Mayumi Yamano, Keiji Miyata and Toshimitsu Yamada
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi
Pharmaceutical Co., Ltd., 2I Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan
Abstract: Protective effect of trifluoroacetyl-L-lysyl-L-alaninanilide
hydrochloride (compound 1), a pancreatic elastase inhibitor, on three types
of acute pancreatitis models was examined in rats. Mild, moderate and severe
acute pancreatitis were induced by cerulein, the closed duodenal loop method
and retrograde injection of a taurocholate plus trypsin solution into the
pancreatic duct, respectively. Intravenous infusion of compound 1 at a dose
of 30 mg/kg/hr resulted in lower increases in serum amylase, lipase, blood
urea nitrogen (BUN) and creatinine levels in rats with mild cerulein-induced
edematous pancreatitis. Compound 1 had no beneficial effect on pancreatitis
in rats with moderate pancreatitis. In rats with severe pancreatitis, prophylactic
treatment of compound 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
partially responsible for pancreatic edema and hemorrhage exhibited by rats
with severe acute pancreatitis.
Keywords: Acute pancreatitis, Pancreatic elastase, Closed duodenal loop,
Cerulein, Taurocholate