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 sought to define the role of oxygen-derived free radicals during ischemia and reperfusion in the production of acute damage to the gastric mucosa of baboons. The protective effect of the xanthine oxidase inhibitor, allopurinol, the superoxide scavenger, superoxide dismutase (SOD), and a long-acting SOD-albumin was determined. Mucosal damage was evaluated using light and scanning electron microscopy. Evidence for oxidative insult to the gastric mucosa was sought by measuring tissue concentrations of reduced (GSH) and oxidized (GSSG) glutathione. Gastric mucosal blood flow was estimated using the microsphere technique. A similar pattern of tissue damage was found at the end of ischemia in all three groups. Thirty minutes after reperfusion, severe mucosal damage (grade 3) increased only in the untreated control. In the two treated groups, grade 3 damage remained unchanged during reperfusion and a decrease in the percentage of moderate damage (grade 2) was seen. Both GSH and GSSG tissue concentrations were lower in the untreated controls as compared to the scavenger-treated groups, making it questionable whether GSH/GSSG tissue levels adequately reflect oxidative stress. We conclude that in our ischemia-reperfusion model the generation of oxygen-derived free radicals produces mucosal damage and prevents the restitution of moderate mucosal damage during reperfusion. In ischemia, factors other than free radicals seem to be responsible for mucosal damage. The protective effect of allopurinol and SOD was not mediated by changes in gastric mucosal blood flow.
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PMID:Gastric mucosal lesions induced by hemorrhagic shock in baboons. Role of oxygen-derived free radicals. 337 79

Evidence is presented that, as in cardiomyocytes, vascular endothelial cells use fatty acids, in addition to glucose, as a respiratory fuel. Attention is focused on the cardiac interstitium, lined by vascular cells and cardiomyocytes, which may be enriched with metabolic products from these cells. Also, certain proteins are present in the interstitial fluid (Qi) such as plasma proteins and fatty acid binding protein (FABP). However, the concentration of FABP is so low in Qi that albumin is more important to shuttle long chain fatty acids in the interstitial fluid between cardiomyocytes and the vascular compartment. Under hypoxic conditions (hypo)xanthine, lactate and fatty acids may be expected to accumulate in the interstitium, as well as proteins from adjacent cells, such as xanthine oxidase from endothelial cells. This enzyme, acting upon the elevated level of (hypo)xanthine, giving rise to O2-., may be involved in the damage of the ischaemic heart. The significance of the interstitium in ischaemia and in fibrosis following long standing cardiac lipidosis is briefly discussed, as well as the possible mechanisms involved in fatty acid transport in the heart.
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PMID:Substrates for energy metabolism in the heart: the role of the interstitial compartment. 366 8

Ischemia in a stomach that contains acid may produce severe gastric mucosal injury. The extent to which oxygen-derived free radicals are involved in the pathogenesis of this injury was investigated in the present study. Local gastric ischemia was achieved by reducing celiac artery pressure to 30 mmHg for 1 h. Ischemic injury was assessed by recording the loss of 125I-albumin and 51Cr-red cells across the gastric mucosa. Cats were treated with a xanthine oxidase inhibitor (allopurinol), a superoxide radical scavenging enzyme (superoxide dismutase), and a scavenger of hydroxyl radicals (dimethyl sulfoxide). The damage associated with ischemia only occurred during reperfusion of the stomach and was worst in the antrum. The level of xanthine oxidase in the antrum was twice that of the corpus. Treatment with allopurinol, superoxide dismutase, and dimethyl sulfoxide reduced 51Cr-red cell loss to 15%, 25%, and 21% of control (untreated) animals, respectively. The data indicate that oxygen-derived free radicals play a role in ischemic injury to the stomach and that the hydroxyl radical, a secondary radical produced from the superoxide anion, appears to be the major oxygen radical contributing to ischemic damage.
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PMID:Role of oxygen radicals in ischemia-induced lesions in the cat stomach. 375 93

To determine whether reactive oxygen molecules could directly and reversibly increase the transfer of albumin across an endothelial barrier, we measured albumin transfer across monolayers of endothelium cultured on micropore filters before and after exposure to xanthine and xanthine oxidase. Xanthine and xanthine oxidase increased endothelial albumin transfer in a dose-dependent fashion. Parallel phase contrast and fluorescence microscopy demonstrated retraction of adjacent cells from one another and disruption of the actin filaments. The oxidant-induced increases in albumin transfer and changes in cell shape were reversed by removing xanthine oxidase and then incubating the monolayers for 3 1/2 hours in tissue culture media enriched with fetal bovine serum. However, incubation in tissue culture media without serum resulted in progressive injury and cell death. Hence, the brief exposure to oxidants initiated a progressive injury process that was reversed by incubation in serum. Because intracellular and extracellular calcium are important determinants of cell shape, and because some oxidized membrane lipids act as calcium ionophores, we asked whether oxidants altered endothelial calcium homeostasis. Xanthine-xanthine oxidase increased release of 45Ca++ from preloaded cells. The calcium antagonist lanthanum chloride prevented xanthine-xanthine oxidase increases in endothelial albumin transfer and prevented the changes in cell shape; chelation of extracellular calcium inhibited lysis of endothelium by xanthine-xanthine oxidase; and the calcium ionophore A23187 increased endothelial albumin transfer and mimicked the oxidant-induced changes in cell shape. Lanthanum chloride inhibited these effects of A23187. These data suggest that oxygen radicals can reversibly increase endothelial permeability to macromolecules, that this is associated with reversible changes in endothelial cell shape and actin filaments, and that the changes in cell shape are related to oxidant-induced changes in endothelial calcium homeostasis.
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PMID:Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis. 383 56

Copper (Cu2+) ions at physiological concentrations can promote the formation of hydroxyl radical (OH) or a species of equivalent reactivity. The reaction requires H2O2 and a reducing agent. Reduction of Cu2+ can be achieved by superoxide ion generated by a mixture of hypoxanthine and xanthine oxidase or added directly as its potassium salt. Reduction of Cu2+ can also be achieved by ascorbic acid. Hence both O2- -dependent and ascorbate-dependent formation of OH from H2O2 in the presence of Cu2+ can be observed. Only the former reaction is significantly inhibited by superoxide dismutase. The binding of Cu2+ to histidine or albumin at physiological concentrations decreases the formation of OH radicals in free solution in the presence of either ascorbate or an (O2- -generating system. It is suggested that OH is still formed but reacts immediately with the binding molecule.
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PMID:Superoxide-dependent and ascorbate-dependent formation of hydroxyl radicals in the presence of copper salts: a physiologically significant reaction? 631 Nov 5

Luminol-dependent chemiluminescence of normal human polymorphonuclear leucocytes (PMN) which were resting, or stimulated by unopsonized latex beads, opsonized zymosan or the chemotactic peptide N-formyl-met-leu-phe was decreased more than 80% in the presence of physiological concentrations of albumin (4%, w/v). This inhibition did not result from impairment of light transmission, cellular toxicity, luminol excited-state quenching or a dialysable contaminant in the albumin preparation, but was reduced by 30% when the fall induced by albumin in extracellular free Ca2+ concentration was corrected. The inhibition was most apparent in the larger second phase of the PMN chemiluminescent response to chemotactic peptide or opsonized zymosan stimulation. The smaller first phase of these responses was in fact enhanced by low concentrations of albumin (0.05-0.5%, w/v) and only inhibited up to 50% by 4% (w/v) albumin. Albumin in the range 0.1-4% (w/v) exerted a similar effect on chemiluminescence resulting from superoxide anion (O-2) and hydrogen peroxide (H2O2) production by xanthine oxidase catalysed oxidation of xanthine in the presence of luminol. We suggest that the effect of albumin on PMN luminol-dependent chemiluminescence is mediated by modification of the oxygen radical generating pathway, or oxygen radical scavenging. This previously undocumented property of the major extracellular protein requires further examination if oxygen radicals are to be established as important mediators of inflammation.
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PMID:Albumin inhibits human polymorphonuclear leucocyte luminol-dependent chemiluminescence: evidence for oxygen radical scavenging. 671 82

[14C]Misonidazole (MISO) becomes bound to macromolecules of mammalian cells upon hypoxic incubation. Intracellular enzyme processes are implicated since the temperature dependence for this process showed an activation energy of 33.5 kcal/mol. The sensitizer bound to both hypoxic and aerobic cells was associated with the macromolecular fraction and the soluble fraction in the proportion, 23 and 77%, respectively. The initial rate of binding of [14C]MISO to the macromolecular (acid-insoluble) fraction of hypoxic EMT-6 mouse tumor and V-79 hamster cells increased proportionally with the square root of extracellular concentration of MISO up to at least 5mM. High concentrations of dimethyl sulfoxide (an effective OH radical scavenger), allopurinol (an effective inhibitor of xanthine oxidase), and diamide (a chemical which can deplete cellular levels of glutathione) had little or no effect on this metabolism-induced binding process. The addition of high concentrations of exogenous cysteamine to hypoxic cell cultures resulted in almost complete inhibition of binding. Extracellular bovine albumin at high concentration in hypoxic cell cultures had little effect on the production of adducts to cell macromolecules and only small amounts of [14C]MISO were found to bind to the extra-cellular bovine albumin. This result suggests that MISO preferentially binds to molecules within the cell in which it is metabolically activated. In experiments where cells labeled under hypoxic conditions with [14C]MISO were subsequently permitted to proliferate in aerobic monolayers, a half-life of the acid-insoluble addition products of approximately 55 hr was measured. A large number of [14C]MISO adducts (approximately 10(9)/cell) can be generated in hypoxic cells without any evidence of cytotoxicity, and they are slowly cleared from cells. These are favorable characteristics as regards the development of this technique as a marker for hypoxic cells in solid tumors.
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PMID:Characteristics of the metabolism-induced binding of misonidazole to hypoxic mammalian cells. 683 1

Mucosal albumin clearance was measured in jejunal segments of dogs under control conditions, after arterial occlusions of varying duration (15 min-4 h), and during intraluminal perfusion with hypoxanthine-xanthine oxidase. Albumin clearance rates were estimated from the luminal perfusion rate and the activity of protein-bound 125I in the perfusate and plasma. Arterial occlusion of 30-min to 4-h duration produced a significant increase in mucosal albumin clearance. The magnitude of the rise in albumin clearance was directly related to the duration of arterial occlusion. Pretreatment with superoxide dismutase, a superoxide radical scavenger, or allopurinol, a xanthine oxidase inhibitor, did not prevent the increased albumin clearance induced by 1 h of occlusion. Intraluminal perfusion with hypoxanthine-xanthine oxidase significantly increased mucosal albumin clearances. This increase was prevented by superoxide dismutase. The results of this study indicate that arterial occlusions and enzymatically generated superoxide radicals increase mucosal albumin clearance.
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PMID:Effects of ischemia and oxygen radicals on mucosal albumin clearance in intestine. 689 67

Oxygen radicals have been implicated in the pathogenesis of permeability pulmonary edema. To determine directly if O2 radicals can cause increased alveolar-capillary membrane (ACM) permeability and low-pressure permeability edema, we chemically produced O2 radicals in the sale perfusates of isolated rabbit lungs. The O2 radicals generated by xanthine oxidase caused protein-rich edema and increases in lung perfusion pressures that were inhibitable by catalase (hydrogen peroxide scavenger) or dimethylthiourea (hydroxyl radical scavenger) but not by superoxide dismutase. To determine the effect of O2 radicals on ACM permeability without interference from increased perfusion pressures, we used papaverine to maintain baseline perfusion pressures during O2 radical exposure and then assessed ACM integrity by evaluating the response of isolated lungs to elevated outflow pressures (10 mmHg for 10 min). Under these conditions, increased ACM permeability manifested by weight gains and lavage albumin accumulations occurred in lungs treated with xanthine oxidase but not in control lungs. We conclude that O2 radicals can cause increased ACM permeability and vasoconstriction in isolated lungs.
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PMID:Oxygen-radical-mediated permeability edema and vasoconstriction in isolated perfused rabbit lungs. 714 44

Of 29 524 hospitalised medical patients monitored in a drug surveillance programme 1835 (6.2%) received the xanthine oxidase inhibitor allopurinol. After the exclusion of skin reactions adverse effects were attributed to this drug in 33 (1.8%) patients, the most frequent being haematological abnormalities (11 patients, 0.6%) and diarrhoea and drug fever (5 each, 0.3%). Adverse effects were dose-related. Reactions were unrelated to age, weight, reason for therapy, admission blood urea, or albumin concentrations. Acute exacerbation of gout was troublesome in 3 patients (1 in 600 exposed).
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PMID:Acute adverse reactions attributed to allopurinol in hospitalised patients. 724 70


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