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 this study we examined the intracellular sources of superoxide anion (O2-.) in cultured bovine coronary endothelium, employing lucigenin (250 microM)-elicited chemiluminescence (CL). In the homogenate from these cells, 100 microM NADPH increased O2-. by 81% from 8.9 +/- 1.5 to 16.0 +/- 1.5 x 10(5) cpm/mg protein (P < 0.01, n = 8). In the presence of 100 microM NADH, however, CL increased by 458% from 8.9 +/- 1.6 to 49.6 +/- 12.0 x 10(5) cpm/mg protein (P < 0.01, n = 8). Scavengers of O2-., superoxide dismutase (100 micrograms/ml), or 4,5-dihydroxy-1,3-benzenedisulfonic acid disodium salt (Tiron, 10 mM) inhibited NADH-mediated CL by 70 and 83%, respectively. Neither hypoxanthine (100 microM) nor antimycin (10 microM)+succinate (5 mM) had any significant effect on basal CL levels, thereby excluding xanthine oxidase and mitochondria, respectively, as a detectable sources of O2-. generation. The presence of NAD+ (100 microM) and lactate (1 mM) increased CL by 88% (n = 8, P < 0.01). In the intact cells, basal production of CL was increased by 205% (P < 0.01) by 5 mM lactate, but not by 5 mM pyruvate, and CL was inhibited by 10 mM Tiron, suggesting the reduction of cytosolic NAD by lactate dehydrogenase stimulates O2-. production. Diphenyliodonium at 1 and 10 microM inhibited both NADH-mediated CL in homogenate and lactate-mediated CL in intact endothelium by 50 and 33%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:NADH oxidoreductase is a major source of superoxide anion in bovine coronary artery endothelium. 802 19

In the present work, the role of lipid peroxidation in cellular lethal injury induced by various types of oxidative stress has been studied in both normal and tumor thymocytes. The prooxidants included either a xanthine/xanthine oxidase system, which is an exogenous source of oxyradicals, or tert-butyl hydroperoxide (t-BOOH), which enters the cell and endogenously produces free radicals. Our data demonstrate that: (A) Using xanthine/xanthine oxidase system as a prooxidant, normal thymocytes are more sensitive than thymoma cells to oxidative damage, as their lactate dehydrogenase (LDH) and malondialdehyde (MDA) release is higher than that of tumor cells. By varying Fe3+/ADP ratios, a positive correlation can be established between LDH and MDA release only in normal thymocytes. While thymoma cells still show a very high level of vitamin E (80%) after 15 min of incubation with this prooxidant, normal thymocytes lose it after the same incubation time. (B) Using t-BOOH as a prooxidant, normal thymocytes release a higher amount of MDA but a lower amount of LDH than thymoma cells. In agreement with the results obtained with the xanthine/xanthine oxidase system, by varying the concentrations of the prooxidant, a correlation between LDH and MDA release can be established only in normal thymocytes. Although high levels of the antioxidant are still present in both kinds of cells after 15 min of incubation with t-BOOH, normal thymocytes consume vitamin E faster than thymoma cells. These data suggest that the role of lipid peroxidation in cell lethal injury is influenced by the source and the site of radical production as well as by the cell type. With t-BOOH as a prooxidant in normal thymocytes, lipid peroxidation is only partially involved in the induction of irreversible cell injury, but it plays a crucial role when the xanthine/xanthine oxidase system is used as a prooxidant. Moreover, whatever the prooxidant used in tumor thymocytes, membranes are more resistant to lipid peroxidation, suggesting that this mechanism is not causally related to cell death.
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PMID:Different role of lipid peroxidation in oxidative stress-induced lethal injury in normal and tumor thymocytes. 803 Nov 51

Sprague-Dawley rats were given 42 mg/kg xylazine intramuscularly, and lungs were lavaged with phosphate-buffered saline 3, 6, and 12 hr later. Total protein, lactate dehydrogenase (LDH), xanthine oxidase (XO), tumor necrosis factor (TNF), and interleukin 1 (IL-1) were measured in bronchoalveolar lavage fluid (BALF). Protein concentration, LDH, XO, and TNF levels were increased (p < 0.05) in the BALF from xylazine-treated rats as compared to controls. IL-1 level was unchanged at 3 and 6 hr and was reduced (p < 0.05) at 12 hr. Another group of rats was given 42 mg/kg xylazine intramuscularly, and lungs were fixed 0.5 and 12 hr later. Histologically, severe pulmonary edema (PE) involving the alveoli and perivascular stroma was observed. Fibrin, increased numbers of eosinophils, and macrophages with foamy cytoplasm were present in the alveoli of all treated animals. Ultrastructurally, endothelial damage, characterized by thinning, detachment from basement membranes, or bleb formation, was observed. The lesions were similar in both xylazine groups, differing mainly in severity with the 12-hr group having more severe lesions than the 0.5-hr group. To determine whether endothelial injury is caused by direct toxicity of xylazine, bovine pulmonary artery endothelial cells (BPAECs) were incubated with xylazine (0.3, 3, and 30 micrograms) for 0.5 or 3 hr. Xylazine did not have any effects on BPAECs, as indicated by phase-contrast microscopy and dye-exclusion viability assay. These results indicate that xylazine-induced PE is due to increased permeability resulting from endothelial injury, which is not caused by direct effect of xylazine on pulmonary endothelium. While oxygen radicals and TNF are possibly involved, IL-1 does not appear to play a role in xylazine-induced PE.
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PMID:Biochemical and morphological alterations in xylazine-induced pulmonary edema. 805 3

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

The antioxidant effects of SB 211475, a metabolite of carvedilol, a novel antihypertensive agent, were studied and compared with carvedilol and other antioxidants such as U78517F, U74500A and probucol. SB 211475 inhibited Fe(2+)-vitamin C-initiated lipid peroxidation, assessed as thiobarbituric acid reactive substance, in brain-homogenate with an IC50 of 0.28 microM. Under the same conditions, the IC50s of probucol, carvedilol, U74500A and U78517F were 50, 8.1, 0.71 and 0.16 microM, respectively. SB 211475 inhibited oxidation of human low density lipoprotein by mouse macrophages with an IC50 of 0.043 microM. In the same model, the IC50s of carvedilol, U78517F and probucol were 3.8, 0.15, and 0.80 microM, respectively. SB 211475 protected cultured bovine pulmonary artery endothelial cells against hydroxyl radical-initiated lipid peroxidation (IC50 = 0.15 microM) and cell damage (lactate dehydrogenase release, IC50 = 0.16 microM), and promoted cell survival with an EC50 of 0.13 microM. SB 211475 also protected endothelial cells against xanthine/xanthine oxidase-initiated cytotoxicity and protected rat cerebellar neurons from hydroxyl radical-mediated cell death (EC50 = 0.19 microM). Moreover, SB 211475 inhibited superoxide (O2-) release from human neutrophils stimulated by phorbol myristate acetate. These observations indicate that SB 211475 is a potent antioxidant and may potentially contribute to the therapeutic effects of carvedilol in vivo.
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PMID:SB 211475, a metabolite of carvedilol, a novel antihypertensive agent, is a potent antioxidant. 814 79

The mechanisms of hepatocyte injury caused by exogenous superoxide were investigated with the use of cultured rat hepatocytes. Cell viability, cytosolic free calcium concentration and cell surface structure were observed. Superoxide was produced by adding hypoxanthine and xanthine oxidase to the buffer. Cytosolic free calcium concentration was calculated by means of ratio imaging of fura 2 fluorescence with multiparameter digitized microscopy. In the buffer containing 1.27 mmol/L of calcium, lactate dehydrogenase release into the buffer began to increase at 1 hr and reached a plateau in 5 hr. Eighteen minutes after the addition of hypoxanthine and xanthine oxidase, small blebs were recognized on the cell surface with a scanning electron microscope; then a gradual rise in cytosolic free calcium concentration was observed. Thirty minutes after exposure to superoxide, large blebs were recognized with a phase-contrast microscope, when cytosolic free calcium concentration had risen to about 700 nmol/L. Depriving the buffer of calcium (< 10 mumol/L) significantly suppressed bleb formation and cell death, and cytosolic free calcium concentration was found to remain around the basal level (200 nmol/L). When ethylene glycol-bis (beta-amino-ethyl ether)-N,N,N',N'-tetraacetic acid was added to the buffer, bleb formation and cell death were suppressed more completely, and cytosolic free calcium concentration decreased. Superoxide dismutase combined with catalase or nifedipine allowed the hepatocytes to maintain their viability and suppressed cytosolic free calcium concentration elevation. Calpeptin, a Ca(2+)-dependent neutral protease inhibitor, did not affect the rise in cytosolic free calcium concentration but prevented cell injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of intracellular calcium in superoxide-induced hepatocyte injury. 817 45

The effects of allopurinol (AP) on functional and metabolic recovery of the isolated rat heart after global ischemia were studied. Hearts were subjected to aerobic perfusion (30 min), cardioplegic infusion (5 min), normothermic ischemia (37 min), and reperfusion (50 min) which was started with secondary cardioplegic infusion (10 min). AP was injected into rats (44 mg/kg body wt ip 2 h before heart excision) and added to cardioplegic solution (2 mM) prior and after ischemia. AP treatment significantly improved postischemic recovery of the function and reduced the leakage of lactate dehydrogenase from reperfused hearts. These beneficial effects were accompanied by a better preservation of tissue content of ATP, the total adenine nucleotides, phosphocreatine, and the total creatine at the end of reperfusion. Inhibition of xanthine oxidase by AP substantially decreased pre- and postischemic release of xanthine and uric acid and increased postischemic release of hypoxanthine into the coronary effluent. Despite this, AP-treated hearts did not exhibit a reduction in hydroxyl radical adduct formation in the effluents at reperfusion assessed by the spin-trap measurements. The results suggest that AP may protect the heart from ischemia/reperfusion injury due to enhanced energy provision rather than by prevention of oxygen-derived free radical formation.
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PMID:Allopurinol-enhanced postischemic recovery in the isolated rat heart involves repletion of high-energy phosphates. 819 13

1. The ability of dextran sulphate to protect cultured porcine arterial endothelial cells injured by addition of xanthine and xanthine oxidase (X/XO) or hydrogen peroxide to cell medium was examined using a variety of drug preparations. Cell damage was assessed by determining cell viability (by trypan blue exclusion) and release of lactate dehydrogenase into the medium. 2. Dextran sulphates of average molecular weight (M(r)) 5000, 8000 (hydrogenated or unhydrogenated) at 0.05, 0.5, 5 and 50 micrograms ml-1 medium, added 24 h prior to X/XO, protected cells, whereas dextran sulphate M(r) 500,000 was protective only at 0.5 microgram ml-1. 3. None of the dextran sulphates used showed any toxic effect on cells in concentrations up to 500 micrograms ml-1 medium. 4. When the duration of pretreatment with dextran sulphate M(r) 8000 was varied, 6 h was required for a protective effect on cells damaged by X/XO, which was enhanced with durations of 16 and 24 h. 5. Dextran sulphates had a similar protective effect on cells damaged by hydrogen peroxide. 6. This study suggest that dextran sulphates may prevent conditions resulting from free radical injury.
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PMID:Dextran sulphates protect porcine arterial endothelial cells from free radical injury. 820 7

The preventive effects of a traditional Chinese medicine Sho-saiko-to (Kampo prescription, TJ-9) were determined from oxygen toxicity and membrane damage in liver during endotoxemia. The liver lipid peroxide level and xanthine oxidase activity 18 h after administration of endotoxin (6 mg/kg, i.p.) to TJ-9 (500 mg/kg/d, p.o.)-pretreated mice were markedly lower than that in endotoxin-treated mice, whereas the administration of TJ-9 significantly increased superoxide dismutase and glutathione peroxide activities in liver of endotoxin-injected mice. In the mice pretreated with a TJ-9, the levels of alpha-tocopherol and nonprotein SH in liver tissue 18 h after endotoxin injection were markedly increased as compared to those in endotoxin-treated mice. Leakages of acid phosphatase and lactate dehydrogenase isozyme in serum were markedly lower in endotoxin-TJ-9-treated mice than those in mice given endotoxin. The administration of TJ-9 clearly prevented the membrane protein damage arising from endotoxin challenge. Kampo prescription Sho-saiko-to thus appears to protect the liver plasma membrane from injury by free radicals which occur in a tissue ischemic state during endotoxemia.
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PMID:Preventive effects of a traditional Chinese medicine (sho-saiko-to) against oxygen toxicity and membrane damage during endotoxemia. 822 Mar 25

Reactive oxygen metabolites generated from xanthine oxidase play an important role in the pathogenesis of ischemia-induced tissue injury. In a hemorrhagic shock model of ischemia-reperfusion, the intracellular enzyme xanthine oxidase was released into the vasculature. This intravascular source of superoxide (O2.-) and hydrogen peroxide (H2O2) interacted reversibly with glycosaminoglycans of vascular endothelium and markedly concentrated xanthine oxidase at cell surfaces, enhancing its ability to produce extensive damage to remote tissues. Rats were made hypotensive by hemorrhage, maintained for 2h, and reinfused with shed blood. Blood samples were obtained prior to hemorrhage and 15, 30, 60, and 90 min after reperfusion for determination of xanthine oxidase (XO), lactate dehydrogenase (LDH), and alanine transaminase (AST). These enzymes were not significantly elevated in control animals. Reperfusion after hemorrhage-induced ischemia resulted in significantly elevated AST and LDH in both low heparin (100 U/h) and high heparin (1000 U/h) groups. Xanthine oxidase was detected in the circulation only after 90 min reperfusion in the low heparin group and was elevated during the entire reperfusion period in the high heparin group. Studies with cultured vascular endothelium showed significant heparin-reversible binding of XO to cellular glycosaminoglycans. These results suggest that XO can gain access to the circulation following ischemia, where it then binds to the vascular endothelial cells to produce site-specific oxidant injury to organs remote from the site of XO release.
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PMID:Xanthine oxidase activity in the circulation of rats following hemorrhagic shock. 822 22


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