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)

Picroliv, the active principle of Picrorhiza kurrooa, and its main components which are a mixture of the iridoid glycosides, picroside-I and kutkoside, were studied in vitro as potential scavengers of oxygen free radicals. The superoxide (O2-) anions generated in a xanthine-xanthine oxidase system, as measured in terms of uric acid formed and the reduction of nitroblue tetrazolium were shown to be suppressed by picroliv, picroside-I and kutkoside. Picroliv as well as both glycosides inhibited the non-enzymic generation of O2- anions in a phenazine methosulphate NADH system. Malonaldehyde (MDA) generation in rat liver microsomes as stimulated by both the ascorbate-Fe2+ and NADPH-ADP-Fe2+ systems was shown to be inhibited by the Picroliv glycosides. Known antioxidants tocopherol (vitamin E) and butylated hydroxyanisole (BHA) were also compared with regard to their antioxidant actions in the above system. It was found that BHA afforded protection against ascorbate-Fe(2+)-induced MDA formation in microsomes but did not interfere with enzymic or non-enzymic O2- anion generation; and tocopherol inhibited lipid peroxidation in microsomes by both prooxidant systems and the generation of O2- anions in the non-enzymic system but did not interfere with xanthine oxidase activity. The present study shows that picroliv, picroside-I and kutkoside possess the properties of antioxidants which appear to be mediated through activity like that of superoxide dismutase, metal ion chelators and xanthine oxidase inhibitors.
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PMID:Picroliv, picroside-I and kutkoside from Picrorhiza kurrooa are scavengers of superoxide anions. 132 26

Effects of methylflavonolamine (MFA) on arrhythmias induced by myocardial reperfusion were studied with rat hearts in situ and in vitro. In pentobarbital-anesthetized rats, MFA (20 mg.kg-1, i.v.) pretreatment reduced the incidence of reperfusion-induced ventricular fibrillation after left descending coronary artery ligation (15 min) and reperfusion (3 min) (28.6% vs 85.7% in control, P less than 0.05). Malondialdehyde (MDA) production (85 +/- 9 nmol/g wet wt) was inhibited in myocardium from the reperfused area in comparison with control (133 +/- 15 nmol/g wet wt). In isolated rat hearts with local ischemia (15 min) and reperfusion (1 min), MFA 5 mumol.L-1 (perfused 10 min prior to coronary artery ligation) prevented reperfusion-induced arrhythmias (0% vs 85.7% in control, P less than 0.01). In myocardium from the reperfused area, superoxide dismutase (SOD) and catalase (Cat) activity was increased and xanthine oxidase (XOD) activity, MDA production and nonesterified fatty acids (NEFA) contents were decreased. The results show that MFA prevents reperfusion-induced arrhythmia by inhibiting lipid peroxidation and regulating the metabolism of NEFA.
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PMID:[Anti-arrhythmia and anti-lipid peroxidation effects of methylflavonolamine]. 177 85

Involvement of free radicals and their scavenging enzymes in mice pulmonary thromboembolism, induced by intravenous infusion of collagen and adrenaline, has been studied. Malonaldehyde (MDA) and activities of xanthine oxidase (XO), catalase (CAT) and superoxide dismutase (SOD) were estimated in platelets, heart and lung homogenates. MDA increased in all the tissues sharply, while animals showed 70-80% thrombocytopenia. Xanthine oxidase activity in these animals increase significantly in heart. However, increased SOD activity and decreased catalase activity was observed in platelets. Intravenous administration of superoxide dismutase (5 mg/kg), catalase (5 mg/kg) and mannitol (200 mg/kg) protected the mice against pulmonary thromboembolism. The importance of free radicals in mice pulmonary thromboembolism has been demonstrated.
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PMID:Role of free radicals in pulmonary thromboembolism in mice. 251 Mar 58

The purpose of this study was to evaluate the possible involvement of xanthine and xanthine oxidase in reperfusion injury in a low-flow, reflow model of liver perfusion. Livers were perfused at flow rates around 25% of normal for 90 min and then at normal flow rates (4 ml/g/min) for 30 min. When flow was restored to normal, malondialdehyde and lactic dehydrogenase (LDH) were released into the effluent perfusate. Malondialdehyde production rapidly reached values of 300 nmol/g/hr whereas LDH increased from basal levels of 100 to 600 U/l upon reperfusion. Trypan blue was taken up exclusively in cells in pericentral regions of the liver lobule under these conditions. Xanthine and hypoxanthine in the effluent perfusate increased steadily during the low-flow period reaching values around 5 and 10 microM, respectively, and decreased rapidly after the flow was restored to normal. Perfusion with nitrogen-saturated buffer for 3 min before restoration of normal flow rates or infusion of the radical scavenger catechin (400 microM) reduced cell damage by about 50%. Infusion of allopurinol (2-6 mM), an inhibitor of xanthine oxidase, prevented reperfusion injury in a dose-dependent manner. Taken together, these data indicate that a reperfusion injury occurs in liver upon reintroduction of oxygen which is initiated by oxidation of xanthine and hypoxanthine via xanthine oxidase and ultimately leads to production of lipid peroxides. Surprisingly, infusion of xanthine (4 mM), substrate for xanthine oxidase, reduced hepatocellular injury on reperfusion. LDH release was decreased from values around 700 to less than 200 U/l and trypan blue uptake in pericentral region was prevented totally by xanthine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of purines and xanthine oxidase in reperfusion injury in perfused rat liver. 254 32

The present study was undertaken to determine whether significant breakdown of adenine nucleotides to purine bases and oxypurines occurred in mitochondria following myocardial ischemia and ischemia followed by reperfusion, and whether allopurinol prevented this effect. The adenine nucleotides adenosine, hypoxanthine, xanthine and uric acid were measured in the mitochondria and the results suggest that breakdown did occur. Malondialdehyde concentration was determined to gauge lipid peroxidation. This substance did not increase during ischemia or reperfusion, but did so in the presence of allopurinol. Xanthine dehydrogenase was converted to xanthine oxidase during reperfusion and the activity of both enzymes were inhibited by allopurinol. The results also suggested the presence of a mitochondrial 5'-nucleotidase. We conclude that significant breakdown of adenine nucleotide took place in myocardial mitochondria during ischemia and ischemia followed by reperfusion and that allopurinol may have a protective effect.
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PMID:Purine and oxypurine production in mitochondria of ischemic and reperfused myocardium. 261 53

The oxygen paradox refers to the abrupt release of cytoplasmic enzymes and severe cellular disruption that occurs following reoxygenation of anoxic perfused hearts. In this study, the ability of a series of oxygen-derived free radical inhibitors and scavenging agents to protect isolated perfused rat hearts from the oxygen-induced enzyme release following 30 or 60 mins of anoxic perfusion (oxygen paradox) and cumene hydroperoxide-induced injury was evaluated. Malondialdehyde (MDA) release, an indicator of lipid peroxidation, and creatine kinase (CK) release, an indicator of cellular injury, were monitored. We evaluated five agents previously reported to scavenge or inhibit the formation of oxygen free radicals. The putative hydroxyl radical scavengers dimethylthiourea (DMTU) and mannitol; catalase, an agent protective against peroxide injury; allopurinol, an inhibitor of xanthine oxidase; and albumin, a non-specific protein control, were evaluated. Coronary flow rates and myocardial temperature were continuously monitored to ensure uniform perfusion conditions. The MDA assay was carefully monitored by constructing standard curves on each experimental day. Addition of 20 microM cumene hydroperoxide to oxygenated perfused hearts caused peroxidative cell injury as evidenced by significant MDA and CK release in the coronary effluent. DMTU and catalase provided near complete protection from cumene hydroperoxide-induced cell injury but did not reduce CK release from hearts subjected to either the mild (30-min) or the severe (60-min) oxygen paradox (reoxygenation-induced injury). Allopurinol caused a significant reduction in MDA release but not CK release from oxygen paradox-injured hearts. Allopurinol and albumin had no significant effect on MDA release from cumene-hydroperoxide-injured hearts. Catalase (300 U/ml) caused a mild but not statistically significant reduction in MDA release from cumene hydroperoxide injury but did not provide protection from the oxygen paradox at either injury level. Mannitol (120 mM), in contrast to DMTU, was ineffective in reducing cumene-induced injury but showed a significant protective effect against oxygen paradox-induced damage. It is concluded that the ability of mannitol to reduce reoxygenation-induced CK release in the oxygen paradox may be due to its osmotic activity and consequent ability to prevent cellular swelling rather than its activity as an oxygen-free radical scavenger.
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PMID:Effects of the free radical scavenger DMTU and mannitol on the oxygen paradox in perfused rat hearts. 311 97

Xanthine (X) and xanthine oxidase (XO) were injected intratracheally (IT) in hamsters at Day 0 (38 mg X, 100 micrograms XO) and Day 5 (38 mg X, 250 micrograms XO). Control hamsters received saline or X (38 mg) plus boiled XO (100, 250 micrograms). Cytoplasmic superoxide dismutase (SOD) activity increased from control of 286 to 337 and 335 units/lung at Days 12 and 19, respectively, but decreased to 228 units/lung at Day 33; mitochondrial SOD activity increased at Day 12 from control of 57 to 71 units/lung and then decreased at Days 26 and 33 to 42 and 33 units/lung, respectively. Glutathione peroxidase (GP) and glutathione reductase (GR) activities rose from their control values of 1161 and 1151 to 1561 and 2287 units/lung at Day 12, respectively; thereafter, GR activity decreased to 512 and 462 units/lung at Days 19 and 26, respectively. Glutathione transferase declined at Day 12 but increased at Day 26 after initial treatment. Glucose-6-phosphate dehydrogenase activity declined from control of 1071 to 693 units/lung at Day 2 and returned to control thereafter. Catalase activity remained unaffected. Hydroxyproline was increased from 903 micrograms/lung in control to 1080, 1301, 1195, and 1148 micrograms/lung at Days 12, 19, 26, and 33, respectively. Malonaldehyde increased from 40 nmole/lung in control to 70 and 113 nmole/lung at Days 12 and 33, respectively. The ratio of right ventricle to left ventricle and septum increased significantly from control of 0.277 to 0.318 at Day 33. Histopathology at Days 2 and 4 revealed peribronchiolar and arteriolar inflammation, and diffuse alveolitis. By Day 12 there were thickened alveolar septa and foci of fibrotic consolidation.
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PMID:Effects of intratracheal administration of xanthine plus xanthine oxidase on lung antioxidant enzymes, lipid peroxidation, and collagen in hamsters. 319 17

A study has been made of the damage incurred by normal and Plasmodium falciparum-infected human erythrocytes following exposure to a variety of oxidant-generating systems. Hydrogen peroxide, produced by the glucose-glucose oxidase system, increased methaemoglobin formation within normal erythrocytes while normal levels of oxyhaemoglobin were maintained. Exposure to products of the xanthine-xanthine oxidase interaction did not have the same effect. Malondialdehyde measurements indicated that the host cell membranes of parasitized cells had undergone lipid peroxidation even before exposure to the oxidant-generating systems. Lipid peroxidation of normal and parasitized cell membranes was increased upon exposure to reagent-grade hydrogen peroxide and alloxan: this increase was not observed following exposure to the two enzyme-substrate systems that generated reactive oxygen intermediates. In addition, the effects of parasitism on intracellular levels of catalase and superoxide dismutase were assessed. Normal and parasitized erythrocytes were found to possess similar levels of these enzymes, which protect against oxidant-induced damage. It was therefore concluded that the increased susceptibility of infected cells to oxidant damage was probably not related to any decrease in the function of these enzymes.
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PMID:Damage to malaria-infected erythrocytes following exposure to oxidant-generating systems. 352 61

Oxygen free radicals mediate the ischemia-reperfusion damage in animal hearts, but their role in human beings is still controversial because of the low xanthine oxidase level in the human heart. Besides ischemia-reperfusion, cardiac operation also includes other major interventions that might generate free radicals but have not been systematically studied. We studied the cases of nine patients throughout coronary artery operations, including general anesthesia, heparin, protamine and administration of cardioplegic solution, extracorporeal circulation, and heart reperfusion. Arterial plasma was assayed for malondialdehyde, diene conjugates, and fluorescent chromolipids, and plasma antioxidant activity was estimated from the ability to trap peroxyl radicals. Anesthesia, surgical procedures, or heparin administration did not change these parameters. Extracorporeal circulation decreased the plasma concentration of diene conjugates immediately, whereas other compounds remained unaltered. When these concentrations were corrected for hemodilution, the amount of fluorescent chromolipids actually increased after 5 minutes of extracorporeal circulation to 177% +/- 14% (mean +/- standard error of the mean), diene conjugates increased to 138% +/- 12%, and plasma antioxidant capacity increased to 144% +/- 12% of the awake value. Fluorescent chromolipid values remained at 156% to 177% throughout the perfusion and decreased to 130% +/- 13% 1 hour after perfusion. Diene conjugate levels and antioxidant capacity were 123% to 144% and 143% to 161%, respectively, from baseline during perfusion and 119% +/- 5% and 135% +/- 9%, respectively, 1 hour after perfusion. Heart reperfusion or protamine administration showed no additional increases. Malondialdehyde concentrations varied and showed no statistically significant alterations. We conclude that extracorporeal circulation devices induce generation of free radicals and plasma antioxidant activity, which are different from the damage caused by ischemia-reperfusion.
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PMID:Free radical reaction products and antioxidant capacity in arterial plasma during coronary artery bypass grafting. 802 57

The potential of xanthine oxidoreductase to generate oxygen radicals depends on the ratio of xanthine dehydrogenase and xanthine oxidase. Previous studies showed that the lipid peroxidation products, malondialdehyde and 4-hydroxynonenal have different effects on xanthine oxidoreductase activity. These results suggest that the activity of xanthine oxidase, but not xanthine dehydrogenase, is influenced by NH2-group modulation. We therefore investigated the influence of malondialdehyde on xanthine oxidoreductase. Malondialdehyde reacted with NH2-groups to form Schiff bases, and this reaction was associated with inhibition of xanthine oxidase; SH-groups were not affected. Malondialdehyde had no influence on the xanthine dehydrogenase activity. The inhibited xanthine oxidase was converted to an active xanthine dehydrogenase by dithiothreitol treatment. These experiments indicate the importance of NH2-groups for xanthine oxidase but not for xanthine dehydrogenase activity. Beside the well known regulation of the xanthine dehydrogenase/xanthine oxidase ratio by the redox status of SH-groups, substances reacting with NH2-groups of the xanthine oxidoreductase are also able to change the xanthine dehydrogenase/xanthine oxidase activity ratio, thereby influencing the potential to generate oxygen radicals by xanthine oxidoreductase.
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PMID:Modulation of the xanthine oxidase/xanthine dehydrogenase ratio by reaction of malondialdehyde with NH2-groups. 803 67


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