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)

Active oxygen species cause gastric mucosal damage in vivo. However, it is not known if these species are directly cytotoxic toward gastric cells. Prostaglandins have important physiological roles in the gastric mucosa, including direct cell protection against damaging factors. So, to find if active oxygen species affect prostaglandin synthesis in gastric mucosal cells is important, but this also is not known. This study was done to investigate the effects of such species on damage to and prostaglandin synthesis in cultured mucus-producing cells from rat gastric mucosa. Active oxygen species were produced by the addition of xanthine and xanthine oxidase to the culture medium. Cytotoxicity was assayed by 51Cr release. Xanthine (1 mM) and xanthine oxidase (100 mU/ml) increased specific 51Cr release as the thiobarbituric acid reactants increased. This increase in 51Cr release was inhibited by catalase, a scavenger of hydrogen peroxide, or dimethyl sulfoxide, a scavenger of hydroxyl radicals, but not by superoxide dismutase, a scavenger of superoxide, nor deferoxamine, an inhibitor of hydroxyl radical generation. Catalase, dimethyl sulfoxide, and superoxide dismutase each had no effect on prostaglandin E2 synthesis when xanthine and xanthine oxidase were not added. In the presence of xanthine and xanthine oxidase, catalase and dimethyl sulfoxide stimulated the synthesis of prostaglandin E2 and superoxide dismutase inhibited it. Indomethacin, a prostaglandin synthetase inhibitor, did not affect the decrease in 51Cr release caused by catalase in the presence of xanthine and xanthine oxidase, but it abolished the decrease caused by dimethyl sulfoxide. These results suggest that hydrogen peroxide, but not superoxide nor hydroxyl radicals, is involved in damage to cultured rat gastric cells, and that superoxide stimulates prostaglandin E2 synthesis, but that hydrogen peroxide inhibits it. Protection of the cells by dimethyl sulfoxide may be related to stimulation of prostaglandin E2 synthesis in the cells, but not via scavenging hydroxyl radicals.
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PMID:Effects of active oxygen species on damage to and prostaglandin synthesis in cultured rat gastric cells. 132 36

Excessive stimulation of excitatory amino acid (EAA) receptors and abnormal production of oxygen-derived free radicals have repeatedly been implicated in the series of events linking brain hypoxia or ischemia to neuronal death. We report here that in rat hippocampal slices the KCl-stimulated output of labeled D-3H aspartate or of endogenous aspartate and glutamate significantly increased under in vitro simulated hypoxic, hypoglycemic, or ischemic conditions. In particular, when the slices were incubated for 10 min at 32 degrees C under "ischemic" conditions (namely, lack of oxygen and glucose), endogenous aspartate and glutamate in the supernatant increased by 10 and 20 times, respectively. Since radical scavengers (D-mannitol), drugs reducing free radical formation (indomethacin, corticosteroid), or enzymes able to metabolize them (catalase and superoxide dismutase) significantly reduced this output, it was supposed that free radicals caused EAA release. A direct demonstration of this concept was obtained by showing a significant release of EAA after incubation of hippocampal slices with enzymes and substrates known to cause the formation of free radicals, such as xanthine plus xanthine oxidase or arachidonic acid plus prostaglandin synthase. Neither ischemia nor the enzymatic reactions leading to free radical production increased the activity of the cytoplasmic enzyme lactate dehydrogenase in the incubation medium, thus ruling out a nonspecific cellular lysis. It appears therefore that during ischemic states, brain production of reactive molecules (free radicals) causes an increased output of EAA. This may trigger a series of events which could help to explain the delayed loss of neurons after a transient ischemic period.
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PMID:Excitatory amino acid release and free radical formation may cooperate in the genesis of ischemia-induced neuronal damage. 196 65

The lung is especially sensitive to a variety of vastly different agents and conditions including hyperoxia, certain drugs and xenobiotics, particulate debris, and ischemia/reperfusion. There is a growing body of experimental data to suggest that most, if not all, of these agents or conditions mediate pulmonary injury by forming reactive O2 metabolites such as O2-., H2O2.OH, HOCl, and RNHCl. The presence mechanisms by which these different agents converge to produce free radical-mediated pulmonary injury is not entirely clear. The lung does contain several metabolic pathways that will produce large amounts of reactive O2 metabolites. For example, hyperoxia-induced pulmonary injury may be mediated by oxidants produced by both mitochondrial and microsomal electron transport. Certain drugs and xenobiotics may be metabolized by nonspecific flavoproteins found in the mitochondrial electron transport chain and associated with microsomal mixed function oxidase system to yield a variety of free radicals and oxidants. Inhalation of particulate debris will activate resident phagocytic leukocytes to produce large quantities of cytotoxic oxidants. Ischemia and reperfusion appear to produce substantial amounts of xanthine oxidase-derived oxy-radicals that recruit and activate inflammatory phagocytes to produce cytotoxic HOCl and N-chlorinated oxidants. Finally, inappropriate metabolism of arachidonate by prostaglandin synthetase in the presence of NADH (NADPH) produces a burst of O2-. The fact that the lung contains so many different metabolic avenues for oxidant and free radical production suggests that this particular organ may be the most sensitive to oxidative insult.
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PMID:Metabolic sources of reactive oxygen metabolites during oxidant stress and ischemia with reperfusion. 265 Sep 65

Cooxidative metabolism of the urinary bladder carcinogen N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) was examined using solubilized and particulate microsomal preparations from the rabbit renal inner medulla and the ram seminal vesicle. Metabolism was measured by the rate of decrease in absorbance at 400 nm. In these soluble and particulate preparations, FANFT metabolism was observed only in the presence of specific fatty acids. These fatty acids are substrates for prostaglandin endoperoxide synthetase. Structurally dissimilar inhibitors of prostaglandin endoperoxide synthetase such as indomethacin, aspirin, 5,8,11,14-eicosatetraynoic acid, ethoxyquin, and meclofenamic acid specifically inhibited FANFT metabolism. Other inhibitor and substrate specificity studies suggest that FANFT was not metabolized by nitroreductase, xanthine oxidase, lipoxygenase, lipid peroxidation, or mixed-function oxidases. In addition, the lack of detectable 2-amino-4-(5-nitro-2-furyl)thiazole formation suggests that arylformamidase was not participating in FANFT metabolism measured in these experiments. The data indicate that prostaglandin endoperoxide synthetase can mediate FANFT metabolism by a cooxidative process.
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PMID:Metabolism of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide by prostaglandin endoperoxide synthetase. 676 14

The effects of aspirin on N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) -induced urinary bladder lesions, endogenous bladder prostaglandin E2 synthesis, and the metabolism of FANFT by bladder epithelial microsomes were examined. Rats were fed 0.5% aspirin and/or a diet containing 0.1% or 0.2% FANFT. Bladder lesions were observed with light and scanning electron microscopy, and the prostaglandin E2 content of rat bladder was measured by radioimmunoassay. Metabolism of FANFT was measured by decreased absorbance at 400 nm. Aspirin inhibited the appearance of hyperplastic lesions induced by feeding 0.1% or 0.2% FANFT for 6 or 12 weeks. Aspirin reduced bladder prostaglandin E2 content at 1, 2, 6, and 13 weeks compared to corresponding control values. Rat and rabbit microsomal metabolism of FANFT were dependent upon specific fatty acid substrate and prevented by specific inhibitors (including aspirin) of prostaglandin endoperoxide synthetase. Other inhibitor and substrate specificity studies suggest that FANFT was not metabolized by xanthine oxidase, lipoxygenase, lipid peroxidation, or mixed-function oxidases. These results suggest that the metabolism of FANFT by prostaglandin endoperoxide synthetase may be involved in the metabolic activation of FANFT necessary for the induction of bladder cancer in rats.
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PMID:Aspirin inhibition of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide-induced lesions of the urinary bladder correlated with inhibition of metabolism by bladder prostaglandin endoperoxide synthetase. 679 Jan 63

Both distal (canine lung strips) and proximal (bovine trachealis strips) airway smooth muscle contract in isolated organ baths as the percentage of environmental oxygen is increased from 12% to 95%. This effect is blocked by prostaglandin synthetase inhibitors (indomethacin, 10(-4)M; meclofenamate, 10(-4)M). To determine whether this contractile response is due to molecular oxygen, or to other products of oxidative metabolism, we examined the effects of ozone, hydrogen peroxide, and superoxide radical generating systems (paraquat and xanthine-xanthine oxidase) on the smooth muscle preparations. Ozone (3 ppm), paraquat (2 mM), and xanthine (10(-3)M)-xanthine oxidase (1 unit) were without effect. Hydrogen peroxide (10(-5)-10(-3)M) produce consistent contractions in both preparations, an effect which was appreciably greater in an hypoxic environment and which was blocked by both indomethacin and meclofenamate. Contraction from both hyperoxia and hydrogen peroxide was partially reversed by various oxygen radical scavengers, including methional (10 mM), ascorbic acid (10 mM), nitroblue tetrazolium (0.3 mM), butylated hydroxyanisole (1 mM), and 2',7' naphthalonediol (1 mM). These results suggest that hyperoxic contraction in airway smooth muscle is mediated by active oxygen species, perhaps by their effects on prostaglandin metabolism.
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PMID:Hydrogen peroxide contracts airway smooth muscle: a possible endogenous mechanism. 733 Apr 88

Co-oxidative metabolism of ANFT by either the fatty acid cyclo-oxygenase or hydroperoxidase activities of prostaglandin endoperoxide synthetase was examined by using solubilized and particulate microsomes prepared from rabbit renal inner medulla and ram seminal vesicles. The rate of metabolism was measured by the decrease in absorbance at 385 nm. In both soluble and particulate preparations, ANFT metabolism was dependent upon specific fatty acid substrates and prevented by specific inhibitors of prostaglandin endoperoxide synthetase. Other inhibitor and substrate specificity studies suggest that ANFT was not metabolized by xanthine oxidase, lipoxygenase, lipid peroxidation, or mixed-function oxidases. Under incubation conditions which demonstrated co-oxidation of ANFT, a metabolite (peak I) was observed by high-pressure liquid chromatography. In the presence of indomethacin, peak I was not present, and only authentic ANFT was observed. Co-oxidation of ANFT was also observed with cumene hydroperoxide. Cumene hydroperoxide-mediated co-oxidation was not prevented by indomethacin or SKF-525A but was blocked by the antioxidants butylated hydroxytoluene, ethoxyquin, and vitamin E. The data indicate that ANFT is metabolized by a co-oxidative process involving the prostaglandin hydroperoxidase activity of prostaglandin endoperoxide synthetase.
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PMID:Co-oxidative metabolism of 2-amino-4-(5-nitro-2-furyl)-thiazole by prostaglandin hydroperoxidase. 740 Jun 70

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