The effects of a thromboxane A2 synthesis inhibitor and a prostaglandin I2 analogue on experimental acute necrotizing pancreatitis in rats

To elucidate the role of thromboxane A(2) (TxA(2)) and prostaglandin I-2 (PGI(2)) in acute necrotizing pancreatitis (ANP) in rats and to determine the effect of the TxA(2) synthesis inhibitor OKY-046 and the PGI(2) analogue OP-2507, the levels of two prostanoids (TxB(2), 6-keto PGF(1 alpha)) and two types of phospholipase A(2) (PLA(2)) activity (cytosolic and secretory) were measured in plasma and three tissues (pancreas, lung, and kidney) after injection of a mixed solution of 5% sodium taurocholate and 0.1% trypsin into the pancreatic duct to induce ANP. The survival rate 24 h after inducing ANP was 33.3% in the nontreated group, versus 83.3 and 58.3% in the groups treated with OKY-046 and OP-2507, respectively. Only the group treated with OKY-046 showed significant improvement compared with the nontreated group. The plasma, pancreatic, and pulmonary TxB(2) levels decreased significantly in the group treated with OKY-046, and the histopathological changes were not as severe. The levels of pancreatic and pulmonary cytosolic PLA, activities decreased, and plasma and pancreatic secretory PLA, activities also decreased. In conclusion, the levels of both types of PLA(2) activity and TxA(2) production decreased. and the survival rate improved as a result in the group healed with OKY-046, but OP-2507 had no effect on ANP. TxA(2) and two types of PLA, activity play an important role in the process of aggravation of acute pancreatitis.