MONITORING SERUM TRYPTIC ACTIVITY AND EFFECT OF TRYPSIN-INHIBITOR ON RAT ACUTE-PANCREATITIS

The effect of a novel synthetic trypsin inhibitor, 4-(2-succinimidoeth ylthio)-phenyl 4-guanidinobenzoate methanesulfonate (E3123), on severe acute pancreatitis was studied in trypsin-taurocholate-induced acute experimental pancreatitis in rats. Rats were divided into four groups according to difference of subdivided doses of E3123 with fixing the t otal dose at 3 mg/kg body weight. Group A: 1.5 mg/kg of E3123 subcutan eously (SC) each at 1 h before and after induction of pancreatitis. Gr oup B: 1 mg/kg SC each at 1 h before, 1 and 3 h after induction. Group C: 1.5 mg/kg SC each at 1 and 3 h after induction. Group D: 1.5 mg/kg SC each at 3 and 5 h after induction of pancreatitis. The survival ra te at 24 h was significantly improved in group B (77% in group B, vs. 36% in paired control; p < 0.01) and in group C (70 vs. 38%; p < 0.05) , but not in group A or D. Residual tryptic activity of serum alpha(2) -macroglobulin trypsin complex (alpha 2M-TRY) was reduced after the in jection of E3123 though immunoreactive trypsin remained unchanged in t he early phase of pancreatitis. The reduction of alpha 2M-TRY reflecte d the inhibitory capacity of E3123 in plasma. E3123 showed favorable e ffects on the initial stage of severe acute pancreatitis and the effec ts were probably based on the inhibition of alpha 2M-TRY activity in s erum.