Biphasic effect of prostaglandin E(1) on the severity of acute pancreatitis induced by a closed duodenal loop in rats

The effect of prostaglandin E(1) (PGE1) on the severity of acute pancreatitis induced by a closed duodenal loop in the rat was tested. PGE1 was administered subcutaneously at various doses (3, 6, 12, and 24 mu g/kg) at hourly intervals, from the induction of acute pancreatitis up to the 24th hour. A saline-treated group served as the control. The mortality rate was recorded, and pancreatic histology was evaluated by a scoring system. Serum amylase activity and pancreatic amylase, trypsin, protein, and desoxyribonucleic acid (DNA) contents were determined at 24 h. Administration of PGE 1 influenced the severity of acute pancreatitis biphasically. Serum amylase was reduced significantly (p < 0.01) at a dose of 12 mu g/kg/h, but less at 24 mu g/kg/h. Pancreatic weights did not differ in the groups. Pancreatic amylase, trypsin, and protein contents showed significant elevations (p < 0.01), yet the mortality rate was reduced using 6 and 12 mu g/kg/h doses of PGE1 compared to controls, but not at higher and lower doses. The DNA content was significantly higher at the 6 mu g/kg/h dose, compared to the control. The extent of necrosis and the severity of hemorrhage were reduced significantly (p < 0.05) at doses of 6 and 12 mu g/kg/h of PGE1, but less at 24 mu g/kg/h. Leukocyte infiltration was not affected. In conclusion, optimal doses of PGE1 can ameliorate, but higher doses increase, the severity of acute pancreatitis in this experimental model.