Chymase as a Novel Therapeutic Target in Acute Pancreatitis

Abstract

Acute pancreatitis is still a life-threatening disease without an evidenced therapeutic agent. In this study, the effect of chymase in acute pancreatitis and the possible effect of a chymase inhibitor in acute pancreatitis were investigated. Hamsters were subcutaneously administered 3.0 g/kg of L-arginine to induce acute pancreatitis. Biological markers were measured 1, 2, and 8 h after L-arginine administration. To investigate the effect of a chymase inhibitor, a placebo (saline) or a chymase inhibitor TY-51469 (30 mg/kg) was given 1 h after L-arginine administration. The survival rates were evaluated for 24 h after L-arginine administration. Significant increases in serum lipase levels and pancreatic neutrophil numbers were observed at 1 and 2 h after L-arginine administration, respectively. Significant increases in pancreatic neutrophil numbers were observed in the placebo-treated group, but they were significantly reduced in the TY-51469-treated group. A significant increase in the pancreatic tumor necrosis factor-α mRNA level was observed in the placebo-treated group, but it disappeared in the TY-51469-treated group. Chymase activity significantly increased in the placebo-treated group, but it was significantly reduced by treatment with TY-51469. The survival rate significantly improved in the TY-51469-treated group. A chymase inhibitor may become a novel therapeutic agent for acute pancreatitis.