Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The influence of regulatory peptides (somatostatin, calcitonin, and dalargin) on xanthine oxidase activity and lipid peroxidation level in pancreatic tissues as well as on the release of pancreatic enzymes (alpha-amylase, trypsin, lipase, and transamidinase) into blood was studied in 205 rats with experimental acute pancreatitis. Somatostatin and dalargin were shown to have obvious antioxidant effect seen by reduced xanthine oxidase activity and MDA level. All studied peptides stimulate reduced release of pancreatic enzymes. Particularly, reduction of dalargin and somatostatin is caused by inhibition of their synthesis as well as by pancreas protective effect of the peptides. Release of enzymes reduced by calcitonin is probably associated only with inhibition of secretory activity of the pancreas.
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PMID:[Effects of several regulatory peptides on the functional activity of the pancreas in acute experimental pancreatitis]. 259 53

Experiments were conducted on 268 male albino rats with modeled acute pancreatitis to study the xanthine oxidase (XO) activity in the pancreatic tissue during intraperitoneal administration of stimulators of pancreatic exocrine function (pilocarpine) and inhibitors of enzyme activity (allopurinol). Pilocarpine (0.1 mg/kg) increased XO activity by 90-100% one-three hours after injection, which was due to increased synthesis of the enzyme. Allopurinol (500 mg/kg) inhibiting XO activity removes the XO activating effect of pilocarpine in the first two hours after injection. It was established that one of the tranquilizers of the 1,4-benzodiazepine series--seduxen (15 mg/kg) produces an inhibiting effect on XO activity and, like allopurinol, removes the XO activating effect of pilocarpine. Complete parallelism was also revealed between the dynamics of changes of XO activity in the pancreatic tissue and alpha-amylase in blood under the effect of the preparations studied.
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PMID:[Role of xanthine oxidase in the genesis of acute pancreatitis]. 275 30

It has been suggested that oxygen-derived free radicals play a decisive role in the pathogenesis of acute experimental pancreatitis in a model of edematous pancreatitis. Accordingly, allopurinol, a xanthine oxidase inhibitor, was shown to mitigate the development of nonfatal acute pancreatitis in ex vivo perfusion models using dogs. For further evaluation of allopurinol, its effect was studied in two forms of fatal necrotizing acute experimental pancreatitis: sodium taurocholate-induced pancreatitis in rats and choline-deficient ethionine-supplemented diet-induced pancreatitis in mice. Allopurinol did not affect the mortality rate, pancreatic enzyme elevation in serum and ascites, the enzyme content of the pancreas, or any parameter indicating histopathological damage in the pancreas. Although these experiments did not determine the role oxygen-derived free radicals play in the development of pancreatitis, they show, none the less, the absence of any beneficial therapeutic effect of a xanthine oxidase like allopurinol on the development of the disease once it has begun.
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PMID:Xanthine oxidase inhibitor in acute experimental pancreatitis in rats and mice. 276 73

The development of acute pancreatitis involves a number of pathophysiological changes which result in pancreatic tissue damage. Data from several models of acute pancreatitis suggest that the in vivo conversion of the enzyme xanthine dehydrogenase to xanthine oxidase may cause tissue damage by the subsequent generation of oxygen-derived free radical products. In the present studies, acute pancreatitis was induced in mice by the administration of supramaximal secretory doses of caerulein, a cholecystokinin analogue. Pancreatic xanthine oxidase activity was observed to occur in the dehydrogenase form in both control and treated mice. Artifactual conversion to the oxidase form could be induced by exclusion of 2-mercaptoethanol and phenylmethylsulfonyl fluoride from the buffer during tissue preparation. These data indicate that no significant conversion of xanthine dehydrogenase to oxidase is associated with this model of acute pancreatitis in mice.
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PMID:Xanthine oxidase activity in mouse pancreas: effects of caerulein-induced acute pancreatitis. 348 Jul 8

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

Oxygen-derived free radicals play an important role in the pathogenesis of experimental acute pancreatitis in the isolated perfused canine pancreas. We have previously found that pretreatment with allopurinol inhibits xanthine oxidase--apparently the primary source of free radical generation in this model--and prevents the initial development of pancreatitis. In these experiments, we evaluated whether allopurinol administered after the onset of pancreatitis would arrest the progression of the disease process. Edema formation, weight gain, and the release of amylase activity into the perfusate in the ex vivo perfused canine pancreas model were monitored during a 4-hour perfusion period. There were six experimental groups: Group I (control) received no treatment, group II (allopurinol alone) received only allopurinol (100 mg) at the start of perfusion, and groups III through VI were each given an infusion of 0.3 ml of oleic acid (FFA) over a 1-hour period to initiate acute pancreatitis. Group III (FFA alone) received no other treatment. In group IV (pretreatment with allopurinol), group V (concurrent treatment with allopurinol), and group VI (posttreatment with allopurinol), allopurinol (100 mg) was administered 1 hour before, concurrent with, or at the end of the FFA infusion, respectively. Pretreatment with allopurinol prevented edema formation, markedly attenuated weight gain, and the release of amylase caused by the FFA infusion. Administration of allopurinol concurrent with the FFA infusion provided only partial protection, whereas posttreatment with allopurinol failed to arrest the progression of the injury process. Therefore, the use of allopurinol to inhibit oxygen-derived free radical production from xanthine oxidase prevented the development of acute pancreatitis in this model; however, treatment with allopurinol after initiation of the disease process failed to arrest the progression of acute pancreatitis.
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PMID:Temporal efficacy of allopurinol during the induction of pancreatitis in the ex vivo perfused canine pancreas. 382 61

Oxygen free radicals (OFR) are postulated to play a role in the pathogenesis of acute pancreatitis. The aim of this work was to examine the role of xanthine oxidase in the generation of OFR and the activity of the endogenous defense mechanisms as reflected by pancreatic superoxide dismutase (SOD) activity in a model of edematous pancreatitis induced in rats by administration of cerulein at supramaximal doses, as well as in necrohemorrhagic model induced by intraductal administration of sodium taurocholate. Comparison between these two models of pancreatitis suggests important differences in origin and importance in the evolution of injury. In necrohemorrhagic pancreatitis OFR can be produced by xanthine oxidase activity probably associated to cell death. By contrast, in cerulein induced pancreatitis, other sources of oxygen free radicals, such as inflammatory cells, can be of more importance.
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PMID:Xanthine oxidase activation in cerulein- and taurocholate-induced acute pancreatitis in rats. 752 65

Oxygen free radicals and prostaglandins are implicated in the pathophysiology of acute pancreatitis, although their mechanisms of action remain unclear. We have studied the effect of administration of exogenous 16,16-dimethyl prostaglandin E2 and superoxide dismutase on oxygen free radical production in acute pancreatitis. For this purpose, five experimental rat groups were studied: group I, control; group II, sodium taurocholate-induced acute pancreatitis; group III, same as group II but with previous administration of 16,16-dimethyl prostaglandin E2; group IV, same as group II but with previous administration of indomethacin; and group V, same as group II but with previous administration of superoxide dismutase. In sodium taurocholate-treated rats, xanthine dehydrogenase is completely converted to xanthine oxidase within the first 5 min with subsequent oxygen free radical production while in 16,16-dimethyl prostaglandin E2-treated rats this enzyme transformation does not occur. In the superoxide dismutase-treated group xanthine oxidase activation is partially prevented. These data suggest that xanthine oxidase is the main source of oxygen free radicals, which contribute to extending the cellular damage in sodium taurocholate-induced acute pancreatitis.
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PMID:Effect of prostaglandins and superoxide dismutase administration on oxygen free radical production in experimental acute pancreatitis. 822 63

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

The current study was done to evaluate the effects of short term (60 minutes) pancreatic biliary duct obstruction (PBDO) with intraductal hypertension (IDH) stimulated by secretin (0.2 clinical unit per kilogram per hour) and caerulein (0.2 microgram per kilogram per hour) plus 30 minutes of temporary pancreatic ischemia (ISCH) produced by ligation of celiac and superior mesenteric artery on the exocrine pancreas and protective effects of a new potent protease inhibitor, ONO3307 in combination with xanthine oxidase inhibitor, allopurinol, in this multifactor related model of acute pancreatitis in rats. Twelve hours after PBDO with IDH plus ISCH, we observed hyperamylasemia (23 +/- 3 units per milliliter) (p < 0.01); moderate pancreatic histologic changes; pancreatic edema (water content--81 +/- 2 percent) (p < 0.02), as well as the impaired amylase (2,889 +/- 328 units per kilogram per hour) (p < 0.01) and cathepsin B output (7 +/- 3 units per kilogram per hour) (p < 0.01) into the pancreatic juice of rats stimulated by caerulein (control group--serum amylase levels, 6 +/- 1 units per milliliter; pancreatic water content, 74 +/- 1 percent. Furthermore, PBDO with IDH plus ISCH caused the redistribution of lysosomal enzyme from lysosomal fraction (12 kilo times gravity pellet; 40 +/- 3 percent; p < 0.01) to zymogen fraction (1.3 kilo times gravity pellet; 38 +/- 3 percent; p < 0.01) (control group--12 kilo times gravity pellet, 59 +/- 2 percent; 1.3 kilo times gravity pellet, 24 +/- 2 percent) and the impaired pancreatic adenylate energy metabolism (0.79 +/- 0.02, p < 0.02) (control group--energy charge equals 0.88 +/- 0.01). Only PBDO with IDH caused no significant changes. Although only ONO3307 or allopurinol therapy showed the partial significant protective effects against pancreatic injuries, improving serum amylase levels, the administration of ONO3307 in combination therapy with allopurinol showed almost complete protective effects against the pancreatic injuries induced by PBDO with IDH plus ISCH (serum amylase levels, 9 +/- 2 units per milliliter; pancreatic water content, 76 +/- 2 percent; amylase and cathepsin B output, 7,127 +/- 946 and 18 +/- 3 units per kilogram per hour; 1.3 kilo times gravity pellet, 28 +/- 2 percent; 12 kilo times gravity pellet, 54 +/- 2 percent, and energy charge equals 0.85 +/- 0.02).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Protective effects of therapy with a protease and xanthine oxidase inhibitor in short form pancreatic biliary obstruction and ischemia in rats. 846 Apr 15


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