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.