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)

A number of investigations have implicated free radicals in the progression of ischemic/reperfusion injury. alpha-Tocopherol has been found to attenuate alterations due to ischemia and reperfusion in an isolated heart model. The present study was intended to directly examine neonatal rat cardiac ventricular cell cultures exposed to a free radical generating system catalyzed by xanthine oxidase. The effectiveness of alpha-tocopherol in the attenuation of the resultant changes and the mechanism by which the effects of alpha-tocopherol may be exerted were evaluated. Cultures were either nontreated or pretreated for 18 h with 20 microM alpha-tocopherol or the subcomponents of the alpha-tocopherol molecule, phytol and Trolox. Exposure of cell cultures to free radicals resulted in significant increases in lipid peroxidation products, release of both lactate dehydrogenase and 3H-arachidonate, and structural alterations. Pretreatment with alpha-tocopherol showed significant attenuation of the changes associated with exposure to free radicals. Trolox and phytol at equal molar doses were not as effective as alpha-tocopherol in protecting the myocytes against injury. Thus, alpha-tocopherol seems beneficial in its ability to reduce free radical-mediated changes by functioning as a lipophilic antioxidant. Additionally, the intact, native alpha-tocopherol molecule exceeded the protective capabilities of either of its subcomponents.
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PMID:Free radical damage in neonatal rat cardiac myocyte cultures: effects of alpha-tocopherol, Trolox, and phytol. 212 18

Oxygen-derived free radicals have been implicated in damage to membrane phospholipids leading to alterations in membrane function. The purpose of this study was to investigate alterations in intracellular ionic calcium (Ca2+) levels and Ca2+ transients, cellular morphology, conjugated diene levels, arachidonate release, and lactate dehydrogenase release resulting from the exposure of cultured neonatal rat ventricular myocytes to a xanthine oxidase catalyzed free radical generating system capable of producing superoxide and hydroxyl radicals. The ability of alpha-tocopherol to prevent alterations due to free radical exposure was investigated. For measurements of Ca2+, myocytes grown on coverslips for 3-4 days were loaded with fura-2/AM and studied by microspectrofluorometry. Control myocytes superfused with a physiological buffer or buffer containing purine and iron-loaded transferrin exhibited Ca2+ transients associated with spontaneous contractions. For control, buffer perfused myocytes (n = 4), the fura-2 340/380 ratios were 0.5 +/- 0.1 (mean +/- S.E.) and 1.6 +/- 0.03 at the minimum and maximum, respectively, of the Ca2+ transient, after 1 h of perfusion. Exposure to the free radical generating solution (n = 14) altered intracellular Ca2+. The 340/380 minimum ratio was 639% of the control value after approximately 30-70 mins with cessation of normal Ca2+ transients. Bleb development was associated with increased Ca2+. Myocytes reperfused with control medium continued to exhibit an elevated minimum fura-2 ratio at 687% of control. Myocytes pretreated with 10 microM alpha-tocopherol (n = 13) for 18-24 h and exposed to free radicals did not exhibit increases in intracellular Ca2+, having a minimum 340/380 ratio of 0.5 +/- 0.1 after 60-90 mins, and although myocytes often ceased contracting, they resumed spontaneous Ca2+ transients with control medium reperfusion and also maintained normal structure. Exposure of myocyte cultures to free radical generating solutions resulted in increased levels of conjugated dienes and increased release of [3H]arachidonate and lactate dehydrogenase compared to control values after 1 h. alpha-Tocopherol treatment attenuated the increase in conjugated diene levels, and the release of [3H]arachidonate and lactate dehydrogenase. Thus, free radicals alter intracellular Ca2+, conjugated dienes and membrane structure indicating their ability to induce altered ionic homeostasis in association with myocardial membrane damage. alpha-Tocopherol decreased free radical mediated injury.
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PMID:Free radicals alter ionic calcium levels and membrane phospholipids in cultured rat ventricular myocytes. 212 94

Incubation of human erythrocytes oxidized by iron catalysts, ADP/Fe3+ or xanthine/xanthine oxidase/Fe3+, with autologous IgG resulted in IgG binding as detected by enzyme immunoassay using protein A-beta-galactosidase conjugate. The binding of autologous IgG to ADP/Fe3(+)-treated erythrocytes maximized when the cells were treated with 1.8:0.1 mM ADP/Fe3+, and declined when treated above this concentration, suggesting that autologous IgG binds to moderately but not to excessively oxidized erythrocytes. The antibody involved in the binding was anti-Band 3, the autoantibody known to bind to aged erythrocytes, because isolated anti-Band 3 bound to the oxidized cells, but anti-Band 3-depleted autologous IgG did not. In addition, purified Band 3 inhibited the autologous IgG binding. Anti-alpha-galactosyl IgG, another natural antibody which has been reported to bind to aged erythrocytes, did not bind to the oxidized cells. Oxidation of membrane lipids, SH-groups of membrane proteins, and Hb of these cells was slight, but the cells contained an increased amount of membrane-bound native Hb, indicating that the oxidized cell membrane has an altered property. alpha-Tocopherol prevented the lipid oxidation and the subsequent IgG binding. Reduction of the oxidized erythrocytes with dithiothreitol resulted in a loss of the IgG binding. These results suggest that anti-Band 3 binding sites (Band 3 senescent antigen) are formed on moderately oxidized erythrocytes as a result of oxidation of membrane protein SH-groups which can be mediated by the membrane lipid oxidation and that formation of the anti-Band 3 binding sites on the oxidized cells is an essentially reversible membrane event which is linked to oxidation and restoration of the protein SH-groups.
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PMID:Binding of anti-band 3 autoantibody to oxidatively damaged erythrocytes. Formation of senescent antigen on erythrocyte surface by an oxidative mechanism. 230 47

In the present study, the effects of alpha-tocopherol and allopurinol in liver ischemia and reperfusion injury on lipid peroxidation and mitochondrial respiratory function were investigated in rats. Ischemia was induced in the left and median liver lobes clamping the vessels for 90 minutes. After declamping reperfusion was continued for 60 minutes. Liver tissue was taken before and 90 minutes after ischemia and 60 minutes after reperfusion to measure lipid peroxides and mitochondrial respiratory function. In one group of rats alpha-tocopherol (10mg/kg) was given intraperitoneally for three consecutive days preoperatively and in the other group allopurinol (50mg/kg) was given intravenously 10 minutes before ischemia. alpha-Tocopherol caused inhibition of increase in lipid peroxides at reperfusion and improvement in lowering of mitochondrial respiratory function. This improvement was less than previously reported, probably due to not only reperfusion injury but also ischemic injury. Allopurinol, on the other hand, caused neither such inhibition nor such improvement, suggesting the other source of oxygen-derived free radicals than xanthine oxidase system.
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PMID:[The role of alpha-tocopherol and allopurinol in lipid peroxidation and mitochondrial respiration in the ischemic rat liver]. 231 86

To verify the lipid peroxidation in the focal cerebral ischemia, the levels of alpha-tocopherol, ubiquinone and ascorbate were measured in the ischemic center in rats. The former two were endogeneous lipid soluble antioxidants and the last was a water soluble antioxidant. alpha-Tocopherol, reduced ubiquinone-9 and -10, and reduced ascorbate decreased to 79%, 73%, 66%, and 76% 0.5 hour after ischemia, respectively. alpha-Tocopherol decreased to 63% 6 hours after ischemia, and then reached a plateau, while reduced ubiquinones and reduced ascorbate declined further to 16% and 10% 12 hours after ischemia, respectively, and then reached plateau levels. These results suggest their functional and durational differences as antioxidants against lipid peroxidation in this ischemic model. Although the reciprocal increase in oxidized ubiquinones during ischemia was not observed, that in oxidized ascorbate was noted. The complementary antioxidant system between cytoplasmic and membranous components, the combination alpha-tocopherol/ascorbate, was estimated from the calculated consumption ratio of these antioxidants, assuming that the loss of these reduced antioxidants is due to neutralization of free radicals. This system was suggested to play an important role in an early ischemic period. Urate also markedly increased during ischemia. Therefore, xanthine oxidase activity was measured in rats both in normal brain and in ischemic brain induced by four-vessel occlusion method. In the control rat, the enzyme activity was 0.87 +/- 0.13 nmol/g wet brain/min at 25 degrees C (mean +/- S.D.): 92.4% was associated with the NAD-dependent dehydrogenase form and only 7.6% with the oxygen-dependent superoxide-producing oxidase form. However, the ratio of the latter form increased to 43.7% after 0.5 hour of global ischemia despite the same level in total xanthine oxidase activity. This result suggests the involvement of the oxygen free radicals generated from the xanthine oxidase pathway in the pathogenesis of the ischemic injury of the rat brain.
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PMID:[Lipid peroxidation and changes in xanthine oxidase in cerebral ischemia]. 280 15

alpha-Tocopherol dispersed in aqueous media with deoxycholate was found to be oxidized, at a physiological pH, by a xanthine-xanthine oxidase system. This reaction was completely inhibited by the addition of superoxide dismutase, whereas catalase and mannitol (scavenger of hydroxyl radical) did not affect the reaction. This finding indicates that the oxidation of alpha-tocopherol is caused by O2. The reaction product formed was identified as 8 alpha-hydroxy-alpha-tocopherone by thin-layer chromatography and ultraviolet spectroscopy. The product was found to change spontaneously to alpha-tocopherol quinone. beta-, gamma-, and delta-tocopherol dispersed with deoxycholate also reacted with O2. The reaction of tocopherols dispersed in the micellar form may be considered as a model of in vivo reaction of tocopherols, since tocopherols are present in tissues largely in the membranes, where O2 is known to be generated.
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PMID:Oxidation by superoxide of tocopherols dispersed in aqueous media with deoxycholate. 624 95

Superoxide (O2-)-dependent lipid peroxidation on addition of xanthine oxidase (XO) and Fe(3+)-ADP was induced in egg phosphatidylcholine (PC) liposomes containing dicetylphosphate (DCP), which are negatively charged like biological membranes, but not in uncharged egg PC liposomes. Positively charged Fe(3+)-ADP interacted more with negatively charged egg PC-DCP liposomes than with uncharged egg PC liposomes. The activities of Fe(3+)-chelates for initiating O(2-)-dependent lipid peroxidation were in the order Fe(3+)-ADP > Fe(3+)-citrate > Fe(3+)-oxalate = Fe(3+)-malonate > Fe(3+)-EDTA = 0. This order was the same as that for the reduction rates of these Fe(3+)-chelates to Fe(2+)-chelates by O(2-)-generated by XO. Lineweaver-Burk plots showed that the chelators inhibited XO by different mechanisms: uncompetitively by ADP and adenosine and non-competitively by organic acid chelators (citrate and oxalate) and EDTA. These results suggest that ADP interacts with XO in a manner different from the other chelators. Lipid peroxidation by XO-xanthine and Fe(3+)-ADP was induced in egg PC liposomes containing a trace (0.31-0.35 mol%) of peroxidized egg PC (PC-OOH), but not in PC-OOH-free liposomes of egg PC obtained by their pretreatment with triphenylphosphine. PC-OOH incorporated into dimyristoyl phosphatidylcholine (DMPC) liposomes was degraded on addition of both XO-xanthine and Fe(3+)-chelate, but not of either one alone. alpha-Tocopherol in DMPC liposomes was oxidized on addition of XO-xanthine and Fe(3+)-chelates in the presence, but not in the absence of PC-OOH. Furthermore, PC-OOH was required for decrease of the ESR spectrum of the spin probe 12-(N-oxyl-4,4'-dimethyloxazolidin-2-yl)stearic acid, which labels the hydrophobic region of egg PC liposome membranes, on addition of XO-xanthine and Fe(3+)-chelates. These results indicate that the "induction message of lipid peroxidation," which is associated with reduction of Fe(3+)-ADP by O2- and concurrent degradation of PC-OOH, must be transferred from the membrane surface to the inner hydrophobic region of the membranes.
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PMID:Dynamics of xanthine oxidase- and Fe(3+)-ADP-dependent lipid peroxidation in negatively charged phospholipid vesicles. 784 Jun 82

In vivo oxidative change was visualized in the gastric mucosa of rats and the alteration was analysed by using a fluorescence microscope equipped with a digital imaging processor during the development of mucosal damage. Dichlorofluorescein (DCF)-associated fluorescence increased after the repeated electrical stimulation on the gastric artery (irritation), suggesting the occurrence of lipid peroxidation. The increase was enhanced in the mid-zone of two adjacent collecting venules. Allopurinol attenuated the oxidative stress in mucosa, showing the involvement of xanthine oxidase. Luminol-dependent chemiluminescence value in the blood taken from gastric vein was elevated by the irritation, suggesting that leucocyte-generated oxygen radicals also participate in this oxidative process. alpha-Tocopherol attenuated both the DCF activation and the increase in chemiluminescence value and prevented gastric mucosal injury. The present results suggest that alpha-tocopherol may be useful for the prevention of oxidative alteration in gastric mucosa.
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PMID:Fluorographic study on the oxidative stress in the process of gastric mucosal injury: attenuating effect of vitamin E. 851 96

The addition of DL-alpha-tocopherol (vitamin E) at the time of UV irradiation only marginally protects cells from UV-induced cytotoxicity. However, a protective effect of alpha-tocopherol emerged when it was added to the cells before UV irradiation, alpha-Tocopherol was progressively and dose-dependently incorporated into the cells. Washout experiments showed that the intracellular concentration of alpha-tocopherol decreased with an approximate half-life of 14-20 hours, due to the release from the cells and dilution by cell proliferation. Pretreatment of the cells with alpha-tocopherol significantly increased the resistancy against the cytotoxic action of UV irradiation and antioxidants such as sodium ascorbate, gallic acid, n-propyl gallate and caffeic acid. ESR spectroscopy showed that alpha-tocopherol enhanced the ascorbyl radical intensity, whereas it reduced caffeic acid radical intensity, without affecting the radical intensity of gallic acid and n-propyl gallate. Both control and treated cell lysates scavenged superoxide anion (generated by xanthine-xanthine oxidase reaction) and hydroxyl radical (generated by Fenton reaction) to a comparable extent. The present study suggests that the protective effect of alpha-tocopherol might be derived from its incorporation into the cell membranes rather than its scavenging activity.
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PMID:Effect of alpha-tocopherol on cytotoxicity induced by UV irradiation and antioxidants. 921 67

One known and two novel antioxidant compounds have been isolated from bamboo (Phyllostachys edulis). The butanol-soluble extract of the bamboo leaves was found to have a significant antioxidant activity, as measured by scavenging the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and the superoxide anion radical (O(2)(-)) in the xanthine/xanthine oxidase assay system. Antioxidant activity-directed fractionation of the extract led to the isolation and characterization of three structural isomeric chlorogenic acid derivatives: 3-O-(3'-methylcaffeoyl)quinic acid (1), 5-O-caffeoyl-4-methylquinic acid (2), and 3-O-caffeoyl-1-methylquinic acid (3). Compounds 2 and 3 were isolated and characterized for the first time from the natural products. In the DPPH scavenging assay as well as in the iron-induced rat microsomal lipid peroxidation system, compounds 2 (IC(50) = 8.8 and 19.2 microM) and 3 (IC(50) = 6.9 and 14.6 microM) showed approximately 2-4 times higher antioxidant activity than did chlorogenic acid (IC(50) = 12.3 and 28.3 microM) and other related hydroxycinnamates such as caffeic acid (IC(50) =13.7 and 25.5 microM) and ferulic acid (IC(50) = 36.5 and 56.9 microM). Among the three compounds, compound 1 yielded the weakest antioxidant activity, and the DPPH scavenging and lipid peroxidation inhibitory activity (IC(50) = 16.0 and 29.8 microM) was lower than those of chlorogenic and caffeic acids. All three compounds exhibited both superoxide scavenging activities and inhibitory effects on xanthine oxidase. Their superoxide anion (O(2)(-)) scavenging activities (IC(50) = 1, 4.3 microM; 2, 2.8 microM; and 3, 1.2 microM) were markedly stronger than those of ascorbic acid (IC(50) = 56.0 microM), alpha-tocopherol (IC(50) > 100 microM), and other test compounds, although their inhibition effects on xanthine oxidase may contribute to the potent scavenging activity. alpha-Tocopherol exerted a significant inhibitory effect (65.5% of the control) on superoxide generation in 12-O-tetradecanoylphorbol-13-acetate-induced human promyelocytic leukemia HL-60 cells, and compound 3 showed moderate activity (36.0%). On the other hand, other compounds including 1, 2, chlorogenic acid, and other antioxidants were weakly active (24.8-10.1%) in the suppression of superoxide generation.
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PMID:Identification and antioxidant activity of novel chlorogenic acid derivatives from bamboo (Phyllostachys edulis). 1160 2


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