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)

The activities of several enzymes involved in reactive oxygen production and detoxification were quantified in murine skin during the ontogeny of chemically induced skin cancer. Relative to solvent-treated controls, the specific activities of epidermal superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) were reduced approximately 45, approximately 60 and approximately 24% respectively, 24 h after the fourth or tenth topical application of 1 microgram of 12-O-tetradecanoylphorbol-13-acetate (TPA) to the dorsal skin of SENCAR mice. The specific activity of epidermal xanthine oxidase (XO) increased approximately 350% during the same period. SOD and CAT specific activities in papillomas and carcinomas generated in an initiation-promotion protocol were approximately 15 and approximately 40% respectively of the activities measured in age-matched, non-treated mice. CAT and SOD activities were also significantly suppressed in the skin adjacent to the papillomas for several weeks following the cessation of TPA promotion, but eventually recovered to the levels measured in age-matched controls. XO specific activities in papillomas and squamous cell carcinomas (SCC) were approximately 85-350% greater than the activities determined in skin adjacent to the tumors. The increases in XO and the decreases in SOD and CAT activities measured in the tumors were independent of continued treatment with TPA, and thus characteristic of the tumor phenotype. GPX activities in papillomas were comparable to normal, untreated skin, but reduced approximately 22-41% in SCC. Collectively, these studies demonstrate that TPA orchestrates changes in the activities of several enzymes involved in reactive oxygen metabolism that are characteristic of the papilloma and SCC phenotype.
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PMID:Assessment of the antioxidant/prooxidant status of murine skin following topical treatment with 12-O-tetradecanoylphorbol-13-acetate and throughout the ontogeny of skin cancer. Part I: Quantitation of superoxide dismutase, catalase, glutathione peroxidase and xanthine oxidase. 174 37

Induction of ornithine decarboxylase (ODC) enzyme activity occurs after exposure of hamster tracheal epithelial (HTE) cells to asbestos and the soluble tumor promoter 12-O-tetradecanoylphorbol-13-acetate. Since active oxygen species are implicated as mediators of asbestos-induced biological responses studies here were designed to examine whether active oxygen species generated by asbestos or oxidants caused increased ODC activity. In confluent HTE cells, significant blockage of chrysotile or crocidolite asbestos-stimulated ODC activity occurred with simultaneous addition of catalase, but not superoxide dismutase, to medium. The addition of xanthine plus xanthine oxidase caused a dose-dependent increase in ODC activity, which was inhibited significantly after addition of catalase or mannitol, indicating that H2O2 was the principal oxidant produced in that reaction. Addition of phenazine methosulfate, a redox reagent used to generate superoxide, resulted in significant elevation of ODC, which was inhibited by addition of superoxide dismutase but not catalase. Hydrogen peroxide added to culture medium also caused a potent increase in ODC activity inhabitable by catalase. Hypochlorous acid caused increases in ODC activity, although the magnitude of this response was less than that observed with other oxidants. Therefore, although all active oxygen species examined triggered ODC, less reduced species (O2- and H2O2) were more proficient than OH or a halogenated oxidant. All oxidants, except HOCl, caused a significant increase in [3H] thymidine incorporation at 24 or 48 h after their addition to HTE cells. In comparative studies, exposure of HTE cells to either asbestos or xanthine plus xanthine oxide increased the level of ODC mRNAs proportionate to oxidant concentration and the extent of enzyme induction. Thus, data indicate that H2O2 plays a major role in asbestos-stimulated ODC induction and proliferation of epithelial cells of the respiratory tract by altering the regulation of a gene critical to proliferation.
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PMID:Role of asbestos and active oxygen species in activation and expression of ornithine decarboxylase in hamster tracheal epithelial cells. 184 7

The results presented herein demonstrate that the non-steroidal anti-inflammatory drug (NSAID) indomethacin is a strong inhibitor of the formation of HOCl by murine neutrophils (50% inhibition at 15 microM). Addition of 40 microM indomethacin to activated neutrophils caused 80% inhibition of HOCl formation throughout a 60-min time course while slightly increasing the levels of O2- and H2O2 produced. Comparable degrees of inhibition were achieved when the cells were stimulated with phorbol myristate acetate and with opsonized zymosan. Control experiments indicated that the drug did not act by scavenging HOCl. Direct inhibition of the chlorinating activity of myeloperoxidase (MPO) was confirmed using highly purified human enzyme in vitro. Kinetic analysis of the mechanism of inhibition showed that the drug was competitive with respect to Cl- and uncompetitive with respect to H2O2, showing a Ki of 37 microM. In contrast to its inhibition of the oxidation of Cl- by MPO, indomethacin had no effect on the peroxidative activity of the enzyme (oxidation of 4-aminoantipyrene), nor did it inhibit the activity of several other enzymes involved in H2O2 metabolism, including horseradish peroxidase, catalase, xanthine oxidase, and superoxide dismutase. Finally, it was found that inhibition of HOCl formation was a shared but non-uniform property of many NSAIDs; piroxicam, salicylate, sulindac, ibuprofen, and aspirin were all inhibitory but at widely different concentrations [Ki(app) values of 0.05, 0.18, 0.18, greater than 1, and 3 mM respectively] that correlated only partially with their therapeutic dose range. The results encourage further studies into the possibility that inhibition of HOCl formation may constitute an additional mechanism whereby NSAIDs reduce tissue destruction in chronically inflamed tissues.
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PMID:Inhibition of the myeloperoxidase-H2O2-Cl- system of neutrophils by indomethacin and other non-steroidal anti-inflammatory drugs. 184 81

To determine the role of xanthine oxidase in the microvascular dysfunction produced by activated granulocytes, we examined the effect of xanthine oxidase depletion or inhibition on the increase in microvascular permeability produced by infusion of the neutrophil activator phorbol myristate acetate (PMA). Changes in vascular permeability were assessed by measurement of the solvent drag reflection coefficient for total plasma proteins (sigma) in rat hindquarters subjected to PMA infusion in xanthine oxidase-replete and -depleted animals, in animals pretreated with the xanthine oxidase inhibitor oxypurinol, and in animals depleted of circulating neutrophils by pretreatment with antineutrophil serum (ANS). Xanthine oxidase depletion was accomplished by administration of a tungsten-supplemented (0.7 g/kg diet) molybdenum-deficient diet. In animals fed the tungsten diet, muscle total xanthine dehydrogenase plus xanthine oxidase activity was decreased to less than 10% of control values. Estimates of sigma averaged 0.84 +/- 0.04 in control hindquarters, whereas PMA infusion was associated with a marked increase in microvascular permeability (decrease in sigma to 0.68 +/- 0.03). PMA infusion also caused an increase in the amount of the radical-producing oxidase form of xanthine oxidase (from 3.9 +/- 0.05 to 5.6 +/- 0.4 mU/g wet wt). ANS pretreatment attenuated this permeability increase (sigma = 0.77 +/- 0.04) and diminished the rise in xanthine oxidase activity (4.9 +/- 0.5 mU/g wet wt). Xanthine oxidase depletion with the tungsten diet or pretreatment with oxypurinol had no effect on this neutrophil-mediated microvascular injury (sigma = 0.69 +/- 0.06 and 0.67 +/- 0.03, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activated neutrophils increase microvascular permeability in skeletal muscle: role of xanthine oxidase. 186 81

Airway inflammation is often accompanied by accumulation of polymorphonuclear leukocytes (PMN) as well as epithelial sloughing. To determine whether PMN contribute to epithelial damage in inflammatory states, we examined the interaction of PMN and tracheal epithelial cells in culture. Ferret tracheal epithelial (FTE) cells were grown in primary culture on collagen-coated multiwell dishes. Confluent monolayers were loaded with [51Cr]O4 and exposed to resting and activated neutrophils. There was no significant increase in cell death as assessed by [51Cr]O4 release over 8 h of exposure, at effector (PMN)-to-target cell (epithelial cell) ratios up to 90:1, whether PMN were activated by maximal activating concentrations of phorbol myristate acetate or formylmethionylleucylphenylalanine with or without cytochalasin B. This result was confirmed by using a [3H]leucine release assay as well as by uptake of a supravital dye. However, exposure of FTE cells to activated PMN for 4 h resulted in separation of adjacent cells and formation of gaps in the monolayer, without significant detachment of epithelial cells from the dish. Gap formation was prevented by alpha 1-antitrypsin, N-methoxysuccinyl-Ala-Ala-Pro-Val-chloromethylketone, or 10% serum, was mimicked by PMN elastase (24 micrograms/ml), but not by hydrogen peroxide in concentrations up to 10 mM, or superoxide generated by xanthine/xanthine oxidase, and was reversible within 24 h of removal of elastase and exposure to fresh medium. We conclude that activated PMN do not kill FTE cells in culture. However, disruption of the epithelial cell monolayer probably by a proteolytic mechanism can result from exposure to activated PMN and may allow alteration of the epithelial barrier during airway inflammation.
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PMID:Ferret tracheal epithelial cells grown in vitro are resistant to lethal injury by activated neutrophils. 189 42

The authors studied the content of xanthine oxidase and the activity of the reparative process in the border of an acetate ulcer after Okabe in 48 rabbits before and during treatment by HBO, cytochrome c, and thymalin. In treatment by HBO and cytochrome c the activity of the enzyme was normalized rapidly, which coincided with cicatrization of the ulcer. In treatment with thymalin xanthinE oxidase activity was not normalized in this period and mucosal inflammation persisted in the zone of ulcer cicatrization.
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PMID:[Morphohistochemical appraisal of the efficacy of hyperbaric oxygenation, cytochrome c, and thymalin in the management of experimental gastric ulcers]. 196 88

It was reported that Schisanhenol (Sal) isolated from Schisandrae Rubriflora inhibited lipid peroxidation induced by ferrous-cysteine and NADPH-ascorbic acid. In this studies the oxygen radical scavenging activity of Sal was detected by electron spin resonance (ESR) and spin trapping. Sal was shown to scavenge oxygen radicals produced by human neutrophils (Neu) stimulated by tetradecanoylphorbol acetate (TDPA). But no effect of Sal was seen on oxygen consumption measured by spin label oximetry in Neu during respiratory burst. In Fenton reaction system, the inhibitory rate of hydroxyl radical by Sal was 34.4%. In xanthine-xanthine oxidase and uv-irradiation of riboflavin systems, Sal scavenged superoxide anion radical by 26.1% and 21.9%, respectively. In all these systems the action of Sal was more potent than that of vitamin E. It may be concluded that Sal possesses a free radical-scavenging activity.
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PMID:Detection of free radical scavenging activity of schisanhenol by electron spin resonance. 196 55

Reductive metabolism of the hair dye constituent, nitro-p-phenylenediamine (2-nitro-1,4-diaminobenzene, NPDA), and its acetylated metabolite, NPDA N4-acetate, was investigated with rat liver subcellular fractions, microsomes and cytosol. Under anaerobic conditions, these compounds were reduced to their corresponding amines by these fractions. The microsomal nitro-reducing activity was retarded completely by air and strongly by carbon monoxide. Reduced nicotinamide adenine dinucleotide phosphate (NADPH) functioned more effectively than reduced nicotinamide adenine dinucleotide (NADH) as an electron donor in the microsomal reduction of the nitro compounds, and flavin mononucleotide (FMN) gave rise to a marked enhancement in the microsomal activity, especially when added to an anaerobic incubation mixture containing both NADH and NADPH. The cytosolic nitro-reducing activity was attributed to xanthine oxidase, aldehyde oxidase and other unknown enzyme(s), based on the results of cofactor requirements and inhibition experiments.
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PMID:Reductive metabolism of nitro-p-phenylenediamine by rat liver. 204 1

Skin tumor promotion induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) was inhibited by a concurrent and topical application of phthalic acid mono-n-butyl ester cupric salt (PAMBCu) in CD-1 mice initiated with 7,12-dimethylbenz[a]anthracene. PAMBCu inhibited TPA-caused epidermal ornithine decarboxylase (ODC) induction and ear edema formation, i.e. skin inflammation. However, neither PAMBCu nor superoxide dismutase (SOD) inhibited TPA-caused ODC induction in primary cultured mouse epidermal cells. 7-Bromomethylbenz[a]anthracene (BrMBA) is known to be a non-TPA type of tumor promoting agent. Epidermal ODC induction and inflammation caused by BrMBA were not inhibited by a concurrent application of PAMBCu. When mice were topically treated twice with PAMBCu, i.e. concurrently with and 7 h after BrMBA treatment, BrMBA-caused ODC induction was markedly suppressed. The same dose regimen of PAMBCu, however, failed to inhibit tumor promotion and inflammation caused by BrMBA. PAMBCu showed SOD-mimetic activity in superoxide generating systems, i.e. xanthine-xanthine oxidase reaction and TPA-stimulated polymorphonuclear leukocytes (PMN). Mono-n-butyl phthalate, which lacks SOD-mimetic activity, failed to inhibit TPA-caused ODC induction and skin inflammation. Therefore, inhibition by PAMBCu of TPA-caused tumor promotion, epidermal ODC induction and inflammation may be attributable to its SOD-mimetic activity. The results also support the contention that a superoxide anion of non-epidermal cell origin, such as PMN and macrophages, plays a role (probably some enhancing role) in in vivo ODC induction and tumor promotion caused by TPA. Failure of PAMBCu to inhibit BrMBA-caused tumor promotion suggests that superoxide anion generation is not involved in the tumor promoting action of this agent and that the anti-tumor promoting action of PAMBCu is dependent on the nature of the tumor promoting agents.
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PMID:Anti-tumor promoting action of phthalic acid mono-n-butyl ester cupric salt, a biomimetic superoxide dismutase. 211 May 12

The ability of captopril and enalaprilat, 2 angiotensin-converting enzyme (ACE) inhibitors, to scavenge superoxide anion radical was examined. With use of a number of superoxide-generating systems, such as xanthine-xanthine oxidase, phorbol myristate acetate-activated neutrophils, auto-oxidizing dihydroxyfumarate, and auto-oxidation of epinephrine to adrenochrome, captopril was seen not to scavenge superoxide directly, because it did not inhibit superoxide-dependent cytochrome c or nitro-blue tetrazolium reduction. Superoxide-dependent cytochrome c reduction was inhibited only when captopril was preincubated with a lower concentration of cytochrome c (22 microM). This effect was due to a decrease in the concentration of cytochrome c, because captopril reduced cytochrome c directly. When this effect was compensated for, no cytochrome c reduction induced by superoxide was observed. Captopril inhibited the auto-oxidation of epinephrine to adrenochrome at pH 10.2 where this auto-oxidation is superoxide-dependent, and at pH 7.8 where it is superoxide-independent and superoxide dismutase insensitive. It appears that captopril, in this respect, acted as a nonspecific antioxidant, probably by reducing an intermediate in the complex oxidation of epinephrine to adrenochrome. Therefore, caution may be used in interpreting the role of captopril in the attenuation of reperfusion-induced myocardial dysfunction and in attributing this effect to the inhibition of free radical mechanism.
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PMID:Captopril and enalaprilat do not scavenge the superoxide anion. 215 92


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