Biphasic effect of prostaglandin E1 on the severity of acute pancreatitis induced by a closed duodenal loop in rats.

ABSTRACT

The effect of prostaglandin E1 (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 microgram/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 PGE1 influenced the severity of acute pancreatitis biphasically. Serum amylase was reduced significantly (p < 0.01) at a dose of 12 microgram/kg/h, but less at 24 microgram/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 microgram/kg/h doses of PGE1 compared to controls, but not at higher and lower doses. The DNA content was significantly higher at the 6 microgram/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 microgram/kg/h of PGE1, but less at 24 microgram/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.