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)

Isolated pancreatic acini were incubated with either a combination of xanthine and xanthine oxidase which generates superoxide (O2), or hydrogen peroxide (H2O2), and the direct cytotoxic effect of active oxygen species on the pancreatic acini was examined in vitro in the isolated pancreatic acini system of the rat. Both amylase secretion and lactic dehydrogenase discharge were increased dose-dependently by the addition of xanthine and xanthine oxidase, and suppressed by the addition of a superoxide scavenger, superoxide dismutase. In addition, amylase and lectate dehydrogenase discharge was increased dose-dependently by hydrogen peroxide and decreased by catalase. These results suggest that superoxide and hydrogen peroxide directly injure pancreatic acinar cells and that active oxygen species are involved in the pathogenesis of acute pancreatitis.
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PMID:Toxic effects of oxygen-derived free radicals on rat pancreatic acini; an in vitro study. 128 95

A supramaximal dose of caerulein (5 micrograms/kg.hr for 3.5 hours) caused an acute pancreatitis with marked hyperamylasemia and intense interstitial edema in rats. In this model of pancreatitis, the redistribution of lysosomal enzyme in acinar cells as well as the increased lysosomal and mitochondrial fragility were also observed. The combined therapy of a low molecular weight protease inhibitor, FOY, a synthetic platelet activating factor (PAF) antagonist, CV 6209, and a xanthine oxidase inhibitor, allopurinol produced more significant improvements in all the parameters examined than the therapy of any only one of these three agents, each only one therapy exerting a partial significant protective effect. These results indicate that several factors, such as unknown proteases activities, PAF and oxygen-derived free radicals may be involved in the pathogenesis of pancreatic injuries in this caerulein-induced pancreatitis. These results also suggest that such a combined therapy of different kinds of agents, whose therapeutic mechanisms are also different, is useful in the clinical treatment of acute pancreatitis.
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PMID:"Cocktail" therapy for acute pancreatitis: combined therapy of protease inhibitor, xanthine oxidase inhibitor and platelet activating factor antagonist in rat caerulein-induced pancreatis. 130 81

To explore the role of active oxygen species in the development and progression of acute pancreatitis, we studied the direct toxic effect on the rat pancreas of active oxygen species: superoxide anions generated by xanthine/xanthine oxidase (X/XO), and hydrogen peroxide (H2O2). After a continuous injection of X (10(-3)M, 0.9 ml/hour)/XO (1 U/ml, 0.3 ml/hour) into the celiac artery supplying the pancreas, hemorrhages and extensive edema developed in the pancreas. The amylase and lipase concentrations in the peritoneal fluid rose to 10.3 and 13.8 times the control values, respectively. The subsequent infusion of superoxide dismutase (SOD, 3600 U/hour) into the external jugular vein completely suppressed hemorrhages, and reduced edema and the amylase and lipase concentrations in the peritoneal fluid. After continuous injection of H2O2 (100 microM, 1.2 ml/hour), via the celiac artery, marked hemorrhages and edema appeared in the pancreas, and the amylase and lipase concentrations in the peritoneal fluid were 11.1 and 17.3 times higher than the control values, respectively. These abnormalities were significantly suppressed by the intravenous infusion of catalase (10 mg/kg/hour) or gabexate mesilate (10 mg/kg/hour). These results indicate that active oxygen species have a direct toxic effect on the pancreas and that free radicals may play an important role in the development of acute pancreatitis.
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PMID:Effect of intraarterial active oxygen species on the rat pancreas. 137 10

The protective effect of a new potent protease inhibitor, ONO 3307, in combination with a xanthine oxidase inhibitor, allopurinol, was tested in pancreatico-biliary duct obstruction (PBDO) with temporary pancreatic ischemia in rats. After PBDO with ischemia, we observed hyperamylasemia, pancreatic edema, congestion of amylase and lysosomal enzyme cathepsin B as well as impaired output of amylase and cathepsin B into the pancreatic juice and a redistribution of lysosomal enzyme from the lysosomal fraction to the zymogen fraction. The administration of ONO 3307 plus allopurinol almost completely prevented the pancreatic injuries induced by PBDO with ischemia. These results indicate the important roles of temporary pancreatic ischemia in the pathogenesis of pancreatic damage and the usefulness of combination therapy with a new potent protease inhibitor and xanthine oxidase inhibitor in the protection against clinical acute pancreatitis.
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PMID:Protective effects of combined therapy with a protease inhibitor, ONO 3307, and a xanthine oxidase inhibitor, allopurinol on temporary ischaemic model of pancreatitis in rats. 144 2

Acetaldehyde (AA), the first product of ethanol metabolism, has been suggested as an important mediator in alcoholic pancreatitis, but experimental evidence has not been convincing. Prior work using the isolated perfused canine pancreas preparation has suggested that toxic oxygen metabolites generated by xanthine oxidase (XO) may mediate the early injury in pancreatitis. Xanthine oxidase is capable of oxidizing AA, and during this oxidation free radicals are released. The hypothesis that acute alcoholic pancreatitis may be initiated by AA in the presence of active XO (converted from xanthine dehydrogenase [XD]) was tested in the authors' experimental preparation by converting XD to XO by a period of ischemia, and infusing AA. Control preparations remained normal throughout the 4-hour perfusion (weight gain, 7 +/- 4 g; amylase activity, 1162 +/- 202 U/dL). One hour of ischemia or infusion of AA at 25 mg/hr or at 50 mg/hr without ischemia did not induce changes in the preparation. Acetaldehyde at 250 mg/hr induced minimal edema and weight gain (16 +/- 4 g; p less than 0.05), but not significant hyperamylasemia. Changes also were not observed when 1-hour ischemia was followed by a bolus of ethanol (1.5 g) or sodium acetate (3.0 g), or by infusion of 25 mg/hr of AA. One hour of ischemia followed by infusion of AA at 50 mg/hr or at 250 mg/hr induced edema, hemorrhage, weight gain (22 +/- 7 g [p less than 0.05] and 26 +/- 17 g [p less than 0.05]) and hyperamylasemia (2249 +/- 1034 U/dL [p less than 0.05] and 2602 +/- 1412 U/dL [p less than 0.05]). Moreover infusion of AA at 250 mg/hr after 2 hours of ischemia potentiated the weight gain (62 +/- 20 g versus 30 +/- 14 g [p less than 0.05]), but not the hyperamylasemia (3404 +/- 589 U/dL versus 2862 +/- 1525 U/dL) as compared with 2 hours of ischemia alone. Pancreatitis induced by 1 hour of ischemia followed by AA at 50 mg/hr could be inhibited by pretreatment with the free radical scavengers superoxide dismutase and catalase and ameliorated with the XO inhibitor allopurinol. The authors conclude that AA, in the presence of active XO, can initiate acute pancreatitis in the isolated canine pancreas preparation and may be important in the initiation of acute alcoholic pancreatitis in man. Toxic oxygen metabolites appear to play an important intermediary role.
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PMID:The role of acetaldehyde in the pathogenesis of acute alcoholic pancreatitis. 172 Jun 11

Many reports concerning the involvement of active oxygen free radicals in the pathogenesis and progression of acute pancreatitis have been published. In this study, the direct toxic effect of active oxygen free radicals on the rat pancreas was evaluated in vivo. Superoxide anions, generated via the xanthine/xanthine oxidase (X/XO) system, and hydrogen peroxide (H2O2) were used. After continuous arterial injection of X/XO into the celiac artery hemorrhage and extensive edema developed. However, additional continuous injection of superoxide dismutase (SOD) into the external jugular vein completely suppressed the hemorrhage and relieved the edema. When hydrogen peroxide (100 microM/Kg/hour) was injected continuously through the celiac artery made hemorrhage and edema were recognized in the pancreas, both of which were suppressed by continuous injection of catalase (10 mg/Kg/hour) or gabexate mesilate (10 mg/Kg/hour) into the external jugular vein. The amylase and lipase levels in the intraperitoneal fluid rose to more than 10 times the preoperative values 5 hours after drug administration. These levels were lowered to 2 times the preoperative values by the continuous venous injection of SOD or catalase (which are specific scavengers of superoxide anions or hydrogen peroxide, respectively) or by gabexate mesilate. On the other hand, serum amylase and lipase levels remained almost constant throughout the entire experiment. Thus, the administration of active oxygen free radicals caused acute pancreatitis, which was suppressed by the systemic administration of specific scavengers for each free radical. Active oxygen free radicals were shown to have a direct, toxic effect on the pancreas.
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PMID:[Effect of oxygen free radicals on the rat pancreas in vivo]. 182 4

In order to investigate the role of the oxygen-derived free radicals in the pathogenesis of acute pancreatitis, an experimentally induced pancreatic damage was prepared in rats by the injection of diethyldithiocarbamate (DDC), which was known to be an inhibitor of Cu, Zn-superoxide dismutase (SOD). Male Wistar rats weighing 200-250 g received a single subcutaneous injection of DDC at a dose of 1000 mg/kg. Serum activities of amylase were significantly increased at 3 and 5 hours after the injection of DDC. Thiobarbituric acid reactants (TBA reactants) concentrations in the pancreatic tissue were increased at 30 minutes after the injection of DDC. At 7 hours after the injections of DDC, focal necrosis and degeneration of pancreatic acinar cells were observed. Peroral administration of allopurinol, an inhibitor of xanthine oxidase, before the injection of DDC suppressed the increase of TBA reactants concentration in the pancreatic tissue, but did not suppress the increase of serum activities of amylase. These results indicate that oxygen-derived free radicals may play an important role in the pathogenesis of acute pancreatic damage. However, since allopurinol did not suppress the increase of serum activities of amylase, further examination is needed to analyze the mechanism of DDC-induced pancreatic damage.
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PMID:[Studies on oxygen-derived free radicals in acute pancreatic damage in rats--pancreatic damage experimentally induced by diethyldithiocarbamate]. 217 Jul 14

Oxygen derived free radicals have been implicated in the pathogenesis of acute pancreatitis in numerous animal models of the disease. The xanthine oxidase inhibitor allopurinol has been shown to attenuate pancreatic damage in canine and mouse models of acute pancreatitis presumably by preventing the generation of cytotoxic superoxide anions. We therefore examined whether allopurinol could attenuate pancreatic injury in conscious rats with caerulein induced acute pancreatitis. A continuous intravenous infusion of allopurinol (20 mg/kg/h) for six hours along with an acute pancreatitis producing dose of caerulein (10 micrograms/kg/h) reduced pancreas weights by approximately 45% and serum amylase concentrations by approximately 60% compared with rats intravenously infused with either caerulein alone or caerulein plus a lower dose (10 mg/kg/h) of allopurinol. We conclude that the generation of oxygen derived free radicals via pancreatic xanthine oxidase represents an early and perhaps pivotal mechanism in the pathogenesis of acute pancreatitis.
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PMID:Allopurinol attenuates caerulein induced acute pancreatitis in the rat. 245 57

The role of free radicals in the development of pancreatitis was evaluated by measuring the level of activities of xanthine oxidase (XOD), lipid peroxide (LPO) and superoxide dismutase (SOD). Acute pancreatitis was induced in female mice fed a choline-deficient meal containing 0.5% DL-ethionine (CDE meal). Acute pancreatitis was confirmed by the changes in serum amylase level and other typical features observed microscopically 24 h after the meal was taken. Activity of XOD was elevated significantly (p less than 0.05) from the baseline of 1.13 +/- 0.19 U/g tissue to 2.34 +/- 0.46, 2.59 +/- 0.33 and 3.46 +/- 0.70 U/g tissue, 8, 12 and 24 h, respectively, after the CDE meal. The LPO level was also increased from an undetectable amount to 1.10 +/- 0.47 nmol/ml (p less than 0.05), 1.03 +/- 0.18 (p less than 0.01) at 6 and 8 h, respectively, and then returned to an undetectable amount at 12 h. The peak level of LPO was shown at 24 h, 1.76 +/- 0.40 nmol/ml (p less than 0.01) and gradually decreased until 48 h, 1.17 +/- 0.37 nmol/ml (p less than 0.01) after the CDE meal. Changes of LPO took a biphasic pattern. SOD was decreased significantly from 47.1 +/- 3.4 mU/g tissue to 30.7 +/- 2.5, 24.8 +/- 1.7 and 20.6 +/- 1.1 mU/g tissue at 8 (p less than 0.01), 12 (p less than 0.01), and 24 (p less than 0.01) h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes of xanthine oxidase, lipid peroxide and superoxide dismutase in mouse acute pancreatitis. 247 6

Recent experimental work has suggested that oxygen-derived free radicals may play an important role in initiating the early capillary injury in acute pancreatitis. Data from models of ischemic injury in other organs have suggested the enzyme xanthine oxidase is important in generating oxygen-derived free radicals. The present study was performed to determine whether xanthine oxidase is the source of free radical production in experimental pancreatitis. Utilizing the isolated, perfused, ex vivo canine pancreas preparation, three models of pancreatitis were initiated with (1) free fatty acid infusion (FFA), (2) partial duct obstruction and secretin stimulation (POSS), and (3) ischemia (ISCH). In each model, during a 4-hour perfusion, edema developed, weight gain occurred (FFA 120.6 +/- 21.1 gm; POSS 44.5 +/- 6.9 gm; ISCH 63.3 +/- 14.0 gm), and the serum amylase became elevated (FFA 1827 +/- 397 u/dl; POSS 10,171 +/- 1487 u/dl; ISCH 1860 +/- 365 u/dl). When the xanthine oxidase enzyme inhibitor allopurinol was added to the perfusate prior to the 4-hour perfusion, edema formation was absent or minimal, weight gain was significantly less (FFA 15.2 +/- 2.5 gm p less than 0.05; POSS 8.8 +/- 2.7 gm p less than 0.001; ISCH 12.3 +/- 2.8 gm p less than 0.01), and the amylase remained normal or the elevation was significantly decreased (FFA 996 +/- 189 u/dl p less than 0.05; POSS 3021 +/- 1074 u/dl p less than 0.001; ISCH 993 +/- 214 u/dl p less than 0.002). These data confirm that oxygen-derived free radicals play an important role in the pathogenesis of experimental acute pancreatitis, and suggest that the enzyme xanthine oxidase may well be the source of their production.
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PMID:The pathogenesis of acute pancreatitis. The source and role of oxygen-derived free radicals in three different experimental models. 258 19


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