*Xanthine Oxidase Inhibitor in Acute Experimental Pancreatitis in Rats and Mice

Lankisch, P. G.; Pohl, U.; Otto, J.; Wereszczyńska-Siemiątkowska, Urszula; Gröne, Hermann Josef

doi:10.1097/00006676-198908000-00007

Cited by 23 publications

(5 citation statements)

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“…Disappointingly, allopurinol did not show any beneficial effect on the incidence of post-ERCP pancreatitis in the present study. This finding is in accordance with several experimental studies in which induced pancreatitis was not reduced by the application of allopurinol [22,23]. Wisner and Renner [10] found that only high doses of allopurinol were effective in preventing pancreatic edema, weight gain, and rises in amylase concentration in cerulein-induced pancreatitis in rats.…”

Section: Discussionsupporting

confidence: 90%

A Prospective, Randomized, Placebo-Controlled Trial of Prednisone and Allopurinol in the Prevention of ERCP-Induced Pancreatitis

Budzyńska¹,

Trněný²,

Nowak³

et al. 2001

Endoscopy

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Section: Discussionsupporting

confidence: 90%

A Prospective, Randomized, Placebo-Controlled Trial of Prednisone and Allopurinol in the Prevention of ERCP-Induced Pancreatitis

Budzyńska¹,

Trněný²,

Nowak³

et al. 2001

Endoscopy

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“…In this study we have confirmed several recent reports [36][37][38][39][40] describing the protec tive effects of such protease inhibitors against secretagogue-induced pancreatitis and other several models of experimental pancreatitis, and in these reports hyperamvlasemia. mor phological changes of acinar cells and survival rate were improved by such protease inhibi tors [36][37][38][39][40], As similarly reported in these reports both ONO3307 and FOY007 were found to prevent hyperamylasemia, pan creatic edema, and congestion of digestive enzymes that follow the supramaximal infu sion of caerulein in vivo.…”

Section: Discussionsupporting

confidence: 91%

“…mor phological changes of acinar cells and survival rate were improved by such protease inhibi tors [36][37][38][39][40], As similarly reported in these reports both ONO3307 and FOY007 were found to prevent hyperamylasemia, pan creatic edema, and congestion of digestive enzymes that follow the supramaximal infu sion of caerulein in vivo. In addition, in this secretogogue-induced pancreatitis, subcellu lar fractionation studies have demonstrated the redistribution of cathepsin B activity from the lysosome-and mitochondria-rich pellet to the more dense zymogen-rich fraction.…”

Section: Discussionmentioning

confidence: 77%

Protection by a New Synthetic Protease Inhibitor, ONO3307, of the Rat Exocrine Pancreas during Acute Edematous Pancreatitis Induced by a Supramaximal Dose of Caerulein in Comparison with FOY007

Hirano

Manabe²,

Tobe³

1992

Pharmacology

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The present study investigated the protective effects of the new potent synthetic protease inhibitors, ONO3307 (4-sulfamoyl phenyl-4-guanidinobenzoate methanesulfonate) and FOY007 (gabexate misilate), on the exocrine pancreas in rat caerulein-induced acute pancreatitis in both in vitro and in vivo experiments. These protease inhibitors prevented hyperamylasemia, pancreatic edema, congestion of amylase, redistribution of lysosomal enzyme in acinar cells, and lactic dehy-drogenase (LDH) discharge from dispersed acini. They also inhibited the cathepsin B leakage from the lysosomes in a dose-dependent manner in doses of 2–10 mg/kg·h of ONO-3307 and 20-50 mg/kg·h of FOY007. These results indicate that both ONO3307 and FOY007 exert protective effects against pancreatitis at subcellular levels in lysosomes and cellular or organelle membranes. Proteases appear to be important in the pathogenesis and development of acute pancreatitis, and low-molecular-weight protease inhibitors may be of clinical use in the treatment of acute pancreatitis.

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“…catabolism of LDL has not been studied. Although controversial [25][26][27], in acute pancreatitis it is possible that LDL would be subjected to both pancreatic proteases as well as free radicals generated from xanthine oxidase [28,29].…”

Section: Introductionmentioning

confidence: 99%

Altered hepatic catabolism of low-density lipoprotein subjected to lipid peroxidation in vitro

Stone

Heimberg

Scott

et al. 1994

Biochemical Journal

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Recent evidence suggests that oxidatively modified forms of low-density lipoprotein (LDL) may be particularly atherogenic. In this investigation, the catabolism of human LDL modified by lipid peroxidation in vitro was studied with a recirculating rat liver perfusion system. A dual-labelling technique was used that permitted native LDL and modified LDL to be studied simultaneously in the liver perfusion system. Native human LDL was found to have a fractional catabolic rate (FCR) of 1.00 +/- 0.21%/h, in agreement with other investigators. Subjecting LDL to oxidation for 12 h in the presence of 30 microM FeEDTA did not significantly affect its FCR. LDL treated with a superoxide-generating system (xanthine oxidase, hypoxanthine, O2) in the presence of 30 microM FeEDTA did, however, show a significant increase in FCR (3.23 +/- 0.19%/h). The hepatic uptakes of native LDL and LDL oxidized with FeEDTA+O2 were similar, but both were significantly lower than the hepatic uptake of LDL treated with the superoxide-radical-generating system. The proteolysis of LDL with pancreatin did not influence either its susceptibility to oxidation or its FCR. LDL oxidation resulted in the preferential loss of alpha-tocopherol rather than gamma-tocopherol. These data indicate that the rat liver effectively catabolizes LDL oxidatively modified by treatment with the superoxide-generating system. Furthermore, our results suggest that only very low plasma levels of highly oxidized LDL could be found under conditions in vivo. The liver may therefore play a major role in protecting the arterial vasculature from highly atherogenic forms of LDL.

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*Xanthine Oxidase Inhibitor in Acute Experimental Pancreatitis in Rats and Mice

Cited by 23 publications

References 0 publications

A Prospective, Randomized, Placebo-Controlled Trial of Prednisone and Allopurinol in the Prevention of ERCP-Induced Pancreatitis

A Prospective, Randomized, Placebo-Controlled Trial of Prednisone and Allopurinol in the Prevention of ERCP-Induced Pancreatitis

Protection by a New Synthetic Protease Inhibitor, ONO3307, of the Rat Exocrine Pancreas during Acute Edematous Pancreatitis Induced by a Supramaximal Dose of Caerulein in Comparison with FOY007

Altered hepatic catabolism of low-density lipoprotein subjected to lipid peroxidation in vitro

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