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 myocardial necrosis produced by isoproterenol (beta-adrenergic agonist) marked increase in creatine phosphokinase, phospholipase and significant decrease in cardiac glycogen and phospholipid levels were observed. The enhanced levels of lipid peroxides, xanthine oxidase activity and lowering of superoxide dismutase may lead to excessive formation of free radicals resulting in cardiac cell damage. Nifedipine--a calcium antagonist, Propranolol--a beta-blocker and guggulsterone a lipid lowering agent showed marked reversal of these metabolic changes related to ischemia induced by isoproterenol.
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PMID:Reversal of changes of lipid peroxide, xanthine oxidase and superoxide dismutase by cardio-protective drugs in isoproterenol induced myocardial necrosis in rats. 263 88

We hypothesize that oxygen free radicals are involved in the genesis and maintenance of volume and pressure overload heart failure. Pressure and volume overload would produce myocardial ischemia. During ischemia there will be an increase in xanthine and xanthine oxidase; and a decrease in the superoxide dismutase and glutathione peroxidase activity leading to an increase in the oxygen free radicals. A decrease in the cellular pH during ischemia would release phospholipase which would, in turn, release arachidonic acid from phospholipids. Leukotrienes and prostaglandins will be synthesized through arachidonic acid metabolism. During this synthesis not only oxygen free radicals will be produced but also there will be formation of leukotriene, LTB4, which is known to activate neutrophil and hence increased secretion of oxygen free radicals. Increased circulatory catecholamines due to compensatory mechanism would also lead to an increase in the oxygen free radicals. Oxygen free radicals are known to depress Ca++ binding and uptake of sarcoplasmic reticulum which would lead to a decrease in the myocardial contractility. We have shown that oxygen free radicals depress cardiac function and cardiac contractility. It is, therefore, suggested that oxygen free radicals might be involved in the development of heart failure. The use of agents that reduce the amount of oxygen free radicals would be of value in the prevention and treatment of heart failure.
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PMID:Oxygen free radicals and heart failure. 283 9

Pretreatment of cerebral synaptic membrane preparations with phospholipase (PLase) A2 invariably induced a significant enhancement of [3H]muscimol binding in a dose-dependent manner with a concomitant elevation of the content of total free fatty acids in the membrane. In vitro addition of various free fatty acids exhibited no profound alteration in [3H]muscimol binding, whereas a significant enhancement of the binding was induced by the pretreatment of the membrane with unsaturated free fatty acids such as arachidonic acid and linoleic acid, but not by that with saturated free fatty acids. None of the inhibitors of arachidonic acid metabolism including indomethacin (an inhibitor of cyclo-oxygenase) and nordihydroguaiaretic acid (an inhibitor of lipoxygenase), however, had a significant preventive action on the augmentation of [3H]muscimol binding. On the other hand, various scavengers for superoxide anion radical such as superoxide dismutase, tiron and nitroblue tetrazolium (NBT) not only suppressed the PLase A2-induced enhancement of [3H]muscimol binding, but also diminished the augmentation of the binding due to PLase C and arachidonic acid. It was also found that a remarkable facilitation of the formation of superoxide anion radical was induced by the treatment of synaptic membrane with PLase A2, PLase C and arachidonic acid, all of which exhibited a prominent stimulation of the binding. In addition, treatment of the membrane with xanthine and xanthine oxidase, a superoxide anion radical generating system, resulted in a profound stimulation of the binding. The PLase A2-induced enhancement of the binding was also attenuated by the scavengers for hydrogen peroxide like catalase as well as by those for hydroxyl radical such as dimethylnitrosoaniline, mannitol, methanol and ethanol, but not by those for singlet oxygen radical including alpha-tocopherol and beta-carotene. The present results suggest that membrane phospholipids may play an important role in the modulation of the association of GABA with its relevant receptor through the generation of active oxygen radicals from unsaturated free fatty acids which are yielded by the catalytic action of PLase A2 and/or PLase C.
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PMID:Modulation of synaptic GABA receptor binding by membrane phospholipids: possible role of active oxygen radicals. 298 68

Cultured rat mesangial cells were exposed to a reactive oxygen species (ROS) generating system (xanthine plus xanthine oxidase) to explore the effect of ROS on their metabolism of arachidonic acid (AA). Cell viability, as assessed by 51Cr release, was not affected by the concentrations of xanthine plus xanthine oxidase used. Prostaglandin E2 (PGE2) production following exposure to increasing quantities of xanthine plus xanthine oxidase was significantly decreased to 38.1 +/- 9.7 or 30.8 +/- 6.9% of control levels (P less than 0.05) when cells were stimulated with the calcium ionophore A23187 (1 microgram/ml) or AA (10(-6) M), respectively. Maximum suppression of production was seen within 10 min of ROS exposure. Thromboxane B2 production was similarly decreased to 83.1 +/- 7.6 (0.05 less than P less than 0.10) or 54.9 +/- 2.5% (P less than 0.05). This effect was reversed by addition of catalase to the ROS generating system but not by superoxide dismutase or mannitol, which suggested that H2O2 was the responsible metabolite. High levels of H2O2 (5 x 10(-4) M) suppressed PGE2 production to 44.0 +/- 4.1 or 17.4 +/- 6.2% of A23187- or AA-stimulated production (P less than 0.05). Lower levels of H2O2 resulted in significant stimulation of base-line PGE2 production. Analysis of release of [3H]AA-labeled metabolites from A23187-stimulated cells showed no effect of H2O2 on phospholipase activity. Thus ROS can stimulate or inhibit AA metabolism in the glomerular mesangium, which may have important effects on glomerular hemodynamics during glomerular injury.
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PMID:Biphasic effect of oxygen radicals on prostaglandin production by rat mesangial cells. 310 32

Free radicals and lipid peroxides have recently been identified by us [1, 2, 3] as metabolic intermediates during acute myocardial ischemia. The mechanisms by which evolving myocardial ischemia initiates free radical production are not clear. Based on studies in vitro, it is feasible to consider the following possibilities: (a) dissociation of intramitochondrial electron support system and altered phospholipid integrity with inactivation of cytochrome oxidase, which results in release of ubisemiquinone, flavoprotein and superoxide radicals; (b) accumulation and increased release of intra/extracellular metabolites like NADH, lactate flavoproteins and catecholamines which react either with themselves or with O2 and ascorbic acid; (c) interaction of the metabolic product hypoxanthine with O2 in the presence of xanthine oxidase and (d) activation of phospholipase by calcium influx with enhanced arachidonic acid metabolism and superoxide radical production. Detailed in vitro radiobiological studies [4] have demonstrated that free radical reactions occur even at very low O2 tensions (83% of maximum rate of PO2 approximately 6 mmHg and 50% at PO2 approximately 1 mmHg), and Smith [5] has demonstrated that free radical peroxidation takes place quite rapidly in rat brain homogenates incubated in gas mixtures containing only 5% O2. Thus, the low oxygen tensions in ischemic tissue are adequate to support free radical reactions. The free radicals thus produced may initiate and enhance lipid peroxidation by attacking polyunsaturated membrane lipids.
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PMID:Production of free radicals and lipid peroxides in early experimental myocardial ischemia. 631 60

Polymorphonuclear leukocytes secreting oxygen radicals are found in the glomerular capillaries at an early stage of experimental acute glomerulonephritis. The aim of this work was to study the effects of these radicals on prostaglandin (PG) production by the glomeruli. Glomeruli were isolated from rat renal cortex and incubated in the presence of a biochemical system capable of generating oxygen radicals (addition to 100 microM xanthine of increasing concentrations of xanthine oxidase). Synthesis of PGE2, PGF2alpha, 6 keto PGF1alpha, and TXB2 estimated using specific radioimmunoassays was twofold greater in the presence of oxygen radicals. This effect was inhibited by catalase, slightly stimulated by superoxide dismutase, unaffected by hydroxyl radical scavengers, thus suggesting that hydrogen peroxide was the by-product responsible. This was confirmed by the stimulatory effect of hydrogen peroxide itself (1 to 100 microM) on PG synthesis. The effect of mepacrine, an inhibitor of phospholipase activity, on PG production was more marked in the presence of hydrogen peroxide and the stimulation of PG synthesis by hydrogen peroxide or oxygen radicals was progressively inhibited in the presence of arachidonic acid. Moreover, oxygen radicals stimulated the release of 14C-arachidonic acid previously incorporated in isolated glomeruli. This demonstrates that the increase in PG synthesis in response to oxygen radicals is due to activation of glomerular phospholipase by these radicals. This effect that is likely to occur at an early stage of experimental glomerulonephritis could play a role in the mechanism of the inflammatory process.
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PMID:Stimulation by oxygen radicals of prostaglandin production by rat renal glomeruli. 730 Jan 22

The direct neurotoxic action of the beta-amyloid protein, the major constituent of senile plaques, may represent the underlying cause of neuronal degeneration observed in Alzheimer's disease. The apoptotic-mediated neuronal death induced by beta-amyloid appears to reside in its ability to form Ca(2+)-permeable pores in neuronal membranes resulting in an excessive influx of Ca2+ and the induction of neurotoxic cascades. It is possible that during beta-amyloid exposure a Ca(2+)-mediated increase in free radical generation may exceed the defensive capacity of cells and thus lead to cell death. Consequently, in the present study we have investigated the effect of a panoply of antioxidants and inhibitors of free radical formation on the development of beta-amyloid neurotoxicity. Acute exposure of rat hippocampal neurons to "aged" beta-amyloid25-35 peptide (5-50 microM) induced a slow, concentration-dependent apoptotic neurotoxicity (25-85%) during a 6 day exposure. Co-incubation of cultures with beta-amyloid25-35 peptide (25 microM) and inhibitors of nitric oxide synthase and/or xanthine oxidase (NG-monomethyl-L-arginine [1 mM), N omega-nitro-L-arginine [1 mM], oxypurinol [100 microM], allopurinol [100 microM]), important mediators of nitric oxide, superoxide, and hydroxyl radical formation, did not attenuate beta-amyloid neurotoxicity. Similarly, a reduction in free radical generation by selective inhibition of phospholipase-A2 cyclooxygenase, and lipoxygenase activities with quinacrine (0.5 microM), indomethacin (50 microM), and nor-dihydroguaiaretic acid (0.5 microM), respectively, did not reduce the proclivity of beta-amyloid to induce cell death. Exposure of cultures to catalase (25 U/ml) and/or superoxide dismutase (10 U/ml) as well as the free radical scavengers vitamin E (100 microM), vitamin C (100 microM), glutathione (100 microM), L-cysteine (100 microM), N-acetyl-cysteine (100 microM), deferoxamine (5 microM), or haemoglobin (35 micrograms/ml) failed to attenuate the neurotoxic action of beta-amyloid. On the other hand, pre-treatment of cultures with subtoxic concentrations of beta-amyloid peptide significantly increased the vulnerability of neurons to H2O2 exposure and suggest that beta-amyloid peptide renders neurons more sensitive to free radical attack. However, a potential beta-amyloid-mediated increase in free radical formation is not a proximate cause of the neurotoxic mechanism of beta-amyloid in vitro.
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PMID:Inhibitors of free radical formation fail to attenuate direct beta-amyloid25-35 peptide-mediated neurotoxicity in rat hippocampal cultures. 753 47

The purpose of this study was to determine the effect of superoxide dismutase (SOD) on canine experimental pancreatitis. Pancreatitis was induced by retrograde biliary juice injection (0.5 ml/kg) to accessory pancreatic duct. Twenty-one mongrel dogs were divided into two groups, i.e. control (untreated) group (n = 13) and SOD-treated group (n = 8). In SOD-treated group, SOD 5000 units/kg was administered from celiac artery immediately after onset of pancreatitis. Xanthine oxidase (XOD), malondialdehyde (MDA), phospholipase (PL), and SOD were assayed from pancreatic tissue 1 and 3 hours after onset of pancreatitis. Serum amylase, elastase I, calcium, and WBC were assayed for 7 days after onset of pancreatitis. XOD and MDA levels were increased in untreated group, and not significantly changed in treated group with statistical difference. PL levels were increased after onset of pancreatitis in both groups and SOD levels were not changed even in treated group. No statistical difference was seen in PL and SOD levels between two groups. Increase of XOD levels suggests continuous generating of free radical species from pancreatic tissue, and SOD inhibits this increase. Increase of PL level was not improved by SOD. Serum laboratory findings and survival rates were not improved by SOD treatment.
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PMID:[Role of free radicals on canine bile-induced pancreatitis and effect of superoxide dismutase]. 766 54

The luteolytic mechanism was investigated in rat corpora lutea (CL). This study focused on the changes that occur in the plasma membrane. Previous experiments with rat luteal cells indicated that in vitro generation of superoxide radicals by xanthine oxidase disrupted LH-stimulated cAMP production and progesterone secretion similar to the effect of prostaglandin F2 alpha, the luteolytic hormone. In the present study, we observed that xanthine oxidase treatment of plasma membrane samples from CL caused a large decrease in fluidity, which also occurs during prostaglandin F2 alpha-induced luteolysis. This fluidity change was blocked by catalase, bromophenacyl bromide, an inhibitor of phospholipase-A activity, indomethacin, and free radical scavengers, and it was reversed by removal of FFA from the membrane. In addition, xanthine oxidase treatment caused phospholipid breakdown, formation of neutral lipids, a burst of inorganic peroxides, and a sustained rise in the level of lipid peroxides. These results indicate that free radical generation causes several changes that disrupt the plasma membrane of CL cells, and they raise the possibility that phospholipid breakdown could be involved in the mechanism that inhibits LH stimulation of steroidogenesis during luteolysis.
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PMID:Plasma membrane changes in the rat corpus luteum induced by oxygen radical generation. 834 94

An early increase in ROS production is characteristic of cerebellar granule cells undergoing apoptosis in the presence of 5 mM KCl. However, the sources of this increase have not been investigated in detail. In particular whether there is a single enzymatic source or the increase in ROS production is the consequence of the involvement of different enzymes has not been studied in depth. Different enzymatic pathways may indeed contribute to the up-regulation of intracellular ROS production either directly or via side-chain reactions and a number of candidate enzymes are known to be involved in the apoptotic process in various cell types. The aim of this study was to identify the cellular sources of the ROS generated by CGCs undergoing apoptosis by low K+. A panel of specific inhibitors against phospholipase, cytochromes P450, cyclooxygenase, lipoxygenase, xanthine oxidase, ribonucleotide reductase and NADPH oxidase were used. We provide evidence that no single source of ROS can be identified in apoptotic CGCs, but the ROS generated through the arachidonic acid (AA) pathways, mainly via lipoxygenase activities, seems to be the most prominent.
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PMID:Different sources of reactive oxygen species contribute to low potassium-induced apoptosis in cerebellar granule cells. 1850 67


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