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.