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)

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

This study evaluated the role of endogenous and exogenous sulphydryl compounds in the defense of rat gastric epithelial cells against damage brought about by oxygen reactive metabolites in vitro. Toxic oxygen species were generated by xanthine oxidase in the presence of xanthine. Cell damage was assessed by 51 chromium release assay. Our data confirm that xanthine oxidase, in the presence of xanthine damages cultured rat gastric cells in a dose dependent manner (r = 0.0885, p less than 0.05). Depletion of endogenous thiols by N-ethylmaleimide significantly increases the amount of damage induced by oxygen radicals causing, at the concentration of 0.005 mM, a 60% increase in 51 chromium release (p less than 0.001). The sulphydryl agent cysteamine did not prevent cell damage induced by oxygen reactive metabolites. In conclusion, 1) depletion of endogenous thiols significantly increases the susceptibility of rat gastric epithelial cells to oxygen radical-induced damage; 2) this damage is not prevented by an exogenous agent containing a SH group.
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PMID:Role of sulphydryl compounds in the defense of rat gastric epithelial cells against oxygen reactive metabolite-induced damage. 174 3

Superoxide radicals or products generated by these radicals in a xanthine/xanthine oxidase system lyse cultured rat and human corneal epithelial cells as measured in a chromium-51 release assay. Partial protection from this lysis is afforded by superoxide dismutase and complete protection is obtained with catalase. Hydrogen peroxide, a product of the dismutation of superoxide radicals, lyses these cells directly and is implicated as the toxic agent in the xanthine/xanthine oxidase reaction. Hydrogen peroxide also decreases cell proliferation and decreases the intact DNA. Therefore, hydrogen peroxide appears to be toxic to corneal epithelial cells. The implications of these data on the safety of hydrogen peroxide as a contact lens disinfectant are discussed.
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PMID:Cytolysis of corneal epithelial cells by hydrogen peroxide. 230 90

To determine the mechanism responsible for the enhanced susceptibility of endothelial cells to oxidant injury in the absence of glucose, we induced endothelial cell injury with oxygen radicals in the presence of various oxygen radical scavengers and measured endothelial cell levels of glutathione after oxidant injury in the presence and absence of glucose. Endothelial cells were damaged with toxic oxygen radicals generated by phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs) or xanthine-xanthine oxidase in the presence and absence of glucose and catalase (scavenger of hydrogen peroxide), superoxide dismutase (scavenger of superoxide radical), isoleucine, valine, and serine (scavengers of hypochlorous acid), or mannitol, ethanol, benzoic acid, dimethyl sulfoxide, and dimethyl thiourea (scavengers of hydroxyl radical). Endothelial cell injury was quantitated by 2-deoxy-[1-3H] glucose or chromium 51 release assays or both. In each oxidant-generating system, in the presence and absence of glucose, only catalase significantly protected endothelial cells from oxidant injury (P less than 0.001). When endothelial cells were damaged by hydrogen peroxide generated with xanthine-xanthine oxidase in the presence of glucose, endothelial cell levels of glutathione remained unchanged. In contrast, when endothelial cells were damaged with xanthine-xanthine oxidase in the absence of glucose, endothelial cell levels of glutathione fell to less than 50% of baseline (P less than 0.05). Xanthine-xanthine oxidase-mediated endothelial cell damage and depletion of glutathione in the absence of glucose were similar to results obtained in the presence of glucose when glutathione was depleted with buthionine sulfoximine, diethyl maleate, or 1-chloro-2,4-dinitrobenzene.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of glutathione in protecting endothelial cells against hydrogen peroxide oxidant injury. 309 44

Significant pulmonary toxicity is associated with the use of nitrofurantoin; however, the mechanism of cellular toxicity remains poorly characterized. By using a novel in vitro red blood cell (RBC) chromium 51 cytotoxicity assay, cell injury induced by nitrofurantoin was quantified with normocatalasemic BALB/c RBCs and hypocatalasemic (but otherwise genetically identical) CCN RBCs as target cell populations. Nitrofurantoin at concentrations of 2 x 10(-4) and 4 x 10(-4) mol/L resulted in significant injury to normocatalasemic RBCs with a cytotoxic index (CI) of 21.7% +/- 3.7% and 65.3% +/- 3.7% (p less than 0.05, both comparisons). This injury was substantially increased when nitrofurantoin (2 x 10(-4) and 4 x 10(-4) mol/L was incubated with hypocatalasemic RBCs, resulting in CIs of 59.0% +/- 7.4% and 91.0% +/- 2.0% respectively (p less than 0.05, both comparisons with normocatalasemic RBCs). Direct oxidant-mediated cytotoxicity induced by either H2O2 or the superoxide anion radical (as generated by xanthine-xanthine oxidase) also resulted in more significant injury to hypocatalasemic RBCs than to normocatalasemic RBCs (p less than 0.05, both comparisons). Catalase levels of CCN RBCs were approximately 7% of control BALB/c RBC values; however, the activities of superoxide dismutase and glutathione peroxidase were identical in both populations of RBCs. This model, using genetically defined target cell populations, clearly demonstrates the importance of endogenous catalase in protecting against nitrofurantoin-induced cytotoxicity, suggesting that H2O2 is a critical intermediary in the direct cell injury mediated by the drug.
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PMID:Importance of hydrogen peroxide in nitrofurantoin-induced cytotoxicity: evidence from an inbred catalase-deficient strain of mice. 341 Nov 91

To develop a sensitive in vitro assay for detecting endothelial cell damage, we radiolabeled endothelial cell monolayers with tracer amounts of 2-deoxy-D-[1-3H]-glucose (3HDOG). We damaged identical cohorts of endothelial cells radiolabeled with 3HDOG or chromium 51 by exposing monolayers to toxic oxygen radicals generated by xanthine-xanthine oxidase or phorbol myristate acetate (PMA)-activated polymorphonuclear leukocytes (PMNs), a surface active agent (Triton X-100), and anti-HLA antibodies and complement. With each mechanism of injury, the 3HDOG assay detected significant (P less than 0.01) endothelial cell damage at lower concentrations of the injurious agent than the 51Cr assay. When endothelial monolayers were damaged by xanthine-xanthine oxidase or PMA-activated PMNs, efflux of 3HDOG was reduced (range 71% to 94% reduction) by superoxide dismutase and catalase, indicating that efflux of 3HDOG was mediated by toxic oxygen radicals. When monolayers were damaged with xanthine oxidase in the absence of glucose, a much lower concentration of xanthine oxidase was required to initiate efflux of 3HDOG as compared with xanthine oxidase injury in the presence of glucose. Additional studies compared the 3HDOG assay with 3H-adenine, 3H-leucine, and lactate dehydrogenase (LDH) release when endothelial cells were exposed to toxic oxygen radicals generated by PMA-activated PMNs and xanthine-xanthine oxidase. Again, the 3HDOG assay was more sensitive in detecting in vitro endothelial cell damage. We conclude that the 3HDOG assay is more sensitive than the 51Cr, 3H-adenine, 3H-leucine, or LDH release assays in detecting endothelial cell damage in vitro.
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PMID:In vitro detection of endothelial cell damage using 2-deoxy-D-3H-glucose: comparison with chromium 51, 3H-leucine, 3H-adenine, and lactate dehydrogenase. 383 30

Oxygen radicals are suspected as being a cause of the cellular damage that occurs at sites of inflammation. The phagocytic cells that accumulate in areas of inflammation produce superoxide, hydrogen peroxide, hydroxyl radical, and probably singlet oxygen in the extracellular fluid. The mechanism by which these oxygen molecules kill cells is unknown. To determine which of the oxygen species is responsible for the cellular killing, we exposed human fibroblasts in culture to oxygen radicals generated by the enzymatic action of xanthine oxidase upon acetaldehyde. Using the amount of chromium-51 released from labeled fibroblasts as an index of cellular death, we found that cells were protected only by interventions that reduce hydrogen peroxide concentration. Agents that inactivate superoxide, hydroxyl radical, and singlet oxygen were ineffective in limiting oxygen radical-induced cellular death.
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PMID:Hydrogen peroxide causes the fatal injury to human fibroblasts exposed to oxygen radicals. 626 40

The responses of pig aortic endothelial cells to sublethal doses of potentially toxic stimuli were investigated by monitoring K+ efflux, prostaglandin production, and the release of cytoplasmic purines. Xanthine plus xanthine oxidase reversibly stimulated these three parameters of endothelial cell function at doses that were not cytotoxic, as measured by chromium release, adenine uptake, and vital dye exclusion. The effects of xanthine plus xanthine oxidase were inhibited by catalase but not by superoxide dismutase, suggesting that H2O2 was responsible. Reagent H2O2 also reversibly stimulated K+ efflux, prostaglandin production, and the release of purines. The threshold concentration of H2O2 for these effects was approximately 10 microM, which was at least 30-fold lower than that which caused cytotoxicity. In addition to the direct effect of H2O2 in stimulating prostaglandin production (PGI2 and PGE2), prior exposure of endothelial cells to lower doses of H2O2 (less than 0.1 microM) at high oxygen tension inhibited the subsequent stimulation of prostaglandin production by ATP, A23187, and H2O2 itself. We conclude that H2O2 has substantial effects on endothelial physiology at doses up to 3,000-fold lower than those which induce cytotoxicity.
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PMID:Differential effects of hydrogen peroxide on indices of endothelial cell function. 636 99

Tetrandrine is a benzylisoquinoline alkaloid that has been used in China as an antifibrotic drug to treat the lesions of silicosis. Its mechanism in the treatment of silicosis is unclear. Electron spin resonance (ESR) spin trapping was employed to investigate the antioxidant properties of tetrandrine. The spin trap used was 5,5-dimethyl-1-pyrroline N-oxide (DMPO). Tetrandine efficiently reacted with hydroxyl (.OH) radicals with a reaction rate of approximately 1.4 x 10(10) M-1 s-1. The .OH radicals were generated by the Fenton reaction [Fe(II) + H2O2) as well as by reaction of chromium(V) with H2O2. Similar results were obtained using .OH radicals generated by reaction of freshly fractured quartz particles with aqueous medium. Tetrandrine also scavenged superoxide (O2-) radicals produced from xanthine/xanthine oxidase. The effect of tetrandrine on lipid peroxidation induced by freshly fractured quartz particles was evaluated using linoleic acid as a model lipid. The results showed that tetrandrine caused a significant inhibition on freshly fractured quartz-induced lipid peroxidation.
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PMID:Antioxidant activity of tetrandrine and its inhibition of quartz-induced lipid peroxidation. 756 20

We aimed to determine the status of iron in mediating oxidant-induced damage to cultured bovine aortic endothelial cells. Chromium-51-labeled cells were exposed to reaction mixtures of xanthine oxidase/hypoxanthine and glucose oxidase/glucose; these produce superoxide and hydrogen peroxide, or hydrogen peroxide, respectively. Xanthine oxidase caused a dose dependent increase of 51Cr release. Damage was prevented by allopurinol, oxypurinol, and extracellular catalase, but not by superoxide dismutase. Prevention of xanthine oxidase-induced damage by catalase was blocked by an inhibitor of catalase, aminotriazole. Glucose oxidase also caused a dose-dependent increase of 51Ci release. Glucose oxidase-induced injury, which was catalase-inhibitable, was not prevented by extracellular superoxide dismutase. Both addition of and pretreatment with deferoxamine (a chelator of Fe3+) prevented glucose oxidase-induced injury. The presence of phenanthroline (a chelator of divalent Fe2+) prevented glucose oxidase-induced 51Cr release, whereas pretreatment with the agent did not. Apotransferrin (a membrane impermeable iron binding protein) failed to influence damage. Neither deferoxamine nor phenanthroline influenced cellular antioxidant defenses, or inhibited lysis by non-oxidant toxic agents. Treatment with allopurinol and oxypurinol, which inhibited cellular xanthine oxidase, failed to prevent glucose oxidase injury. We conclude that (1) among the oxygen species extracellularly generated by xanthine oxidase/hypoxanthine, hydrogen peroxide induces damage via a reaction on cellular iron; (2) deferoxamine and phenanthroline protect cells by chelating Fe3+ and Fe2+, respectively; and (3) reduction of cellular stored iron (Fe3+) to Fe2+ may be prerequisite for mediation of oxidant-induced injury, but this occurs independently of extracellular superoxide or cellular xanthine oxidase-derived superoxide.
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PMID:Reactive oxygen metabolite-induced toxicity to cultured bovine endothelial cells: status of cellular iron in mediating injury. 802 Dec 93


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