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)

Free radicals in the small intestine were quantified by using an electron spin resonance spectrometer, and the amounts of TBA (thiobarbituric acid) reactants in arterial plasma, portal venous plasma and intestinal tissue were determined at the several stages. The effects of allopurinol, alpha-tocopherol, the simultaneous occlusion of superior mesenteric artery or the porto-jugular venous bypass, with the temporary occlusion of the portal vein, were also investigated. 1) Free radical concentration (mostly, semiquinones of CoQ and/or flavin in mitochondria) decreased with portal vein occlusion but showed a temporary increase at 10 sec after reperfusion. Allopurinol suppressed such temporary increase. 2) TBA reactants increased with the temporary occlusion of the portal vein. TBA reactants decreased during the portal vein occlusion with alpha-tocopherol and during reperfusion with allopurinol. Lipid peroxidation in the small intestine was also diminished by using the methods of simultaneous occlusion of the superior mesenteric artery or the porto-jugular venous bypass. In conclusion, there may be three sources for the generation of superoxide: the xanthine oxidase system, semiquinone radicals and paramagnetic metal irons. They may induce lipid a peroxidation, which accelerates the injury on the small intestine, in acute portal vein occlusion and the following restoration of portal vein flow in rats.
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PMID:[Experimental study of injury on the small intestine in acute portal vein occlusion and the following restoration of portal vein flow in rats--free radicals in the small intestine and lipid peroxidation]. 255 37

Direct and spin-trapping electron spin resonance methods have been used to study the reactivity of semiquinone radicals from the anthracycline antibiotics daunorubicin and adriamycin towards peroxides (hydrogen peroxide, t-butyl hydroperoxide and cumene hydroperoxide). Semiquinone radicals were generated by one-electron reduction of anthracyclines, using xanthine/xanthine oxidase. It is shown that the semiquinones are effective reducing agents for all the peroxides. From spin-trapping experiments it is inferred that the radical product is either OH (from H2O2) or an alkoxyl radical (from the hydroperoxides) which undergoes beta-scission to give the methyl radical. The rate constant for reaction of semiquinone with H2O2 is estimated to be approx. 10(4)-10(5) M-1 X s-1. The reduction does not appear to require catalysis by metal ions.
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PMID:An electron spin resonance study of the reduction of peroxides by anthracycline semiquinones. 632 17

The properties of the semiquinone radical from [3-hydroxy-5-aziridinyl-1-methyl-2-(1H-indole-4,7-indi one)-prop-beta-en-alpha-ol], EO9, have been studied using pulse-radiolysis techniques. The reduction potential of the semiquinone of EO9 at pH7.4, E(EO9/EO9-), is -253 +/- 6 mV and hence this quinone can be readily reduced by one-electron reducing enzymes such as cytochrome P450 reductase and xanthine oxidase. However, the radical is unstable in the presence of oxygen (k = 1.3 +/- 0.15 x 10(8) M-1 s-1). The semiquinone radicals and the hydroquinone are in equilibrium although the formation of the hydroquinone is favoured t physiologically relevant pH. The hydroquinone of EO9 is also unstable in the presence of oxygen and it is predicted that in fully aerated solutions, its half life is 1.5 +/- 0.3 seconds. These results are discussed in view of the selective cytotoxicity of EO9 and its ability to undergo bioreductive activation by one-electron reducing enzymes and DT-diaphorase.
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PMID:The autoxidation of the reduced forms of EO9. 888 32

It is generally accepted that the protection effect of biological tissues by vitamin E is due to its radical scavenging potency in membranes, thereby being transformed to a vitamin E radical. A deficiency of appropriate reductants, which recycle vitamin E radicals back to its antioxidative active form, causes an irreversible degradation of vitamin E leading to tocopheryl quinone (TQ). TQ-like compounds were shown to result from both vitamin E and corresponding hydrophilic analogues of this antioxidant in vitro. In vivo elevated concentrations of tocopheryl quinones were detected after oxidative stress and TQ supplementation as well. Quinones in general are known to be efficient one-electron donors and acceptors. Therefore the question arises whether TQ-like compounds can undergo redox-cycling in conjunction with redox-active enzymes in the heart, thereby producing harmful oxygen radicals, or whether these compounds exhibit antioxidant properties. In order to elucidate this question we focused our interest on the interaction of TQ and a corresponding short-chain homologue (TQ(0)) with xanthine oxidase and heart mitochondria. Furthermore, we tested the influence of TQ on the recovery of isolated perfused rat hearts after ischemia/reperfusion. Our experiments revealed that hydrophilic TQ(0) was univalently reduced by xanthine oxidase (XOD) yielding semiquinone radicals in the absence of oxygen. However, under aerobic conditions TQ(0) enhanced the O(2)(*)(-) radical output of XOD. In the mitochondrial respiratory chain TQ was shown to interact with high potential cytochrome b in the bc(1) complex specifically. In contrast to the system XOD/TQ(0), lipophilic TQ in submitochondrial particles decreased the O(2)(*)(-) radical release during regular respiration possibly due to its interaction with b-cytochromes in the mitochondrial respiratory chain. In isolated rat hearts perfused with liposomes containing lipophilic TQ, it was efficiently accumulated in the heart tissue. When hearts were subjected to conditions of ischemia/reperfusion, infusion of TQ prior to ischemia significantly improved the recovery of hemodynamic parameters. Our results demonstrate that TQ derivatives may induce pro-oxidative and antioxidative effects depending on the distribution of TQ derivatives in the heart tissue and the interacting redox system.
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PMID:Effects of tocopheryl quinone on the heart: model experiments with xanthine oxidase, heart mitochondria, and isolated perfused rat hearts. 1129 29

The radical scavenging activity of oxidized and reduced idebenone (ID-O and ID-H, respectively) against superoxide radical (O2(-*) was studied in vitro using two methods: (1) O2(-*) radicals were generated enzymatically in a hypoxanthine (HPX)-xanthine oxidase (XOD) system and detected by 5,5-dimethyl-1-pyrroline N-oxide (DMPO) spin trapping. Superoxide dismutase and other scavengers added to this system competed to various extents with DMPO to trap O2(-*) radicals, resulting in a decrease of the ESR signal intensity of the DMPO-OOH spin adduct. ID-O reacted about 12-fold quicker (k = 4.48 x 10(4) M(-1)s(-1)) with the O2(-*) radicals than ID-H (k = 3.62 x 10(3) M(-1)s(-1)) x (2) O2(-*) radicals were generated chemically in potassium superoxide (KO2)-crown ether system. Quinoid compounds reacted with the O2(-*)radicals to form semiquinone radicals that could be observed by ESR. At liquid nitrogen temperature (-196 degrees C), the ESR signal of O2(-*) radicals could be observed directly, thus allowing us to estimate the scavenging activity of ID-O and ID-H. These experiments also revealed that ID-O possesses an O2(-*) radical scavenging activity, whereas ID-H reacts quantitatively much slower. Analyzing various quinone compounds, it has been established that the O2(-*) radical scavenging process is a reversible, most probably oscillating, monovalent electron transfer from superoxide to the quinone, and that the O2(-*) radical scavenging activity depends on the redox potential, i.e., on the actual state of oxidation of the quinones.
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PMID:Superoxide radical scavenging activity of idebenone in vitro studied by ESR spin trapping method and direct ESR measurement at liquid nitrogen temperature. 1537 69

To clarify the mechanism of the cardiotoxic action of adriamycin (ADM), the participation of free radicals from ADM in cardiotoxicity was investigated through the protective action of glutathione (GSH) or by using electron spin resonance (ESR). Oxidation of ADM by horseradish peroxidase and H2O2 (HRP-H2O2) was blocked by GSH concentration dependently. Inactivation of creatine kinase (CK) induced during interaction of ADM with HRP-H2O2 was also protected by GSH. Other anthracycline antitumor drugs that have a p-hydroquinone structure in the B ring also inactivated CK, and GSH inhibited the inactivation of CK. These results suggest that ADM was activated through oxidation of the p-hydroquinone in the B ring by HRP-H2O2. Although ESR signals of the oxidative ADM B ring semiquinone were not detected, glutathionyl radicals were formed during the interaction of ADM with HRP-H2O2 in the presence of GSH. ADM may be oxidized to the ADM B ring semiquinone and then reacts with the SH group. However, ESR signals of ADM C ring semiquinone, which was reductively formed by xanthine oxidase (XO) and hypoxanthine (HX) under anaerobic conditions, were not diminished by GSH, but they completely disappeared with ferric ion. These results indicate that oxidative ADM B ring semiquinones oxidized the SH group in CK, but reductive ADM C ring semiquinone radicals may participate in the oxidation of lipids or DNA and not of the SH group.
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PMID:Thiol oxidation induced by oxidative action of adriamycin. 1562 14

Polychlorinated biphenyls (PCBs) can be oxygenated to form very reactive hydroquinone and quinone products. A guiding hypothesis in the PCB research community is that some of the detrimental health effects of some PCBs are a consequence of these oxygenated forms undergoing one-electron oxidation or reduction, generating semiquinone radicals (SQ (*-)). These radicals can enter into a futile redox cycle resulting in the formation of reactive oxygen species, that is, superoxide and hydrogen peroxide. Here, we examine some of the properties and chemistry of these semiquinone free radicals. Using electron paramagnetic resonance (EPR) to detect SQ (*-) formation, we observed that (i) xanthine oxidase can reduce quinone PCBs to the corresponding SQ (*-); (ii) the heme-containing peroxidases (horseradish and lactoperoxidase) can oxidize hydroquinone PCBs to the corresponding SQ (*-); (iii) tyrosinase acting on PCB ortho-hydroquinones leads to the formation of SQ (*-); (iv) mixtures of PCB quinone and hydroquinone form SQ (*-) via a comproportionation reaction; (v) SQ (*-) are formed when hydroquinone-PCBs undergo autoxidation in high pH buffer (approximately >pH 8); and, surprisingly, (vi) quinone-PCBs in high pH buffer can also form SQ (*-); (vii) these observations along with EPR suggest that hydroxide anion can add to the quinone ring; (viii) H 2 O 2 in basic solution reacts rapidly with PCB-quinones; and (ix) at near-neutral pH SOD can catalyze the oxidization of PCB-hydroquinone to quinone, yielding H 2 O 2. However, using 5,5-dimethylpyrroline-1-oxide (DMPO) as a spin-trapping agent, we did not trap superoxide, indicating that generation of superoxide from SQ (*-) is not kinetically favorable. These observations demonstrate multiple routes for the formation of SQ (*-) from PCB-quinones and hydroquinones. Our data also point to futile redox cycling as being one mechanism by which oxygenated PCBs can lead to the formation of reactive oxygen species, but this is most efficient in the presence of SOD.
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PMID:Semiquinone radicals from oxygenated polychlorinated biphenyls: electron paramagnetic resonance studies. 1854 51

The modification of 5-hydroxyindoleacetic acid (5HIAA) by myeloperoxidase with a xanthine oxidase system was investigated by chromatographic analyses. Two major products were identified as a dimer and quinone (indoleacetate dione) of 5HIAA. The formation of a quinone moiety was also confirmed by chemical trapping with o-phenylenediamine. In the presence of N-acetyl-cysteine (NAC), a quinone-NAC adduct was formed. When glyceraldehyde 3-phosphate dehydrogenase was exposed to the myeloperoxidase system with 5HIAA, quinone adducts were formed on the protein molecule. A monoclonal antibody was prepared using a quinone-modified protein as an immunogen to immunochemically detect the quinone on a protein. The established antibody recognized the quinone-NAC adduct, quinone-modified poly-L-lysine, and quinone-modified low-density lipoprotein. Quinone-modified proteins in human atherosclerotic lesions were immunohistochemically observed using the established antibody to the quinone and also a monoclonal antibody to tryptamine dione-modified protein, suggesting an occurrence of in vivo oxidation of serotonin and 5HIAA, accompanied by covalent adduction to biomolecules.
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PMID:A novel quinone derived from 5-hydroxyindoleacetic acid reacts with protein: Possible participation of oxidation of serotonin and its metabolite in the development of atherosclerosis. 2785 48

Superoxide (O2.- ) generation in biological systems is achieved through some of the most complex enzymatic systems. Of these, only xanthine/xanthine oxidase has been used for in vitro biochemical studies. However, it suffers from limitations such as a lack of suitable heterologous expression system for xanthine oxidase and the irreversible consumption and low solubility of xanthine under physiological conditions. Herein, we report a redox-based, enzyme-catalyzed system, in which autoxidation of hydroquinone to quinone via semiquinone results in superoxide generation. Quinone is reduced back to hydroquinone by using the NfsB (oxygen-insensitive nitroreductase) enzyme of Escherichia coli strain K-12 and nicotinamide adenine dinucleotide phosphate hydride (NADPH; which is regenerated by using the glucose/glucose dehydrogenase system). This new system relies on quinones that can be recycled and have superior water solubility, as well as enzymes that are heterologously expressed. By using a variety of quinones and reaction conditions, along with a comparison of real-time fluorescence, menadione has been identified as the optimal substrate for superoxide generation. The new redox-based system presents a viable alternative for studying the biochemistry of superoxide under different physiological and pathological conditions.
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PMID:A Redox-Based Superoxide Generation System Using Quinone/Quinone Reductase. 2979 Jun 50