Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.17.3.2 (xanthine oxidase)
 8,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutrophils (PMNs) are believed to play a key role in the pathogenesis of postinjury adult respiratory distress syndrome. We have previously shown that gut ischemia/reperfusion (I/R) produces lung injury by a process that requires PMNs. More recently, we have shown that xanthine oxidase (XO) plays a role. The purpose of this study was to characterize the mechanistic sequencing of XO activity versus the PMN in this model of gut I/R-induced lung injury. Normal and XO-inactivated (tungsten enriched, molybdenum depleted diet) rats underwent 45 min of superior mesenteric artery occlusion. After 6 hr reperfusion, blood was sampled and gut and lungs harvested. Myeloperoxidase (MPO) was used to quantitate PMN presence in the gut and lungs, while circulating PMN priming was measured as the difference in superoxide production with and without the activating stimulus, fMLP. 125I-labeled albumin leak was used as a marker for lung endothelial permeability. We observed that the gut I/R increased gut MPO levels, primed circulating PMNs, increased lung MPO levels, and provoked distant lung leak. XO inactivation abolished gut MPO activity, attenuated circulating PMN priming, and blocked lung leak. In conclusion, XO plays a proximal role in the pathogenesis of remote organ injury following splanchnic hypoperfusion.
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PMID:Gut ischemia mediates lung injury by a xanthine oxidase-dependent neutrophil mechanism. 839 21

The peroxidation of lipids and changes in the activities of related enzymes, such as xanthine-xanthine oxidase (XOD), superoxide dismutase (SOD), and glutathione peroxidase (GSH-px) in the gastric mucosa were studied in rat model of ischemia-reperfusion with pylorus ligation. Myeloperoxidase (MPO), a marker enzyme of leucocytes, was also studied. Thiobarbituric acid reactive substances (TBA RS) in gastric mucosa were significantly increased by clamping the celiac artery for 30 min and reperfusion for 60 min after 3 h of pylorus ligation. XOD activity in gastric mucosa increased with the development of gastric mucosal injury. Allopurinol significantly suppressed XOD activity but did not inhibit mucosal injury or the increase in TBA RS. MPO activity in the gastric mucosa was significantly increased by gastric mucosal injury. Famotidine significantly inhibited the increase in MPO activity in gastric mucosa, while allopurinol did not. SOD and GSH-px activities in the gastric mucosa were decreased significantly by gastric mucosal injury. SOD activity was normal following treatment with famotidine and allopurinol. Moreover, GSH-px activity recovered to the normal level with famotidine and allopurinol treatment. These findings suggest that oxygen radicals and lipid peroxidation can cause gastric mucosal injury by ischemia-reperfusion in the pylorus-ligated rat. The generation of oxygen free radicals may be derived mainly from activated polymorphonuclear leukocytes (PMN), and the decrease in SOD and GSH-px activity in gastric mucosa seems to aggravate mucosal injury by free radicals and lipid peroxidation.
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PMID:Role of lipid peroxidation in gastric mucosal lesions induced by ischemia-reperfusion in the pylorus-ligated rat. 839 87

Myeloperoxidase (MPO) is a lysosomal enzyme found in the primary granules of mammalian neutrophils. Together with MPO, peroxide and halide form a system of defense against bacteria. The present investigation was undertaken to study the bactericidal effects of the bovine-MPO/peroxide/halide system on pathogenic bacteria associated with bovine mastitis. We demonstrated that MPO together with oxidizing agents generated by xanthine oxidase, hypoxanthine and chloride form a potent antibacterial system against the common udder pathogens Staphylococcus aureus, Streptococcus uberis, Streptococcus agalactiae, Streptococcus dysgalactiae and Escherichia coli in a synthetic medium. However, when milk was added to the reaction mixture, the bactericidal properties of this enzyme system were completely inhibited. Loss of bactericidal activity in the milk-containing cultures was unable to be restored by increasing the concentration of MPO. Nor did an increase in concentrations of hypoxanthine and xanthine oxidase, or the replacement of the above-mentioned peroxidase generating system with a high concentration of hydrogen peroxide, significantly elevated the bactericidal activity that was inhibited by milk. The addition of bovine serum albumin to the synthetic medium reduced the bactericidal activity of the MPO/peroxide/chloride system in a dose-dependent manner. Therefore, milk proteins probably form adducts with strong bactericidal agents that are generated by the MPO system and thereby reduce the bactericidal potential of this system.
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PMID:Bactericidal activity of the bovine myeloperoxidase system against bacteria associated with mastitis. 856 Jul 39

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

The role of active oxygen species and lipid peroxidation in the pathogenesis of duodenal ulcers induced by mepirizole was investigated in rats. Oral administration of mepirizole (200 mg/kg) resulted in ulcer lesions in the proximal duodenum. Thiobarbituric acid-reactive substances (TBA-reactive substances), an indicator of lipid peroxidation, also significantly increased in the duodenal mucosa. Myeloperoxidase (MPO) activity in the duodenal mucosa, a sign of polymorphonuclear leukocyte (PMN) accumulation, significantly increased. Combination treatment with polyethylene glycol-modified Serratia Mn-SOD and catalase significantly decreased the size of the ulcers and TBA-reactive substances in the duodenal mucosa. Allopurinol, a xanthine oxidase inhibitor, also reduced the size of duodenal ulcers. Both the size of the ulcers and the increase in TBA-reactive substances in the duodenal mucosa were significantly lower in PMN-depleted rats. Mepirizole increased the surface expression of adhesion molecule CD18 on PMNs in vitro. These results suggest that lipid peroxidation, mediated by active oxygen species generated from xanthine oxidase and PMNs, plays an important role in the pathogenesis of duodenal ulcers induced by mepirizole.
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PMID:Role of active oxygen species and lipid peroxidation in mepirizole-induced duodenal ulcers in rats. 972 47

Oxidative modification of low density lipoprotein (LDL) appears to play an important role in atherogenesis. Although the precise mechanisms of LDL oxidation in vivo are unknown, several lines of evidence implicate myeloperoxidase and reactive nitrogen species, in addition to ceruloplasmin and 15-lipoxygenase. Myeloperoxidase generates a number of reactive species, including hypochlorous acid, chloramines, tyrosyl radicals, and nitrogen dioxide. These reactive species oxidize the protein, lipid, and antioxidant components of LDL. Modification of apolipoprotein B results in enhanced uptake of LDL by macrophages with subsequent formation of lipid-laden foam cells. Nitric oxide synthases produce nitric oxide and, under certain conditions, superoxide radicals. Numerous other sources of superoxide radicals have been identified in the arterial wall, including NAD(P)H oxidases and xanthine oxidase. Nitric oxide and superoxide readily combine to form peroxynitrite, a reactive nitrogen species capable of modifying LDL. In this review, we examine the reaction pathways involved in LDL oxidation by myeloperoxidase and reactive nitrogen species and the potential protective effects of the antioxidant vitamins C and E.
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PMID:Oxidation of LDL by myeloperoxidase and reactive nitrogen species: reaction pathways and antioxidant protection. 1089 8

The protective action of zinc compounds in Crohn's disease-like inflammatory bowel disease in animals has been shown. A similar action of zinc sulfate on ulcerative colitis has not been defined. The present study aimed to delineate the protective action of zinc sulfate and the pathogenic mechanisms of 2,4-dinitrobenzene sulfonic acid (DNBS)-induced ulcerative colitis in rats. Zinc sulfate at different concentrations was given either orally (p.o.) or rectally (p.r.) to rats at 42, 48, 66 and 72 h following the induction of colonic inflammation by DNBS. Rats were killed 96 h after instillation of DNBS rectally to assess the severity of colonic damage, myeloperoxidase and xanthine oxidase activities. The involvement of mast cell degranulation and histamine release in the pathogenesis of DNBS-induced colitis was determined by using a mast cell stabilizer (ketotifen) and histamine receptor blockers (terfenadine and ranitidine). DNBS given rectally produced inflammation and ulceration in rats with a pathology resembling ulcerative colitis. Myeloperoxidase activity but not xanthine oxidase activity was sharply increased by this agent. Intrarectal administration of zinc solution and parenteral injection of histamine blockers significantly reduced tissue damage and myeloperoxidase but not xanthine oxidase activity. Ketotifen, a mast cell stabilizer, also significantly decreased mucosal injury and myeloperoxidase activity in the colon. In conclusion, mast cell degranulation followed by histamine release plays an important role in the pathogenesis of DNBS-induced ulcerative colitis. Zinc given rectally has a therapeutic effect against this colitis model, perhaps through the reduction of inflammation and inhibition of the above pathogenic mechanisms.
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PMID:Delineation of the protective action of zinc sulfate on ulcerative colitis in rats. 1204 10

Conjugation with glucuronic acid is a prevalent metabolic pathway of orally administrated curcumin, the bioactive diphenol of the spice turmeric. The major in vitro degradation reaction of curcumin is autoxidative transformation resulting in oxygenation and cyclization of the heptadienedione chain to form cyclopentadione derivatives. Here we show that curcumin-glucuronide is much more stable than curcumin, degrading about two orders of magnitude slower. Horseradish peroxidase-catalyzed oxidation of curcumin-glucuronide occurred at about 80% of the rate with curcumin, achieving efficient transformation. Using LC-MS and NMR analyses the major products of oxidative transformation were identified as glucuronidated bicyclopentadione diastereomers. Cleavage into vanillin-glucuronide accounted for about 10% of the products. Myeloperoxidase and lactoperoxidase oxidized curcumin-glucuronide whereas tyrosinase and xanthine oxidase were not active. Phorbol ester-activated primary human leukocytes showed increased oxidative transformation of curcumin-glucuronide which was inhibited by the peroxidase inhibitor sodium azide. These studies provide evidence that the glucuronide of curcumin is not an inert product and may undergo further enzymatic and non-enzymatic metabolism. Oxidative transformation by leukocyte myeloperoxidase may represent a novel metabolic pathway of curcumin and its glucuronide conjugate.
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PMID:Oxidative metabolism of curcumin-glucuronide by peroxidases and isolated human leukocytes. 2827 15

Male albino rats of Wistar strain were injected intraperitoneally with nicotine or/and resveratrol for 4 weeks. Serum Interleukin-2, Interleukin-6, alpha-fetoprotein and tumor necrosis-alpha, as well as plasma 8-hydroxydeoxyguanosine of nicotine-treated rats were increased significantly. Myeloperoxidase, xanthine oxidase, nitric oxide, lipid peroxidation and total oxidative status of the lung in nicotine-treated rats were increased significantly, which were brought down to normal in resveratrol co-treated group. Endogenous antioxidant status as the activity of superoxide dismutase, catalase, glutathione peroxidase, and glucose-6-phosphate dehydrogenases were found to be decreased significantly in the lung of the nicotine-treated group, which were significantly raised in resveratrol-administered groups. The non-enzymatic antioxidants as total antioxidant and thiol levels were decreased significantly as the effect of nicotine that was effectively enhanced by resveratrol treatment. The lung of nicotine-treated rats showed severe congestion of the alveolar lung tissues with scattered congestion per bronchiolar and perivascular cells, as well as, inflammatory cells were observed. The data suggested that resveratrol exerts its protective effect by modulating the extent of oxidative status and improving the enzymatic/non-enzymatic antioxidant defense system, moreover, decreases the pathological changes in animals against the lung damage caused by nicotine.
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PMID:Anti-inflammatory and antioxidant role of resveratrol on nicotine-induced lung changes in male rats. 2895 65


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