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)

1. Endothelial barrier function was assessed by use of an in vitro model in which transfer of trypan blue-labelled albumin was measured across monolayers of bovine aortic endothelial cells grown on polycarbonate membranes. 2. Addition of either hypoxanthine (0.2 mM) or xanthine oxidase (20 mu ml-1) alone during a 90 min incubation did not affect albumin transfer across endothelial cell monolayers, but a combination of both increased transfer. 3. The increase in albumin transfer induced by hypoxanthine and xanthine oxidase was abolished by catalase (3 u ml-1), reduced by allopurinol (4 mM), but unaffected by superoxide dismutase (6000 u ml-1), the hydroxyl radical scavengers, mannitol (15 mM), dimethylthiourea (10 mM) and N-(2-mercaptopropionyl)-glycine (1 mM), the iron chelator, deferoxamine (0.5 mM), ferric chloride (50 microM), an inhibitor of nitric oxide synthase, NG-nitro-L-arginine (30 microM), or the antioxidant, dithiothreitol (3 mM). 4. Hydrogen peroxide (0.1-30 mM) itself increased albumin transfer across endothelial cell monolayers, exhibiting a biphasic concentration-response curve. The increase induced by 0.1 mM hydrogen peroxide was abolished in the presence of 0.3 u ml-1 catalase whilst that induced by 10 mM hydrogen peroxide was abolished by 3000 u ml-1 catalase. 5. Homocysteine (0.5-1.5 mM) did not affect albumin transfer across endothelial monolayers when added alone, but when added in combination with copper sulphate (50 microM), which catalyses its oxidation, a significant increase in albumin transfer was observed. 6. The increase in albumin transfer induced by the combination of homocysteine (1.5 mM) and copper sulphate was abolished by catalase (1 u ml-1), but was unaffected by superoxide dismutase (6000 u ml-1), mannitol (15 mM), dimethylthiourea (1 mM) or deferoxamine (0.5 mM).7. The data suggest that the endothelial barrier dysfunction induced by the combination of hypoxanthine and xanthine oxidase is mediated solely by the action of hydrogen peroxide and not by superoxide anion, hydroxyl radical, peroxynitrite anion or hypochlorous acid. The copper-catalysed oxidation of homocysteine also induces endothelial barrier dysfunction through the generation of hydrogen peroxide.These findings may have relevance to the endothelial barrier dysfunction associated with ischaemia reperfusion injury and the atherogenic actions of homocysteine.
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PMID:Arterial endothelial barrier dysfunction: actions of homocysteine and the hypoxanthine-xanthine oxidase free radical generating system. 848 31

beta(2)-Agonists are known to have anti-inflammatory efficacy. In this context, beta(2)-agonists are also capable of inhibiting oxidant production of cultured inflammatory cells. As the mechanisms of this function still remain speculative, the purpose of this study was to quantify the efficacy of beta(2)-agonists in vitro to inhibit superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH.) and hypochlorous acid (HOCl). We tested the following antiasthma drugs: ipratropium bromide, salbutamol (salbutamol base), fenoterol (fenoterol hydrobromide), terbutaline (terbutaline sulfate), isoproterenol, prednisolone (prednisolone hydrogensuccinate), beclomethasone (beclomethasone dipropionate) and theophylline (theophylline sulfate). Antioxidant function was quantified by using the following assay systems: O2- (ferricytochrome c + xanthine/xanthine oxidase), H2O2 (phenol red + 5.10(-6) M H2O2), OH. (deoxyribose assay) and HOCI (HOCl/OCl- in luminol-dependent chemiluminescence). At 10(-4) M, the anti-H2O2 and anti-O2- capacity was as follows: salbutamol/terbutaline < fenoterol < isoproterenol. All beta(2)-agonists (10(-4) M) tested reduced HOCl activity by > 50% (p < 0.01). In contrast, moderate OH. reduction (10-30%) by the beta(2)-agonists is regarded as an nonspecific effect, due to the high concentrations needed (10(-3) M). Corticosteroids and theophylline had no antioxidant effect. These results demonstrate the different redox potentials of different phenol types within the molecular structure of the beta(2)-agonists. The good antioxidative function of isoproterenol is related to ortho formation of the phenol ring, whereas fenoterol has tow phenol rings which can be oxidized. A direct oxidant scavenger function may explain the ability of beta(2)-agonists to reduce the oxidant production of inflammatory cells in vitro.
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PMID:Beta-2-agonists have antioxidant function in vitro. 1. Inhibition of superoxide anion, hydrogen peroxide, hypochlorous acid and hydroxyl radical. 904 70

Reactive oxygen species such as OH, peroxynitrite and the non-radical, hypochlorous acid, play outstanding roles in many disease. The formation of OH (Fenton)-type radicals is catalyzed by enzymes such as xanthine oxidase (XOD) via one-electron reduction of molecular oxygen producing superoxide radical anions (O2). Subsequent transfer of one electron to hydrogen peroxide by Fe2+ or Cu+ -ions yields OH-radicals measurable as ethene release from 1-keto-4-methylthiobutyrate (KMB). Xanthine oxidase or activated neutrophils are prominent sources of this strong oxidant produced at inflammatory sites. Many natural compounds such as salicylates or flavonoids interfere either with the production of these activated oxygen species or function as radical scavengers and thus as antioxidants. Extracts from willow-bark (Salix spec.) and also other species such as ash-tree (Fraxinus spec.) or poplar (Populus spec.) have been used as antiinflammatory drugs since a long time. In this communication we wish to report on model reactions to demonstrate a) the radical scavenging activities of such plant extracts inhibiting ethene release from KMB induced by Fenton-type oxidants and b) the inhibition of the formation of nitrogen monoxide (NO) from hydroxylamine including XOD either in the presence or absence of myoglobin (MYO) measurable as nitrite formation: In the absence of MYO, superoxide dismutase is an excellent inhibitor of nitrite formation but is inactive in its presence. Extracts from the willow-bark or the drug Phytodolar however, are inhibitory both in the presence and absence of MYO. As active principle, the flavonoid rutin included in these extracts is likely to function as one inhibitor of the XOD-mediated reaction.
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PMID:Superoxide-dependent and -independent nitrite formation from hydroxylamine: inhibition by plant extracts. 968 63

We have studied the ability of propofol and Intralipid to inhibit reactive oxygen species generated either by stimulated human leucocytes or cell-free systems using luminol chemiluminescence. Human leucocytes were stimulated by a chemotactic peptide, FMLP 1 mumol litre-1, or by a phorbol ester, PMA (protein kinase C activator) 0.1 mumol litre-1. In cell-free experiments, superoxide-hydrogen peroxide, hypochlorous acid or hydroxyl radical-induced chemiluminescence responses were initiated by xanthine 0.1 mmol litre-1 with xanthine oxidase 10 mu. ml-1, NaOCl 70 mumol litre-1 and FeSO4 3 mumol litre-1, respectively. Propofol with Intralipid, and to a lesser degree Intralipid alone, produced a concentration-dependent reduction in chemiluminescence from stimulated leucocytes. Similar attenuations were also observed using propofol with Intralipid on xanthine with xanthine oxidase-, HOCl- and ferrous iron-induced chemiluminescence. However, Intralipid produced a reduction only at high concentrations. Intralipid produced marked decreases in ferrous iron-induced chemiluminescence. This study suggests that propofol had a direct scavenging activity against HOCl, superoxide-hydrogen peroxide and hydroxyl radical in the concentrations used. These direct scavenging effects may contribute to the effect of propofol on human leucocyte chemiluminescence.
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PMID:Propofol and intralipid interact with reactive oxygen species: a chemiluminescence study. 969 71

This study aimed to determine structural alterations occurring in cardiac myofilaments after exogenous application of oxidants and the effects of oxidants on contractile protein function in a rabbit coronary artery ligation model of heart failure. Myocardial "stiffness" was higher in the ligated animals (Lig) than sham-operated controls (Sh, 4.9+/-1.5 versus 1.6+/-0.8 mN.mm-1). Superoxide anion (O2-) exposure decreased active stiffness in both groups, whereas hypochlorous acid (HOCl) had no effect in Lig but increased stiffness in Sh. Resting stiffness was higher in Lig than Sh (0.6+/-0.2 versus 0.2+/-0.1 mN.mm-1), remaining unchanged after O2- exposure but increasing after HOCl in both groups. The frequency at minimum stiffness was lower in Lig than Sh (0.9+/-0.2 versus 1. 7+/-0.6 Hz) and was reduced in both groups after oxidant exposure. Myofilament calcium sensitivity (pCa50) was not altered by O2- in Sh but increased in Lig (pCa50 increased from 5.41+/-0.05 to 5.56+/-0. 06). Protease contamination in the xanthine oxidase used to generate O2- did not affect myofilament ultrastructure at the concentrations used here. These data demonstrate that contractile proteins from "failed" myocardium have a similar response to exogenously applied oxidants as controls and that application of protease-contaminated xanthine oxidase system does not degrade the contractile protein structure.
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PMID:Effects of reactive oxygen species on myofilament function in a rabbit coronary artery ligation model of heart failure. 1039 58

The lipophilic aglycone 5,7-dihydroxy-3,8-dimethoxyflavone (gnaphalin) isolated from the aerial flowering parts of Helichrysum picardii Boiss. & Reuter (Asteraceae) was tested for interactions with the cyclo-oxygenase and 5-lipoxygenase pathways of arachidonate metabolism in stimulated rat peritoneal leukocytes, and for its effects on leukocyte granular enzyme release, cell viability and interactions with reactive oxygen species. Gnaphalin dose-dependently inhibited generation of the cyclo-oxygenase metabolite thromboxane B2 (IC50 = 39.9 +/- 3.9 microM), and of the 5-lipoxygenase metabolite leukotriene B4, although the potency was two-fold less (IC50 = 81.8 +/- 12.9 microM). At concentrations of 6 to 320 microM, gnaphalin did not affect secretion of the pro-inflammatory enzymes lysozyme, myeloperoxidase and beta-glucuronidase from the neutrophil secretory granules, and did not scavenge hydrogen peroxide or hypochlorous acid. However, gnaphalin effectively scavenged superoxide radicals generated in the hypoxanthine/xanthine oxidase system (IC50 = 40 microM) and by PMA-stimulated leukocytes (> 60% at 500 microM), directly inhibited xanthine oxidase (85% at 395 microM) and inhibited Fe(3+)-ascorbate-induced liposomal peroxidation (IC50 = 215 microM). Thus, like some other flavonoids found in medicinal herbs, gnaphalin possesses an array of potentially beneficial anti-eicosanoid and free-radical scavenging properties which may alongside other constituents contribute to the claimed medicinal properties of the plant from which it is derived.
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PMID:Inhibition of leukocyte eicosanoid generation and radical scavenging activity by gnaphalin, a lipophilic flavonol isolated from Helichrysum picardii. 1048 68

The antioxidant content and activity of commercial tomato products differing in variety and processing were studied. Two procedures for extracting hydrophilic and lipophilic antioxidants, namely, two-step 0.1 M phosphate buffer (pH 3.0 and 7.4) extraction and tetrahydrofuran extraction followed by petroleum ether fractionation, were developed. Carotenoids (lycopene, beta-carotene, and lutein) and ascorbic acid were analyzed by HPLC with spectrophotometric and electrochemical detectors, respectively. Total phenolics were determined by using the Folin-Ciocalteu reagent. The antioxidant activity was studied by the following three model systems: (a) the xanthine oxidase (XOD)/xanthine system, which generates superoxide radical and hydrogen peroxide; (b) the myeloperoxidase (MPO)/NaCl/H(2)O(2) system, which produces hypochloric acid; and (c) the linoleic acid/CuSO(4) system, which promotes lipid peroxidation. Results showed that the hydrophilic and lipophilic fractions of all tomato products were able to affect model reactions, whatever reactive oxygen species and catalysts were used to drive oxidation. In the XOD/xanthine system both the hydrophilic and lipophilic fractions displayed an inhibitory activity. The hydrophilic fractions were more effective (I(50) ranging from 680 to 3200 microg, dry weight) than the lipophilic fractions (I(50) ranging from 4000 to 7750 microg, dry weight). In the MPO/NaCl/H(2)O(2) system the hydrophilic fractions inhibited oxidation (I(50) ranging from 2300 to 2900 microg, dry weight), whereas the lipophilic fractions had a lower inhibitory effect at the same concentration. Conversely, in the copper-catalyzed lipid peroxidation only the lipophilic fractions were effective (I(50) ranging from 1030 to 2100 microg, dry weight), whereas the hydrophilic fractions had a pro-oxidant effect in the same concentration range. The extent of inhibition varied according to the tomato sample in the superoxide and hydrogen peroxide generating system and in lipid peroxidation, but was substantially the same in the HClO generating system. Fresh tomato varieties differed considerably in the antioxidant activities of their hydrophilic and lipophilic fractions. Processed tomatoes showed a significantly lower antioxidant activity than fresh tomatoes in their hydrophilic fractions but had a high antioxidant activity in their lipophilic fractions. Because the oxidative reactions produced by the above-mentioned model systems are also involved in the pathogenesis of several chronic diseases, the antioxidant activity of tomato fractions might be related to their in vivo activity. Hence, these measurements may be used for optimizing tomato technologies.
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PMID:Antioxidant activity of tomato products as studied by model reactions using xanthine oxidase, myeloperoxidase, and copper-induced lipid peroxidation. 1082 40

Oxidative modification of low density lipoprotein (LDL) appears to play an important role in atherogenesis. Although the precise mechanisms of LDL oxidation in vivo are unknown, several lines of evidence implicate myeloperoxidase and reactive nitrogen species, in addition to ceruloplasmin and 15-lipoxygenase. Myeloperoxidase generates a number of reactive species, including hypochlorous acid, chloramines, tyrosyl radicals, and nitrogen dioxide. These reactive species oxidize the protein, lipid, and antioxidant components of LDL. Modification of apolipoprotein B results in enhanced uptake of LDL by macrophages with subsequent formation of lipid-laden foam cells. Nitric oxide synthases produce nitric oxide and, under certain conditions, superoxide radicals. Numerous other sources of superoxide radicals have been identified in the arterial wall, including NAD(P)H oxidases and xanthine oxidase. Nitric oxide and superoxide readily combine to form peroxynitrite, a reactive nitrogen species capable of modifying LDL. In this review, we examine the reaction pathways involved in LDL oxidation by myeloperoxidase and reactive nitrogen species and the potential protective effects of the antioxidant vitamins C and E.
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PMID:Oxidation of LDL by myeloperoxidase and reactive nitrogen species: reaction pathways and antioxidant protection. 1089 8

Acute and chronic lung diseases both lead to an extensive recruitment of neutrophils in the lungs. These cells play a major defensive role but, when activated, they are also an important source of reactive oxygen species, which generate a cytotoxic oxidant stress that triggers a self-sustaining phlogogenic loop. Erdosteine (CAS 84611-23-4) is a mucoactive drug whose metabolization leads to active metabolites with an SH group, and molecules bearing an SH group are also considered to have antioxidant activity. Luminol amplified chemiluminescence was used to investigate the oxidative bursts of human neutrophils and it was found that concentrations of 2.5, 5, 10 and 20 micrograms/ml of metabolite I of erdosteine significantly inhibit oxidative bursts in a concentration-related manner that overlaps the inhibition induced by the control drug N-acetylcysteine. Chemiluminescence was also studied in cell-free systems to see whether the drug also has direct scavenger activity, which was observed from 2.5 to 20 micrograms/ml of metabolite I using the xanthine/xanthine oxidase assay and at concentrations of 0.039 to > or = 2.5 micrograms/ml using the highly-sensitive hypochlorous acid/H2O2 assay. The findings indicate that the metabolite I of erdosteine has antioxidant activity which, together with the drug's mucomodifying activity, may lead to a useful antiphlogistic effect.
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PMID:Assessment of the antioxidant activity of the SH metabolite I of erdosteine on human neutrophil oxidative bursts. 1099 58

Vascular disease and vasomotor responses are largely influenced by oxidant stress. Superoxide is generated via the cellular oxidase systems, xanthine oxidase, and NADH/NADPH oxidases. Once formed, superoxides participate in a number of reactions, yielding various free radicals such as hydrogen peroxide, peroxynitrite, oxidized low-density lipoprotein, or hypochlorous acid. Numerous cellular antioxidant systems exist to defend against oxidant stress; glutathione and the enzymes superoxide dismutase and glutathione peroxidase are critical for maintaining the redox balance of the cell. However, the redox state is disrupted by certain vascular diseases. It appears that oxidant stress both promotes and is induced by diseases such as hypertension, atherosclerosis, and restenosis as well as by certain risk factors for coronary artery disease including hyperlipidemia, diabetes, and cigarette smoking. Once oxidant stress is invoked, characteristic pathophysiologic features ensue, namely adverse vessel reactivity, vascular smooth muscle cell proliferation, macrophage adhesion, platelet activation, and lipid peroxidation.
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PMID:Oxidant stress in the vasculature. 1112 5


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