Metabolic and ultrastructural effects of cyclosporin A on pancreatic islets

We investigated the effect of different doses of cyclosporin A (CyA) on glu cose and insulin levels, as well as its residual effects on pancreatic isle ts ultrastructure after discontinuation of the drug. We studied four groups of Wistar rats. One control- (n = 5) and three experimental groups, n = 10 each, were treated with different doses of CL-A IM for 14 days: group I, 5 mg/Kg; group II, 15 mg/Kg; and group III, 25 mg/Kg. Five animals of each g roup were sacrificed after 14 days, and the remaining five after 21 days to assess residual CyA effects. On the day of sacrifice, the rats underwent m altose absorption test, and glucose and insulin levels were measured. Pancr eatic biopsies were obtained on day 21 to evaluate islets ultrastructure by electron microscopy. As a result, statistically significant, dose dependen t (P < 0.05) increases in glucose and insulin levels were observed in CyA-t reated groups. Groups II and III showed insulin levels significantly higher after fasting (P < 0.05) on day 14 comparing to the controls, while in gro ups I and II values returned to normal after CyA discontinuation. Group III showed persistently increased insulin levels on day 21. Pancreatic ultrast ructural changes were observed only in group III. We can conclude that CyA effects on glucose and insulin levels were temporary and reversible at low doses. Ultrastuctural changes in the pancreatic islets may occur with high doses of CyA.