PROTECTIVE EFFECT OF A PANCREATIC ELASTASE INHIBITOR AGAINST A VARIETY OF ACUTE-PANCREATITIS IN RATS

Protective effect of trifluoroacetyl-L-lysyl-L-alaninanilide hydrochlo ride (compound 1), a pancreatic elastase inhibitor, on three types of acute pancreatitis models was examined in rats. Mild, moderate and sev ere acute pancreatitis were induced by cerulein, the closed duodenal l oop method and retrograde injection of a taurocholate plus trypsin sol ution into the pancreatic duct, respectively. Intravenous infusion of compound 1 at a dose of 30 mg/kg/hr resulted in lower increases in ser um amylase, lipase, blood urea nitrogen (BUN) and creatinine levels in rats with mild cerulein-induced edematous pancreatitis. Compound 1 ha d no beneficial effect on pancreatitis in rats with moderate pancreati tis. In rats with severe pancreatitis, prophylactic treatment of compo und 1 (30 mg/kg/hr) reduced both elevated serum BUN level and ascitic volume, and it histologically inhibited the extent of pancreatic edema and hemorrhage. These results suggest that pancreatic elastase is par tially responsible for pancreatic edema and hemorrhage exhibited by ra ts with severe acute pancreatitis.