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)

Methane (CH(4)) production from the anti-inflammatory agent, dimethyl sulfoxide (DMSO), was used to measure .OH from chemical reactions or human phagocytes. Reactions producing .OH (xanthine/xanthine oxidase or Fe(++)/EDTA/H(2)O(2)) generated CH(4) from DMSO, whereas reactions yielding primarily O-(2) or H(2)O(2) failed to produce CH(4). Neutrophils (PMN), monocytes, and alveolar macrophages also produced CH(4) from DMSO. Mass spectroscopy using d(6)-DMSO showed formation of d(3)-CH(4) indicating that CH(4) was derived from DMSO. Methane generation by normal but not chronic granulomatous disease or heat-killed phagocytes increased after stimulation with opsonized zymosan particles or the chemical, phorbol myristate acetate. Methane production from DMSO increased as the number of stimulated PMN was increased and the kinetics of CH(4) production approximated other metabolic activities of stimulated PMN. Methane production from stimulated phagocytes and DMSO was markedly decreased by purportedly potent .OH scavengers (thiourea or tryptophane) and diminished to lesser degrees by weaker .OH scavengers (mannitol, ethanol, or sodium benzoate). Superoxide dismutase or catalase also decreased CH(4) production but urea, albumin, inactivated superoxide dismutase, or boiled catalase had no appreciable effect. The results suggest that the production of CH(4) from DMSO may reflect release of .OH from both chemical systems and phagocytic cells. Interaction of the nontoxic, highly permeable DMSO with .OH may explain the anti-inflammatory actions of DMSO and provide a useful measurement of .OH in vitro and in vivo.
 ...
PMID:Generation of hydroxyl radical by enzymes, chemicals, and human phagocytes in vitro. Detection with the anti-inflammatory agent, dimethyl sulfoxide. 50 Aug 30

To help settle controversy as to whether the chelating agent diethylenetriaminepentaacetate (DTPA) supports or prevents hydroxyl radical production by superoxide/hydrogen peroxide systems, we have reinvestigated the question by spectroscopic, kinetic, and thermodynamic analyses. Potassium superoxide in DMSO was found to reduce Fe(III)DTPA. The rate constant for autoxidation of Fe(II)DTPA was found (by electron paramagnetic resonance spectroscopy) to be 3.10 M-1 s-1, which leads to a predicted rate constant for reduction of Fe(III)DTPA by superoxide of 5.9 x 10(3) M-1 s-1 in aqueous solution. This reduction is a necessary requirement for catalytic production of hydroxyl radicals via the Fenton reaction and is confirmed by spin-trapping experiments using DMPO. In the presence of Fe(III)DTPA, the xanthine/xanthine oxidase system generates hydroxyl radicals. The reaction is inhibited by both superoxide dismutase and catalase (indicating that both superoxide and hydrogen peroxide are required for generation of HO.). The generation of hydroxyl radicals (rather than oxidation side-products of DMPO and DMPO adducts) is attested to by the trapping of alpha-hydroxethyl radicals in the presence of 9% ethanol. Generation of HO. upon reaction of H2O2 with Fe(II)DTPA (the Fenton reaction) can be inhibited by catalase, but not superoxide dismutase. The data strongly indicate that iron-DTPA can catalyze the Haber-Weiss reaction.
 ...
PMID:Catalysis of the Haber-Weiss reaction by iron-diethylenetriaminepentaacetate. 133 36

In the regulation of GTP biosynthesis, complex interactions are observed. A major factor is the behavior of the activity of IMPDH, the rate-limiting enzyme of de novo GTP biosynthesis, and the activity of GPRT, the salvage enzyme of guanylate production. The activities of GMP synthase, GMP kinase and nucleoside-diphosphate kinase are also relevant. In neoplastic transformation, the activities and amounts of all these biosynthetic enzymes are elevated as shown by kinetic assays and by immunotitration for IMPDH. In cancer cells, the up-regulation of guanylate biosynthesis is amplified by the concurrent decrease in activities of the catabolic enzymes, nucleotidase, nucleoside phosphorylase, and the rate-limiting purine catabolic enzyme, xanthine oxidase. The up-regulation of the capacity for GTP biosynthesis is also manifested in the stepped-up capacity of the overall pathways of de novo and salvage guanylate production. The linking with neoplasia is also seen in the elevation of the activities of IMPDH and GMP synthase and de novo and salvage pathways as the proliferative program is expressed as cancer cells enter log phase in tissue culture. The activity of GMP reductase showed no linkage with neoplastic or normal cell proliferation; however, in induced differentiation in HL-60 cells the activity increased concurrently with the decline in the activity of IMPDH. This reciprocal regulation of the two enzymes is observed in differentiation induced by retinoic acid, DMSO or TPA in HL-60 cells. In support of enzyme-pattern-targeted chemotherapy, evidence was provided for synergistic chemotherapy with tiazofurin (inhibitor of IMPDH) and hypoxanthine (competitive inhibitor of GPRT and guanine salvage activity) in patients and in tissue culture cell lines. These investigations should contribute to the clarification of the controlling factors of GMP biosynthesis, the role of the various enzymes, the behavior of GMP reductase in mammalian cells and the application of the approaches of enzyme-pattern-targeted chemotherapy in patients.
 ...
PMID:Regulation of GTP biosynthesis. 135 38

The relative roles of hydroxyl radical and neutrophils in the pathogenesis of shock-induced mucosal injury and gut origin infection (GOI) were determined. The incidence of GOI was higher in the shocked rats (30 mmHg for 30 min) than the sham-shock controls (87% vs 12.5%; P less than 0.01). Administration of the hydroxyl radical scavenger, dimethyl sulfoxide (DMSO) or iron chelator and deferoxamine reduced the incidence of GOI from 87% to 20% and 40% respectively (P less than 0.05). DMSO and deferoxamine appeared to prevent shock-induced GOI by blunting the magnitude of shock-induced mucosal injury. In contrast, neutrophil depletion did not prevent GOI or protect the intestinal mucosal in the shocked rats. Instead, the incidence of systemic spread of bacteria past the mesenteric lymph nodes to the livers and spleens of the shocked rats was higher in the neutrophil depleted rats (56%) than any other group (7%) (P less than 0.01). Thus, shock-induced GOI and intestinal injury appears to be mediated by xanthine oxidase generated oxidants such as hydroxyl radical rather than neutrophil-generated factors. In addition, neutrophil depletion may be clinically deleterious, since it promotes systemic sepsis rather than preventing shock-induced GOI.
 ...
PMID:[Role of neutrophil and hydroxyl radical in shock-induced gut origin infection]. 149 30

The influence of oxygen-derived free radical scavengers on survival in gastric cancer, with serosal invasion and metastases to the lymph nodes surrounding the stomach, was assessed in a prospective randomized controlled double-blind trial conducted for 5 years. To this end, allopurinol (inhibits the enzyme xanthine oxidase which is responsible for the formation of superoxide radicals and scavengers hydroxyl radicals) and dimethyl sulphoxide (DMSO; scavengers hydroxyl radicals) were used. Following potentially curative distal two-thirds partial gastrectomy, 228 patients making an uneventful recovery from surgery were randomized to the control group or to receive allopurinol (50 mg by mouth 4 times a day) or DMSO (500 mg by mouth 4 times a day). In 160 fully evaluable patients who were studied for 5 years, allopurinol and DMSO incurred a significant (p less than 0.01) survival advantage over the whole period of study. The similarity in efficacy between allopurinol and DMSO and the fact that the only action they share is scavenging oxyradicals suggest that these radicals mediate the aggressiveness of gastric cancer by producing tissue damage, thus allowing the cancer to spread. Consequently, oxygen-derived free radicals are implicated in the mechanism of gastric cancer, and removing them provides patients with a survival advantage.
 ...
PMID:Oxygen-derived free-radical scavengers prolong survival in gastric cancer. 159 48

The mechanism of xanthine oxidase (XO) inactivation by hydrogen peroxide (H2O2) and its biologic significance are unclear. We found that addition of increasing concentrations of H2O2 progressively decreased xanthine oxidase activity in the presence but not the absence of xanthine in vitro. Inactivation of XO by H2O2 was also enhanced by anaerobic reduction of XO by xanthine. Inactivation of XO by H2O2 was accompanied by production of hydroxyl radical (.OH), measured as formation of formaldehyde from dimethylsulfoxide (DMSO). In contrast, addition of H2O2 to deflavo XO did not produce .OH. Inactivation of XO by H2O2 was decreased by simultaneous addition of the .OH scavenger, DMSO. However, inactivation of XO by H2O2 and formation of .OH were not decreased following addition of the metal chelator. DETAPAC, and/or the O2 scavenger, superoxide dismutase. The results suggest that inactivation of XO by H2O2 occurs by production of .OH following direct reduction of H2O2 by XO at the flavin site.
 ...
PMID:Inactivation of xanthine oxidase by hydrogen peroxide involves site-directed hydroxyl radical formation. 164 51

Mercuric ion, a well-known nephrotoxin, promotes oxidative tissue damage to kidney cells. One principal toxic action of Hg(II) is the disruption of mitochondrial functions, although the exact significance of this effect with regard to Hg(II) toxicity is poorly understood. In studies of the effects of Hg(II) on superoxide (O2-) and hydrogen peroxide (H2O2) production by rat kidney mitochondria, Hg(II) (1-6 microM), in the presence of antimycin A, caused a concentration-dependent increase (up to fivefold) in mitochondrial H2O2 production but an apparent decrease in mitochondrial O2- production. Hg(II) also inhibited O(2-)-dependent cytochrome c reduction (IC50 approximately 2-3 microM) when O2- was produced from xanthine oxidase. In contrast, Hg(I) did not react with O2- in either system, suggesting little involvement of Hg(I) in the apparent dismutation of O2- by Hg(II). Hg(II) also inhibited the reactions of KO2 (i.e., O2-) with hemin or horseradish peroxidase dissolved in dimethyl sulfoxide (DMSO). Finally, a combination of Hg(II) and KO2 in DMSO resulted in a stable UV absorbance spectrum [currently assigned Hg(II)-peroxide] distinct from either Hg(II) or KO2. These results suggest that Hg(II), despite possessing little redox activity, enhances the rate of O2- dismutation, leading to increased production of H2O2 by renal mitochondria. This property of Hg(II) may contribute to the oxidative tissue-damaging properties of mercury compounds.
 ...
PMID:Reactivity of Hg(II) with superoxide: evidence for the catalytic dismutation of superoxide by Hg(II). 166 57

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

Oxygen-derived free radicals are cytotoxic and promote tissue damage. Dimethyl sulfoxide (DMSO) and allopurinol scavenge hydroxyl radicals, and the latter agent also inhibits the enzyme xanthine oxidase, which is responsible for the formation of superoxide anions. These agents were given daily by gavage (1 ml/d). After 2 days of administration as 1, 2, or 5% solutions, the H+ output of the rat with or without pyloric ligation was not significantly affected. After six hours reserpine (5 mg/kg i.p.) or serotonin (50 mg/kg i.p.) produced ischemic mucosal injury in all stomachs (39 +/- 5.2 mm2 and 25.9 +/- 2.8 mm2, mean +/- standard error of the mean [SEM], n = 10). Pretreatment for 2 days with 1 ml/d of 1% allopurinol or DMSO significantly (p less than 0.001) protected the rat against the reserpine (23 +/- 2.1 mm2 and 24 +/- 1.9 mm2, respectively, vs 39 +/- 5.2 mm2, n = 10) and serotonin injury (10 +/- 1.5 mm2 and 11 +/- 1.8 mm2, respectively, vs 25.9 +/- 2.8 mm2, n = 10). However, 2 days pretreatment with 1 ml/d of 2% allopurinol or DMSO was more effective (p less than 0.001) in this respect, and injury only developed in 40% of the rats given reserpine (8 +/- 1.2 mm2 and 9 +/- 1.6 mm2) and in 20% of those given serotonin (2.4 +/- 0.4 mm2 and 1.9 +/- 0.5 mm2). Similar pretreatment with 5% solutions completely protected the rat stomach against the reserpine and serotonin injuries without significantly influencing the H+ output.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Gastric mucosal cytoprotection in the rat by scavenging oxygen-derived free radicals. 175 Apr 47

In newborn pigs, vasodilation in response to hypercapnia is dependent on prostaglandin (PG) H synthase. We investigated the contribution of activated oxygen by-products to hypercapnia-induced PGH synthase-dependent dilation of pial arteries and arterioles in anesthetized newborn pigs. Activated oxygen species were generated on the cerebral surface using xanthine oxidase and hypoxanthine. Catalase, H2O2, and iron or N-(2-mercaptopropionyl)-glycine (MPG) were used to separate effects of superoxide anion and hydroxyl radical. All the activated oxygen species tested caused vasodilation of both arteries and arterioles. Vasodilation to all activated oxygen species was largely reversible with only the hydroxyl radical encouraging combination of xanthine oxidase, hypoxanthine, H2O2, and FeCl3, causing significant dilation 20 min after removal of treatment. Cotreatment with MPG blocked this residual dilation. Neither pretreatment with the extracellular superoxide anion radical scavenger, superoxide dismutase (SOD), the intracellular superoxide anion radical scavenger, Tiron, the H2O2 scavenger, catalase, nor hydroxyl radical scavengers, dimethyl sulfoxide (DMSO) and MPG, altered vasodilation of pial arteries or arterioles in response to hypercapnia. Furthermore, the increase in cerebral prostanoid synthesis in response to hypercapnia was not affected by pretreatment with SOD, Tiron, catalase, DMSO, or MPG. We conclude that the progressively reduced forms of oxygen that would be produced during PGH synthase metabolism of arachidonic acid can dilate pial arteries and arterioles of newborn pigs. However, these activated oxygen species are not responsible for the vasodilation to hypercapnia in the newborn pig, suggesting that eicosanoids cause the dilation.
 ...
PMID:Activated oxygen species do not mediate hypercapnia-induced cerebral vasodilation in newborn pigs. 187 61


1 2 3 4 5 6 7 8 9 Next >>