Effect of a Selective Inhibitor of Secretory Phospholipase A₂, S-5920/LY315920Na, on Experimental Acute Pancreatitis in Rats

Abstract

We investigated the efficacy of a potent inhibitor of secretory phospholipase A₂ (sPLA₂), S-5920/LY315920Na, in an experimental model of acute pancreatitis in rats. Combined intraductal injection of sodium taurocholate (5 mg/rat) and porcine pancreatic sPLA₂-IB (300 μg/rat) caused severe hemorrhagic necrotizing pancreatitis resulting in high mortality, along with rapid increases of catalytic PLA₂ and lipase activities in plasma and ascites and with gradual increases of plasma amylase and aspartate aminotransferase levels over 9 h after the pancreatitis. Prophylactic intravenous treatment with S-5920/LY315920Na significantly reduced mortality at 7 days, and strongly abrogated PLA₂ activities in both plasma and ascites along with significant reduction of lipase activity, amylase, aspartate aminotransferase, and hemorrhage at 6 h. It also significantly reduced histological damage such as edema and parenchymal and fat necroses of the pancreatic tissue. This sPLA₂ inhibitor could become an effective agent for the treatment of severe acute pancreatitis.