Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.17.3.2 (xanthine oxidase)
8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We hypothesized that xanthine oxidase (XO)-derived hydrogen peroxide (H2O2) contributes to ischemic skeletal muscle injury during reperfusion. We found that after ischemia (3 h) and then reperfusion (4 h) rat gastrocnemius muscles had decreased contractile function following direct stimulation. Three lines of investigation suggested that XO-derived H2O2 contributes to reperfusion injury of ischemic skeletal muscle. First, treatment with dimethylthiurea (DMTU), a highly permeant O2 metabolite scavenger, but not urea, just before reperfusion improved muscle function in legs subjected to ischemia and then reperfusion. Second, gastrocnemius muscles from rats fed tungsten or allopurinol had negligible XO activities and increased muscle function after ischemia and reperfusion. Third, as assessed by measurement of skeletal muscle catalase activity in the presence of aminotriazole, H2O2 was measured during reperfusion of ischemic muscles from untreated or urea-treated rats but not during reperfusion of muscles from rats treated with DMTU, tungsten, or allopurinol.
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PMID:Xanthine oxidase-derived H2O2 contributes to reperfusion injury of ischemic skeletal muscle. 211 Jul 80

The enzyme xanthine oxidase participates in the pathogenesis of tissue ischemia-reperfusion injury by depleting purine pools and generating toxic oxygen metabolites. The role of xanthine oxidase in inflammatory cell populations has not been defined. We examined the level of xanthine oxidase activity expressed by murine leukocytes both in the resting state, and after in vivo and in vitro exposure to inflammatory stimuli. The contribution of xanthine oxidase to inflammation may vary among tissue compartments, so leukocytes harvested from several tissues were studied. Resident murine peritoneal macrophages consistently expressed xanthine oxidase activity (291 +/- 55 microIU/10(6) cells). Thioglycolate-elicited peritoneal macrophages contained similar levels of xanthine oxidase activity (265 +/- 42 microIU/10(6) cells). By contrast, resident murine alveolar macrophages expressed one tenth the xanthine oxidase activity (24 +/- 4 microIU/10(6) cells). Xanthine oxidase activity was also consistently found in murine peritoneal neutrophils (127 +/- 28 microIU/10(6) cells) but not in splenic lymphocytes. In vitro studies were performed to determine whether xanthine oxidase activity of resident peritoneal macrophages could be modulated by exogenous stimuli relevant to the pathogenesis of inflammation. Lipopolysaccharide caused a 62% +/- 9% reduction in cellular xanthine oxidase activity (p less than 0.02). Interferon-gamma alone had no effect on xanthine oxidase activity; however, interferon-gamma and lipopolysaccharide together caused a striking reduction in cellular xanthine oxidase activity, reaching 25% +/- 2% of unstimulated control cells (p less than 0.001). We conclude that murine macrophages and neutrophils are potentially important sources of xanthine oxidase activity in inflamed tissues. In addition, the activity of xanthine oxidase in macrophages is tissue specific and is modulated in vitro by proinflammatory stimuli.
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PMID:Expression of xanthine oxidase activity by murine leukocytes. 211 59

We have observed that pial arteriolar dilation in response to hypercapnia and hypotension is abolished after cerebral ischemia in newborn pigs. We determined whether direct generation of activated oxygen on the brain surface (OX: xanthine oxidase, hypoxanthine, FeCl3, and FeSO4) or topical arachidonate altered pial arteriolar responsiveness in a manner similarly to cerebral ischemia. OX, which generated more brain surface superoxide than reperfusion after ischemia, dilated pial arterioles. This dilation was reversed within 10 min of the end of exposure. OX produced ultrastructural changes in pial vessel endothelium and appeared to cause intravascular aggregation of granulocytes. After OX, prostanoid-dependent pial arteriolar dilations in response to hypercapnia and hypotension were attenuated, whereas constrictor responses to norepinephrine and acetylcholine and dilator responses to prostaglandin E2 and isoproterenol were not affected. After OX, hypercapnia increased cortical periarachnoid cerebrospinal fluid prostanoids modestly, whereas acetylcholine produced the normal strong stimulation of prostanoid synthesis. Arachidonate (10(-4) M and 7 x 10(-4) M) also caused reversible pial arteriolar dilation but did not alter subsequent pial arteriolar responses. Therefore, although arachidonate did not mimic the effects of ischemia-reperfusion on pial arteriolar reactivity, OX produced alterations that are qualitatively similar, although quantitatively less, than those produced by ischemia.
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PMID:Activated oxygen and arachidonate effects on newborn cerebral arterioles. 212 Oct 51

A number of investigations have implicated free radicals in the progression of ischemic/reperfusion injury. alpha-Tocopherol has been found to attenuate alterations due to ischemia and reperfusion in an isolated heart model. The present study was intended to directly examine neonatal rat cardiac ventricular cell cultures exposed to a free radical generating system catalyzed by xanthine oxidase. The effectiveness of alpha-tocopherol in the attenuation of the resultant changes and the mechanism by which the effects of alpha-tocopherol may be exerted were evaluated. Cultures were either nontreated or pretreated for 18 h with 20 microM alpha-tocopherol or the subcomponents of the alpha-tocopherol molecule, phytol and Trolox. Exposure of cell cultures to free radicals resulted in significant increases in lipid peroxidation products, release of both lactate dehydrogenase and 3H-arachidonate, and structural alterations. Pretreatment with alpha-tocopherol showed significant attenuation of the changes associated with exposure to free radicals. Trolox and phytol at equal molar doses were not as effective as alpha-tocopherol in protecting the myocytes against injury. Thus, alpha-tocopherol seems beneficial in its ability to reduce free radical-mediated changes by functioning as a lipophilic antioxidant. Additionally, the intact, native alpha-tocopherol molecule exceeded the protective capabilities of either of its subcomponents.
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PMID:Free radical damage in neonatal rat cardiac myocyte cultures: effects of alpha-tocopherol, Trolox, and phytol. 212 18

The perfused isolated kidney is a partial ischemic system that is characterised by glomerular proteinuria and release of glomerular heparan sulfate. Metabolic changes associated with the levels of glutathione, xanthine oxidase and glyceraldehyde 3-dehydrogenase indicated that oxygen radical metabolites were being produced during the perfusion. We have demonstrated that a mixture of oxygen metabolite scavengers containing mannitol, superoxide dismutase and catalase included in the perfusion medium significantly reduced protein excretion. Similar results were obtained with the administration of allopurinol to the rat 24h prior to kidney removal and allopurinol in the perfusion medium. [35S]Heparan sulfate loss from the glomerulus was totally inhibited by the scavenger mixture. These results suggest that reactive oxygen metabolites may be involved in damage to renal capillaries, specifically to heparan sulfate proteoglycan, which leads to proteinuria as a result of partial ischemia produced during perfusion.
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PMID:The inhibitory action of oxygen radical scavengers on proteinuria and glomerular heparan sulphate loss in the isolated perfused kidney. 214 Dec 55

The free radical-generating enzyme xanthine oxidase has been hypothesized to be a central mechanism of the injury which occurs in postischemic tissues; however, its importance remains controversial. Much attention has focused on the role of this enzyme in myocardial reperfusion injury. While xanthine oxidase has been observed in ischemic tissue homogenates, the presence and importance of radical generation by the enzyme in intact tissues are unknown. Therefore, we performed electron paramagnetic resonance, nuclear magnetic resonance and hemodynamic studies to measure the presence and significance of xanthine oxidase-mediated free radical generation in the isolated rat heart. When isolated perfused rat hearts were reperfused after 30 min of global ischemia, myocardial function and coronary flow were significantly improved in the presence of the definitive xanthine oxidase blocker oxypurinol. Free radical concentrations measured by spin-trapping with 5,5'-dimethyl-1-pyrroline-N-oxide were significantly decreased by oxypurinol and the energetic state of the heart was improved as reflected by an increased recovery of phosphocreatine and a higher phosphocreatine/Pi ratio. ATP recovery, however, was not altered, indicating that the improved functional and metabolic state of the heart was not due to ATP salvage. Spectrophotometric assays for the enzyme showed an increase in the amount of xanthine oxidase relative to dehydrogenase following ischemia, and a total available xanthine oxidase pool in the rat heart of approximately 150 milliunits/g of protein. Thus, xanthine oxidase is a significant source of the oxidative injury which occurs upon reperfusion of the ischemic rat heart.
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PMID:Evaluation of the role of xanthine oxidase in myocardial reperfusion injury. 215 6

While studying xanthine-xanthine oxidase system it was found, that a considerable accumulation of xanthine and uric acid occurred whereas xanthine dehydrogenase did not transfer in xanthine oxidase during 2 hours of total rat liver ischemia. These data make it possible to reject the generally accepted hypothesis of xanthine oxidase key role in free radical mechanism of ischemia damage.
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PMID:[Is xanthine oxidase a universal source of superoxide radicals in ischemic and reperfusion lesions?]. 216 71

The reaction of xanthine and xanthine oxidase generates superoxide and hydrogen peroxide. In contrast to earlier works, recent spin trapping data (Kuppusamy, P., and Zweier, J.L. (1989) J. Biol. Chem. 264, 9880-9884) suggested that hydroxyl radical may also be a product of this reaction. Determining if hydroxyl radical results directly from the xanthine/xanthine oxidase reaction is important for 1) interpreting experimental data in which this reaction is used as a model of oxidant stress, and 2) understanding the pathogenesis of ischemia/reperfusion injury. Consequently, we evaluated the conditions required for hydroxyl radical generation during the oxidation of xanthine by xanthine oxidase. Following the addition of some, but not all, commercial preparations of xanthine oxidase to a mixture of xanthine, deferoxamine, and either 5,5-dimethyl-1-pyrroline-N-oxide or a combination of alpha-phenyl-N-tert-butyl-nitrone and dimethyl sulfoxide, hydroxyl radical-derived spin adducts were detected. With other preparations, no evidence of hydroxyl radical formation was noted. Xanthine oxidase preparations that generated hydroxyl radical had greater iron associated with them, suggesting that adventitious iron was a possible contributing factor. Consistent with this hypothesis, addition of H2O2, in the absence of xanthine, to "high iron" xanthine oxidase preparations generated hydroxyl radical. Substitution of a different iron chelator, diethylenetriaminepentaacetic acid for deferoxamine, or preincubation of high iron xanthine oxidase preparations with chelating resin, or overnight dialysis of the enzyme against deferoxamine decreased or eliminated hydroxyl radical generation without altering the rate of superoxide production. Therefore, hydroxyl radical does not appear to be a product of the oxidation of xanthine by xanthine oxidase. However, commercial xanthine oxidase preparations may contain adventitious iron bound to the enzyme, which can catalyze hydroxyl radical formation from hydrogen peroxide.
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PMID:Hydroxyl radical is not a product of the reaction of xanthine oxidase and xanthine. The confounding problem of adventitious iron bound to xanthine oxidase. 217 Mar 83

Oxygen-derived free radicals have been implicated in the pathogenesis of various disease states, including myocardial ischemia and reperfusion. In this article, we review 1) the evidence linking free radical production and myocardial injury during myocardial ischemia and reperfusion and 2) results of studies of the effects of the pharmacological therapies available potentially to prevent free radical-mediated injury. Free radicals can be produced during ischemia and reperfusion by several different biochemical pathways. Of these, the xanthine oxidase reaction and the output of free radicals by neutrophils that have accumulated in damaged tissue have been studied extensively. When produced, free radicals can potentially damage myocytes or endothelial cells through peroxidation of membrane lipids or damage to proteins or nucleic acids. Using electron spin resonance spectroscopy, several studies have shown a 'burst' of oxygen free radicals immediately after reperfusion. Moreover, exogenous generation of intravascular free radicals has been shown to produce marked vascular and myocyte damage, as well as contractile dysfunction. 'Anti-free radical' interventions, such as xanthine oxidase inhibitors and free radical scavengers have been reported to prevent contractile dysfunction and reperfusion-induced arrhythmias after an episode of reversible ischemic injury. However, after more severe episodes of ischemia, such interventions have had conflicting effects on myocardial infarct size. 'Anti-free radical' interventions could be of potential use in situations where reversible ischemic injury occurs. In situations where reperfusion is achieved after irreversible ischemic injury has occurred, the potential beneficial effect of these treatments on infarct size is more doubtful.
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PMID:Oxygen-derived free radicals and postischemic myocardial reperfusion: therapeutic implications. 218 85

Free radicals have recently been implicated in a number of biochemical and chemical reactions in the body. Lipid peroxidation induced by free radical reaction is believed to be one of the major causes of cell damage and injuries in cell membranes. In recent years, reports have appeared citing the contribution of free radicals and active oxygen species in the etiology of various digestive diseases. For example, gastric mucosal injuries and the increases in thiobarbituric acid-reactive substances in the gastric mucosa induced by ischemia or ischemia/reperfusion were significantly inhibited by treatment with superoxide dismutase and catalase. It has been suggested that superoxide radical or hydroxyl radical may be the major oxygen radicals contributing to ischemia or ischemia/reperfusion injury in the stomach, small intestine, and liver. There reactive species can attack and damage important biological molecules. Within cellular membranes, hydroxyl radical can initiate a free radical chain reaction known as lipid peroxidation, in which polyunsaturated fatty acids are broken down into water soluble products and toxic lipid peroxides are produced with the consequent destruction of membrane integrity. The major source of active oxygen species produced after ischemia or ischemia/reperfusion seems to be the enzymatic xanthine oxidase and activated polymorphonuclear leukocytes (PMN). In the large intestine which has little activity in xanthine oxidase, PMNs are a more important source of active oxygen species and play a role in the pathogenesis of the inflammatory bowel diseases. The above information suggests that oxygen-derived free radicals are involved in the fundamental mechanism of tissue injury in various disorders of the digestive system.
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PMID:[Free radicals in digestive diseases]. 220 Sep 14


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