EFFECT OF THE ORAL-ADMINISTRATION OF SEPIMOSTAT MESILATE ON CERULEIN-INDUCED ACUTE-PANCREATITIS IN RATS

The effect of a potent protease inhibitor, sepimostat mesilate (GAS 10 3926-82-5, FUT-187), on acute interstitial edematous pancreatitis indu ced by a supramaximal dose of cerulein, a cholecystokinin (CCK) analog ue war evaluated The serum amylase activity increased 18-fold over nor mal control after the infusion of cerulein at 5 mu g/kg/h for 6 h. The serum lipase activity showed a 235-fold increase An elevated pancreat ic water content, pancreatic interstitial edema, inflammatory infiltra tion and vacuolization of the acinar cells were found Redistribution o f cathepsin B shifted from the lysosomal pellet fraction to the zymoge n granule pellet fraction was noted in the early stages. All these par ameters of pancreatitis mentioned above were inhibited by FUT-187 pret reatment at doses of 30 to 300 mg/kg. These observations suggest that FUT-187 inhibits the redistribution of cathepsin B shift from the lyso somal fraction to the zymogen fraction in cerulein-induced acute pancr eatitis and improves the parameters of acute pancreatitis.