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)

In an isolated, normothermic rat heart model (Langendorff, 37 degrees C), dimethylthiourea (DMTU) infusion only during reperfusion reduced both injury and measurable hydrogen peroxide (H2O2) concentrations after global ischemia. Cardiac function was assessed by measurement of ventricular developed pressure (DP). H2O2 was assessed using H2O2 dependent aminotriazole inactivation of myocardial catalase. Depletion of xanthine oxidase by two methods (tungsten or allopurinol inhibition) also improved recovery of function and H2O2 production. The results indicate that XO derived H2O2 contributes to myocardial reperfusion injury.
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PMID:Hydrogen peroxide mediates reperfusion injury in the isolated rat heart. 314 10

Previous studies have proposed and supported a role for the proteolytic, irreversible conversion of xanthine dehydrogenase to xanthine oxidase (XO) in postischemic injury in a wide variety of organs. A second mechanism of conversion, due to sulfhydryl modification and reversible with dithiothreitol (DTT), is potentially important but has not been well investigated. In this study rat liver and kidney were found to produce significant amounts of DTT-reversible XO during normothermic global ischemia. Formation of reversible XO precedes that of irreversible XO by approximately 0.5 h with a strong correlation (r = 0.92) existing between the rate of irreversible XO formation and the concentration of reversible XO. The formation of reversible XO is preceded by a depletion of glutathione with concentrations of glutathione during ischemia correlating (r = 0.85) with the observed concentration of reversible XO. While a large increase in the extent of liver damage occurs concurrently with conversion in an in vivo liver model of liver ischemia, an ischemia-reperfusion regimen (1 h of ischemia plus 0.5 h of reperfusion) that resulted in no conversion caused significant elevations in serum glutamic pyruvic transaminase and serum glutamic-oxaloacetic transaminase. Rats depleted of XO by tungsten dieting release 65% less enzyme after the same insult, suggesting that endogenous XO may also participate in the damage process independent of any conversion.
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PMID:Mechanisms of conversion of xanthine dehydrogenase to xanthine oxidase in ischemic rat liver and kidney. 316 35

1. Xanthine oxidase (XO) was purified from livers of C57B1/6 mice. Antibodies generated against the purified protein were used in an immunoassay to measure total XO protein. 2. Both the specific activity and amount of XO protein were greater in the proximal small intestine than in the liver. A pool of inactive enzyme was present in the small intestine which developed after weaning. 3. Male C57B1/6 mice had the same XO specific activity as females and neither the hepatic nor the intestinal XO activity were affected by the level of dietary protein. 4. When mice were fed diets with tungsten, XO activity was lost and the amount of XO protein in the small intestine was decreased.
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PMID:Xanthine oxidase activity and immunologically detectable protein in the C57B1/6 mouse. 324 66

Experiments were performed to determine whether bacterial translocation (BT) after hemorrhagic shock is due to a reperfusion injury mediated by xanthine oxidase-derived oxidants. Rats were subjected to 30 minutes of shock (30 mm Hg) followed by reinfusion of shed blood. Twenty-four hours after hemorrhage and reinfusion, the mesenteric lymph node, liver, and spleen were harvested from each animal for bacterial culture, and the ileum and cecum were examined histologically. Sham-shocked (control) rats were instrumented, but blood was not withdrawn. The incidence of BT was higher in the shocked rats (61%) than in the sham-shocked animals (7%) (p less than 0.01). Allopurinol (50 mg/kg, administered orally), a competitive inhibitor of xanthine oxidase, reduced the incidence of shock-induced BT to 14% (p = 0.02). Similarly, rats fed a tungsten-supplemented molybdenum-free diet, which inactivates xanthine oxidase, reduced shock-induced BT to 10% (p = 0.02). The histologic damage cause by hemorrhagic shock was prevented by blocking xanthine oxidase activity. Thus hemorrhagic shock-induced bacterial translocation from the gut appears to be mediated by oxidants generated by activation of the xanthine oxidase system.
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PMID:Hemorrhagic shock-induced bacterial translocation is reduced by xanthine oxidase inhibition or inactivation. 340 55

The administration of tungsten to rats maintained on a low molybdenum diet resulted in a dose- and time-dependent loss of sulfite oxidase (EC 1.8.3.1) and xanthine oxidase (EC 1.2.3.2) activities and hepatic molybdenum. These tungsten-treated animals appeared healthy, but were more susceptible to bisulfite toxicity. The median lethal dose for intraperitoneal bisulfite was found to be 181 mg of NaHSO(3) per kg for the animals deficient in sulfite oxidase, compared to 473 mg/kg for normal rats. The survival time of rats exposed to SO(2) at concentrations of 590 ppm and higher was seen to be inversely related to the level of SO(2). At 590 ppm and 925 ppm, control animals displayed symptoms of severe respiratory toxicity before death. At 2350 ppm of SO(2), death was preceded by seizures and prostration, symptoms observed with the systemic toxicity of injected bisulfite. At 590 ppm, animals deficient in sulfite oxidase were indistinguishable from control animals. However, at 925 ppm and 2350 ppm, the deficient animals displayed symptoms of systemic toxicity and had much shorter survival times. It is concluded that sulfite oxidase is instrumental in counteracting the toxic systemic effects of bisulfite, either injected or derived from respired SO(2). Respiratory death probably results from the toxicity of gaseous SO(2) before absorption as bisulfite and cannot be alleviated by sulfite oxidase. Sulfite oxidase does not appear to be inducible by either bisulfite or SO(2).
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PMID:Molecular basis of the biological function of molybdenum: the relationship between sulfite oxidase and the acute toxicity of bisulfite and SO2. 451 54

The role of xanthine oxidase as a source of reactive oxygen species in puromycin aminonucleoside nephrosis was examined. The effects of allopurinol (a xanthine oxidase inhibitor as well as a reactive oxygen species scavenging enzyme) and tungsten (a specific xanthine oxidase inhibitor) on glomerular epithelial cell ultrastructure, renal xanthine oxidase and xanthine dehydrogenase activity, and urinary protein excretion were examined in puromycin aminonucleoside-treated rats. Co-administration of allopurinol to such rats reduced proteinuria by approximately 70% over the 10 days studied, and reduced the degree of glomerular epithelial cell foot process effacement at both 5 and 10 days, compared to rats that received puromycin aminonucleoside alone. Unexpectedly, co-administration of allopurinol to puromycin aminonucleoside-treated rats did not reduce xanthine oxidase activity; however, the combined activity of xanthine oxidase and xanthine dehydrogenase in such animals was reduced on day 5. Co-administration of tungsten to puromycin aminonucleoside-treated rats did not reduce proteinuria or alter the number of filtration slits. Rats co-administered tungsten and puromycin aminonucleoside had significantly reduced renal xanthine oxidase and combined xanthine oxidase and xanthine dehydrogenase activities on days 5 and 10, compared to rats treated with puromycin aminonucleoside alone. These results provide evidence that the protection provided by allopurinol in puromycin aminonucleoside-treated rats is due to the antioxidant properties of allopurinol, rather than to its activities as a xanthine oxidase inhibitor.
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PMID:Podocyte architecture in puromycin aminonucleoside-treated rats administered tungsten or allopurinol. 758 48

Acute inflammatory lung injury often complicates hemorrhagic shock, a systemic ischemia-reperfusion syndrome. Because oxygen radicals are generated during ischemia-reperfusion, and oxygen radicals can activate nuclear regulatory factors that affect transcription of proinflammatory cytokines, we examined the premise that oxygen radicals increase interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) expression in lung mononuclear cells after hemorrhage. Intraparenchymal pulmonary mononuclear cells isolated 1 h after hemorrhage from control mice had increased levels of mRNA for IL-1 beta (P < 0.001) and TNF-alpha (P < 0.05) compared with cells from sham-hemorrhaged mice. Hemorrhaged mice treated with the oxygen radical scavenger dimethylthiourea (DMTU) had decreased levels of mRNA for IL-1 beta in pulmonary mononuclear cells, compared with hemorrhaged controls (P < 0.05). In hemorrhaged mice depleted of xanthine oxidase (XO) by a tungsten-enriched diet, pulmonary mononuclear cell mRNA levels for IL-1 beta and TNF-alpha were significantly decreased (P < 0.01 and 0.05, respectively), compared with cells from hemorrhaged control mice fed a normal diet. Similarly, mRNA transcripts for IL-1 beta and TNF-alpha among pulmonary mononuclear cells from hemorrhaged mice treated with allopurinol, an inhibitor of XO, were also significantly reduced (P < 0.05 and 0.001, respectively), compared with hemorrhaged control mice not treated with allopurinol. Our results indicate that XO-derived oxygen radicals contribute to the increased expression of mRNA for IL-1 beta and TNF-alpha, which occurs among pulmonary mononuclear cell populations immediately after hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Xanthine oxidase-derived oxygen radicals increase lung cytokine expression in mice subjected to hemorrhagic shock. 769 23

The modulation of paraquat toxicity by tungsten was studied in vitro using cultured MDCK epithelial cells. MDCK cells were cultured in minimal essential medium with or without 1 ppm tungsten. Proliferation of cells cultured with tungsten was not inhibited after exposure to 0.25 mM or 0.5 mM paraquat. In addition, lactate dehydrogenase release into the culture medium was lower for tungsten-treated cells than for cells cultured without tungsten. Cells cultured in medium alone showed reduced viability compared with controls after exposure to 0.5 mM paraquat, but 0.25 mM paraquat did not decrease cell viability. Tungsten-treated cells showed no decrease viability in after exposure to either concentration of paraquat. Cells exposed to paraquat developed a honeycomb morphology with scanty cytoplasm and abnormal nucleoli. However, these major structural changes were not observed in cells cultured with tungsten. Our study showed that cell damage after paraquat exposure was modulated by addition of tungsten to the culture medium. It is suggested that cytosolic xanthine oxidase activity was reduced by tungsten, leading to less production of superoxide and other radicals and thus conferring resistance to paraquat toxicity.
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PMID:Tungsten modulates the toxicity of paraquat for epithelial cells. 814 10

Neutrophil accumulation in alveolar spaces is a conspicuous finding in hyperoxia-exposed lungs. We hypothesized that xanthine oxidase (XO)-derived oxidants contribute to retention of neutrophils in hyperoxic lungs. Rats were subjected to normobaric hyperoxia (100% O2) for 48 h, and lungs were assessed for neutrophil sequestration (morphometry and lavage cell counts) and injury (lavage albumin levels and lung weights). In rats exposed to hyperoxia, we found increased (P < 0.05) lung neutrophil retention, lavage albumin levels, and lung weights compared with normoxia-exposed control rats. Suppression of XO activity by pretreatment with allopurinol decreased (P < 0.05) lung neutrophil retention but increased (P < 0.05) lavage albumin concentrations and lung weights in hyperoxic rats. Allopurinol treatment had no effect (P > 0.05) on the numbers of macrophages or lymphocytes recoverable by lung lavage. Depletion of XO activity by an independent method, tungsten feeding, also decreased (P < 0.05) lung lavage neutrophil counts and increased (P < 0.05) lavage albumin concentrations. We conclude that XO may be involved in lung neutrophil retention but not lung injury during exposure to hyperoxia.
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PMID:Xanthine oxidase promotes neutrophil sequestration but not injury in hyperoxic lungs. 817 9

This study was conducted with rats to assess the involvement of leukocytes in a model of CO-mediated brain injury. Myeloperoxidase activity, measured as an index of leukocyte sequestration, was found to be increased 10-fold in brain microvessel segments prepared from rats immediately or 90 min after exposure to CO. Fluorescence and light microscopic examinations revealed leukocytes in microvessels taken from CO-poisoned rats, but not in that from control rats. Studies were then conducted with rats that had been made leukopenic or treated with monoclonal anti-CD-18 F(ab')2 fragments to inhibit leukocyte adherence to the vasculature. Neither of these groups of animals exhibited the biochemical changes observed in the brains of sham-treated rats: conversion of xanthine dehydrogenase (XD) to sulfhydryl-irreversible xanthine oxidase (XO), and lipid peroxidation, at 90 min following CO poisoning. Treatment with a synthetic serine protease inhibitor, gabexate mesylate, also prevented these biochemical changes if administered immediately after CO poisoning, but the agent did not inhibit leukocyte sequestration. Rats depleted of XD and XO by a tungsten diet, and those treated with allopurinol to inhibit XD and XO, also exhibited at least a 10-fold increase in myeloperoxidase activity in microvessels immediately after CO poisoning, but only a 5-fold increase at 90 min. In vitro studies demonstrated that B2 integrin-dependent polymorphonuclear leukocyte adherence was impaired immediately following CO poisoning although the adherence molecules were expressed on the membrane surface. Adherence function normalized by 45 min. The results suggest that leukocytes are responsible for the development of biochemical changes in brain following CO poisoning, and the sequence of events is as follows: leukocyte sequestration in the microvasculature, B2 integrin-dependent adherence, protease-mediated conversion of XD to XO, O2 radical-dependent lipid peroxidation.
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PMID:Leukocytes in carbon monoxide-mediated brain oxidative injury. 824 31


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