Effect of short-termed pancreatico-biliary duct obstruction on lysosomal enzyme in rats: protective effect of a potent new protease inhibitor, E-3123.
To investigate the mechanism by which the pancreatic acinar cells are injured in animals with an obstructed common channel, we measured the amount of lysosomal enzymes and of amylase in the pancreatico-biliary juice in rats with pancreatico-biliary duct obstruction (PBDO). We tested the protective effect of a new potent synthetic protease inhibitor, E3123 (4-guanidinobenzoate methanesulfonate), on the exocrine pancreas in this model of PBDO and secretin infusion. Blockage of PBD for 4 hours and secretin (0.2 CU/kg.hr) infusion caused a significant rise in portal serum amylase and cathepsin B levels, pancreatic water content, and pancreatic amylase content, as well as redistribution of cathepsin B in acinar cells. These changes tended to continue for 12 hours after the removal of PBDO and disappeared at 24 hours. All the changes induced by PBDO with secretin infusion were no longer observed at 48 hours. The administration of 5 mg/kg.hr of E3123 during PBDO markedly attenuated all the parameters examined in this study. Thus, it had a significant protective effect on acinar cells in this model. E3123 in a dose of 2 mg/kg.hr had a partial, but significant, protective effect. These results indicate the possible usefulness of E3123 in the treatment of pancreatic duct obstructed pancreatitis.
D000208:Acute Disease; D000681:Amylases / Q000378:metabolism; D000818:Animals; D001652:Bile Ducts; D002401:Cathepsin B / Q000378:metabolism; D003250:Constriction; D006146:Guanidines / Q000627:therapeutic use*; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000201:enzymology*; D010183:Pancreatic Ducts; D010195:Pancreatitis / Q000188:drug therapy* / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use*
D006146:Guanidines; D015842:Serine Proteinase Inhibitors; C057059:4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate; D000681:Amylases; D002401:Cathepsin B