E-3123, a new synthetic protease inhibitor, protects against deoxycholic acid-induced acute pancreatitis in dogs.
The effects of intravenous infusion of 4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate (E-3123), a new synthetic protease inhibitor, on deoxycholic acid-induced acute pancreatitis in a canine pancreas were investigated. The retrograde injection of 1% deoxycholic acid into the pancreatic duct significantly and time-dependently increased venous serum amylase and lipase activities. E-3123 significantly decreased these increased amylase and lipase activities. Two hours after deoxycholic acid injection, the amylase activity was reduced by 23 +/- 3% and 34 +/- 4% after infusion of 0.1 and 1 mg/kg/hr of E-3123, respectively, compared to the corresponding values in the control group, and the lipase activity was reduced by 13 +/- 3% and 29 +/- 3%, respectively. The potency of 1 mg of E-3123 to decrease these enzymes was almost the same as that of 5 mg of gabexate, a novel protease inhibitor. Pancreatic wet weight/body weight also decreased after treatment with E-3123 in dogs injected with deoxycholic acid. Histologic examination revealed that injection with deoxycholic acid caused marked interstitial edema, hemorrhage, vacuolization and inflammation as well as focal acinar cell necrosis, while in the E-3123-treated group, only mild changes in these parameters were seen. These results suggest that E-3123 may be useful in suppressing the progression of acute pancreatitis induced by deoxycholic acid, at least in part, through its protease-inhibiting ability.
Iwatsuki
K
K
Department of Pharmacology, Shinshu University School of Medicine, Matsumoto, Japan.
Horiuchi
A
A
Yonekura
H
H
Ren
L M
LM
Chiba
S
S
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D003840:Deoxycholic Acid / Q000037:antagonists & inhibitors*; D004285:Dogs; D005260:Female; D016670:Gabexate; D006146:Guanidines / Q000494:pharmacology*; D008049:Lipase / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*
D006146:Guanidines; D015842:Serine Proteinase Inhibitors; D003840:Deoxycholic Acid; C057059:4-(2-succinimidoethylthio)phenyl 4-guanidinobenzoate; D016670:Gabexate; D008049:Lipase; D000681:Amylases