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

Mucin hypersecretion in the gallbladder is thought to be a key factor in the nucleation of cholesterol gallstones. In this study, we evaluated the effect of several oxygen radical-generating systems on glycoprotein release from guinea pig gallbladder explants. Hydroxyl radicals (OH.) released by hypoxanthine-xanthine oxidase or FeCl3-ascorbate caused a significant increase in glycoprotein secretion from gallbladder explants pre-incubated with [3H] glucosamine. Human neutrophils activated with f-Met-Leu-Phe, a chemotactic peptide, released oxygen radicals that also stimulated gallbladder glycoprotein release. The mechanism of this effect is most probably related to perturbation of lipid membrane structure by the oxygen radicals with subsequent activation of glycoprotein release.
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PMID:Oxygen radicals stimulate gallbladder glycoprotein secretion. 256 90

The role of oxygen-derived free radicals in the pathogenesis of acute pancreatitis has been investigated in a series of studies using an ex vivo, perfused canine pancreas preparation. Three models of experimental acute pancreatitis have been developed in this preparation: ischemic pancreatitis, gallstone pancreatitis, and alcohol-induced pancreatitis. In each model, the pancreas becomes edematous, gains weight, and the perfusate develops hyperamylasemia during the 4 hour period of perfusion. Pretreatment with the free radical scavengers superoxide dismutase and catalase significantly ameliorates these manifestations of pancreatic injury in each of the three models. The source of the free radical generation was investigated by pretreating the preparation with allopurinol, a quite specific inhibitor of xanthine oxidase. In each of the three models, this also significantly ameliorated the injury process. These experiments demonstrate that oxygen-derived free radicals, generated by activated xanthine oxidase, appear to play a central role in the pathogenesis of acute pancreatitis in these models. These findings shed light on the fundamental pathophysiology of this disease and may provide the basis for more effective therapy in the future.
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PMID:Oxygen-derived free radicals and acute pancreatitis: a review. 352 21

Four models of acute pancreatitis have been previously developed that use the ex vivo perfused isolated canine pancreas preparation. The four models include the intraarterial infusion of oleic acid (FFA) that mimics hyperlipemic pancreatitis, partial obstruction of the pancreatic duct with secretin stimulation (POSS) that mimics gallstone pancreatitis, a 2-hour period of ischemia before perfusion (ISCH 2) that mimics shock pancreatitis, and the infusion of cerulein at supramaximal stimulatory doses (CER), which lacks an obvious clinical counterpart. In the FFA, POSS, and ISCH 2 pancreatitis, but not in the CER pancreatitis, toxic oxygen metabolites, generated by the enzyme xanthine oxidase (XO), have been shown to be important mediators in the early pathogenesis. Ordinarily XO primarily occurs as xanthine dehydrogenase (XD) but can be converted to XO, which is the form that generates toxic oxygen metabolites. This conversion of XD to XO may take place either reversibly by way of sulfhydryl group oxidation or irreversibly by means of proteolytic cleavage of XD. This study was undertaken to investigate the mechanism of conversion of XD to XO in the FFA-, POSS-, and ISCH 2-induced pancreatitis models. CER pancreatitis was studied for comparison. After 4 hours of perfusion, pancreatitis was manifest by edema, weight gain, and hyperamylasemia in all four models. Dithiothreitol, a sulfhydryl group protector, ameliorated the weight gain in the FFA (40 +/- 14 gm to 18 +/- 13 gm; p < 0.05), POSS (28 +/- 10 gm to 9 +/- 3 gm; p < 0.05), and ISCH 2 pancreatitis (30 +/- 13 gm to 15 +/- 3 gm; p < 0.05), and ameliorated the hyperamylasemia in the POSS pancreatitis (12,062 +/- 4304 units/dl to 5877 +/- 2659 units/dl; p < 0.05). The CER pancreatitis was not ameliorated with dithiothreitol. A serine protease inhibitor of low molecular weight, phenylmethylsulfonyl fluoride, ameliorated only the CER pancreatitis (weight gain from 28 +/- 10 gm to 17 +/- 10 gm, p < 0.05; amylase activity from 38,116 +/- 6491 units/dl to 23,372 +/- 11,654 units/dl, p < 0.05), and not the FFA, POSS, or ISCH 2 pancreatitis. We conclude that in the three models of pancreatitis (FFA, POSS, and ISCH 2) that are mediated by toxic oxygen metabolites, XD is converted to XO reversibly by way of sulfhydryl group oxidation rather than irreversibly by way of proteolysis. In the CER pancreatitis, where XO does not play a role in the pathogenesis, proteolytic enzymes may be important mediators in the injury.
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PMID:The mechanism of conversion of xanthine dehydrogenase to xanthine oxidase in acute pancreatitis in the canine isolated pancreas preparation. 841 95