Protective effect of a pancreatic elastase inhibitor against a variety of acute pancreatitis in rats.
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.
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan.
M
M
Yamano
K
K
Miyata
T
T
Yamada
D000208:Acute Disease; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D002108:Ceruletide / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology*; D004195:Disease Models, Animal; D007668:Kidney / Q000503:physiopathology; D008099:Liver / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology; D008297:Male; D010179:Pancreas / Q000503:physiopathology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D010195:Pancreatitis / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D000813:Anilides; D004151:Dipeptides; D015842:Serine Proteinase Inhibitors; C114977:trifluoroacetyl-lysyl-alaninanilide; D002108:Ceruletide; D010196:Pancreatic Elastase