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)

We measured lipid peroxidation of plasma, lung, and liver in anaesthetized sheep after third-degree burns involving 30% of total body surface. Animals were resuscitated to baseline filling pressures with lactated Ringer's solution and killed 10 hours after burn. Six sheep were pretreated with ibuprofen (12.5 mg/kg) and five with allopurinol (50 mg/kg). We used conjugated dienes and malondialdehyde as measures of lipid peroxidation. Circulating conjugated dienes increased from a baseline of 0.48 +/- 0.06 to 0.64 +/- 0.05 after burn, while protein-rich burn tissue lymph flow increased up to eightfold. We also noted a significant increase in lung tissue malondialdehyde from 45 +/- 4 to 60 +/- 6 nmol/gm and liver malondialdehyde from 110 +/- 20 to 271 +/- 34 nmol/gm along with increased tissue neutrophil sequestration. Ibuprofen attenuated lung-tissue malondialdehyde but had no effect on lung inflammation, circulating lipid peroxides or burn edema, indicating that ibuprofen most likely decreased O2 radical release in lung tissue by the already-sequestered neutrophils. Allopurinol, possibly via xanthine oxidase inhibition, markedly attenuated burn QL and circulating lipid peroxides and prevented all pulmonary lipid peroxidation and inflammation, indicating that release of oxidant from burn tissue was in part responsible for local burn edema, as well as distant inflammation and oxidant release, the latter most likely from complement activation. Neither antioxidant decreased lipid peroxidation in the liver; this indicates that its mechanism of production was different from that seen in burn tissue, in plasma, or in the lung. An ischemic event resulting from a selective decrease in splanchnic blood flow may be the cause of the liver changes.
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PMID:Early postburn lipid peroxidation: effect of ibuprofen and allopurinol. 229 60

"Declamping shock" is observed after aortic crossclamping, with hypovolemia, hypotension, and metabolic acidemia invariably present. We hypothesized that oxidants derived from xanthine oxidase influence the resuscitative interventions required to maintain baseline hemodynamic and acid-base status after aortic occlusion and reperfusion in rabbits. We also hypothesized that inactivation of xanthine oxidase with sodium tungstate could reduce systemic injury as assessed by the release of lactate dehydrogenase and alkaline phosphatase. To test these hypotheses, we established aortic occlusion in rabbits (n = 10, standard diet; n = 8, tungstate diet) for 40 minutes by inflation of a 4F Fogarty catheter in the descending thoracic aorta followed by 2 hours of reperfusion. Sham-operated rabbits (n = 10, standard diet; n = 9, tungstate diet) served as controls. Tungstate-pretreated rabbits required significantly less Ringer's solution (28%), phenylephrine (68%), and sodium bicarbonate (30%) during reperfusion (p < 0.005). Lactate dehydrogenase and alkaline phosphatase release during reperfusion was significantly attenuated by tungstate pretreatment (p < 0.05). Tungstate pretreatment resulted in plasma xanthine oxidase activities significantly lower than those in the sham group administered a standard diet (p = 0.007). Resuscitation requirements and systemic injury were reduced by inactivation of xanthine oxidase in a rabbit model that simulates the situation of human thoracic aorta operations.
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PMID:Xanthine oxidase inactivation attenuates postocclusion shock after descending thoracic aorta occlusion and reperfusion in rabbits. 756 38

The conversion from xanthine dehydrogenase (XD) to xanthine oxidase (XO) and the effect of trifluoperazine (TFP), a calmodulin inhibitor, on the conversion were examined during the normothermic ischemia of the rat small intestine. Rat jejunums were stored in lactated Ringer's solution (LR) at 37 degrees C for various hours after intravascular flushing with LR. The extents of the conversion from XD to XO (%XO) constituted 21.1% +/- 3.0%, 36.2% +/- 7.0%, 63.2% +/- 8.1%, and 88.2% +/- 8.6% after 0, 2, 4, and 6 hours of the preservation, respectively (control group). The preservation without the intravascular flushing showed significant increase in the %XO (99.5% +/- 6.0%) only after 6 hours compared with those in the control group (P < .05). When the intestines were stored in LR containing 50 mg/L of TFP at 37 degrees C, or stored in LR at 37 degrees C after the intraperitoneal pretreatment with 10 mg/kg of TFP 1 hour before laparotomy showed significant decrease in the extents of the conversion after 4 hours (P < .005) and 6 hours (P < .025) of the preservation, compared with those in the control group. When the dose of TFP for the pretreatment was increased to 50 mg/kg, the suppressive effect on the conversion was found even after 2 hours (P < .025) as well as after 4 hours (P < .005) and 6 hours (P < .025) of the preservation. These results suggest that TFP could be effective on reducing the XO-mediated postischemic reperfusion injury by means of inhibiting the conversion during ischemia of the rat small intestine.
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PMID:Conversion of xanthine dehydrogenase to xanthine oxidase during ischemia of the rat small intestine and the effect of trifluoperazine on the conversion. 848 75

The effects of NBP on concentrations of some purine metabolites in extracellular fluid of rat striatum during global ischemia and reperfusion were studied. Global ischemia was produced by the four-vessel occlusion method. Push-pull cannula was implanted stereotaxically into the striatum of rat and was perfused with Ringer's solution at a flow rate of 2.5 microliters.min-1. The level of adenosine(Ade), inosine(Ino), hypoxanthine(Hyp) and xanthine(Xan) in perfusates were measured with HPLC connected with a UV detector. The results indicate that the levels of ade, ino, hyp and xan were significantly increased (about 3-5 times of initial value) during cerebral ischemia and reperfusion. NBP at the dose of 20 or 40 mg.kg-1 given intra-peritoneally 20 min before ischemia was shown to depress the increase of ade, ino, hyp and xan during ischemia and reperfusion dose dependently. But no change in the level of purine metabolites was found in sham operated rats. It has been known that harmful free radicals were produced when xan and uric acid were formed by xanthine oxidase during reperfusion. This might be important for the development of ischemic injuries. Our findings suggest that the effect of NBP might be beneficial for protection against post-ischemic neuronal damage.
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PMID:[Effect of dl-3-n-butylphthalide (NBP) on purine metabolites in striatum extracellular fluid in four-vessel occlusion rats]. 876 58

We examined the protective effect of diltiazem, a calcium antagonist, on myocardial ischemic injury associated with generation of hydroxyl free radicals (.OH). Salicylic acid in Ringer's solution (0.5 nmol.microliter-1.min-1) was infused directly through a microdialysis probe to detect the generation of .OH as reflected by the formation of 2,3-dihydroxybenzoic acid (DHBA) in the myocardium. Cardiac dialysate was assayed for 2,3-DHBA by a high-performance liquid chromatographic-electrochemical (HPLC-EC) procedure. The heart was subjected to myocardial ischemia for 15 min by occlusion of left anterior descending artery (LAD). The presence of .OH was indicated in the ischemic reperfused rat heart. However, when heart was reperfused, the elevation of 2,3-DHBA by 15-min ischemia was not observed in the ischemic zone following systemic administration of diltiazem (100 micrograms.min-1.kg-1), a calcium antagonist. When corresponding experiments were performed with allopurinol (10 mg.kg-1) administration of i.v. injection, the elevation of 2,3-DHBA was not observed. These results suggest that diltiazem may suppress the .OH generation from xanthine-xanthine oxidase system by ischemia-reperfusion.
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PMID:Protective effect of diltiazem on myocardial ischemic injury associated with .OH generation. 917 83

Lung injury often occurs after hepatoenteric ischemia, with xanthine oxidase (XO, an oxidant-generating enzyme), released from reperfusing liver and intestines, mediating a significant component of this injury. Since pentastarch administration decreases intestinal reperfusion injury, we determined whether resuscitation with PentaLyte (a pentastarch-containing solution) would decrease hepatoenteric reperfusion injury, xanthine oxidase release, and concomitant lung injury after aortic occlusion- reperfusion. Aortic occlusion was established in rabbits for 40 min, and was followed by 3 h of reperfusion, during which either PentaLyte or lactated Ringer's solution-based resuscitation was administered. Sham-operated animals served as controls. Hepatoenteric reperfusion injury, as manifested by release of the enzyme aspartate aminotransferase and decreased gastric intramucosal pH, was significantly (p < 0.0167) attenuated by PentaLyte administration after aortic occlusion-reperfusion, as compared with its occurrence in animals given lactated Ringer's solution. The release of XO after aortic occlusion-reperfusion was 4-fold smaller after PentaLyte administration than after resuscitation with lactated Ringer's solution (p < 0.05). Pulmonary injury, as defined by an increase in bronchoalveolar lavage fluid (BALF) protein content and lactate dehydrogenase (LDH) activity, was 4-fold less after PentaLyte administration following aortic occlusion-reperfusion than after administration of lactated Ringer's solution (p < 0.05). We conclude that remote pulmonary injury is significantly decreased by concomitant PentaLyte-mediated reduction of hepatoenteric reperfusion injury and XO release.
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PMID:PentaLyte decreases lung injury after aortic occlusion-reperfusion. 962 Sep 36

The present study examined the effect of glibenclamide, an ATP-sensitive K+ (K(ATP)) channels antagonist, on the potassium chloride (KCl)-induced hydroxyl free radical (.OH) generation. Sodium salicylate in Ringer's solution (0.5 nmol/microl per min) was infused directly through a microdialysis probe to detect the generation of .OH as reflected by the formation of dihydroxybenzoic acid (DHBA) in the myocardium of anesthetized rat. The high concentration of KCl (70 mM) significantly increased the level of 2,3- and 2,5-DHBA by the action of depolarization by KCl. However, in the presence of glibenclamide (10 microM), KCl failed to increase the 2,3- and 2,5-DHBA formation. Moreover, when allopurinol (10 mg/kg), a xanthine oxidase inhibitor, was administered by i.v. injection, the elevation of DHBA was not observed. These results suggest that openings of cardiac K(ATP) channel by depolarization evokes .OH generation via xanthine oxidase reaction.
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PMID:Glibenclamide, an antagonist of ATP sensitive K+ channels, blocks free radical generation in the rat myocardium. 985 65

We examined the effect of N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, on extracellular potassium ion concentration ([K(+)](o))-enhanced hydroxyl radical (.OH) generation due to 1-methyl-4-phenylpyridinium ion (MPP(+)) was examined in the rat striatum. Rats were anesthetized, and sodium salicylate in Ringer's solution (0.5 nmol/microl per min) was infused through a microdialysis probe to detect the generation of.OH as reflected by the non-enzymatic formation of 2,3-dihydroxybenzoic acid (DHBA) in the striatum. Induction of KCl (20, 70 and 140 mM) increased MPP(+)-induced.OH formation trapped as 2,3-dihydroxybenzoic acid (DHBA) in a concentration dependent manner. However, the application of L-NAME (5 mg/kg i.v.) abolished the [K(+)](o) depolarization-induced.OH formation with MPP(+). Dopamine (DA; 10 microM) also increased the levels of DHBA due to MPP(+). However, the effect of DA after application of L-NAME did not change the levels of DHBA. On the other hand, the application of allopurinol (20 mg/kg i.v., 30 min prior to study), a xanthine oxidase (XO) inhibitor was abolished the both [K(+)](o)- and DA-induced.OH generation. Moreover, when iron(II) was administered to MPP(+) then [K(+)](o) (70 mM)-pretreated animals, a marked increase in the level of DHBA. However, when corresponding experiments were performed with L-NAME-pretreated animals, the same results were obtained. Therefore, NOS activation may be no relation to Fenton-type reaction via [K(+)](o) depolarization-induced.OH generation. The present results suggest that [K(+)](o)-induced depolarization augmented MPP(+)-induced.OH formation by enhancing NO synthesis.
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PMID:Nitric oxide enhances MPP(+)-induced hydroxyl radical generation via depolarization activated nitric oxide synthase in rat striatum. 1138 16

We examined the effect of NG-nitro-L-arginine methyl ester (L-NAME), a NOS inhibitor, on extracellular potassium ion concentration ([K+]o) and induced hydroxyl free radical (.OH) generation by an in vivo microdialysis technique. A flexibly mounted microdialysis technique was used to detect the generation of .OH in in-vivo rat hearts. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rats and tissue was perfused with Ringer's solution through the microdialysis probe at a rate of 1.0 microl/min. To measure the level of .OH, sodium salicylate in Ringer's solution (0.5 nmol/microl per min) was infused directly through a microdialysis probe to detect the generation of .OH as reflected by the nonenzymatic formation of 2,3-dihydroxybenzoic acid (2,3-DHBA). Induction of high-concentration [K+]o (20, 70 and 140 mM) significantly increased formation of .OH trapped as 2,3-DHBA in a concentration-dependent manner. However, the application of L-NAME (50 mg/kg, i.v.) and allopurinol, a xanthine oxidase inhibitor, abolished the [K+]o depolarization-induced .OH generation. Tyramine (1.0 mM) increased the level of 2,3-DHBA. However, the application of L-NAME did not change the level of 2,3-DHBA. On the other hand, pretreatment with allopurinol (10 mg/kg, i.v.) abolished the KCl- or tyramine-induced .OH generation. Moreover, when iron (II) was administered to [K+]o (70 mM)-pretreated animals, there was a marked increased in the level of 2,3-DHBA. However, the application of L-NAME was not related to a Fenton-type reaction via [K+]o depolarization-induced .OH generation. To examine the effect of L-NAME on ischemic/reperfused rat myocardium, the heart was subjected to myocardial ischemia for 15 min by occlusion by left anterior descending coronary artery branch (LAD). When the heart was reperfused, a marked elevation of the level of 2,3-DHBA was observed. However, L-NAME attenuated .OH generation by ischemic/reperfused rat heart. These results suggest that NOS inhibition is associated with a cardioprotective effect due to the suppression of [K+]o depolarization-induced .OH generation.
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PMID:Nitric oxide induces hydroxyl radical generation in rat hearts via depolarization-induced nitric oxide synthase activation. 1148 40