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)

It has been proposed that beta-blockers and agents affecting Ca2+ metabolism might exert cardioprotective actions because of their ability to act as antioxidants in vivo. The feasibility of this proposal was tested by examining the reaction of a series of such compounds with various oxygen-derived species. None of the compounds tested was sufficiently reactive with superoxide radical, hydrogen peroxide or hypochlorous acid for scavenging of these species to be feasible in vivo at the drug concentrations present in patients given the usual therapeutic doses. All the drugs tested were powerful scavengers of hydroxyl radical except for flunarizine, which stimulated iron ion-dependent hydroxyl radical generation from hydrogen peroxide. However, none of the drugs significantly inhibited production of hydroxyl radicals in this system. Propranolol, verapamil and flunarizine had significant inhibitory effects on the peroxidation of rat liver microsomes in the presence of iron ions and ascorbic acid. All three compounds exerted weaker inhibitory effects on peroxidation of arachidonic acid caused by a mixture of myoglobin and H2O2: pindolol stimulated peroxidation in this system. It is concluded that the ability of beta-blockers and "Ca(2+)-blockers" to inhibit lipid peroxidation varies with the lipid substrate used and the mechanism by which peroxidation is induced. We conclude that suggestions that beta-blockers and "Ca(2+)-blockers" exert antioxidant effects in vivo are not well founded, although there is a possibility that verapamil and propranolol might have some inhibitory effects against peroxidation if they accumulate in membranes to a sufficiently-high concentration in vivo. We could not confirm the reported ability of propranolol to inhibit the enzyme xanthine oxidase.
 ...
PMID:Free radical scavenging and inhibition of lipid peroxidation by beta-blockers and by agents that interfere with calcium metabolism. A physiologically-significant process? 167 58

The oxidative demethylenation reactions of (methylendioxy)phenyl compounds (MDPs), (methylenedioxy)benzene (MDB), (methylenedioxy)amphetamine (MDA), and (methylenedioxy)methamphetamine (MDMA), were evaluated by using two hydroxyl radical generating systems, the autoxidation of ascorbate in the presence of iron-EDTA and the iron-catalyzed Haber-Weiss reaction conducted by xanthine/xanthine oxidase with iron-EDTA. Reaction products generated when MDB, MDA, and MDMA were incubated with the ascorbate or xanthine oxidase system were catechol, dihydroxyamphetamine (DHA), and dihydroxymethamphetamine (DHMA), respectively. The reaction required the presence of either ascorbic acid or xanthine oxidase. Levels of each catechol increased in proportion to ferric ion concentration and were suppressed by desferrioxamine B methanesulfonate (desferal). Catalase (CAT) inhibited the oxidation by the ascorbate system whereas superoxide dismutase (SOD) had little effect. The addition of hydrogen peroxide to the reaction mixture stimulated the oxidation, but the reaction was not initiated by hydrogen peroxide alone, suggesting that hydrogen peroxide acts as a precursor of hydroxyl radical. SOD and CAT suppressed the demethylenation reactions in the xanthine oxidase system. Hydroxyl radical scavenging agents such as ethanol, benzoate, DMSO, and thiourea effectively inhibited the oxidation by both systems. Urea, which has little effect on hydroxyl radical, was without any effect. These results indicated that hydroxyl radical can effect the cleavage of methylenedioxy group on MDPs.
 ...
PMID:Hydroxyl radical mediated demethylenation of (methylenedioxy)phenyl compounds. 168 Apr 77

The effects of azelastine, an orally active anti-allergic drug, on several inflammatory parameters of human neutrophils, including human neutrophil chemotaxis, phagocytosis and generation of reactive oxygen species (ROS), was examined. ROS generated in a cell-free, xanthine-xanthine oxidase system was also assessed. The species investigated were superoxide radical anion (O2-), hydrogen peroxide (H2O2) and hydroxyl radical (OH.). Azelastine significantly inhibited human neutrophil phagocytosis and the generation of O2-, H2O2, OH. by human neutrophils. However, the drug did not markedly affect human neutrophil chemotaxis or the ROS levels generated in the xanthine-xanthine oxidase system. The present study indicates that azelastine may exert an anti-inflammatory action by inhibiting human neutrophil phagocytosis as well as oxygen radical generation at the sites of inflammation.
 ...
PMID:Effects of azelastine on neutrophil chemotaxis, phagocytosis and oxygen radical generation. 168 70

Bleomycin, in the presence of ferric salts, oxygen and a suitable reductant, degrades DNA with the release of base propenals, detected as thiobarbituric acid (TBA) reactivity, and the formation of 8-hydroxydeoxyguanosine (8OHdG) detected by HPLC. When xanthine oxidase is added to the incubated mixture of DNA degradation products, TBA-reactivity is destroyed but 8OHdG formation is increased. EPR Spin trapping experiments show that hydroxyl radicals (OH) are formed in the reaction mixture and can be inhibited by the inclusion of either superoxide dismutase or catalase. These findings suggest that the base propenals and possibly malondialdehyde, formed from them, are aldehydic substrates for xanthine oxidase and, the product of this reaction is superoxide (O2-) and hydrogen peroxide (H2O2). Thus, TBA reactivity is destroyed in the formation of O2- and H2O2 which stimulate further oxidative damage to DNA resulting in increased 8OHdG formation.
 ...
PMID:Bleomycin-iron damage to DNA with formation of 8-hydroxydeoxyguanosine and base propenals. Indications that xanthine oxidase generates superoxide from DNA degradation products. 169 21

Hydrogen peroxide produces marked antigonadotropic and lytic actions in luteal cells, but the effects of superoxide, the archetypal oxygen radical, are unknown. Xanthine oxidase generates superoxide, and the activity of this enzyme, and purine substrate, are increased under ischemia, such as that seen at luteal regression. We therefore examined the actions of xanthine oxidase on luteal cells to assess the effects of this enzyme and the superoxide anion on luteal function. Xanthine oxidase, in the presence of hypoxanthine (50 microM), produced marked inhibition of LH-sensitive cAMP and progesterone production with complete inhibition at 25 mU/ml and half-maximal inhibition at about 5 mU/ml. These antigonadotropic actions of xanthine oxidase were rapid with maximal effects within 5 min, followed several minutes later by substantial depletion of ATP. Heat, superoxide dismutase, and catalase or catalase alone abolished the actions of xanthine oxidase. While depletion of ATP by xanthine oxidase was prevented by 3-amino-benzamide, an inhibitor of DNA repair, inhibition of cAMP and progesterone production was still evident. Xanthine oxidase also inhibited progesterone synthesis stimulated by 8-bromo-cAMP. Isobutylmethylxanthine, a cAMP phosphodiesterase inhibitor, did not reverse the inhibition of cAMP accumulation by xanthine oxidase, and the enzyme had no effect on LH receptor binding activity. Since catalase reversed the effects of xanthine oxidase, we conclude that superoxide was rapidly dismuted to hydrogen peroxide and mediated the antigonadotropic and antisteroidogenic actions of xanthine oxidase in luteal cells. The sensitivity of luteal cells to xanthine oxidase raises the possibility that this enzyme may serve as a significant source of hydrogen peroxide in the corpus luteum.
 ...
PMID:Inhibition of gonadotropin action and progesterone synthesis by xanthine oxidase in rat luteal cells. 170 32

High performance liquid chromatography with TSK 5000 PW or TSK 6000 PW size exclusion columns combined with a 125I labelled hyaluronic acid binding protein assay was used to study the effects of oxygen derived free radicals on synovial fluid hyaluronate. A continuous flux of free radicals was generated by the xanthine oxidase/hypoxanthine system. When the free radical flux was generated with xanthine oxidase/hypoxanthine in the presence of the iron chelator desferrioxamine and the hydroxyl radical scavenger mannitol a 30-50% decrease in hyaluronate peak was detected, but the molecular weight of synovial fluid hyaluronate remained almost unchanged as a result of reaction with superoxide radicals and hydrogen peroxide. When trace amounts of iron and EDTA were present in the reaction mixture depolymerisation of synovial fluid hyaluronate occurred, and it reached a final molecular weight of about 13,500 daltons. These results suggest that superoxide and hydroxyl radicals may have a different mode of action on synovial fluid hyaluronate. Superoxide radicals and hydrogen peroxide do not induce depolymerisation but, rather, change the molecular configuration of synovial fluid hyaluronate.
 ...
PMID:Oxygen derived free radicals and synovial fluid hyaluronate. 171 35

Reactive oxygen intermediates (ROI) play a major role in the mucosal damage developing during the reperfusion period following intestinal ischemia. We have shown previously that histamine (H) release is related to the ROI generated by xanthine oxidase during intestinal ischemia-reperfusion. The present study sought to determine the possible chain of events leading to H liberation. The artery supplying a segment of the ileum was occluded for 2 hr in 51 anesthetized dogs, and plasma levels of H were determined radioenzymatically in the venous effluent. Catalase was applied to scavenge hydrogen peroxide; dimethylsulfoxide and mannitol were used as hydroxyl radical scavengers; the role of catalytically active iron was assessed by using desferrioxamine. Pretreatment with either catalase or desferrioxamine, but not with dimethyl sulfoxide or mannitol, was effective in reducing the postocclusive H release. The results provide further in vivo evidence that ROI are causative agents in H liberation during reperfusion of the ischemic gut. Hydrogen peroxide can interact with catalytically active iron and generate highly reactive oxidants, which in turn are responsible for H release. The exact nature of these oxidants is still uncertain.
 ...
PMID:Histamine release during intestinal ischemia-reperfusion: role of iron ions and hydrogen peroxide. 172 54

Clinical and experimental data indicate that activated oxygen species interfere with vascular endothelial cell function. Here, the impact of extracellular oxidant injury on the fibrinolytic response of cultured human umbilical vein endothelial (HUVE) cells was investigated at the protein and mRNA levels. Xanthine (50 microM) and xanthine oxidase (100 milliunits), which produces the superoxide anion radical (O2-) and hydrogen peroxide (H2O2), was used to sublethally injure HUVE cells. Following a 15-min exposure, washed cells were incubated for up to 24 h in serum-free culture medium. Tissue-type plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1) antigen, and PAI-1 activity were determined in 1.25 ml of conditioned medium and t-PA and PAI-1 mRNA in the cell extracts of 2 x 10(6) HUVE cells. Control cells secreted 3.9 +/- 1.3 ng/ml (mean +/- S.D., n = 12) within 24 h. Treatment with xanthine/xanthine oxidase for 15 min induced a 2.8 +/- 0.4-fold increase (n = 12, p less than 0.05) of t-PA antigen secretion after 24 h. The t-PA antigen was recovered predominantly in complex with PAI-1. The oxidant injury caused a 3.0 +/- 0.8-fold increase (n = 9, p less than 0.05) in t-PA mRNA within 2 h. Total protein synthesis was unaltered by xanthine/xanthine oxidase. The oxidant scavengers superoxide dismutase and catalase, in combination, abolished the effect of xanthine/xanthine oxidase on t-PA secretion and t-PA mRNA synthesis. Xanthine/xanthine oxidase treatment of HUVE cells did not affect the PAI-1 secretion in conditioned medium nor the PAI-1 mRNA levels in cell extracts. Thus extracellular oxidant injury induces t-PA but not PAI-1 synthesis in HUVE cells.
 ...
PMID:Modulation of the fibrinolytic response of cultured human vascular endothelium by extracellularly generated oxygen radicals. 173 Jun 19

A flow injection analysis (FIA) biosensor system for the determination of phosphate was constructed using immobilized nucleoside phosphorylase and xanthine oxidase and an amperometric electrode (platinum vs silver/silver chloride, polarized at 0.7 V). When a phosphate-containing sample was injected into the detection cell, phosphate reacted with inosine in the carrier buffer to produce hypoxanthine and ribose-1-phosphate in the presence of nucleoside phosphorylase. Hypoxanthine was then oxidized by xanthine oxidase to uric acid and hydrogen peroxide, which were both detected by the amperometric electrode. The response of the FIA biosensor system was linear up to 100 microM phosphate, with a minimum detectable concentration of 1.25 microM phosphate. Each assay could be performed in 5-6 min and the system could be used for about 160 repeated analyses. This system was applicable for the determination of phosphate in various food products and plasma, and the results obtained agreed well with those of the enzymatic assay.
 ...
PMID:An FIA biosensor system for the determination of phosphate. 175 1

The present work reviews the evidence for an involvement of free radicals in the pathophysiology of chronic pancreatitis and the potential of treatment with antioxidant and scavenger substances. Preliminary results indicate that exposure of isolated pancreatic acinar cells to a reaction mixture containing hypoxanthine, xanthine oxidase, and chelated iron causes cell damage and death probably due to generation of superoxide anion and hydrogen peroxide. It still needs to be analyzed which scavengers and antioxidants are able to ameliorate the damage due to oxidant stress in cell models. Such knowledge from cellular studies might help to plan therapeutical trials to evaluate potentially effective antioxidants and scavengers in the experimental animal and in patients with pancreatitis. As yet there are no published studies about the role of free radicals in animal models of chronic pancreatitis. This fact is probably due to the shortcomings of the animal models available. Recent studies presented evidence that activation of oxygen-derived free radicals occurs in patients with chronic pancreatitis. There is also some evidence that the dietary intake of antioxidants may be reduced in patients with chronic pancreatitis. It was suggested that such reduction of antioxidant defenses in the face of an increased demand due to heightened induction of P450 activities may facilitate lipid peroxidation. However, as yet, there is no direct evidence that a reduction of dietary antioxidants with a simultaneous increase in P450 activity is the primary mechanism which initiates chronic pancreatitis without contribution of other factors.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Involvement of free radicals in the pathophysiology of chronic pancreatitis: potential of treatment with antioxidant and scavenger substances. 179 74


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