Effects of IS-741, a Novel Synthetic Agent, on Ethionine-induced Pancreatitis in Rats

In acute pancreatitis, tissue destruction, from neutrophil infiltration of the pancreas and other organs, is thought to be inhibited by IS-741. We studied the effect of IS-741 on acute pancreatitis induced by DL-ethionine in the rat. Rats fed a low-protein diet for 11 days received a daily intraperitoneal dose of DL-ethionine (20 mg/ 100 g) for the last 4 days. To evaluate its preventive potential, IS-741 (10 mg / kg s.c.) was administered every 8 h beginning on the first day of the low-protein diet. In another group, IS-741 was administered as described above, beginning with the second ethionine injection, this time to evaluate the therapeutic effect on ethionine-induced pancreatitis. The rats were killed 24 h after the final ethionine injection. Blood was sampled to measure concentrations of the inflammatory cytokines, interleukin-6 and -8. The pancreas was weighed, DNA and protein levels were determined, and neutrophil infiltration was assessed by the myeloperoxidase assay. The pancreas was also examined histologically. Pancreatic sections from saline-treated controls showed considerable infiltration by inflammatory cells, and acinar cell necrosis was widespread. The histologic severity of acute pancreatitis was alleviated by the administration of IS-741. Pancreatic weight and DNA content in rats treated with IS-741 were significantly higher than in control rats. Interleukin-6 concentrations were undetectable at baseline in all groups while those of interleukin-8 were higher in controls, compared to rats treated with IS-741. Preventive or therapeutic administration of IS-741 ameliorated acute pancreatitis induced in rats by DL-ethionine, and may become a useful drug to treat patients with this condition.