Cytoprotective and Dose-Dependent Inhibitory Effects of Prostaglandin E<sub>1</sub> on Rat Pancreas Treated with Ciclosporin A

Abstract

The prostaglandin E1 analogue rioprostil protects the pancreas from the noxious effect of ciclosporin A (CsA). To determine whether this cytoprotective action of rioprostil is dependent on or independent of inhibitory effects on pancreatic exocrine and endocrine secretion we studied the effect of different doses of rioprostil on pancreatic exocrine and endocrine secretions in the presence or absence of CsA. Rats received either CsA at a dose of 10 mg/kg body weight by tube feeding once in the morning, rioprostil at linearly increasing doses from 1.8 to 120 micrograms/kg body weight subcutaneously twice daily, a combination of both substances or NaCl. After 8 treatment days, the animals were operated on, and the pancreas isolated and arterially perfused. Insulin secretion was determined after stimulation with glucose, and amylase secretion after stimulation with CCK-8. Insulin and amylase secretion were significantly impaired by CsA. Rioprostil at doses of 1.8, 3.6 and 7.5 micrograms/kg body weight had no significant effect on insulin secretion in the absence of CsA but significantly improved insulin secretion in the presence of CsA. Higher doses of rioprostil significantly inhibited insulin secretion both in the presence or absence of CsA. Amylase secretion was not influenced by rioprostil at doses up to 15 micrograms/kg body weight but improved significantly amylase secretion in the presence of CsA. CsA blood and pancreatic tissue levels were not influenced by rioprostil at doses up to 120 micrograms/kb body weight. We conclude that the cytoprotective effect of the prostaglandin E1 analogue rioprostil against the noxious effect of CsA is dose dependent and is not related to its inhibitory action on endocrine and exocrine pancreatic secretion.