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)

Superoxide scavenging activities (SSA) of newly synthesized spin-labeled nitrosourea and triazene derivatives, and their precursor nitroxides were investigated by the ESR/spin-trapping method using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and hypoxanthine/xanthine oxidase as the superoxide-generating system. The spin-labeled nitrosoureas, triazenes and their precursor nitroxides exhibited excellent SSA, whereas clinically used nitrosourea and triazene, which do not contain the nitroxide moiety, did not show any SSA. Furthermore, it was deduced that these nitroxides scavenge superoxide by redox cycling between nitroxide and corresponding hydroxylamine.
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PMID:Superoxide scavenging activity of spin-labeled nitrosourea and triazene derivatives. 798 88

The formation of carbon centered free radicals, identified as methylcarbonyl species, was observed using ESR spectroscopy and the spin trapping agent 4-pyridyl-1-oxide-N-t-butyl nitrone (4-POBN) during the oxidation of acetaldehyde by xanthine oxidase. The reaction was dependent upon the presence of OH. radicals and was inhibited by the addition of superoxide dismutase, catalase or OH. radical scavengers. The generation of methylcarbonyl radicals was associated with a doubling of stable acetaldehyde adducts with serum albumin, and 4-POBN or superoxide dismutase and catalase, completely blocked this effect. Thus, methylcarbonyl radicals contributed to acetaldehyde-mediated protein alkylation which is involved in causing toxic as well as immunological reactions ascribed to acetaldehyde.
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PMID:Free radical activation of acetaldehyde and its role in protein alkylation. 802 86

Microsomes and reconstituted systems containing cytochrome P450 can oxidize glycerol to formaldehyde in a reaction catalyzed by an oxidant produced from the interaction of nonheme iron with H2O2. To evaluate the mechanism for this oxidation, the generation of glycerol radicals by various systems was compared to rates of formaldehyde production from glycerol. Photolysis of H2O2, oxidation of xanthine by xanthine oxidase in the presence of iron catalysts, or NADPH-dependent microsomal electron transfer in the presence of ferric-EDTA produced hydroxyl radicals. In the presence of glycerol these reaction systems produced DMPO-glycerol radical adducts which were detected by ESR spectroscopy. Despite the production of .OH and glycerol spin-trapped adducts by these reaction systems, very low amounts or nondetectable amounts of formaldehyde were produced from the glycerol. However, significant amounts of formaldehyde were observed when microsomes were incubated in the presence of ferric ammonium sulfate or ferric-ATP, although .OH production was lower with these iron catalysts than with ferric-EDTA. These results fail to support correlation between .OH production and oxidation of glycerol to formaldehyde. Under conditions in which glycerol was oxidized to formaldehyde, no glycerol radical species could be observed with DMPO as the spin-trapping agent. These results suggest the oxidant (not .OH) derived from the interaction of H2O2 with iron apparently cleaves glycerol to formaldehyde without the formation of a radical intermediate. Alternatively, the radical intermediate may be produced at a too low concentration to be detected or the radical intermediate may not be formed as a free species and therefore cannot be spin-trapped.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxidation of glycerol to formaldehyde by microsomes: are glycerol radicals produced in the reaction pathway? 806 25

We previously isolated the strain Z-54 (Serratia marcescens O5:H1) which produces a reddish-violet pigment. The structure of this pigment was confirmed to be that of a peptide complex containing Fe2+ and L-2(2-pyridyl)-1-pyrroline-5-carboxylic acid (pyrimine), as a chromophore. We measured the superoxide dismutase mimetic activities for the pyrimine-metal complexes by xanthine oxidase/nitroblue tetrazolium and cytochrome c methods and found that the pyrimine-Cu2+ (2:1) complex shows the highest activity yet reported (IC50 = 0.11 microM) among the complexes tested. Pyrimine-Cu+, -Fe2+ and -Mn2+ complexes also gave relatively high SOD mimetic activities. ESR spectra observed for pyrimine-Cu2+ (4:1) showed the structure of the Cu(2+)-complex to be tetrahedral and coordinated with four nitrogen atoms. These results support the idea that the pyrimine-metal complexes might be potent SOD mimics.
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PMID:Superoxide dismutase mimetic activities of metal complexes of L-2(2-pyridyl)-1-pyrroline-5-carboxylic acid (pyrimine). 826 87

MPP+ is redox active in the presence of cytochrome P450 reductase and induces the formation of O2.- and HO(.). In this study, we report the redox cycling capability of MPP+ with additional enzymes and with UV photolysis detected through ESR techniques. The treatment of MPP+ with UV light resulted in the production of HO. trapped as a spin adduct. Two of the enzymes examined in this study, xanthine oxidase and aldehyde dehydrogenase, produced O2.- in the presence of substrate. However, when MPP+ was added to the incubations, the radical trapped by DMPO was HO(.). This indicates that MPP+ redox cycles in the presence of these two enzymes or UV light, which produces HO.. Our data also suggest that MPP+ is reduced by lipoamide dehydrogenase. MPP+ stimulated the oxidation of reduced nicotinamide adenine dinucleotide (NADH) by the enzyme at concentrations between 2 mM and 8 mM of MPP+. Higher concentrations of MPP+ inhibited lipoamide dehydrogenase. MPP+ appears to be redox active with a number of redox enzymes. The mechanism involved may be hydride transfer from the enzymes to MPP+, rather than a direct single-electron reduction.
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PMID:Redox cycling of MPP+: evidence for a new mechanism involving hydride transfer with xanthine oxidase, aldehyde dehydrogenase, and lipoamide dehydrogenase. 839 42

Sodium 5,6-benzylidene ascorbate (SBA) is a conjugate of ascorbic acid (Asc) with benzyaldehyde. It has been found that the antioxidant activity of SBA is more stable and has a longer lifetime in living cells and organs than Asc. In this study, we investigated the effect of SBA on the induction of melanin in cultured melanoma (B-16) cells irradiated by UV-A. Melanin content of B-16 cells was significantly increased by UV-A irradiation. The induction was abolished by mannitol and particularly by superoxide dismutase, suggesting the involvement of O2- in the biosynthesis of melanin in cultured melanoma cells. This was theorized by the fact that the induction was also observed in B-16 cells treated with superoxide anion radicals chemically generated in the hypoxanthine/xanthine oxidase-reaction system, instead of UV-A irradiation. The induction of melanin caused by UV-A irradiation was suppressed by SBA in a dose-dependent manner. To elucidate the mechanism of this suppressive effect, the scavenging activity against O2-, and the inhibitory effect of SBA on tyrosinase activity were examined. ESR spectrometric analysis showed that SBA strongly scavenged O2-, and the presence of SBA in the medium remarkably inhibited the tyrosinase activity in cultured B-16 melanoma cells. It can be concluded that SBA effectively inhibits the melanin biosynthesis in B-16 melanoma cells induced by reactive oxygen species (ROS) generated by UV-A irradiation via tyrosinase.
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PMID:Inhibitory effect of sodium 5,6-benzylidene ascorbate (SBA) on the elevation of melanin biosynthesis induced by ultraviolet-A (UV-A) light in cultured B-16 melanoma cells. 853 99

The interaction of NO and O2- free radicals generated from PMA (phorbol myristate acetate)-stimulated PMN (polymorphonuclear leukocytes) was studied by a nitroxide spin trap, DMPO (5,5-dimethyl-1-pyrroline-1-oxide). It was found that addition of L-arginine to the system would significantly decrease the trapped O2- by DMPO and addition of NG-monomethyl-arginine (NGMA) would significantly increase the trapped O2- by DMPO. It was proved that the formation of ONOO- by the reaction of NO and O2- was the main reason for the decrease of trapped O2- in the experiment with xanthine/xanthine oxidase and irradiation of riboflavin systems. The yield of NO during this process was calculated. The generation dynamic of NO was studied by a luminol-dependent chemiluminescence technique and it was found that after stimulation of PMN by PMA, there would be an immediate, significant chemiluminescence, which came mainly from the active oxygen free radicals generated by PMN. If L-arginine was added to this system, the chemiluminescence would increase about 100-fold, but NGMA inhibited the increase of the chemiluminescence. Ten minutes after addition of L-arginine, this increase did not change, the chemiluminescence peak decreased gradually, but the half life increased. The ESR and chemiluminescence properties of NO and ONOO- synthesized were also studied in model systems.
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PMID:Studies on nitric oxide free radicals generated from polymorphonuclear leukocytes (PMN) stimulated by phorbol myristate acetate (PMA). 868 50

The antioxidant properties of 24 hydroxy-flavones were evaluated. Results show that 2',3',4'-OH substitution on the B ring plays a crucial role in radical scavenger activity in the DPPH assay and in the inhibitory effect on pereoxydation of tissue lipids in the MDA test. The formation of stable radicals for this type of compounds has been studied by ESR. In addition, it has been found that 7-hydroxy-flavones are potent competitive inhibitors of xanthine oxidase. It is proposed that the C-7 OH of flavones may take the place of the C-2 or C-6 OH of xanthine in the active site of the enzyme. A C-4' OH or C-4' OMe substitution on the 7-hydroxy flavones is not favourable to a fit in the active site. The 2',3',4'-trihydroxy-flavones inhibited XO by another process, which remains to be determined. In summary, this study provides evidence that hydroxy-flavones exhibit interesting antioxidant properties expressed either by the capacity to scavenge free radicals (for 2',3',4'-trihydroxy-flavones) or to competitively inhibit xanthine oxidase (for 7-hydroxy-flavones). These compounds may be drug candidates for treating pathologies related to free radical oxidation.
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PMID:Antioxidant properties of hydroxy-flavones. 890 77

Reactive oxygen metabolites (ROM) have been reported to be important in the pathogenesis of ischemia/ reperfusion-, ethanol-, nonsteroidal antiinflammatory drug-, or Helicobacter pylori-induced gastric mucosal injury. Rebamipide, a novel antiulcer agent, has been reported either to prevent various acute experimental gastric mucosal lesions or to accelerate the healing of chronic gastric ulcers. The underlying mechanism by which rebamipide exerts its cytoprotective effect in the damaged stomach is not fully determined. We investigated the role of rebamipide in protecting against ROM-mediated cell damage in gastric mucosal cells and in inducing cytoprotective proteins. Cells were exposed to ROM enzymatically generated by hypoxanthine-xanthine oxidase. Cytotoxicity was quantified by measuring specific 51Cr release from prelabeled cells. ROM caused dose-dependent increase in cytotoxicity and amount of thiobarbituric acid-reactive substances (TBA-RS). ROM-induced cytotoxicity and TBA-RS were dose-dependently decreased by the addition of rebamipide and/or catalase, but not by superoxide dismutase alone. The effects of rebamipide on electric spin resonance signal were investigated. We found that the DMPO spin adduct ESR signal of hydroxyl radicals (DMPO-OH) was significantly attenuated by rebamipide. Western blot analysis showed that induction of heat-shock protein (HSP70) was significantly increased following rebamipide administration in a dose-dependent manner. Based on these results, it is concluded that rebamipide exerted a protective effect on HX-XO-induced gastric mucosal cell cytotoxicity through one or more of the following mechanism(s): (1) inhibition of lipid peroxidation of the cell membrane; (2) hydroxyl radical scavenging activity; and (3) induction of cellular cytoprotective protein such as HSP70.
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PMID:Role of rebamipide on induction of heat-shock proteins and protection against reactive oxygen metabolite-mediated cell damage in cultured gastric mucosal cells. 901 34

The purpose of this study is to detect the generation of active oxygens in UVB-irradiated murine fibroblasts and to propose new mechanisms. Decreased survival of fibroblasts under UVB irradiation was partially recovered by addition of catalase, DMSO or deferoxamine, suggesting the contribution of several types of active oxygen species. Then we examined the formation of active oxygen species and found that fibroblasts under UVB irradiation generated superoxide anion radicals (.O2-), intracellular H2O2, and hydroxyl radicals as estimated by the ESR-spin trapping method. Addition of thenoyltrifluoroacetone, which is an inhibitor of the mitochondrial respiratory chain, decreased 29% of the intracellular H2O2 levels in UVB-irradiated cells, but allopurinol, which is an inhibitor of xanthine oxidase, had no effect on them. On the basis of these results, we propose a a possible mechanism for damage of murine fibroblasts exposed to UVB in terms of generation of active oxygen species. The mitochondrial respiratory chain reaction stimulated by UVB irradiation enhances the generation of .O2-, which is in turn dismutated to H2O2 and O2 by superoxide dismutase. H2O2 is then converted to hydroxyl radicals, catalyzed by trace elements such as iron, as suggested by Fenton-like reaction. Thus, hydroxyl radicals with higher reaction rate-constants than those of other active oxygen species to biomolecules are indicated to be responsible for the cytotoxicity in cells under UV irradiation.
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PMID:Increased generation of hydrogen peroxide possibly from mitochondrial respiratory chain after UVB irradiation of murine fibroblasts. 913 78


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