iloprost and Pancreatitis

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 (1 microg/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 A2 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 A2 and lipase activities and by histopathological and ultrastructural examination.

Topics: Acute Disease; Animals; Disease Models, Animal; Ethanol; Iloprost; Intracellular Membranes; Lipase; Lysosomes; Male; Pancreas; Pancreatitis; Phospholipases A; Phospholipases A2; Rats; Rats, Wistar; Taurocholic Acid; Trypsinogen

Prostacyclin (PGI2) and its stable analogue iloprost (I) exert beneficial effect in acute pancreatitis (AP). The aim of the study was to evaluate the role of iloprost in pancreas regeneration after AP in rats.. AP was induced in male Wistar rats by s.c. injections of caerulein 12 micrograms/kg t.i.d. for 2 days. Rats were divided into four groups: control + saline (C); control + iloprost (C/I); AP + saline (AP); AP + I (AP/I). Rats were treated for 7 or 14 days. I (Schering AG) was given at the dose I microgram/kg b.w., i.p., t.i.d. After the rats were killed, the pancreata were weighed and their protein, DNA, RNA, chymotrypsin, alpha-amylase contents were evaluated. Light microscopic examination of representative pieces of pancreas was performed.. Acute pancreatitis resulted in pancreas destruction observed even 7 days after the onset of the disease. The significant decrease of pancreatic weight, RNA and chymotrypsin contents were observed in AP rats when compared to C. The improvement of pancreatic histology and significant increase of DNA content were found in I treated (during 7 days) AP rats in comparison to untreated AP group. Two weeks after pancreatitis induction the pancreas regeneration occurred in both pancreatitis groups and it was connected with pancreas hypertrophy. Treatment with I resulted in slight not significant increase of some of cellular hypertrophy indices when compared to AP untreated animals. Healthy rats injected with I during 7 days showed significant elevation of DNA content in comparison to C. When treatment with I was prolonged up to 14 days such hyperplastic effect was not observed. Our results suggest, that treatment with iloprost exerts temporary hyperplastic influence on the pancreas of healthy rats and pancreas regenerating after caerulein-induced pancreatitis.

Topics: Acute Disease; Animals; Ceruletide; Iloprost; Male; Pancreas; Pancreatitis; Rats; Rats, Wistar; Regeneration

Plasma thromboxane concentrations were found to be significantly elevated in acute necrotizing pancreatitis in rats, whereas prostaglandin I2 levels were not. The significance of these alterations was investigated. Pancreatitis was induced by injecting 5% sodium taurocholate into the pancreatic duct. Iloprost (ZK 36374, a stable analog of prostaglandin I2, 25 ng/kg body weight) decreased the mortality rate from 100% to 50%. When treatment with iloprost was combined with simultaneous administration of either Sibelium (flunarizine R 14,950, 0.2 mg/kg body weight) or dazmegrel (UK 38,485, 50 mg/kg body weight) an additional decrease in the mortality rate was recorded. Dazmegrel is a selective thromboxane A2 synthetase inhibitor and flunarizine (a calcium entry blocker) also inhibits the effects of elevated thromboxane A2 levels. With flunarizine and iloprost the mortality rate was 40% (P less than 0.05); with dazmegrel and iloprost it was 10% (P less than 0.01). The results of the present study suggest that thromboxane A2 and prostaglandin I2 play a role in the course of acute necrotizing pancreatitis.

Topics: Acute Disease; Animals; Epoprostenol; Flunarizine; Iloprost; Imidazoles; Male; Necrosis; Pancreas; Pancreatitis; Rats; Rats, Inbred Strains; Thromboxane A2; Vasodilator Agents