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)

Chemical reduction of mitosenes under aerobic conditions in DMSO showed characteristic ESR signals of the mitosene derived semiquinone free radicals. However, these signals diminished strongly upon addition of water to the reaction mixture, indicating a short lifetime of the mitosene semiquinone free radicals under aqueous conditions. In addition, enzymatic one-electron reduction of these mitosenes with either xanthine oxidase or purified NADPH cytochrome P450 reductase under anaerobic conditions showed no signals of the mitosene semiquinone free radicals. Subsequent cyclic voltammetry measurements demonstrated facilitation of the further one-electron reduction of the mitosene semiquinone free radicals in the presence of water in comparison with non-aqueous conditions. The present results strongly suggest that in the presence of water relatively stable hydroquinones are formed upon reduction of mitosenes. Consequently, the steady state concentrations of mitosene semiquinone free radicals will be lowered substantially in aqueous environment. Thus under physiological conditions, two-electron reduction and formation of the mitosene hydroquinone might be important in processes leading to DNA alkylation by these mitosenes.
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PMID:Reduction of antitumour mitosenes in non-aqueous and aqueous environment. An electron spin resonance and cyclic voltammetry study. 770 82

The quantitation of methanesulfinic acid, the reaction product of dimethylsulfoxide oxidation by the hydroxyl radical, has been reported as a useful tool for the detection of this radical. The present report describes two HPLC methods for determination of methanesulfinate. The first is based on the reversed phase separation and detection of the derivative formed between methanesulfinate and the diazonium salt fast garnet GBC. The second is based on anion exchange HPLC using conductivity detection. In incubations containing xanthine plus xanthine oxidase, the formation of the hydroxyl radical was demonstrated by trapping with DMSO and detection of methanesulfinate. Formation of the sulfinate from DMSO did not occur in the presence of catalase or with the omission of xanthine oxidase. In the absence of xanthine oxidase, methanesulfinate added as an internal standard could be completely recovered. In the presence of of xanthine oxidase, however, the recovery of added methanesulfinate was less than 40%. Using the Fenton reaction to generate these radicals, both methanesulfinate and methanesulfonate were formed in the presence DMSO. In incubations with methanesulfinate, hydroxyl radical generation led to stoichiometric loss of methansulfinate and production of methanesulfonate. Methanesulfinate was only slowly oxidized to methanesulfonate in incubations containing hydrogen peroxide in the absence of iron. The data illustrate that the product of DMSO oxidation by the hydroxyl radical, methanesulfinate, is further oxidized by this radical to methanesulfonate. Determination of methanesulfinate formation from DMSO underestimates the production of the hydroxyl radical.
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PMID:Oxidation of DMSO and methanesulfinic acid by the hydroxyl radical. 774 11

Quin2, a fluorescent calcium probe, has a low affinity for calcium in comparison to its affinities for transition metal ions. Chelation of ferric ion with quin2 strongly enhanced the formation of oxidizing species in the presence of bolus H2O2 as detected with four assays, electron spin resonance with the spin-trap DMPO, the deoxyribose assay, the DMSO assay, and plasmid DNA strand breakage. In comparison, Fe(III)-EDTA reacted with bolus H2O2 only as detected with electron spin resonance and deoxyribose assay, but not as detected with the two latter assays. The addition of reductants, like ascorbate or superoxide generated by hypoxanthine/xanthine oxidase, to Fe(III)-EDTA in the presence of H2O2 produced plasmid DNA strand breakage and strong reactivity in both the DMSO and the deoxyribose assays. Our findings suggest that the main oxidizing species produced in Fenton-type reactions is hydroxyl radical. However, the reaction between Fe(III)-EDTA and bolus H2O2 appears to be exceptional and dominated by a nonhydroxyl radical species.
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PMID:A comparison of four assays detecting oxidizing species. Correlated reactivity of Fe(III)-quin2, but not Fe(III)-EDTA, with hydrogen peroxide. 777 60

The degree of DNA damage by the treatment with various molecular species of active oxygen and its inhibition by pretreatment with different scavengers were evaluated using pUC19 plasmid DNA. DNA damage caused by O2-. generated by xanthine-xanthine oxidase system (X-XOD), .OH by Fenton reactions, and OCl- by NaOCl involved the generation of open circle DNA demonstrating single strand breaks. Catalase (Cat), diethylenetriaminepentaacetic acid (DETAPAC), desferroxiamine (Desferal), dimethyl sulfoxide (DMSO) and ethanol (EtOH) all inhibited 60-80% of DNA damage by the generated O2-.. Superoxide dismutase (SOD) inhibited all DNA damages by O2-.. Cat, DETAPAC and Desferal effectively inhibited DNA break by .OH; complete inhibition of .OH-induced DNA break was achieved by addition of DMSO and EtOH. Desferal and EtOH completely inhibited DNA damage by OCl-. These findings suggested that metal ions are associated with the mechanism of DNA damage by all forms of active oxygen species.
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PMID:DNA damage by various forms of active oxygens and its inhibition by different scavengers using plasmid DNA. 783 95

Antioxidant and antipromotional effects of the soybean isoflavone genistein have been studied in HL-60 cells and the mouse skin tumorigenesis model. Effects of structure-related flavone/isoflavones on hydrogen peroxide (H2O2) production by 12-O-tetradecanoylphorbol-13-acetate (TPA)-activated HL-60 cells and superoxide anion (O2-) generation by xanthine/xanthine oxidase were compared. Of tested isoflavones, genistein is the most potent inhibitor among TPA-induced H2O2 formation by (dimethyl sulfoxide) DMSO-differentiated HL-60 cells, daidzein is second, and apigenin and biochanin A show little effect. In contrast, genistein, apigenin, and prunectin are equally potent in inhibiting O2- generation by xanthine/xanthine oxidase, with daidzein showing a moderate inhibitory effect and biochanin A exhibiting no effect. These results suggest that the antioxidant properties of isoflavones are structurally related and the hydroxy group at Position 4' is crucial in both systems. Dietary administration of 250 ppm genistein for 30 days significantly enhances the activities of antioxidant enzymes in the skin and small intestine of mice. Further studies show that genistein significantly inhibits TPA-induced proto-oncogene expression (c-fos) in mouse skin in a dose-dependent manner. In a two-stage skin carcinogenesis study, low levels of genistein (1 and 5 mumol) significantly prolong tumor latency and decrease tumor multiplicity by approximately 50%. We conclude that genistein's antioxidant properties and antiproliferative effects may be responsible for its anticarcinogenic effect. Its high content in soybeans and relatively high bioavailability favor genistein as a promising candidate for the prevention of human cancers.
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PMID:Antioxidant and antipromotional effects of the soybean isoflavone genistein. 789 86

The objective of this study was to investigate whether quin2, through its metal chelating properties, could affect copper- or iron-driven Fenton reactions. Chelation of ferric ion with quin2 uniformly strongly enhanced the formation of oxidizing species, detected with the DMSO and deoxyribose assays, both by H2O2 and a mixture of superoxide/hydrogen peroxide produced by hypoxanthine/xanthine oxidase. Fe(3+)-EDTA gave the same effects, but lacked reactivity with bolus H2O2 as detected with the DMSO assay. Whereas the formation of oxidizing species with Fe(3+)-EDTA and ferric ions alone were strongly inhibited by superoxide dismutase both in the bolus H2O2 and hypoxanthine/xanthine oxidase systems, such formation in the presence of Fe(3+)-quin2 either did not decrease or decreased only moderately. Fe(3+)-quin2 also strongly enhanced plasmid DNA strand breakage in the presence of H2O2. Our findings suggest that quin2 as chelator of ferric ion may be a more powerful enhancer of oxidant formation than other chelators so far tested. The formation of oxidizing species from copper ions and bolus H2O2 was found to be fundamentally dependent on the choice of buffer system. We could only detect significant amounts of oxidants in both assays in Hepes buffer, but not in the phosphate, cacodylate or unbuffered systems, which all gave low reactivity in the DMSO assay compared to the deoxyribose assay. Quin2 chelation of cupric ion effectively inhibited the formation of oxidants as well as plasmid DNA strand breakage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:New roles for quin2: powerful transition-metal ion chelator that inhibits copper-, but potentiates iron-driven, Fenton-type reactions. 800 13

The abilities of 15 flavonoids as a scavenger of active oxygens (hydroxyl radical and superoxide anion) were studied. Hydroxyl radical (.OH) was generated by the Fenton system, and assayed by the determination of methanesulfonic acid (MSA) formed from the reaction of dimethyl sulfoxide (DMSO) with .OH. (+)-Catechin, (-)-epicatechin, 7,8-dihydroxy flavone, and rutin showed the .OH scavenging effect 100-300 times superior to that of mannitol, a typical .OH scavenger. The other flavonoids showed no .OH scavenging effect at their concentrations up to 50 microM. Baicalein, quercetin, morin, and myricetin unexpectedly increased the .OH production in the Fenton system. The flavonoids tested now, except monohydroxy flavones, were more or less inhibitive to the superoxide anion (O2) generation in the hypoxanthine-xanthine oxidase system. A great part of this inhibitory effect was likely owing to suppression of xanthine oxidase activity by the flavonoids. The flavonoids, which scavenged .OH or O2-, were necessarily antioxidants to the peroxidation of methyl linoleate. However, there was a type of flavonoid such as morin, which have neither .OH nor O2- scavenging effect, but was a strong antioxidant.
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PMID:The correlation between active oxygens scavenging and antioxidative effects of flavonoids. 807 Jun 90

This prospective randomized double blind study examined the influence of free radical scavengers on the healing and recurrence of refractory duodenal ulceration. To this end, allopurinol (50 mg, four times a day) -a hydroxyl radical scavenger and an inhibitor of xanthine oxidase, the enzyme which forms superoxide radicals--and dimethyl sulfoxide (DMSO, 500 mg, four times a day)--a hydroxyl radical scavenger--were administered orally. Three hundred and sixty-three consecutive patients with duodenal ulceration that did not heal despite 3 months of treatment with cimetidine, who were cigarette smokers and social drinkers, were randomized to receive 800 mg cimetidine twice a day alone or with either allopurinol or DMSO. In 315 patients who were evaluable for efficacy analysis, the healing rate at 8 weeks was, for cimetidine alone, 60%; for cimetidine with DMSO, 100%; and for cimetidine with allopurinol, 100%. The healing efficacy of cimetidine was therefore significantly (P < 0.01) heightened by DMSO and allopurinol. The patients whose ulcers healed were instituted on maintenance treatment for 1 year and received 800 mg cimetidine at bedtime alone or with either DMSO or allopurinol. In 218 patients who were evaluable for efficacy analysis, the cumulative relapse rate at 1 year was, for cimetidine alone, 29%; for cimetidine with DMSO, 8%; and for cimetidine with allopurinol, 7% DMSO with cimetidine and allopurinol with cimetidine were, therefore, superior to cimetidine alone (P < 0.01) in preventing ulcer relapse. The results suggest that oxygen-derived free radicals are implicated in the mechanism of refractory duodenal ulceration and that scavenging these radicals stimulates healing and reduces recurrence of the ulceration.
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PMID:Role of free radical scavengers in the management of refractory duodenal ulceration. A new approach. 827 68

Reactive oxygen metabolites have an important role in ischemia-reperfusion injury. One of the sources of reactive oxygen metabolites is xanthine oxidase, which is present in several tissues but is also released into the circulation after ischemia. We studied the effect of several potentially protective compounds on adenine nucleotide depletion induced by extracellular xanthine oxidase and hypoxanthine, in concentrations relevant to human pathophysiology. In umbilical vein endothelial cells prelabeled with 14C-adenine, cellular adenine nucleotides retained 64 +/- 9% of the initial radioactivity over a 4-h incubation with culture medium (controls), whereas in the presence of xanthine oxidase (80 mU/mL) and hypoxanthine (100 microM), only 3 +/- 4% of radioactivity remained in cellular nucleotides, the rest appearing in catabolic products in the medium. Glutathione and 3-aminobenzamide, an inhibitor of poly-ADP-ribose polymerase, partly prevented the nucleotide depletion (adenine nucleotide radioactivity 15 +/- 6% to 33 +/- 13% of total), but scavengers of the hydroxyl radical, dimethylthiourea and DMSO, as well as vitamins E and C, were without effect. Superoxide dismutase prevented the leakage of nucleotides into the culture medium but not intracellular nucleotide catabolism, whereas the latter process was decreased by catalase, consistent with predominant effects of superoxide and hydrogen peroxide at the cell membrane and interior, respectively.
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PMID:Nucleotide depletion due to reactive oxygen metabolites in endothelial cells: effects of antioxidants and 3-aminobenzamide. 828 91

Toward the development of a fluorescence assay in combination with confocal microscopy to image free radicals generated by cells, we synthesized a fluorophore-nitroxide, 5-((2-carboxy)phenyl)-5-hydroxy-1-((2,2,5,5-tetramethyl-1-oxypyrrolid in-3- yl)methyl)-3-phenyl-2-pyrrolin-4-one sodium salt, and tested the applicability of this probe to detect oxygen-centered free radicals. The reaction of the fluorophore-nitroxide with superoxide (10 microM/min) generated either by the reaction of xanthine oxidase on xanthine or by PMA-activated neutrophils in the presence of cysteine (200 microM) resulted in a loss of electron spin resonance (ESR) signal intensity concurrent with an increase in fluorescence emission. The decrease in ESR signal and the augmentation in fluorescence emission were inhibited by the addition of superoxide dismutase. This fluorophore-nitroxide also reacted with methyl radical generated by the reaction of hydroxyl radical with DMSO (0.14 M). In this case a loss in ESR signal intensity concomitant with an increase in fluorescence emission which were inhibited by catalase (300 U/ml), was recorded. These results clearly demonstrated the feasibility of using fluorescence methodology in conjunction with a fluorophore-nitroxide to detect oxygen-centered free radicals in biological systems.
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PMID:A fluorophore-containing nitroxide as a probe to detect superoxide and hydroxyl radical generated by stimulated neutrophils. 839 65


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