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 A2 (TxA2) and prostaglandin I2 (PGI2) in acute necrotizing pancreatitis (ANP) in rats and to determine the effect of the TxA2 synthesis inhibitor OKY-046 and the PGI2 analogue OP-2507, the levels of two prostanoids (TxB2, 6-keto PGF1alpha) and two types of phospholipase A2 (PLA2) 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 TxB2 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 PLA2 activities decreased, and plasma and pancreatic secretory PLA2 activities also decreased. In conclusion, the levels of both types of PLA2 activity and TxA2 production decreased, and the survival rate improved as a result in the group treated with OKY-046, but OP-2507 had no effect on ANP. TxA2 and two types of PLA2 activity play an important role in the process of aggravation of acute pancreatitis.
First Department of Surgery, Mie University School of Medicine, Tsu, Japan.
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Iida
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Yokoi
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Kawarada
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007279:Injections, Subcutaneous; D007668:Kidney / Q000201:enzymology; D008168:Lung / Q000201:enzymology; D008297:Male; D008689:Methacrylates / Q000494:pharmacology*; D010179:Pancreas / Q000201:enzymology / Q000473:pathology; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D013656:Taurocholic Acid; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D013929:Thromboxane B2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D013997:Time Factors
D008689:Methacrylates; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D013656:Taurocholic Acid; C049453:OP 2507; D011464:Epoprostenol; D010741:Phospholipases A; D054467:Phospholipases A2; D013930:Thromboxane-A Synthase; C034364:ozagrel