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)

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

This study shows that peroxisomes are abundant in the Malpighian tubule and gut of wild-type Oregon R Drosophila melanogaster and that the peroxisomal population of the rosy-506 eye-color mutant differs from that of the wild type. Catalase activity in wild-type flies is demonstrable in bodies of appearance and centrifugal behavior comparable to the peroxisomes of vertebrate tissues. Xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.1.3.22) activity of the Malpighian tubule of wild-type flies is demonstrable cytochemically in bodies like those containing catalase. The rosy-506 mutant flies, with a deletion in the structural gene for xanthine dehydrogenase (xanthine:NAD+ oxidoreductase, EC 1.1.1.204), lack cytochemically demonstrable peroxisomal xanthine oxidase activity. In addition, peroxisomes in the rosy-506 mutants show less intense cytochemical staining for catalase than those in wild-type flies, and biochemical assays indicate that catalase in the rosy mutant is much more accessible to substrate in the absence of detergent than in the wild type. Thus, the rosy-506 mutation appears to affect peroxisomes and may mimic aspects of the defects of peroxisomes in some human metabolic disorders.
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PMID:Peroxisomes in wild-type and rosy mutant Drosophila melanogaster. 311 68

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

The present studies were undertaken to determine the effects of reactive oxygen metabolites on erythropoietin (Ep) biosynthesis in Ep-producing renal carcinoma (RC) cells using a sensitive radioimmunoassay for Ep. Xanthine (10-5M) and increasing concentrations of xanthine oxidase (8 x 10(-7) to 5 x 10(-4) units/ml) produced a significant dose-related increase in Ep production at a concentration of greater than or equal to 4 x 10(-6) units/ml, whereas xanthine alone had no effect. Catalase, a scavenger of hydrogen peroxide (H2O2), in concentrations of 50 to 500 micrograms/ml produced a significant inhibition of the increase in Ep production induced by xanthine-xanthine oxidase; while no effect was seen on basal levels of Ep production and the growth of RC cells. Glucose oxidase (greater than or equal to 0.032 mU/ml), a direct H2O2 generator, and exogenous H2O2 (greater than or equal to 4 x 10(-6)M) added to the incubation mixture, caused a significant enhancement of Ep production in a dose-dependent manner. Xanthine-xanthine oxidase, glucose oxidase, and H2O2 in the above concentrations did not produce significant cytotoxicity (51Cr release or trypan blue dye exclusion). The present data suggests that H2O2, a reactive oxygen metabolite may play a significant role in Ep production.
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PMID:Effects of reactive oxygen metabolites on erythropoietin production in renal carcinoma cells. 340 Dec 35

Significant pulmonary toxicity is associated with the use of nitrofurantoin; however, the mechanism of cellular toxicity remains poorly characterized. By using a novel in vitro red blood cell (RBC) chromium 51 cytotoxicity assay, cell injury induced by nitrofurantoin was quantified with normocatalasemic BALB/c RBCs and hypocatalasemic (but otherwise genetically identical) CCN RBCs as target cell populations. Nitrofurantoin at concentrations of 2 x 10(-4) and 4 x 10(-4) mol/L resulted in significant injury to normocatalasemic RBCs with a cytotoxic index (CI) of 21.7% +/- 3.7% and 65.3% +/- 3.7% (p less than 0.05, both comparisons). This injury was substantially increased when nitrofurantoin (2 x 10(-4) and 4 x 10(-4) mol/L was incubated with hypocatalasemic RBCs, resulting in CIs of 59.0% +/- 7.4% and 91.0% +/- 2.0% respectively (p less than 0.05, both comparisons with normocatalasemic RBCs). Direct oxidant-mediated cytotoxicity induced by either H2O2 or the superoxide anion radical (as generated by xanthine-xanthine oxidase) also resulted in more significant injury to hypocatalasemic RBCs than to normocatalasemic RBCs (p less than 0.05, both comparisons). Catalase levels of CCN RBCs were approximately 7% of control BALB/c RBC values; however, the activities of superoxide dismutase and glutathione peroxidase were identical in both populations of RBCs. This model, using genetically defined target cell populations, clearly demonstrates the importance of endogenous catalase in protecting against nitrofurantoin-induced cytotoxicity, suggesting that H2O2 is a critical intermediary in the direct cell injury mediated by the drug.
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PMID:Importance of hydrogen peroxide in nitrofurantoin-induced cytotoxicity: evidence from an inbred catalase-deficient strain of mice. 341 Nov 91

Two dermatophyte strains, Trichophyton quinckeanum and Trichophyton rubrum, were highly susceptible to in vitro killing by components of the H2O2-peroxidase-halide system. Both strains were, however, resistant to relatively high concentrations of reagent H2O2 or H2O2 enzymatically generated by glucose and glucose oxidase, KI, or lactoperoxidase (LPO) alone. Resistance to hydrogen peroxidase killing was found to be in part due to the presence of endogenous catalase in the fungi; susceptibility was increased by pretreatment of the fungi with a catalase inhibitor. Kinetic studies using small quantities of reagent or enzymatically generated H2O2 and LPO-KI showed that the system was lethal for both fungal strains within 1 min. Furthermore, using the glucose-glucose oxidase-LPO-KI system, it was shown that catalase, superoxide dismutase and histidine scavengers of H2O2, superoxide anion and singlet oxygen, respectively, prevented the killing of fungus, whereas scavengers of hydroxyl radicals such as benzoate and mannitol had no effect. T. quinckeanum was found to contain large quantities of superoxide anion, as judged by the nitroblue-tetrazolium test. Consequently, the xanthine (or hypoxanthine) and xanthine oxidase system in which the main product is superoxide anion had no toxic effect on the fungus. The high sensitivity of dermatophytes to killing by the H2O2-peroxidase-halide system active in polymorphonuclear neutrophils and macrophages may account in part for fungal toxicity in vivo.
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PMID:Susceptibility of Trichophyton quinckeanum and Trichophyton rubrum to products of oxidative metabolism. 361 Feb 10

We report in detail the ontogeny and the response of antioxidant enzymes to glucocorticoids in the rat small intestine. Pregnant rats in the treatment group received four injections of dexamethasone starting on days 18, 19, or 20 of gestation; fetuses were killed 2 days later. Control rats were injected with 0.9% saline solution. Postnatal rats reaching 14, 19, and 104 days of age received four injections of hydrocortisone and were killed 2 days later. Age-matched controls were injected with 0.9% saline solution. The activities of xanthine oxidase, superoxide dismutase, and catalase were measured in small intestines from fetal (20 and 21 days gestation), newborn, and older (aged 16, 21, and 106 days) rats. Xanthine oxidase rose with maturation; the major increase occurred on postnatal day 21. Catalase and superoxide dismutase rose minimally during intrauterine life. On day 16 postpartum, catalase and superoxide dismutase values were 160% and 60%, respectively, higher than at birth. Glucocorticoid administration stimulated maltase and sucrase activities, but had no effect on the antioxidant enzymes or xanthine oxidase.
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PMID:Maturation of antioxidant enzymes in rat small intestine: lack of glucocorticoid stimulation. 362 18

We evaluated whether supplemental pharmacologic interventions that altered formation or degradation of reactive oxygen metabolites, when added to hypothermic crystalloid cardioplegic solution (procaine-free St. Thomas' Hospital solution), alter postischemic function of isolated rabbit hearts. Hypoxic, substrate-free cardioplegic solutions cooled to 27 degrees C were perfused through isolated rabbit hearts for 5 minutes before and after an uninterrupted 2 hour period of global ischemia at 27 degrees C. Hearts were then reperfused with standard buffer for 1 hour at 37 degrees C. In some experiments, the cardioplegic solution was supplemented with the following: superoxide dismutase (30 micrograms/ml; degrades superoxide anion); catalase (1.7 micrograms/ml; degrades hydrogen peroxide); allopurinol (1 mmol/L; inhibits xanthine oxidase); or deferoxamine (Desferal, 0.5 mmol/L; selectively chelates ferric iron). Postreperfusion contractile parameters of supplemented hearts, including left ventricular pressure development and its first derivative, left ventricular compliance, spontaneous heart rate, and coronary vascular resistance, were statistically compared to data obtained from hearts arrested with unsupplemented cardioplegic solution. Catalase supplementation provided statistically significant improvement of most functional parameters; somewhat less protection was obtained with allopurinol. Deferoxamine provided little added protection except for the ability to prevent ischemia-induced increases of coronary vascular resistance. There was no evidence of added protection by superoxide dismutase. The data suggest that an important component of ischemia-induced cardiac cell damage in an asanguineous setting is hydrogen peroxide-dependent, and interventions that either inhibit production of superoxide anion or degrade hydrogen peroxide offer best protection. They may be clinically efficacious additives to crystalloid cardioplegic solutions.
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PMID:Effects of supplementing hypothermic crystalloid cardioplegic solution with catalase, superoxide dismutase, allopurinol, or deferoxamine on functional recovery of globally ischemic and reperfused isolated hearts. 394 95

Neutrophil-mediated injury to lung parenchymal cells has been proposed as an important step in the pathogenesis of many acute and chronic lung disorders. As an in vitro model of neutrophil-mediated injury, this study used activated human neutrophils as effector cells in an 18-h cytotoxicity assay with 51Cr-labeled bovine pulmonary artery endothelial cells serving as target cells. Neutrophils effectively injured pulmonary endothelial cells, expressed as cytotoxic index (CI), of 63.8 +/- 5.4, and this injury could be significantly reduced by several agents, including 1% dimethyl sulfoxide (CI, 51.3 +/- 3.7), 50 micrograms/ml ascorbic acid (CI, 40.8 +/- 4.7), and especially 1,100 U/ml catalase (CI, 14.3 +/- 4.1). As cell-free models of neutrophil-mediated endothelial cell injury, H2O2 (30 microM), O2- (generated by 0.5 mU xanthine oxidase), and the myeloperoxidase-dependent (0.32 U) hypohalite ion were each capable of injuring the target cells with CI of 6.21 +/- 2.8, 53.6 +/- 5.3, and 21.2 +/- 1.5, respectively. Catalase was effective in reducing the injurious effect of each of these oxidant-generating systems (p less than 0.01, all comparisons), confirming the important role for H2O2 in the mediation of this injury. The data indicate that neutrophils are capable of killing pulmonary endothelial cells by a pathway largely dependent on the generation of H2O2, and suggest the possibility that removal of H2O2 from the alveolar structures in subjects with these disorder might be an effective future therapeutic approach.
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PMID:Neutrophils kill pulmonary endothelial cells by a hydrogen-peroxide-dependent pathway. An in vitro model of neutrophil-mediated lung injury. 608 99

Catalase was inhibited by a flux of O2- generated in situ by the aerobic xanthine oxidase reaction. Two distinct types of inhibition could be distinguished. One of these was rapidly established and could be as rapidly reversed by the addition of superoxide dismutase. The second developed slowly and was reversed by ethanol, but not by superoxide dismutase. The rapid inhibition was probably due to conversion of catalase to the ferrooxy state (compound III), while the slow inhibition was due to conversion to the ferryl state (compound II). Since neither compound III nor compound II occurs in the catalatic reaction pathway, they are inactive. This inhibition of catalase by O2- provides the basis for a synergism between superoxide dismutase and catalase. Such synergisms have been observed in vitro and may be significant in vivo.
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PMID:Superoxide radical inhibits catalase. 627 12


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