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)

Activities of alanine and aspartate transaminases, glutamine synthetase, adenylate deaminase, glutamate and xanthine dehydrogenases and lactate dehydrogenase were measured in leg and breast muscles of developing chicks from day 10 in ovo to day 5 of free life, and compared with measurements for adult hens. Xanthine dehydrogenase activity was low in both muscles with adult levels attained on day 15 in ovo. Glutamine synthetase for chicks was maintained higher during development than for adults in both muscles. Minor differences were observed between both muscles in all enzymes tested up to day 18. With low embryonic values and important rises before hatching, the differences were initiated in the posthatching period. Important differences were observed between adult levels of activity. Leg muscle revealed higher enzyme values except for lactate dehydrogenase and indistinguishable levels for adenylate deaminase and xanthine dehydrogenase in both muscles. Alanine, instead of glutamine, is postulated as the main nitrogen transport between muscle and liver in the domestic fowl.
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PMID:Patterns of amino acid enzyme in domestic fowl breast and leg muscle during development. 286 43

To determine the site of reperfusion damage after ischaemia the leakage of xanthine dehydrogenase and xanthine oxidase was assessed in vascular and interstitial effluents. Contractile function was reduced during hypoperfusion but improved after the addition of superoxide dismutase and vasoxin to the perfusion medium. Both interstitial fluid and coronary effluent showed dehydrogenase and oxidase activity after no flow ischaemia. Furthermore, the ratio of lactate dehydrogenase to creatine kinase in coronary effluents was reduced. These findings indicate that the myocardial interstitium may be a site of ischaemic membrane damage since this space contains hypoxanthine and xanthine oxidase. The protective effect of superoxide dismustase also indicates the possibility of damage due to oxygen derived radicals in the cardiac interstitium during low flow perfusion.
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PMID:Early damage of vascular endothelium during cardiac ischaemia. 289 82

Oxidative damage to the vascular endothelium may play an important role in the pathogenesis of atherosclerosis and aging, and may account in part for reduced vascular prostacyclin (PGI2) synthesis associated with both conditions. Using H2O2 to induce injury, we investigated the effects of oxidative damage on PGI2 synthesis in cultured endothelial cells (EC). Preincubation of EC with H2O2 produced a dose-dependent inhibition (inhibitory concentration [IC50] = 35 microM) of PGI2 formation from arachidonate. The maximum dose-related effect occurred within 1 min after exposure although appreciable H2O2 remained after 30 min (30% of original). In addition, H2O2 produced both a time- and dose-dependent injury leading to cell disruption, lactate dehydrogenase release, and 51Cr release from prelabeled cells. However, in dramatic contrast to H2O2 effects on PGI2 synthesis, loss of cellular integrity required doses in excess of 0.5 mM and incubation times in excess of 1 h. The superoxide-generating system, xanthine plus xanthine oxidase, produced a similar inhibition of PGI2 formation. Such inhibition was dependent on the generation of H2O2 but not superoxide in that catalase was completely protective whereas superoxide dismutase was not. H2O2 (50 microM) also effectively inhibited basal and ionophore A23187 (0.5 microM)-stimulated PGI2 formation. However, H2O2 had no effect on phospholipase A2 activity, because ionophore A23187-induced arachidonate release was unimpaired. To determine the effects on cyclooxygenase and PGI2 synthase, prostaglandin products from cells prelabeled with [3H]arachidonate and stimulated with ionophore A23187, or products formed from exogenous arachidonate were examined. Inhibition of cyclooxygenase but not PGI2 synthase was observed. Incubation of H2O2-treated cells with prostaglandin cyclic endoperoxide indicated no inhibition of PGI2 synthase. Thus, in EC low doses of H2O2 potently inhibit cyclooxygenase after brief exposure whereas larger doses and prolonged exposure are required for classical cytolytic effects. Surprisingly, PGI2 synthase, which is known to be extremely sensitive to a variety of lipid peroxides, is not inhibited by H2O2. Lipid solubility, enzyme location within the EC membrane, or the local availability of reducing factors may explain these results, and may be important determinants of the response of EC to oxidative stress.
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PMID:Effect of hydrogen peroxide on prostaglandin production and cellular integrity in cultured porcine aortic endothelial cells. 299 39

Recent data suggest that oxygen free radicals are implicated in the pathogenesis of ischemic injury. This study evaluates the effects of allopurinol, a xanthine oxidase (XO) inhibitor, on malonaldehyde generation, free sulfhydryl levels, oxygen consumption, and water contents of rat gastrocnemius muscles of female Sprague-Dawley rats subjected to tourniquet shock and after hind-limb reperfusion. Serum lactic dehydrogenase isozyme patterns after ligature release were also examined. Our results show that the four muscle parameters were not altered during 5 hr of ischemia, but that on hind-limb reperfusion, malonaldehyde production, SH levels, O2 consumption, and water contents were significantly altered in the control animals, but not in those pretreated with allopurinol. LDH serum patterns of the untreated animals showed the presence of all five isoforms; these were much less evident in the drug-protected rats. Our data suggest that following ischemia, the affected muscles are unable to recover their normal function when reperfusion is resumed. The subsequent damage is probably due to the generation of cytotoxic superoxide radicals formed during the XO-catalyzed transformation of hypoxanthine to uric acid on tissue reoxygenation. The severity of tissue damage is related to the duration of the ischemic episode possibly due to hypoxanthine accumulation during ischemia.
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PMID:Tourniquet shock in rats: effects of allopurinol on biochemical changes of the gastrocnemius muscle subjected to ischemia followed by reperfusion. 301 Oct 37

We have found that pretreatment of human neutrophils with ibuprofen (0.10-1.0 mg/ml) results in an irreversible, concentration-dependent inhibition of superoxide anion generation and release of lysosomal enzymes (myeloperoxidase, lysozyme) stimulated by the synthetic peptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP), the complement fragment C5a, and to a lesser extent by serum opsonized zymosan. Inhibition of granule exocytosis and oxygen radical generation at ibuprofen concentrations less than 5 mg/ml was not due to drug cytotoxicity since release of the cytoplasmic enzyme lactate dehydrogenase was not affected by ibuprofen. In contrast to neutrophil responses mediated by C5a or FMLP, ibuprofen did not inhibit either enzyme release or superoxide anion generation by neutrophils stimulated with phorbol myristate acetate. Ibuprofen did not function as an oxygen radical scavenger in a cell-free system in which superoxide anion was generated by the aerobic action of xanthine oxidase on hypoxanthine. Ibuprofen also inhibited in a concentration-dependent fashion both directed migration (chemotaxis) and stimulated random migration (chemokinesis) of neutrophils exposed to either FMLP or C5a. Inhibition of neutrophil adherence to plastic surfaces and bovine pulmonary artery endothelial cells was equally effective when the neutrophils were treated with ibuprofen before stimulation with FMLP or phorbol myristate acetate. The inhibitory effects of ibuprofen pretreatment of neutrophils could not be overcome by addition of prostaglandins E1 or E2 (0.3-300 nM). These results demonstrate that ibuprofen is capable of suppressing many functions thought to be important in neutrophil-mediated acute pulmonary inflammatory processes. Results of these experiments further suggest that ibuprofen may inhibit neutrophil functions by acting on cellular components separate from membrane receptors or by blockade of cyclo-oxygenase products which may be involved in these neutrophil functions.
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PMID:Inhibition of human polymorphonuclear leukocyte functions by ibuprofen. 303 52

While free radical-mediated reperfusion injury is clearly important in a variety of disparate organs, the particular cellular source of these radicals is unclear. To address this question, we subjected relatively pure (92% +/- 3% by factor VIII immunoassay) cultures of rat pulmonary artery endothelial cells to 0 to 45 minutes of anoxia (95% N2, 5% CO2), followed by reoxygenation (95% air, 5% CO2), to simulate ischemia/reperfusion. Cell injury was assayed after reoxygenation by the release of previously incorporated 51chromium and/or lactate dehydrogenase, and viability was determined by means of trypan blue exclusion. These three end points correlated closely. Without anoxia, the cells remained viable, with minimal evidence of injury for the entire experimental period, while 45 minutes of hypoxia followed by 30 minutes of reoxygenation produced substantial evidence of cell injury in 71% +/- 6% of the cells. This injury was reduced to 21% +/- 2% by treatment with the highly specific free radical scavengers superoxide dismutase and catalase together, either before anoxia or after anoxia, but just before reoxygenation. Similar protection was provided by xanthine oxidase inhibition with allopurinol. The injury was mimicked (without anoxia) by the exogenous generation of superoxide radicals with xanthine and xanthine oxidase. These experiments establish the essential components of free radical generation at reperfusion to be localized within the isolated endothelial cell in the absence of neutrophils or parenchymal cells.
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PMID:The primary localization of free radical generation after anoxia/reoxygenation in isolated endothelial cells. 303 75

Oxidant injury to the alveolar epithelium can be mediated by exposure to oxidant gases such as O2 at high concentrations and O3, inflammatory cell-derived reactive O2 species, and the intracellular metabolism of xenobiotics such as paraquat. An in vitro model of alveolar epithelial oxidant injury was developed based on exposure of cultured rat type II pneumocytes to superoxide and hydrogen peroxide (H2O2) enzymatically generated in the culture medium. Cytotoxicity was assessed by the release of lactate dehydrogenase (LDH) into the culture medium, which was a more reliable indicator of damage than release of 51Cr by prelabeled cells. Incubation of cells for 6-8 h with xanthine plus xanthine oxidase and glucose plus glucose oxidase induced the release of greater than 50% of total intracellular LDH. Oxidant exposure also resulted in significant detachment of cells from culture dishes. Modulation of oxidant damage was accomplished using liposomes as vectors for the delivery of catalase. Treatment of cells with catalase liposomes for 2 h resulted in augmentation of cellular catalase specific activities up to 631% of controls. Catalase was partitioned into intracellular and surface-associated compartments in catalase liposome-treated cells. Partial and complete protection against oxidant injury, induced by xanthine plus xanthine oxidase and glucose plus glucose oxidase, respectively, was achieved by pretreatment of cells with catalase liposomes. LDH release during oxidant exposure was inversely related to augmentation of cellular catalase activities. Catalase liposome-treated cells also exhibited an enhanced ability to scavenge enzymatically generated H2O2 from the culture medium. These observations suggest a useful approach to modulation of alveolar injury induced by reactive O2 species.
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PMID:Liposome-mediated augmentation of catalase in alveolar type II cells protects against H2O2 injury. 304 Jun 61

This study was designed to evaluate the effect of an exogenous free radical generating system consisting of purine plus xanthine oxidase on the isolated rat heart and in particular to assess the possible contribution of arachidonic acid or its metabolites to toxicity produced by this drug combination. Purine plus xanthine oxidase produced a time-dependent depression in cardiac contractility which was associated with stimulated release of lactate dehydrogenase (LDH). Electron microscopic analysis revealed a distinct separation of the glycocalyx from the sarcolemmal membrane with no apparent intracellular defects. Purine plus xanthine oxidase was a potent stimulus for 6-keto-prostaglandin F1 alpha (6K-PGF1 alpha) synthesis but leukotriene production was undetectable under any condition. Eicosatetraynoic acid, which totally prevents the metabolism of arachidonic acid, accelerated the loss in force and increased LDH release invoked by purine plus xanthine oxidase, but produced no noticeable change in sarcolemmal ultrastructure. Cyclooxygenase inhibitors produced little influence although pretreatment with either acetylsalicylic acid or ibuprofen decreased contractility toward the end of purine plus xanthine oxidase perfusion. Nordihydroguarietic acid, a purported inhibitor of 5'-lipoxygenase accelerated the loss in force produced by purine plus xanthine oxidase. The nordihydroguarietic acid effects were associated with reduced 6K-PGF1 alpha efflux but LDH release was unaffected. We also examined whether modification of arachidonic acid release through changes in calcium concentration was associated with altered response to purine plus xanthine oxidase. Lowering the calcium concentration to 0.41 mM (from 1.25 mM control) reduced markedly 6K-PGF1 alpha, efflux as well as LDH release. Although the latter is suggestive of protection, hypocalcemic perfusion resulted in a greater loss in force due to free radical generation. Furthermore, cells from these hearts exhibited a greater degree of glycocalyx separation. Increasing the calcium concentration to 2.50 mM produced no further toxic manifestations in the response to purine plus xanthine oxidase, although the release of 6K-PGF1 alpha was increased. Our results suggest complex toxicity induced by an exogenously generated free radical system. The injury produced by this method is restricted to sarcolemmal changes, the latter being dependent on the external calcium concentration. The study further suggests that accumulation of intracellular unesterified arachidonic acid, which may result from peroxidation of membrane lipids, increases tissue injury caused by exogenous free radicals.
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PMID:Injury to rat hearts produced by an exogenous free radical generating system. Study into the role of arachidonic acid and eicosanoids. 311 69

Cultured canine gastric chief cells exposed to a toxic oxygen metabolite-generating system (xanthine plus xanthine oxidase) demonstrated minimal cytolysis, suggesting that these cells have important endogenous antioxidant mechanisms. We have quantified the role of glutathione for protection against toxic oxygen metabolites by measuring cell lysis by lactate dehydrogenase release after variable depletion and repletion of cellular glutathione content. In the absence of exogenous oxidant stress, the glutathione content of chief cells can be depleted to less than 0.2 nmol total glutathione/micrograms DNA or 22% of control without cell lysis over 5 h. However, when challenged with the oxygen metabolite-generating system, cytolysis was greatly enhanced by glutathione depletion. Oxygen metabolite-mediated cytolysis after glutathione depletion was inhibited by exogenous catalase, thiourea, and deferoximine, but not superoxide dismutase or mannitol. These data suggested that hydrogen peroxide and hydroxyl radical mediated cytolysis in glutathione-depleted chief cells. If a substrate for glutathione synthesis, N-acetyl-L-cysteine, was provided to the depleted cells for 1 h before challenge with the oxygen radical-generating system, cell lysis was markedly decreased. However, if glutathione synthesis was blocked during the repletion period by buthionine sulfoximine, protection was not restored. The data supported an important role for glutathione as an endogenous antioxidant, which modulated the sensitivity of cultured chief cells to toxic oxygen metabolite injury.
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PMID:Glutathione modulates toxic oxygen metabolite injury of canine chief cell monolayers in primary culture. 327 18

Isolated perfused livers from fasted, but not from fed rats showed hepatotoxic responses when subjected to 30 min of hypoxia followed by 60 min of reoxygenation. Toxicity was evident by a release of glutamate-pyruvate-transaminase, lactate dehydrogenase and glutathione into the perfusate, by a depletion of hepatic glutathione and by an accumulation of calcium in the liver. This indicates, that the liver is resistant to hypoxic injury as long as glycogen is present to maintain anaerobic ATP-synthesis. This is substantiated by the fact that addition of fructose--but not glucose--to the medium resulted in a protection of the liver against hypoxic injury concomitant with its degradation to lactate + pyruvate. Superoxide dismutase, catalase, desferrioxamine and allopurinol prevented hypoxic liver injury suggesting a substantial role of reactive oxygen species formed via the xanthine oxidase reaction in mediating hypoxic liver injury.
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PMID:The involvement of reactive oxygen species in hypoxic injury to rat liver. 336 21


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