Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Interferon, interferon inducers, and a variety of other immunomodulators are known to depress the hepatic cytochrome P-450 drug-metabolizing system. Two concepts have been proposed to explain this phenomenon. (a) The steady-state of cytochrome P-450 is altered through decreased synthesis and increased degradation of cytochrome P-450 apoprotein. (b) Interferon induces xanthine oxidase; superoxide generated by interferon-induced xanthine oxidase destroys cytochrome P-450. The current study investigated the second concept. Administered polyribonucleotides [polyriboinosinic acid.polyribocytidylic acid (poly IC), polyriboinosinic acid.polycytidylic acid, polylysine and carboxymethylcellulose, mismatched poly IC], recombinant murine gamma-interferon, and a natural murine alpha/beta-interferon were shown to depress hepatic cytochrome P-450 and selected microsomal cytochrome P-450-dependent monooxygenase reactions and to induce hepatic xanthine oxidase activity. The feeding of tungstate in the drinking water largely depleted xanthine oxidase in mice; cytochrome P-450 levels and monooxygenase activities were not affected by tungstate treatment. Tungstate rendered the level of xanthine oxidase much below that in mice that had not received tungstate regardless of whether or not they had received poly IC or interferon; nevertheless, poly IC and interferon produced losses of cytochrome P-450 and monooxygenase activities in these tungstate-treated mice equivalent to those observed in mice that had not received tungstate. The administration of N-acetylcysteine did not prevent the loss of cytochrome P-450 induced by poly IC, as has been reported, nor did the incubation of microsomal cytochrome P-450 with buttermilk xanthine oxidase and hypoxanthine cause a loss of cytochrome P-450, which has also been reported. It is concluded from these studies that the induction of xanthine oxidase and the loss of cytochrome P-450 generated by interferon are coincidental rather than causally related phenomena.
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PMID:Role of xanthine oxidase in the interferon-mediated depression of the hepatic cytochrome P-450 system in mice. 245 Jun 44

Dietary fat-type and copper (Cu) deficiency have been independently identified as potentially important factors in the etiology of ischemic heart disease (IHD); a disease that has been linked to inflammation and oxygen free radical (OFR) mediated damage. Group (n = 6) of male, weanling, Wistar rats were provided ad libitum with deionized water and control or low Cu diets containing (200 g/kg) either saturated or polyunsaturated fatty acids (SFA or PUFA, respectively) for 56 d. Measurement of several indices of Cu status indicated that both groups fed the low Cu diets were Cu-deficient. SFA consumption resulted in significantly increased hepatic Cu (p less than 0.001) and iron (Fe) (p less than 0.001) concentrations and xanthine oxidase activity (p less than 0.05) and significantly decreased hepatic glucose-6-phosphate dehydrogenase activity (p less than 0.001). Although Cu deficiency resulted in significantly decreased hepatic copper-zinc superoxide dismutase (CuZnSOD) activity (p less than 0.01), no significant effect on the activities of the other hepatic antioxidant enzymes, manganese superoxide dismutase, catalase, and glutathione peroxidase, or glutathione reductase, were observed. Cu deficiency also resulted in significantly decreased hepatic Cu levels (p less than 0.001) and cytochrome c oxidase activity (p less than 0.01). No significant difference in hepatic thiobarbituric acid reactive substances (TBARS), a measure of lipid peroxidation, was found between groups consuming SFA or PUFA, but both Cu-deficient groups exhibited significantly increased hepatic TBARS (p less than 0.001), compared to controls. This was probably owing to the significantly decreased hepatic CuZnSOD activity observed in the Cu-deficient, compared to control animals.
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PMID:Dietary saturated or polyunsaturated fat and copper deficiency in the rat. 248 34

Inasmuch as xanthine oxidase (XO)-derived O2* metabolites may contribute to vascular endothelial injury and Factor VIII antigen (F8Ag) is a component of endothelial cells, we hypothesized that XO-derived O2* might damage and cause distant organ endothelial cells to release F8Ag in rats subjected to skin burn. We found that serum F8Ag (ELISA) increased in the blood of rats subjected to skin burn (70 degrees C water to shaved dorsal skin for 30 seconds) but not in sham control rats (30 degrees C water). Coincidentally, F8Ag levels also decreased in lung and kidney tissue sections (immunofluorescent staining) of burned rats but not sham rats. Increases in circulating F8Ag levels and decreases in tissue F8Ag levels appeared to result from XO-derived O2* metabolites: F8Ag levels did not increase in the blood and did not decrease in the tissues of rats pretreated with allopurinol (a specific XO inhibitor, 50 mg/kg) or dimethylthiourea (DMTU) (a permeable O2* metabolite scavenger, 250 mg/kg). Lung injury as assessed by permeability studies (I125-albumin leak) paralleled changes in blood F8Ag levels in sham, burn, allopurinol-, and DMTU-treated groups. We conclude that skin burn causes a systemic vascular injury that can be inhibited by allopurinol or DMTU and is reflected by increased circulating and tissue decreased Factor VIII antigen levels. Release of Factor VIII antigen may serve as a valuable marker of distant organ injury in patients with skin burn.
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PMID:Local skin burn causes systemic (lung and kidney) endothelial cell injury reflected by increased circulating and decreased tissue factor VIII-related antigen. 250 1

We investigated the effects of the xanthine oxidase inhibitor allopurinol and its metabolite oxypurinol on isolated rabbit hearts. To assess the potential role of these drugs in preventing reperfusion injury, hearts were perfused using Langendorff techniques, held globally ischemic for 3 h at 15 degrees C, and then reperfused. During perfusion, hearts received Krebs-Henseleit solution maintained at 37 degrees C. Aortic perfusion pressure was held constant at 80 cm H2O. Prior to ischemia, hearts were arrested with a constant volume of KCl cardioplegia. Using a left ventricular (LV) balloon, developed pressures were measured prior to and following global ischemia. In addition, coronary circulation (CC) was measured before and after ischemia. All hearts were paced at 260 beats/min. We studied four groups: group 1 received 1 mM allopurinol, group 2 received 1 mM oxypurinol, group 3 received 90 IU/ml superoxide dismutase (SOD) plus 8085 IU/ml catalase (CAT), and group 4 received no treatment and served as a control. Each group consisted of 8 animals. Hearts receiving drug treatment did so during the first 5 min of reperfusion. Displaying all data as a function of LV volume, postischemic values were compared to preischemic values. Multivariate analysis and Tukey tests were used to detect significant differences between groups. When compared to the control group, all drug-treated groups significantly recovered end-diastolic function. Peak systolic pressure decreased significantly in the SOD/CAT group as compared to all other groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevention of reperfusion injury in ischemic-reperfused hearts by oxypurinol and allopurinol. 262 64

Although oxygen has been known to be toxic for more than 200 years, the clinical importance of oxygen toxicity was not appreciated until an epidemic of retrolental fibroplasia occurred in the early 1950s. Oxygen at high partial pressures is toxic to the respiratory, cardiovascular, nervous, and gastrointestinal systems. Toxicity results from the formation of oxygen-free radicals. These arise within mitochondria as oxygen is reduced to water, as byproducts of prostaglandin and thromboxane synthesis, and by the xanthine oxidase catalyzed reduction of xanthine or hypoxanthine. They are also produced by activated macrophages as part of the immune response. Superoxide anion is the radical most commonly produced. It dismutes to hydrogen peroxide, which is able to diffuse through lipid membranes. Hydrogen peroxide reacts with transition metals to produce the highly reactive hydroxyl radical which can initiate chain reactions of lipid peroxidation leading to cell rupture. Oxygen radical scavengers such as superoxide dismutase and catalase protect the body against normal levels of oxygen-free radicals. Oxygen toxicity can result from either reperfusion of ischemic tissue or prolonged exposure to high concentrations of oxygen. Limiting hyperoxia to maintain arterial oxygen percent saturation (SaO2) greater than or equal to 90% is recommended.
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PMID:Oxygen toxicity: an introduction. 267 91

Both Trolox (a water-soluble analogue of alpha-tocopherol) and ascorbic acid were more effective than superoxide dismutase or catalase in protecting myocyte cell cultures from free radical attack (induced by hypoxanthine and xanthine oxidase). In a canine model of two hours of left anterior descending coronary artery occlusion followed by four hours of reperfusion, Trolox and ascorbic acid reduced the area of infarction within the area at risk. The Trolox group received 500 mL of deoxygenated saline solution containing 2.0 g of Trolox, 3.0 g of ascorbic acid, and 18 mg of EDTA (ethylenediaminetetraacetic acid) infused into the ascending aorta 30 seconds before and four minutes after reperfusion. Saline controls received 500 mL of deoxygenated saline solution containing 18 mg of EDTA. The angioplasty group had unmodified reperfusion by simple release of the occlusion. The area at risk and the area infarcted were estimated with Evans blue and triphenyl tetrazolium hydrochloride stains, respectively. The ratio of the area infarcted to the area at risk was significantly lower with Trolox (angioplasty, 30.4% +/- 5.1%; saline, 20.8% +/- 2.9%; and Trolox, 8.7% +/- 4.0%; p less than 0.01). In summary, the antioxidants Trolox and ascorbic acid effectively reduced myocardial necrosis after ischemia.
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PMID:Myocardial salvage with trolox and ascorbic acid for an acute evolving infarction. 271 29

Postischemic renal dysfunction (PIRD) is characterized by a reduction in glomerular filtration and tubular reabsorption of solute. The relative contribution of oxygen free radicals (OFRs) generated during reperfusion remains unclear. This study characterized the renal response to OFRs--independent of an ischemic insult. Isolated rat kidneys were perfused at 37 degrees C and 90-100 mm Hg with a modified Krebs' buffer. Hypoxanthine (25 mumole) and xanthine oxidase (1 unit) were combined and infused proximal to the kidney. There was a 50% increase in vascular resistance. This was accompanied by a 30% reduction in perfusate flow rate and a 70% reduction in glomerular filtration rate. There was also a significant reduction in urine flow rate and oxygen consumption. The percentage reabsorption of filtered water and sodium by the renal tubules was not diminished, however. This pattern was not observed when the xanthine oxidase was inactivated or when the perfusate was pretreated with superoxide dismutase (250 units/ml) and catalase (500 units/ml). The generation of OFRs, independent of an ischemic insult, causes a decrease in glomerular filtration out of proportion to the decrease in renal flow similar to that observed with PIRD. OFRs may contribute to the hemodynamic and glomerular alterations seen with PIRD. Factors other than OFRs, probably associated with ischemia, must be responsible for the tubular dysfunction.
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PMID:Oxygen free radical mediated renal dysfunction. 271 9

To verify whether lipid peroxidation is associated with focal cerebral ischemia, a unilateral middle cerebral artery occlusion was carried out in rats. The concentrations of various endogenous antioxidants in the ischemic center were measured, including alpha-tocopherol and ubiquinones as lipid-soluble antioxidants and ascorbate as a water-soluble antioxidant. At 30 minutes after ischemia, alpha-tocopherol decreased to 79% of baseline, reduced ubiquinone-9 to 73%, ubiquinone-10 to 66%, and reduced ascorbate to 76%. Six hours after ischemia, alpha-tocopherol decreased to 63% and reached a plateau, whereas reduced ubiquinones and reduced ascorbate declined further to 16% and 10%, respectively, 12 hours after ischemia and then reached plateau levels. These results suggest functional and durational differences between antioxidants and lipid peroxidation in this ischemic model. Although the reciprocal increase in oxidized ubiquinones during ischemia was not observed, that of 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 on the basis that the loss of these reduced antioxidants is due to neutralization of free radicals. This system is suggested to play an important role in the early ischemic period. Urate also increased during ischemia. The possible involvement of the xanthine-xanthine oxidase system in initiating free radical reactions in cerebral ischemia is also discussed.
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PMID:Lipid peroxidation in focal cerebral ischemia. 276 92

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

We examined the basis of reperfusion-induced pulmonary edema produced by pulmonary artery occlusion and subsequent reperfusion. After a 24-h period of occlusion of a rabbit pulmonary artery followed by a 2-h period of reperfusion, the lungs were removed from the animal and perfused with a 0.5 g% Ringer's-albumin solution. An increase in lung weight was observed within 60 min compared with control lungs (i.e., lungs subjected to pulmonary arterial occlusion but not reperfusion) (p less than 0.05). Shorter periods of occlusion (6 or 12 h) did not result in edema, which suggests that a period of ischemia was required for the reperfusion-induced pulmonary edema. The extravascular lung water content also increased in the contralateral lung (i.e., the lung not subjected to pulmonary arterial occlusion and reperfusion). The capillary filtration coefficient increased in reperfused lungs compared with controls (p less than 0.05), indicating an increase in lung vascular permeability following reperfusion. Infusion of allopurinol (a xanthine oxidase inhibitor) and superoxide dismutase during the reperfusion period prevented the increases in lung weight and vascular permeability; infusion of catalase was ineffective. We conclude that pulmonary reperfusion following pulmonary artery occlusion increases pulmonary vascular permeability, which is mediated by the generation of oxidants.
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PMID:Pulmonary edema after pulmonary artery occlusion and reperfusion. 281 6


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