Beneficial effect of iloprost on the course of acute taurocholate pancreatitis in rats and its limitation by antecedent acute ethanol intake

The effects of stable prostacyclin analogue iloprost on the trypsinogen activation, labilization of lysosomal membranes, lipolytic enzymes activities, histopathological and ultrastructural changes in the pancreas of rats with severe, taurocholate acute pancreatitis (AP), preceded for 6 h by acute ethanol intake have been investigated. Iloprost (1μg/kg b.w., i.p.) was applied every 6 hours after inducing of taurocholate AP. The antecedent intragastric 40% ethanol intake (5 g/kg b.w.) increased an index of trypsinogen activation in AP lasting 18 h. Treatment with iloprost prevented this increase in the rats with AP given earlier alcohol, and limited the labilization of lysosomal membranes in nonalcoholized rats with AP. Phospholipase A 2 and lipase activities were reduced by iloprost only in the rats not given ethanol. The additional damaging effect of acute ethanol abuse prior to AP could be dependent on augmented activation of trypsinogen. The protective effect of iloprost in AP seems to be dependent on the attenuation of trypsinogen activation, decrease of total potential trypsin and the decrease of lysosomal membranes labilization. Its protective effect could be limited in taurocholate acute pancreatitis preceded by acute ethanol intake as evidenced by the differences in the cathepsin B, phospholipase A 2 and lipase activities and by histopathological and ultrastructural examination.