn2+ were without effect. In the presence of 1 microM Fe2+, GSH alone produced a slight increase in transport activity, but this was markedly enhanced by the addition of Chelex-treated GSSG. The results indicate that stimulation of exchange activity requires the presence of both a reducing agent (DTT, GSH, O-.2, or Fe2+) and an oxidizing agent (H2O2, GSSG, and perhaps O2) and that the effects of these agents are mediated by metal ions (e.g. Fe2+).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Redox modification of sodium-calcium exchange activity in cardiac sarcolemmal vesicles. 300 82


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