Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of perfusate calcium reduction, allopurinol and dimethylthiourea on reperfusion-induced arrhythmias and purine wash-out in isolated rabbit and rat hearts were compared. The overall incidence of reperfusion-induced ventricular tachycardia (VT) was 88% and 94% and that of ventricular fibrillation (VF) was 44% and 88% in the control rabbit and rat hearts, respectively. VF was reduced to 10% and 0% in rat and rabbit hearts subjected to perfusate calcium reduction (0.4 mM for 1 min before ischemia and for 1 min before and throughout reperfusion), respectively. In allopurinol, 1 mM, perfused rat hearts the overall incidence of VF was not changed and only the incidence of a sustained VF (that lasting for at least 10 min) was reduced. VT and VF were prevented in allopurinol-perfused rabbit hearts. Dimethylthiourea, 10 mM, reduced the incidence of VF in rat hearts to 16% and did not significantly affect VT and VF in rabbit hearts. In untreated rat hearts, the major purine compounds washed out upon reperfusion were inosine, hypoxanthine, xanthine and urate. Allopurinol augmented the wash-out of adenosine and abolished that of xanthine and urate. In untreated rabbit hearts, the major purine washed out were inosine, adenosine and hypoxanthine. Allopurinol did not cause further increase in adenosine wash-out in rabbit hearts. We speculate that: (1) calcium mediated arrhythmogenic mechanism is operating both in reperfused rat and rabbit heart; (2) free radical mediated mechanism is of an importance only in rat heart; (3) neither a decreased free radical production secondary to xanthine oxidase inhibition nor the augmentation of adenosine wash-out is a likely explanation for the antiarrhythmic effect of allopurinol in reperfused hearts; and (4) high level of myocardial adenosine accumulation during ischemia, probably secondary to low xanthine oxidase activity, may play a role of a natural defence mechanism in ischemic/reperfused rabbit heart.
J Mol Cell Cardiol 1993 Jul
PMID:Reperfusion arrhythmias and purine wash-out in isolated rat and rabbit heart. Effect of allopurinol, dimethylthiourea and calcium reduction. 823 Feb 46

The purpose of this study was to determine the radical species which mediates the toxic effects of exogenous oxygen-derived free radicals on endothelial function of chronic diabetic rat aorta. Endothelium-dependent relaxation to acetylcholine was impaired in diabetic vessels. Exposure to the exogenous free radical generating system of xanthine plus xanthine oxidase selectively impaired endothelium-dependent relaxation to acetylcholine in control and diabetic aorta with relaxations essentially abolished in diabetic aorta. The loss of relaxation to acetylcholine in diabetic aorta was prevented or attenuated by pretreatment with catalase, dimethylthiourea or desferrioxamine, but not by mannitol or superoxide dismutase. These results suggest that hydroxyl radicals play an important role in the endothelial injury produced by oxygen-derived free radicals in chronic diabetic rat aorta. Furthermore, the site of the injury is likely due to intracellular generation of hydroxyl radicals.
Mol Cell Biochem 1993 May 26
PMID:Hydroxyl radicals mediate injury to endothelium-dependent relaxation in diabetic rat. 823 45

This study looks at the role of xanthine oxidase (XO) in ischemia/reperfusion (I/R) induced intestinal mucosal damage using normal and xanthine oxidase deficient rats. Tungstate feeding for 3 days depleted the intestinal mucosal XO by 80%. A ligated loop of the rat small intestine (both normal and XO-deficient) was subjected to 1 h of total ischemia followed by 5 min revascularisation. The ensuing mucosal damage was assessed by biochemical and histological studies. Ischemia or I/R increased the XO levels in normal rats without any change in XO-deficient rats. Myeloperoxidase (a neutrophil marker) level was increased in both group of rats but it was comparatively higher in the XO-deficient rats. Accumulation of peroxidation products such as malondialdehyde, conjugated diene and increased production of hydroxyl radicals by microsomes were seen after ischemia and I/R and were similar in normal and XO-deficient rats. Studies on other parameters of peroxidation showed a decrease in polyunsaturated fatty acids and alpha-tocopherol, an increase in cysteine and cystine levels after I/R and were similar in both normal and XO-deficient rats. Histological results indicated gross morphological changes in the intestinal mucosa due to ischemia and I/R, and the damage was more severe in XO-deficient rats. These observations suggest that oxygen-derived free radicals are involved in the intestinal mucosal damage during I/R and infiltrated neutrophils rather than XO may be the primary source of free radicals under these conditions.
Mol Cell Biochem 1993 Jul 07
PMID:Oxygen free radical induced damage during intestinal ischemia/reperfusion in normal and xanthine oxidase deficient rats. 823 77

DNA adduct formation by enzyme-activated antibiotics, mitomycin C (MMC) or porfiromycin (PFM), at pH 7.6 or pH 6.0 under anaerobic conditions was analyzed by a 32P-postlabeling method. Antibiotic activation by rat liver NADPH-cytochrome P-450 reductase (EC 1.6.2.4) and bovine milk xanthine oxidase (EC 1.2.3.2) produced similar results. Five 32P-labeled MMC adducts were separated by thin layer chromatography and high performance liquid chromatography from DNA alkylated at either pH. Four of the radioactive spots separated by thin layer chromatography were identified as two monofunctional monoadducts [1" alpha and 1" beta forms of N2-(2" beta,7"-diaminomitosen-1"-yl)-2'-deoxyguanylic acid], one bifunctional monoadduct [N2-(10"-decarbamoyl-2",7"-diaminomitosen-1" alpha-yl)-2'-deoxyguanylic acid], and one cross-linked adduct [N2-(2" beta,7"-diamino-10"-deoxyguanyl-N2-yl-mitosen- 1" alpha-yl)-2'-deoxyguanylic acid]. One minor radioactive spot was not identified. By comparing DNA alkylated at the two pH values, based on equal amounts of 32P radioactivity, similar amounts of cross-links were detected. However, the DNA showed different ratios of the alpha and beta isomers of the monofunctional monoadduct. Furthermore, the DNA alkylated at pH 6.0 showed more bifunctional monoadducts than did the DNA alkylated at pH 7.6. Analysis of alkylated DNA by enzyme-activated PFM showed a similar spectrum of DNA adduct formation. The effect of pH on the distribution of the five PFM-DNA adducts was similar to that observed for the five MMC-DNA adducts. The distribution of adducts in DNA alkylated at the same pH was similar irrespective of which enzyme activated MMC or PFM. The pH of the reaction during DNA and MMC interaction was the determining factor for the quantitative distribution of the adducts. This pH effect may be important for the cytotoxicity of MMC and PFM in tumor cells that have high levels of reductive enzymes with low optimal pH values.
Mol Pharmacol 1993 Jun
PMID:Effect of pH on DNA alkylation by enzyme-activated mitomycin C and porfiromycin. 839 Nov 16

Production of oxygen radicals by phagocytic cells and loss of surfactant function have each been implicated in the pathogenesis of acute lung injury. Therapeutic administration of exogenous surfactant to injured lungs in which neutrophils are the dominant cell type has been proposed. To understand the role of surfactant in modulating pulmonary inflammation and the impact of surfactant supplementation on diseased lungs, we studied the effect of native porcine and synthetic surfactant preparations on human neutrophil respiratory burst oxidase activity in vitro. We found that surfactant inhibited neutrophil superoxide production induced by either receptor-mediated [formylmethionylleucylphenylalanine (fMLP)] or non-receptor-mediated [phorbol myristate acetate (PMA)] agonists with an IC50 of approximately 0.015 mg phospholipid/ml for porcine surfactant or approximately 0.050 mg phospholipid/ml for synthetic surfactant. Surfactant had no effect on detection of superoxide generation in a noncellular system using xanthine and xanthine oxidase and only minimally inhibited superoxide generation by neutrophils that had been fully stimulated by prior exposure to PMA. There was no effect of surfactant on neutrophil calcium mobilization in response to fMLP, on lactoferrin release in response to PMA, or on membrane protein kinase C activity in response to PMA. Suspensions of dipalmitylphosphatidylcholine alone had no effect on neutrophil superoxide production. Taken together, these findings indicate that certain components of lung surfactant may effect relatively late steps in the activation of the respiratory burst or may alter subsequent steps involved in the assembly of the respiratory burst oxidase.
Am J Respir Cell Mol Biol 1996 May
PMID:Inhibition of the human neutrophil respiratory burst by native and synthetic surfactant. 862 55

Hemorrhage rapidly increases plasma xanthine oxidase levels as well as the expression of proinflammatory and immunoregulatory cytokines in the lungs. To determine the role of circulating xanthine oxidase (XO), as well as other plasma factors, in affecting pulmonary cytokine expression, we conducted studies in which plasma from hemorrhaged mice was transferred into unhemorrhaged recipient mice. Administration of posthemorrhage plasma to recipient mice increased the levels of mRNA for interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha), and transforming growth factor-beta 1 (TGF-beta 1) in lung mononuclear cells. No enhancement of mRNA levels for these cytokines was found in the lungs of mice given allopurinol-treated posthemorrhage plasma or fed a tungsten-enriched, XO-depleting diet prior to transfer of posthemorrhage plasma. Among the nuclear transcriptional regulatory factors examined, only the cyclic AMP response-element binding protein (CREB) was activated in nuclear extracts from lung mononuclear cells of mice that were given posthemorrhage plasma. No activation of nuclear factor-kappa B (NF-kappa B), nuclear factor interleukin 6 (NF-IL6), activating protein-1 (AP-1), or serum protein-1 (SP-1) was found. These results suggest that the mechanism for hemorrhage-induced increases in pulmonary cytokine expression is by activation of the enhancer CREB through a tissue XO-dependent pathway initiated by plasma-borne mediators.
Am J Respir Cell Mol Biol 1996 Feb
PMID:Plasma from hemorrhaged mice activates CREB and increases cytokine expression in lung mononuclear cells through a xanthine oxidase-dependent mechanism. 863 Feb 71

The pathways participating in the metabolism of the nitrofuran antimicrobial drug N-[5-nitro-2-furfurylidene]-3-amino-2-oxazolidinone (furazolidone) in intact cells were investigated in the human intestinal cell line Caco-2. One-electron reduction of furazolidone led to the formation of a free radical intermediate that could be monitored in dense cell suspensions by noninvasive electron spin resonance spectroscopy. The effects of enzyme inhibitors on the kinetics of radical production and decay were used to estimate the relative contribution of different enzymes to the reductive activation of the drug. Although many enzymes are known to reduce nitrofurans in vitro (e.g., xanthine oxidase, aldehyde oxidase, DT-diaphorase, mitochondrial redox chain components), their contributions were insignificant in living Caco-2 cells. The first reducing equivalent required for the formation of the nitroanion derivative of furazolidone appeared to be provided essentially by the microsomal cytochrome P450 reductase. This was confirmed through studies of the NADPH-dependent radical formation by microsomes. Differentiated Caco-2 cells, an established enterocyte model, showed only modestly increased radical formation and the same enzyme-specificity pattern as undifferentiated cells. Consistently, only a small increase in P450 reductase activity was found in differentiated cells, in contrast to the 10-fold increase seen in typical differentiation marker enzymes. With the electron spin resonance method that we describe, it is possible to distinguish between sites of bioactivation of redox active drugs in intact cells.
Mol Pharmacol 1996 Mar
PMID:N-[5-nitro-2-furfurylidene]-3-amino-2-oxazolidinone activation by the human intestinal cell line Caco-2 monitored through noninvasive electron spin resonance spectroscopy. 864 95

Reactive oxygen species (ROS) have been shown to stimulate proliferation and growth responses in a variety of mammalian cell types and to act as important mediators in many cellular processes, including hematolymphopoiesis. We examined the effect on primitive murine hematopoietic progenitor cells (HPC) of ROS generated by xanthine plus xanthine oxidase (xanthine/XO) and various antioxidants. Pretreatment of murine HPC (C57BL/6) with xanthine/XO produced a dose-dependent enhancement of clonogenic response to granulocyte/macrophage colony-stimulating factor (GM-CSF) but not to interleukin-3 or granulocyte colony-stimulating factor. Stem cell factor (SCF), a potent comitogen for many hematopoietic growth factors, also synergized with GM-CSF. However, the synergistic enhancement of GM-CSF with xanthine/XO and SCF was not additive, indicating that xanthine/XO and SCF may target the same subpopulation of HPC. Support for this conclusion came from experiments demonstrating that 1) mutant mice strains constitutively lacking a SCF-responsive population of HPC [White spotted (W/WV) and Steel (SI/SId)] are unresponsive to xanthine/XO- and SCF-induced enhancement of GM-CSF and 2) 3,4-epoxybutene, which selectively abrogates SCF synergy with GM-CSF, inhibits xanthine/XO-induced enhancement. As xanthine/XO can mimic SCF in this population of HPC, the possibility exists that ROS also play a role in normal SCF-mediated proliferation of these cells. To test this hypothesis, we used the antioxidants N-tert-butyl-alpha-phenylnitrone, exogenous superoxide dismutase, and catalase. Both N-tert-butyl-alpha-phenylnitrone and superoxide dismutase effectively inhibited SCF and xanthine/XO synergism with GM-CSF, whereas catalase had no effect, indicating that the superoxide anion may be involved. Also, none of these compounds affected SCF synergism with other hematopoietic growth factors, such as interleukin-3 or granulocyte colony-stimulating factor, suggesting a population-specific phenomenon. These findings indicate that xanthine/XO mimics SCF in stimulating a subpopulation of murine HPC to proliferate and that SCF synergy with GM-CSF in this population is sensitive to antioxidant inhibition.
Mol Pharmacol 1996 Jun
PMID:Reactive oxygen species mediate stem cell factor synergy with granulocyte/macrophage colony-stimulating factor in a subpopulation of primitive murine hematopoietic progenitor cells. 864 49

The specificity of 2,2,6,6-tetramethylpiperidine to singlet oxygen was shown using Rose Bengal as a singlet oxygen generator, and Xanthine-Xanthine Oxidase and KO2 as the sources for the superoxide radical. The highest concentration of produced-singlet oxygen occurred at 25% of O2 by Rose Bengal photosensitization. The linewidth of the EPR signal for photosensitized nitroxyl radical, increasing solvent polarity. Deuterated solvents enlarge the EPR signal intensity in a dose-dependent manner. No EPR signal increase was observed in xanthine-xanthine oxidase reaction or KO2 systems, indicating that TEMP does not react with the superoxide anion. Thus, reaction of TEMP with 1O2 is highly specific.
Biochem Mol Biol Int 1995 Oct
PMID:The specificity and product of quenching singlet oxygen by 2,2,6,6-tetramethylpiperidine. 867 11

Using low temperature electron spin resonance (ESR) technique, we found that Salvia miltiorrhiza injection could scavenge the oxygen free radicals generated from ischemia-reperfusion injury in the myocardium as effectively as SOD. Using ESR spin trapping technique we found that one of its effective components, Danshensu, could scavenge superoxide anion free radicals generated from the reaction system of xanthine and xanthine oxidase, and that lipid free radicals generated from lipid peroxidation of myocardial mitochondrial membranes could be scavenged by another effective component, Tanshinone. The membrane fluidity of the mitochondria isolated from the ischemia-reperfused hearts was studied with the ESR spin labelling technique, and the TBA-method was used to detect the lipid peroxidation. It was found that Danshensu could protect the mitochondrial membrane from the ischemia-reperfusion injury and lipid peroxidation.
Biochem Mol Biol Int 1996 May
PMID:Scavenging effects of salvia miltiorrhiza on free radicals and its protection for myocardial mitochondrial membranes from ischemia-reperfusion injury. 873 39


<< Previous 1 2 3 4 5 6 7 8 9 10