Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of unscheduled DNA synthesis (UDS) of different agents that induce oxidative stress was investigated using human mononuclear leukocytes (HML). It was found that Xanthine plus Xanthine oxidase increased UDS by 47%. Hydrogen peroxide had no significant effect. Cumene hydroperoxide increases UDS by 50% with a large interindividual variation (7-100%). Bleomycin and Mitomycin C increase UDS 189% and 295%, respectively. The validity of UDS induced by these agents for screening interindividual differences in susceptibility to oxidative stress is discussed.
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PMID:Induction of unscheduled DNA synthesis in human mononuclear leukocytes by oxidative stress. 242 23

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

1. Benzo[a]pyrene (BaP) metabolism was studied in microsomes of the pyloric caeca (main digestive tissue and site of P450) of the echinoderm sea star (starfish) Asterias rubens. 2. NADPH-dependent metabolism of BaP produced phenols (36% of total metabolism), quinones (19%), dihydrodiols (25%) and putative protein adducts (20%). 3. NADH-dependent rates of BaP metabolism were approximately twice those found for NADPH-dependent metabolism, and metabolite formation was shifted towards dihydrodiols and quinones. 4. Cumene hydroperoxide (CHP)-dependent rates of BaP metabolism were also higher than NADPH-dependent rates by a factor of six for quinone and putative protein adduct production, and by a factor of four for phenol and dihydrodiol production. 5. Microsomal rates of BaP metabolism in BaP-exposed sea stars appeared to be elevated more in the case of NADPH-dependent than for CHP-dependent metabolism (respectively, increases of 130 and 41%), indicating the induction of forms of P450 preferentially catalysing NADPH-dependent metabolism. 6. 1,1,1-Trichloropropene-2,3-oxide (TCPO) inhibited dihydrodiol formation from both NADPH- and CHP-dependent BaP metabolism, indicating the involvement of epoxide hydratase in BaP metabolism. 7. Incubations of pyloric caeca microsomes with BaP and a superoxide anion radical-generating system (xanthine/xanthine oxidase) produced putative protein adducts but no free metabolites.
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PMID:NADPH-, NADH- and cumene hydroperoxide-dependent metabolism of benzo[a]pyrene by pyloric caeca microsomes of the sea star Asterias rubens L. (Echinodermata: Asteroidea). 790 Apr 14

In recent years, considerable efforts have been made to identify new chemopreventive agents which could be useful for man. Myrica nagi, a subtropical shrub, has been shown to possess significant activity against hepatotoxicity and other pharmacological and physiological disorders. We have shown a chemopreventive effect of Myrica nagi on cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in mice. Cumene hydroperoxide treatment at a dose level of 30 mg/animal/0.2 ml acetone enhances susceptibility of cutaneous microsomal membrane for iron-ascorbate-induced lipid peroxidation and induction of xanthine oxidase activity which are accompanied by decrease in the activities of cutaneous antioxidant enzymes such as catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and depletion in the level of cutaneous glutathione. Parallel to these changes a sharp decrease in the activities of phase II metabolizing enzymes such as glutathione S-transferase and quinone reductase has been observed. Application of Myrica nagi at doses of 2.0 mg and 4.0 mg/kg body weight in acetone prior to that of cumene hydroperoxide (30 mg/animal/0.2 ml acetone) treatment resulted in significant inhibition of cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in a dose-dependent manner. Enhanced susceptibility of cutaneous microsomal membrane for lipid peroxidation induced by iron ascorbate and xanthine oxidase activities were significantly reduced (P<0.05). In addition the depleted level of glutathione, the inhibited activities of antioxidants, and phase II metabolizing enzymes were recovered to a significant level (P<0.05). The protective effect of Myrica nagi was dose-dependent. In summary our data suggest that Myrica nagi is an effective chemopreventive agent in skin and capable of ameliorating cumene hydroperoxide-induced cutaneous oxidative stress and toxicity.
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PMID:Myrica nagi attenuates cumene hydroperoxide-induced cutaneous oxidative stress and toxicity in Swiss albino mice. 1086 2

Hemidesmus indicus has been shown to possess significant activity against immunotoxicity and other pharmacological and physiological disorders. In this communication, we have shown the modulating effect of H. indicus on cumene hydroperoxide-mediated cutaneous oxidative stress and tumor promotion response in murine skin. Cumene hydroperoxide treatment (30 mg per animal) increased cutaneous microsomal lipid peroxidation and induction of xanthine oxidase activity which are accompanied by decrease in the activities of cutaneous antioxidant enzymes and depletion in the level of glutathione. Parallel to these changes a sharp decrease in the activities of phase II metabolizing enzymes was observed. Cumene hydroperoxide treatment also induced the ornithine decarboxylase activity and enhanced the [3H]-thymidine uptake in DNA synthesis in murine skin. Application of ethanolic extract of H. indicus at a dose level of 1.5 and 3.0mg/kg body weight in acetone prior to that of cumene hydroperoxide treatment resulted in significant inhibition of cumene hydroperoxide-induced cutaneous oxidative stress, epidermal ornithine decarboxylase activity and enhanced DNA synthesis in a dose-dependent manner. Enhanced susceptibility of cutaneous microsomal membrane for lipid peroxidation and xanthine oxidase activity were significantly reduced (P<0.01). In addition the depleted level of glutathione, inhibited activities of antioxidants and phase II metabolizing enzymes were recovered to significant level (P<0.05). In summary, our data suggest that H. indicus is an effective chemopreventive agent in skin and capable of ameliorating hydroperoxide-induced cutaneous oxidative stress and tumor promotion.
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PMID:Modulation of biochemical parameters by Hemidesmus indicus in cumene hydroperoxide-induced murine skin: possible role in protection against free radicals-induced cutaneous oxidative stress and tumor promotion. 1257