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)

Nitric oxide which was released in aqueous solutions (> or = 10 microM) of direct NO-donors such as 3-morpholinesydnonimine (SIN-1) and S-nitroso-N-acetyl-penicillamine (SNAP) consumed avidly sulfhydryl groups of N-acetylcysteine > cysteine > glutathione. In case of SIN-1 generation of nitrites run in parallel to disappearance of sulfhydryl groups of N-acetylcysteine and glutathione, however, for a pair of SIN-1 and cysteine the rate of formation of nitrites was much slower than the rate of consumption of sulfhydryl groups. We infer that kinetics of formation and breakdown of S-nitrosothiols varies depending on the type of a thiol which reacts with a NO-donor. Indirect NO-donors such as glyceryl trinitrate (GTN), molsidomine (MSD) or sodium nitroprusside (NaNP) at concentrations < 100 microM did not consume sulfhydryl groups of cysteine unless pretreated with the xanthine/xanthine oxidase system. We suppose that in this last case superoxide anions react with nitric oxide to form peroxynitrites with a higher potency than nitric oxide itself to destroy sulfhydryl groups. We conclude that out of three studied thiols N-acetylcysteine is the best substrate for the formation of S-nitrosothiols, while S-nitrosocysteine is the slowest releaser of nitric oxide. Moreover, unlike SIN-1 and SNAP, NaNP is not a direct NO-donor but behaves rather like GTN. Minute amounts of nitric oxide released either from NaNP or GTN gain from superoxide anions an amplification as SH-scavengers.
Pol J Pharmacol
PMID:In vitro generation and decomposition of S-nitrosothiols from direct and indirect nitric oxide donors. 755 May 51

Reactive oxygen species (ROS) are generated when oxygen is supplied in excess and/or its reduction is insufficient. The best explored ROS are superoxide anions, hydroxyl radicals and hydrogen peroxide. The first two are free radicals. ROS are harmful for the living cells and are implicated in a variety of pathological processes and diseases. Drugs used in the treatment of these states are either stimulators of endogenous defense mechanisms against ROS or inhibitors of ROS formation. Six groups of anti-ROS substances have been described in this paper. 1) Antioxidant substances used in substitutive therapy such as enzymes (e.g. superoxide dismutase), substances containing thiol groups and vitamins (A, E, P, C). 2) Chelating agents (e.g. desferoxamine), which lower the level of prooxidative transition metal ions. 3) Inhibitors of superoxide ions generation by stimulated cells or xanthine oxidase. Such mechanism of action was described for xanthine oxidase inhibitor-allopurinol. 4) Superoxide scavengers. Many known drugs were investigated for this activity, but the best documentation was presented for flavonoids. 5) Substances which eliminate hydrogen peroxide, mainly glutathione and its precursors. 6) Scavengers of hydroxyl radicals. Studies of the above activity were conducted mainly using an unspecific method--estimation of malondialdehyde generated during the action of hydroxyl radicals on lipids or on desoxyribose. Inhibition of malondialdehyde formation was described for many drugs of plant and synthetic origin.
Pol J Pharmacol
PMID:Scavenging of reactive oxygen species as the mechanism of drug action. 868 96

Some sterically hindered N-substituted derivatives of daunorubicin are known to be poor substrates for NADH dehydrogenase, NADPH cytochrome P450 reductase and xanthine oxidase. In consequence, poor oxygen radical generation by these compounds is observed. In this study we examined a new family of sugar-N-substituted derivatives of daunorubicin bearing a bulky substituent introduced on the nitrogen atom through the amidine spacer. These compounds were found to be very active in radical formation catalyzed by all three studied enzymes. Thus, the introduction of a heterocyclic ring, even if it is bulky but flexible, on the nitrogen atom of daunosamine moiety through the one-atom spacer (amidine group), does not induce the steric hindrance effect on the interaction of daunorubicin derivatives with these flavoprotein enzymes.
Acta Biochim Pol 2000
PMID:The ability of new formamidine sugar-modified derivatives of daunorubicin to stimulate free radical formation in three enzymatic systems: NADH dehydrogenase, NADPH cytochrome P450 reductase and xanthine oxidase. 1096 87

The aim of the study was to evaluate the activity of the pro- and antioxidant systems in cervical mucus of healthy women and women with pathological of disorders cervical. After cervical mucus liquefaction, the activity of superoxide dismutase, catalase and xanthine oxidase was determined by means of chemiluminescence assays. The activity of the antioxidant system in cervical mucus of healthy women was higher as compared to the group with pathological cervical disorders. Moreover, in mucus samples obtained from women with dysplasia, the significantly heightened activity of xanthine oxidase (strong pro-oxidant) was observed. The antioxidant system present in cervical mucus may protect both the cells of the uterine cervix and the viable sperm.
Ginekol Pol 2002 Jul
PMID:[Pro- and antioxidant system activity in cervical mucosa]. 1236 77

Role of lipid peroxidation products, particularly 4-hydroxynonenal (4-HNE) in cell cycle signaling is becoming increasingly clear. In this article, recent studies suggesting an important role of 4-HNE in stress mediated signaling for apoptosis are critically evaluated. Evidence demonstrating the modulation of UV, oxidative stress, and chemical stress mediated apoptosis by blocking lipid peroxidation by the alpha-class glutathione S-transferases (GSTs) is presented which suggest an important role of these enzymes in protection against oxidative stress and a role of lipid peroxidation products in stress mediated signaling. Overexpression of 4-HNE metabolizing GSTs (mGSTA4-4, hGSTA4-4, or hGST5.8) protects cells against 4-HNE, oxidative stress (H(2)O(2) or xanthine/xanthine oxidase), and UV-A mediated apoptosis by blocking JNK and caspase activation suggesting a role of 4-HNE in the mechanisms of apoptosis caused by these stress factors. The intracellular concentration of 4-HNE appears to be crucial for the nature of cell cycle signaling and may be a determinant for the signaling for differentiation, proliferation, transformation, or apoptosis. The intracellular concentrations of 4-HNE are regulated through a coordinated action of GSTs (GSTA4-4 and hGST5.8) which conjugate 4-HNE to GSH to form the conjugate (GS-HNE) and the transporter 76 kDa Ral-binding GTPase activating protein (RLIP76), which catalyze ATP-dependent transport of GS-HNE. A mild stress caused by heat, UV-A, or H(2)O(2)with no apparent effect on the cells in culture causes a rapid, transient induction of hGST5.8 and RLIP76. These stress preconditioned cells acquire ability to metabolize and exclude 4-HNE at an accelerated pace and acquire relative resistance to apoptosis by UV and oxidative stress as compared to unconditioned control cells. This resistance of stress preconditioned cells can be abrogated by coating the cells with anti-RLIP76 antibodies which block the transport of GS-HNE. These studies and previous reports discussed in this article strongly suggest a key role of 4-HNE in stress mediated signaling.
Acta Biochim Pol 2003
PMID:Lipid peroxidation and cell cycle signaling: 4-hydroxynonenal, a key molecule in stress mediated signaling. 1283 61

Although the long-term administrations of macrolide antibiotics are effective for diffuse panbronchiolitis, otitis media with effusion (OME), and some other diseases, their mechanism of action has not been fully understood. In order to elucidate the mechanisms of possible effects of macrolide antibiotics on activities of erythrocyte nitric oxide synthase (NOS), xanthine oxidase (XO), and malondialdehyde (MDA) levels in experimental OME, we aimed to evaluate the effect of macrolide antibiotics (erythromycin, azithromycin, roxithromycin, and clarithromycin) using an experimental guinea pig otitis media model. Erythrocyte NOS, XO activities, and MDA level were measured in all groups. Erythrocyte NOS activities were significantly higher in erythromycin-, azithromycin-, roxithromycin-, and clarithromycin-treated groups than in the experimental group. Erythrocyte XO activities were significantly lower in erythromycin-, azithromycin-, roxithromycin-, and clarithromycin-treated groups than in the control group. However, erythrocyte XO activities in experimental group were significantly higher than those of control group. Erythrocyte MDA levels were significantly lower in erythromycin-, azithromycin-, roxithromycin-, and clarithromycin-treated groups than those of the experimental group. The MDA levels in erythromycin- and roxithromycin-treated groups were significantly higher than those of azithromycin-treated group. The MDA levels in azithromycin-treated group were significantly lower than those of roxithromycin-treated group. In conclusion, the present study shows that the macrolide antibiotics (erythromycin, azithromycin, roxithromycin, and clarithromycin) increase NOS activity, decrease XO activity and MDA level, which is an important indicator of oxidative stress.
Pol J Pharmacol
PMID:Effect of macrolide antibiotics on nitric oxide synthase and xanthine oxidase activities, and malondialdehyde level in erythrocyte of the guinea pigs with experimental otitis media with effusion. 1473 Jan 7

Allopurinol, an inhibitor of xanthine oxidase, is indicated in the management of patients with elevated serum and urinary uric acid levels. It was also reported to be beneficial in patients with epilepsy when added to traditional antiepileptic drug. Here, we investigated the effect of allopurinol upon the electrical seizure threshold and its effect on the protective efficacy of common antiepileptic drugs, carbamazepine (CBZ) and valproate (VPA) against maximal electroshock (MES)-induced convulsions in mice. We found that allopurinol administered at doses of 5, 15 or 45 mg/kg, did not affect electrical seizure threshold. When administered acutely or for a prolonged period of time (5 times every 24 h), it did not affect anticonvulsant activity of CBZ and VPAin MES. Free plasma concentration of both anticonvulsants was not affected by allopurinol given at a dose of 45 mg/kg for 5 days. Thus, our results did not support suggestions that allopurinol can be beneficial as add-on drug in the management of epilepsy at least in patients treated with CBZ or VPA.
Pol J Pharmacol
PMID:Allopurinol does not affect the anticonvulsant activity of carbamazepine and valproate in maximal electroshock-induced convulsions in mice. 1504 79

The 6-oxopurine xanthine (Xan, neutral form 2,6-diketopurine) differs from the corresponding 6-oxopurines guanine (Gua) and hypoxanthine (Hyp) in that, at physiological pH, it consists of a approximately 1:1 equilibrium mixture of the neutral and monoanionic forms, the latter due to ionization of N(3)-H, in striking contrast to dissociation of the N(1)-H in both Gua and Hyp at higher pH. In xanthosine (Xao) and its nucleotides the xanthine ring is predominantly, or exclusively, a similar monoanion at physiological pH. The foregoing has, somewhat surprisingly, been widely overlooked in studies on the properties of these compounds in various enzyme systems and metabolic pathways, including, amongst others, xanthine oxidase, purine phosphoribosyltransferases, IMP dehydrogenases, purine nucleoside phosphorylases, nucleoside hydrolases, the enzymes involved in the biosynthesis of caffeine, the development of xanthine nucleotide-directed G proteins, the pharmacological properties of alkylxanthines. We here review the acid/base properties of xanthine, its nucleosides and nucleotides, their N-alkyl derivatives and other analogues, and their relevance to studies on the foregoing. Included also is a survey of the pH-dependent helical forms of polyxanthylic acid, poly(X), its ability to form helical complexes with a broad range of other synthetic homopolynucleotides, the base pairing properties of xanthine in synthetic oligonucleotides, and in damaged DNA, as well as enzymes involved in circumventing the existence of xanthine in natural DNA.
Acta Biochim Pol 2004
PMID:Xanthine, xanthosine and its nucleotides: solution structures of neutral and ionic forms, and relevance to substrate properties in various enzyme systems and metabolic pathways. 1521 45

Molybdenum-containing enzymes, aldehyde oxidase and xanthine oxidase, are important in the oxidation of N-heterocyclic xenobiotics. However, the role of these enzymes in the oxidation of drug-derived aldehydes has not been established. The present investigation describes the interaction of eleven structurally related benzaldehydes with guinea pig liver aldehyde oxidase and bovine milk xanthine oxidase, since they have similar substrate specificity to human molybdenum hydroxylases. The compounds under test included mono-hydroxy and mono-methoxy benzaldehydes as well as 3,4-dihydroxy-, 3-hydroxy-4-methoxy-, 4-hydroxy-3-methoxy-, and 3,4-dimethoxy-benzaldehydes. In addition, various amines and catechols were tested with the molybdenum hydroxylases as inhibitors of benzaldehyde oxidation. The kinetic constants have shown that hydroxy-, and methoxy-benzaldehydes are excellent substrates for aldehyde oxidase (Km values 5x10(-6) M to 1x10(-5) M) with lower affinities for xanthine oxidase (Km values around 10(-4) M). Therefore, aldehyde oxidase activity may be a significant factor in the oxidation of the aromatic aldehydes generated from amines and alkyl benzenes during drug metabolism. Compounds with a 3-methoxy group showed relatively high Vmax values with aldehyde oxidase, whereas the presence of a 3-hydroxy group resulted in minimal Vmax values or no reaction. In addition, amines acted as weak inhibitors, whereas catechols had a more pronounced inhibitory effect on the aldehyde oxidase activity. It is therefore possible that aldehyde oxidase may be critical in the oxidation of the analogous phenylacetaldehydes derived from dopamine and noradrenaline.
Acta Biochim Pol 2004
PMID:Kinetics and specificity of guinea pig liver aldehyde oxidase and bovine milk xanthine oxidase towards substituted benzaldehydes. 1544 27

The aim of this study was to investigate whether endogenous superoxide anion is involved in the regulation of renal Na(+),K(+)-ATPase and ouabain-sensitive H(+),K(+)-ATPase activities. The study was performed in male Wistar rats. Compounds modulating superoxide anion concentration were infused under general anaesthesia into the abdominal aorta proximally to the renal arteries. The activity of ATPases was assayed in isolated microsomal fraction. We found that infusion of a superoxide anion-generating mixture, xanthine oxidase (1 mU/min per kg) + hypoxanthine (0.2 mumol/min per kg), increased the medullary Na(+),K(+)-ATPase activity by 49.5% but had no effect on cortical Na(+),K(+)-ATPase and either cortical or medullary ouabain-sensitive H(+),K(+)-ATPase. This effect was reproduced by elevating endogenous superoxide anion with a superoxide dismutase inhibitor, diethylthiocarbamate. In contrast, a superoxide dismutase mimetic, TEMPOL, decreased the medullary Na(+),K(+)-ATPase activity. The inhibitory effect of TEMPOL was abolished by inhibitors of nitric oxide synthase (L-NAME), soluble guanylate cyclase (ODQ) and protein kinase G (KT5823). The stimulatory effect of diethylthiocarbamate was not observed in animals pretreated with a synthetic cGMP analogue, 8-bromo-cGMP. An inhibitor of NAD(P)H oxidase, apocynin (1 mumol/min per kg), decreased the Na(+),K(+)-ATPase activity in the renal medulla and its effect was prevented by L-NAME, ODQ or KT5823. In contrast, a xanthine oxidase inhibitor, oxypurinol, administered at the same dose was without effect. These data suggest that NAD(P)H oxidase-derived superoxide anion increases Na(+),K(+)-ATPase activity in the renal medulla by reducing the availability of NO. Excessive intrarenal generation of superoxide anion may upregulate medullary Na(+),K(+)-ATPase leading to sodium retention and blood pressure elevation.
Acta Biochim Pol 2004
PMID:Nitric oxide -- superoxide cooperation in the regulation of renal Na(+),K(+)-ATPase. 1562 65


1 2 Next >>