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)

Pretreatment of porcine aortic endothelial cells with high D-glucose results in enhanced endothelium-derived relaxing factor (EDRF) formation (39%) due to increased endothelial Ca2+ release (57%) and Ca2+ entry (97%) to bradykinin. This study was designed to investigate the intracellular mechanisms by which high D-glucose affects endothelial Ca2+/EDRF response. The aldose-reductase inhibitors, sorbinil and zopolrestat, failed to diminish high D-glucose-mediated alterations in Ca2+/EDRF response, suggesting that aldose-reductase does not contribute to high D-glucose-initiated changes in Ca2+/EDRF signaling. Pretreatment of cells with the nonmetabolizing D-glucose analog, 3-O-methylglucopyranose (3-OMG), mimicked the effect of high D-glucose on Ca2+ release (41%) and Ca2+ entry (114%) to bradykinin, associated with elevated EDRF formation (26%). High D-glucose and 3-OMG increased superoxide anion (O2-) formation (133 and 293%, respectively), which was insensitive to inhibitors of cyclooxygenase (5,8,11,14-eicosatetraynoic acid [ETYA], indomethacin), lipoxygenase (ETYA, gossypol, nordihydroguaiaretic acid [NDGA]), cytochrome P450 (NDGA, econazole, miconazole), and nitric oxide (NO) synthase (L-omega N-nitroarginine), while it was diminished by desferal, a metal chelator. The gamma-glutamyl-cysteine-synthase inhibitor, buthioninesulfoximine (BSO), also increased formation of O2- by 365% and mimicked the effect of high D-glucose on Ca2+/EDRF signaling. The effects of high D-glucose, 3-OMG, and BSO were abolished by co-incubation with superoxide dismutase. Like high D-glucose, pretreatment with the O2(-)-generating system, xanthine oxidase/hypoxanthine, elevated bradykinin-stimulated Ca2+ release (+10%), Ca2+ entry (+75%), and EDRF (+73%). We suggest that prolonged exposure to pathologically high D-glucose concentration results in enhanced formation of O2-, possibly due to metal-mediated oxidation of D-glucose within the cells. This overshoot of O2- enhances agonist-stimulated Ca2+/EDRF signaling via a yet unknown mechanism.
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PMID:High D-glucose-induced changes in endothelial Ca2+/EDRF signaling are due to generation of superoxide anions. 882 76

We previously reported that the topical application of ascorbic acid 2-O-alpha-glucoside (AA-2G) suppressed the cutaneous inflammation by ultraviolet irradiation in human and guinea pigs (Miyai et al., Nishinihon J. Dermatol., 58, 439-443 (1996)). In this paper, the effect of AA-2G on the lethal damage induced by ultraviolet B (UVB) was studied using a human keratinocyte cell line, SCC, established from squamous cell carcinoma. The photoprotective effect of AA-2G on cytotoxicity of UVB in SCC cells was dose dependent (0.125-1 mM) and more effective than that of ascorbic acid (AsA) at 1 mM. This protection was completely abolished in the presence of an alpha-glucosidase inhibitor, castanospermine, indicating that release of AsA from this derivative was essential for reduction of the actinic injury. AA-2G significantly suppressed cytotoxicities of hydrogen peroxide and superoxide anion produced by xanthine and xanthine oxidase. AA-2G exhibited a preventive effect against the cytotoxicity produced by tert-butylhydroperoxide, an inducer of lipid peroxidation, in the presence of alpha-tocopherol, but not in the absence of alpha-tocopherol. Cytotoxicity of UVB was also effectively reduced by the combination of AA-2G and alpha-tocopherol. In addition, AA-2G reduced UVB-promoted formation of lipid peroxide and accumulation of lipofuscin, which is known to be a complex of cellular proteins and metabolites of lipid peroxide. These data suggest that AA-2G prevents the acute inflammation induced by UVB irradiation partly through scavenging reactive oxygen species and potentiating the antioxidative activity of alpha-tocopherol.
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PMID:Ascorbic acid 2-O-alpha-glucoside-induced redox modulation in human keratinocyte cell line, SCC: mechanisms of photoprotective effect against ultraviolet light B. 921 80

The antioxidant activities of isoorientin-6"-O-glucoside were studied using various models. Isoorientin-6"-O-glucoside was more potent than Trolox, probucol and butylated hydroxytoluene (BHT) in reducing the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). It also scavenged superoxide anion, peroxyl and hydroxyl radicals that were generated by xanthine/xanthine oxidase, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and Fe3+-ascorbate-EDTA-H2O2 system, respectively. The IC50 value, stoichiometry factor and second-order rate constant were 9.0+/-0.8 microM, 1.8+/-0.1 and 2.6 X 10(10) M(-1) s(-1) for superoxide generation, peroxyl and hydroxyl radicals. However, isoorientin-6"-O-glucoside did not inhibit xanthine oxidase activity or scavenge hydrogen peroxide (H2O2), carbon radical or 2,2'-azobis(2,4-dimethyl-valeronitrile) (AMVN)-derived peroxyl radical in hexane. Isoorientin-6"-O-glucoside inhibited Cu2+-induced oxidation of human low-density lipoprotein (LDL) as measured by fluorescence intensity, thiobarbituric acid-reactive substance formation and electrophoretic mobility. Since isoorientin-6"-O-glucoside did not possess pro-oxidant activity, it may be an effective water-soluble antioxidant that can prevent LDL against oxidation.
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PMID:Isoorientin-6"-O-glucoside, a water-soluble antioxidant isolated from Gentiana arisanensis. 946 Dec 49

The effects of acute hyperglycemia on endothelial Ca2+ signaling, formation of endothelium-derived relaxing factor (EDRF) and bioactivity of EDRF were investigated. Hyperglycemia increased 2,5-tert-butyl-1,4-hydrochinone (BHQ)-initiated Ca2+ signaling and EDRF formation in a concentration-dependent manner. The effect of elevated D-glucose on Ca2+/EDRF response could be diminished by co-incubation with the antioxidants vitamin E, probucol, GSH, vitamin C and superoxide dismutase. Convincingly, hyperglycemic conditions yielded an increase in superoxide anion release from endothelial cells and the superoxide anion-generating mixture xanthine oxidase/hypoxanthine mimicked the effect of hyperglycemia on Ca2+/EDRF signaling. Besides an enhanced formation of the vasodilatatory NO compound EDRF, hyperglycemia enhanced NO degradation by endothelial cells and, thus, reduced bioactivity of EDRF. We suggest that vasoactivity during acute hyperglycemia depends on the superoxide anion scavenging properties of the vascular wall. In acute hyperglycemia and early stages of diabetes, radical scavenging capacity may be suitable to protect NO degradation, resulting in an enhanced vasodilation. In contrast, decreased free radical scavenging properties of the vasculature in prolonged hyperglycemia and in later stages of diabetes might promote NO degradation by an overshoot of superoxide anions, resulting in an attenuation of endothelium-dependent vasodilation.
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PMID:Role of superoxide anions in changes of endothelial vasoactive response during acute hyperglycemia. 949 99

The methanolic extracts from five kinds of rhubarb were found to show scavenging activity for DPPH radical and .O2-. Two new anthraquinone glucosides were isolated from the rhizome of Rheum undulatum L. together with two anthraquinone glucosides, a naphthalene glucoside, and 10 stilbenes. In the screening test for radical scavenging activity of rhubarb constituents, stilbenes and a naphthalene glucoside showed activity, but anthraquinones and sennosides did not. In addition, most stilbenes inhibited lipid peroxidation of erythrocyte membrane by tert-butyl hydroperoxide. Detailed examination of the scavenging effect on various related compounds suggested the following structural requirements; 1) phenolic hydroxyl groups are essential to show the activity; 2) galloyl moiety enhances the activity; 3) glucoside moiety reduces the activity; 4) dihydrostilbene derivatives maintain the scavenging activity for the DPPH radical, but they show weak activity for .O2-. In addition, several stilbenes with both the 3-hydroxyl and 4'-methoxyl groups inhibited xanthine oxidase.
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PMID:Antioxidant constituents from rhubarb: structural requirements of stilbenes for the activity and structures of two new anthraquinone glucosides. 1119 44

Bridelia ferruginea Benth. (Euphorbiaceae) is a subtropical medicinal plant widely used in traditional African medicine against various diseases, including rheumatic pains. Seven of its constituents (3-O-methylquercetin (1), 3,7,3',4'-tetra-O-methylquercetin (rutisin, 2), myricetin (3), 3',4',5'-tri-O-methylmyricetin (ferrugin, 4), 3,3',4',5'-tetra-O-methylmyricetin (5), quercetin 3-O-glucoside (6), and a biflavanol gallocatechin-[4'-O-7]-epigallocatechin (7)) have been evaluated in-vitro in the xanthine-xanthine oxidase enzymatic system for inhibition of xanthine oxidase and radical scavenging activity. Results indicated that compounds 1, 3, 4 and 6 exhibited, at different levels, xanthine oxidase inhibiting and superoxide scavenging activity at micromolar concentrations, whereas compound 7 showed scavenging activity only. Compounds 2 and 5 were inactive in both cases. Study of the structure-activity relationship demonstrated that for flavonoids the xanthine oxidase inhibitory activity was reduced by methylation of the hydroxyl functionality at C-3 and in rings A and B. These results may partly explain and support the use of B. ferruginea stem bark for the treatment of rheumatic pains in traditional medicine.
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PMID:Radical scavenging and xanthine oxidase inhibitory activity of phenolic compounds from Bridelia ferruginea stem bark. 1137 Jul 16

Surgical operations often induce acute hyperglycemia, which is known to affect endothelial functions. In this study, we examined the effects of propofol, a commonly used general anaesthetic, on bovine aortic endothelial cell (BAEC) dysfunction induced by glucose overload. 2 D-glucose overload (23 mM) induced an accumulation of superoxide anion (O2-), assessed by MCLA chemiluminescence, to a similar extent as that generated by 233 microU ml(-1) xanthine oxidase (XO) and 100 micro M xanthine. Propofol inhibited this accumulation with an IC50 of 0.21 micro M, whereas much higher concentrations of propofol were required to scavenge O2- generated by 250 microU ml(-1) XO and 100 microM xanthine (IC50: 13.5 micro M). 3 D-glucose overload attenuated ATP-induced NO production which was detected using diaminofluorescence-2 (DAF-2). The inhibition was reversed by propofol with an EC50 of 0.60 microM. In contrast, inhibitions caused by xanthine/XO were not altered by propofol (1 microM). 4 D-glucose overload suppressed ATP-induced Ca2+ oscillations and capacitative Ca2+ entry (CCE), which were both restored by superoxide dismutase, indicating that O2- was responsible. Propofol restored these attenuated Ca2+ oscillations and CCE with EC50 of 0.31 and 1.0 microM, respectively. 5 D-glucose overload (23 mM) increased the intracellular glucose concentration 4 fold, compared with cells exposed to 5.75 mM glucose, and 1 micro M propofol reduced this increase to 2.8 fold. 6 We conclude from these results that anaesthetic concentrations of propofol prevent the impairment of Ca2+-dependent NO production in BAEC induced by glucose overload. This effect is mainly due to the reduction of O2- accumulation, and involves, at least in part, the inhibition of cellular glucose uptake.
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PMID:Propofol prevents endothelial dysfunction induced by glucose overload. 1238 82

Two new myricetin glycosides, myricetin 7-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside (1) and myricetin 7-O-alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside (2), together with the known compounds quercetin 3-O-beta-D-glucopyranoside (3), quercetin 3-O-alpha-L-rhamnopyranoside (4), quercetin 3-O-beta-D-galactopyranoside (5), methyl gallate (6), isovanillin (7), 4-hydroxymethylbenzoate (8), 3,4-dihydroxymethylbenzoate (9), and caffeoyl aldehyde (10) were isolated from the leaves of Tachigalia paniculata. The structures of these compounds were determined by spectroscopic methods. Their antioxidant activity was determined by measuring free-radical scavenging effects using three different assays, namely, the Trolox Equivalent Antioxidant Capacity (TEAC) assay, the coupled oxidation of beta-carotene and linoleic acid (autoxidation assay), and the inhibition of xanthine oxidase activity. Compounds 1, 2, and 6 showed activity in the TEAC test, compounds 5-7 and 10 were moderately active in the autoxidation assay, while compounds 1 and 2 were the most potent of the isolates in the xanthine oxidase test.
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PMID:Antioxidant and free-radical scavenging activity of constituents of the leaves of Tachigalia paniculata. 1244 71

Chrysoeriol and its glycoside (chrysoeriol-6-O-acetyl-4'-beta-D-glucoside) are two natural flavonoids extracted from the tropical plant Coronopus didymus. The aqueous solutions of both the flavonoids were tested for their ability to inhibit lipid peroxidation induced by gamma-radiation, Fe (III) and Fe (II). In all these assays chrysoeriol showed better protecting effect than the glycoside. The compounds were also found to inhibit enzymatically produced superoxide anion by xanthine/xanthine oxidase system; here the glycoside is more effective than the aglycone. The rate constants for the reaction of the compounds with superoxide anion determined by using stopped-flow spectrometer were found to be nearly same. Chrysoeriol glycoside reacts with DPPH radicals at millimolar concentration, but the aglycone showed no reaction. Using nanosecond pulse radiolysis technique, reactions of these compounds with hydroxyl, azide, haloperoxyl radicals and hydrated electron were studied. The bimolecular rate constants for these reactions and the transient spectra of the one-electron oxidized species indicated that the site of oxidation for the two compounds is different. Reaction of hydrated electron with the two compounds was carried out at pH 7, where similar reactivity was observed with both the compounds. Based on all these studies it is concluded that chrysoeriol exhibits potent antioxidant activity. O-glycosylation of chrysoeriol decreases its ability to inhibit lipid peroxidation and reaction with peroxyl radicals. However the glycoside is a more efficient scavenger of DPPH radicals and a better inhibitor of xanthine/xanthine oxidase than the aglycone.
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PMID:Effect of O-glycosilation on the antioxidant activity and free radical reactions of a plant flavonoid, chrysoeriol. 1278 41

The caffeoyl conjugates of prenylhydroquinone glucoside and of quinic acid, either in the carboxyl-free or carboxymethyl forms, isolated from Phagnalon rupestre (Asteraceae), showed inhibitory activity on lipid peroxidation induced by Fe 2+/ascorbate and by CCl4/NADPH in rat liver microsomes, with IC50 values ranging from 3 to 11 microM. After having demonstrated their effect on the xanthine oxidase-regulated superoxide production, the active compounds were tested for the direct inhibition of this enzyme. Methylated dicaffeoylquinic conjugates competitively inhibited the enzyme and the highest potency was obtained for the 4,5-diester, with an IC50 value of 3.6 microM, nearly ten times lower than that of the 3,5-analogue. In conclusion, the presence of the caffeoyl moiety is essential for both the antiperoxidative and radical scavenging activities, and the methylation of the quinic carboxyl group enhances the potency on xanthine oxidase inhibitory activity.
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PMID:Inhibition of xanthine oxidase by phenolic conjugates of methylated quinic acid. 1280 18


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