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

This study examined the role of oxygen-derived free radicals, the potential involvement of neutrophils and the possible mucosal vascular permeability changes involved in the pathogenesis and evolution of gastric mucosal lesions induced by acetic acid in the rat. Myeloperoxidase activity was assayed and used as an index of leukocyte infiltration. Application of acetic acid produced a significant increase in this activity 7 and 14 days after induction of chronic injury. Administration of hydroxyurea intraperitoneally was associated with a decrease in the severity of chronic ulceration and neutrophil infiltration into the gastric lesion. This effect was detectable enzymatically and microscopically. Orally administered allopurinol did not produce any beneficial effects on either the macroscopic and histological appearance or on vascular permeability. These results suggest that oxygen-derived free radicals may contribute to the formation and development of chronic lesions and that oxygen-derived free radicals were generated from neutrophils, but not from the xanthine oxidase pathway. These inflammatory cells may, therefore, have a lesive role in the origin and course of acetic acid ulcer disease.
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PMID:Role of polymorphonuclear leukocytes and oxygen-derived free radicals in chronic gastric lesion induced by acetic acid in rat. 872 42

Oxygen free radicals have been implicated in the pathogenesis of gastrointestinal mucosal injury. However, their effect on the quality of experimental gastric ulcer healing has not been investigated previously. Gastric ulcers were produced on the anterior wall of the stomach of rats by submucosal injection of 20% acetic acid. To investigate the role of oxygen radicals, rats with gastric ulcers were treated with scavengers for 6 weeks. Rats received either a daily dose of 20,000 U/kg of recombinant human Cu,Zn-SOD, a 1% solution of DMSO administered orally ad libitum, or 50 mg/kg/day of allopurinol administered orally. The quality of ulcer healing was evaluated by histologic and biochemical parameters: ulcer area, lipid peroxide levels, abnormality of regenerated mucosa, angiogenesis, and fibrosis as assessed by Azan staining, mucin content as assessed by the PAS-positive area, and polymorphonuclear leukocyte (PMN) infiltration. The treatments with SOD, DMSO, or allopurinol did not affect the ulcer area or lipid peroxide levels in the gastric mucosa, and SOD did not affect the histologic abnormality score, PMN infiltration in regenerated mucosa, the collagen fiber proliferation index, or the PAS-positive mucous score. DMSO and allopurinol significantly increased the collagen fiber proliferation index and the PAS-positive mucous score compared with controls. These results indicate that scavenging hydroxyl radicals or inhibiting xanthine oxidase enhances the quality but not the speed of gastric ulcer healing.
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PMID:Effects of oxygen radical scavengers on the quality of gastric ulcer healing in rats. 877 96

In previous work certain hydroxylated and peroxylated derivatives of uroporphyrin (URO) have been isolated from the urine of patients suffering from porphyria. We have now investigated the mechanism of production of these oxygenated derivatives of URO, using both enzymic and chemical model systems and also the effect of exposure to light during reoxidation of uroporphyrinogen (URO'gen). When URO'gen was incubated with haemolysates, peaks with the same retention times as peroxyacetic acid URO, meso-hydroxy URO and beta-hydroxypropionic acid URO were all detected. The first of these was formed in sufficient amounts to allow its characterization by mass spectrometry. Under these conditions, peroxyacetic acid derivatives of heptacarboxylate and pentacarboxylate porphyrins could also be produced from the corresponding porphyrinogens, but no peroxylated product could be obtained from coproporphyrinogen (COPRO'gen, where no acetic acid side chains are present) or from the fully oxidized URO. Similar results were obtained on re-oxidation of URO'gen in the xanthine oxidase-xanthine system and in the presence of hydrogen peroxide/Fe-EDTA (ethylenediamine-tetraacetic acid) and here again no peroxylated product could be detected from either COPRO'gen or URO. Finally, formation of peroxyacetic acid URO could be demonstrated during photo-oxidation of URO'gen and this was followed by light-induced loss of both URO and its peroxylated derivative. It is concluded that the oxygenated derivatives arise from the action of reactive oxygen species on the porphyrinogens (rather than the porphyrins), with one of the acetic acid side chain serving as the preferential (or exclusive target) for peroxylation.
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PMID:Peroxylated and hydroxylated uroporphyrins: a study of their production in vitro in enzymic and chemical model systems. 887 26

Cigarette smoking is associated with peptic ulceration in humans. A mechanistic study of the potentiating effects of cigarette smoking on acetic acid-induced gastric ulceration in rats was hence performed. Rats were exposed to 0, 2 or 4% of cigarette smoke for three 1-hr periods during the 24 hr starvation before ulcer induction. Cigarette smoke exposure potentiated ulcer formation which was accompanied by a reduction of gastric blood flow at the ulcer base and ulcer margin. Further studies showed that cigarette smoke exposure alone did not cause any macroscopic injury in the stomach but significantly decreased the basal gastric blood flow in a concentration-dependent manner, which was coupled with an increase in mucosal xanthine oxidase (XO) activity. Pretreatment with allopurinol (Allo, 5 mg/kg, i.v.), a XO inhibitor, partially prevented the potentiating effect of cigarette smoke exposure on ulcer formation and also significantly improved the gastric blood flow. Ulcer induction itself dramatically increased constitutive nitric oxide synthase (cNOS) activity and prostaglandin E2 (PGE2) level in the gastric mucosa. However, the increment of cNOS activity but not PGE2 level was markedly attenuated by cigarette smoke exposure. Sodium nitroprusside (SNP, 25 or 50 microg/kg, i.v.), a nitric oxide (NO) donor, completely abolished the potentiating effect of cigarette smoke exposure on ulcer formation and also reversed the adverse effect on gastric blood flow. Thus, XO activation and cNOS reduction in the gastric mucosa are closely associated with the potentiating action of cigarette smoke exposure on ulcer formation in rats.
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PMID:Mechanistic study of adverse actions of cigarette smoke exposure on acetic acid-induced gastric ulceration in rats. 948 4

The synthetic flavonoid flavone acetic acid (FAA) has anti-tumor activity against a variety of transplanted tumors in mice through mechanisms which likely involve effects on tumor vasculature and the host immune system. The aims of the present in vitro study were to compare the sensitivity of tumor and endothelial cells to FAA treatment and to assess if nitric oxide and superoxide are involved in the FAA-mediated suppression of cell proliferation. FAA at 1 mM concentration was approximately two times more effective in suppressing proliferation of endothelial than tumor cells. The anti-proliferative effect of 1 mM FAA on endothelial cells was partially blocked by inhibitors to various superoxide-producing enzymes (xanthine oxidase, cyclooxygenase, poly-ADP-ribose polymerase, ribonucleotide reductase) and completely inhibited by the direct scavengers of superoxide lucigenin and Tiron. In contrast, inhibitors of nitric oxide were unable to prevent the effects of FAA on proliferation. FAA induced apoptosis of endothelial cells, which was not affected by inhibitors of nitric oxide or superoxide. Our data imply that FAA inhibits proliferation of endothelial cells by a superoxide-dependent mechanism and induces apoptosis by a nitric oxide and superoxide-independent mechanism.
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PMID:Oxidative stress contributes to the anti-proliferative effects of flavone acetic acid on endothelial cells. 1095 82

An HPLC method has been developed for the separation and the determination of caffeine and its metabolites in urine samples using a one extraction-analysis run and UV detection. The compounds were extracted by liquid-liquid extraction using chloroform-isopropylalcohol (85:15, v/v). Chromatographic separation was accomplished on an ODS analytical column with a mobile phase containing 0.05% acetic acid/methylalcohol (92.5:7.5, v/v). Compounds were monitored at 280 nm. The method was validated for the determination of AFMU, 1X, 1U, 17X and 17U caffeine metabolites required to assess the metabolic activity of the enzymes subject to in vivo caffeine testing. The validated assay was applied to urine samples from ten healthy volunteers. The method was proved to be suitable to assess simultaneously the enzymatic activity of cytochrome P450 CYP1A2 and CYP2A6, as well as N-acetyltransferase and xanthine oxidase.
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PMID:Liquid chromatographic method for the simultaneous determination of caffeine and fourteen caffeine metabolites in urine. 1107 88

We studied whether reactive oxygen species (ROS) generated by normal colonic mucosa affect 5-hydroxytryptophan (5-HTP)-evoked 5-HT formation (measured as the sum of 5-HT plus 5-hydroxyindole acetic acid (5-HIAA) accumulation) of guinea pig's isolated colonic mucosa. Catalase (3000-6000 U/ml), a hydrogen peroxide (H2O2) scavenger or diphenylene iodonium (DPI, 10-100 microM), an NADPH oxidase inhibitor, concentration-dependently caused an increase of the sum of 5-HT plus 5-HIAA accumulation in the presence of 5-HTP (10 microM), but these drugs did not significantly affect the 5-HT-metabolite in the colonic mucosa measured as the ratio of 5-HIAA/5-HT. Exogenously applied H2O2 (10-100 microM) concentration-dependently inhibited the sum of 5-HT plus 5-HIAA accumulation. In contrast, neither superoxide dismutase (SOD, 100-300 U/ml), superoxide anion scavenger, nor dimetyl sulfoxide (1-5%, DMSO), a hydroxyl radical scavenger affected the sum of 5-HT plus 5-HIAA accumulation. Moreover, mucosa ROS generation was estimated using the chemiluminescence technique. SOD (100-300 U/ml), catalase (3000-6000 U/ml) or DPI (10-100 microM), concentration-dependently reduced luminol-enhanced chemiluminescence signal from the colonic mucosa, while allopurinol (10-100 microM), a xanthine oxidase inhibitor, did not affect the chemiluminescence signal. These results suggest that ROS is formed through an NADPH oxidase system in the guinea pig colonic mucosa, where it exerts a modulatory effect on mucosal 5-HT formation upon addition of 5-HTP. Thus, ROS formation from normal colonic mucosa could be considered to contribute to the control of 5-HT production in mucosa enterochromaffin cells.
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PMID:Modification of 5-hydroxytryptophan-evoked 5-hydroxytryptamine formation of guinea pig colonic mucosa by reactive oxygen species. 1185 70

The synthesis of some new aryl acetic acids and amides and a pharmacochemical study and quantitative structure-activity relationships (QSAR) on them are described. The compounds were screened for their biological activity using the carrageenin induced rat paw oedema model and a significant inhibition of oedema occurred (44.1-80.1%) at a concentration of 0.01 mmol/1 kg. The analgesic activity, based on the inhibition of acetic acid-induced writhing in rats was also found to be significant. The compounds were found to interact with the stable free radical 1,1-diphenylhydrazyl DPPH and with DMSO (for hydroxyl radicals). The compounds were screened for radical scavenging activity with the xanthine/xanthine oxidase system for O2-* and for inhibition of soybean lipoxygenase (LOX). The results are discussed in terms of the structural and physicochemical characteristics of the compounds.
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PMID:Anti-inflammatory, antioxidant and analgesic amides. 1500 18

Two new compounds, sodium N-(6, '8-dimercaptooctanoyl)-2-amino ethanesulfonate- and sodium N-(6, 8-dimercaptooctanoyl)-L-aspartate - zinc complex were synthesized from alpha-lipoyl-2-aminoethanesulfonate and alpha-lipoyl-L- aspartate by reduction of zinc/acetic acid respectively. These alpha-lipoyl-amino acids were obtained by a coupling of alpha-lipoic acid and 2-aminoethanesulfonate or L-aspartate, using a mixed anhydride method. Scavenging activities of these derivatives against hydroxyl radicals (*OH) was demonstrated directly using electron spin resonance (ESR) spectrometry with spin trapping. Otherwise an apparent superoxide anion radical (O2*-) scavenging effect of these derivatives may be due to the inhibition of 02*- generation system, i.e., xanthine oxidase. Scavenging activities of these compounds against nitric oxide radicals (NO*), and peroxynitrite (ONOO-) were estimated by the flow injection analysis using the Griess reagent and by a fluorescence spectrometry using dihydrorhodamine 123 respectively. Meanwhile, these derivatives showed protective effects against lipid peroxidation and protein carbonyl formation. Scavenging activities against NO* and ONOO-, and inhibitory effects on protein carbonyl formation of these derivatives were much stronger than these of alpha-lipoic acid itself.
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PMID:Antioxidant activities of novel alpha-lipoic acid derivatives: N-(6, 8-dimercaptooctanoyl)-2-aminoethanesulfonate- and N-(6, 8-dimercaptooctanoyl)-L-aspartate-zinc complex. 1568 13

Oxidative stress caused by excessive reactive species (RS) and lipid peroxidation is known to be casually linked to age-related inflammation. To test the hypothesis that fish oil (FO) intake has a beneficial effect on nephritis due to its suppressive action of oxidative stress and the enhancement of antioxidant defenses, we examined the effect of dietary FO on various oxidative stress-related parameters and guanidino compound (GC) levels using (NZB x NZW) F1 (B/W) mice. These mice were fed diets supplemented with either 5% corn oil (control) or 5% FO. At 4 and 9 months of age, the hepatic oxidative status was estimated by assessing RS generation produced from xanthine oxidase, the prostaglandin pathway and lipid peroxidation. To evaluate the effect of FO on redox status, including antioxidant defenses, GSH and GSSG levels and antioxidant enzyme activities were measured. To correlate the extent of oxidative status with the nephritic condition, creatinine, guanidino acetic acid and arginine levels were measured. Results indicated that increased levels of lipid peroxidation, RS generation and xanthine oxidase activity with age were all significantly suppressed by FO feeding. Furthermore, reduced GSH levels, GSH/GSSG ratio and antioxidant enzyme activities in the FO-fed mice were effectively enhanced compared to the corn oil-fed mice. Among several GCs, the age-related increase of creatinine level was blunted by FO. Based on these results, we propose that dietary FO exerts beneficial effects in aged, nephritic mice by suppressing RS, superoxide and lipid peroxidation, and by maintaining a higher GSH/GSSG ratio and antioxidant enzyme activities.
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PMID:Suppression of oxidative stress in aging NZB/NZW mice: effect of fish oil feeding on hepatic antioxidant status and guanidino compounds. 1629 35


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