Monitoring Serum Tryptic Activity and Effect of Trypsin Inhibitor on Rat Acute Pancreatitis

Abstract

The effect of a novel synthetic trypsin inhibitor, 4-(2-succinimidoethylthio)-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 total dose at 3 mg/kg body weight. Group A: 1.5 mg/kg of E3123 subcutaneously (SC) each at 1 h before and after induction of pancreatitis. Group 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 rate 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 α₂-macroglobulin trypsin complex (α2M-TRY) was reduced after the injection of E3123 though immunoreactive trypsin remained unchanged in the early phase of pancreatitis. The reduction of α2M-TRY reflected the inhibitory capacity of E3123 in plasma. E3123 showed favorable effects on the initial stage of severe acute pancreatitis and the effects were probably based on the inhibition of α2M-TRY activity in serum.

Effect of New Inhibitor of Type II Phospholipase A2 on Experimental Acute Pancreatitis in Rats

“…Before experiments, all rats fasted for 20 h, but with water ad libitum. Experimental acute pancreatitis was induced as previously described ( 15,16). For trypsintaurocholate-induced pancreatitis, a freshly prepared mixture of 0.1% bovine trypsin, 1.5% sodium taurocholate, and 0.021 M glycylglycine buffer was infused retrogradely into the pancreatic duct system at a constant speed of 0.1 ml/min for 5 min (0.5 ml/body) by a syringe pump.…”