RAS inhibitors decrease apoptosis of acinar cells and increase elimination of pancreatic stellate cells after in the course of experimental chronic pancreatitis induced by dibutyltin dichloride.

Chronic pancreatitis (CP) is a progressive disease, in which the exocrine function of the gland is gradually lost and fibrosis develops due to repeated episodes of acute pancreatitis. The aim of the study was to investigate the effects of RAS inhibitors on the apoptosis of acinar cells and pancreatic stellate cells (PSCs) elimination in experimental CP induced by dibutyltin dichloride (DBTC). CP was induced by administration of DBTC to the femoral vein. Simultaneously captopril, losartan, enalapril and lisinopril were administered intraperitoneally. The rats were decapitated after 60 days and tissue of pancreas was collected. In rats treated by DBTC the features of inflammatory infiltration, ductal lumen dilatation, fibrosis were found. Strong reactivity with caspase2(L) and clusterin-beta antibodies was observed in areas of fibrosis. In animals treated with RAS inhibitors inflammatory changes and fibrosis were less severe. In groups of rats treated with DBTC and RAS inhibitors immunoreactivity of caspase(2L) and clusterin-beta was weak. Positive immunostaining against smooth muscle actine and desmin was observed in the elongated cells (PSC-s). This reaction was weak in groups of rat treated with DBTC and RAS inhibitors. Treatment of CP rats with RAS inhibitors alleviate apoptosis of pancreatic acinar cells and induces PSCs elimination.

The role of adenosine A2a receptors in experimental acute pancreatitis.

PURPOSE: The role of adenosine and its receptors in acute pancreatitis remains unelucidated. The aim was to evaluate the effects of the adenosine A2a receptor agonist and antagonist in the severe, taurocholate-induced experimental acute pancreatitis (EAP). MATERIAL AND METHODS: The experiments were performed on 80 male Wistar rats, subdivided into 4 groups: C--the control rats, I--the EAP group, IIA--EAP group treated with the A2a adenosine receptor agonist CGS 21680, IIB--EAP group treated with the A2a adenosine receptor antagonist ZM 241385. The blood for alpha-amylase and lipase and tissues samples for the morphological examinations and immunohistochemistry for A2a receptors were collected in 2, 6, 24 hours of the experiment. RESULTS: The serum alpha-amylase tended to decrease in the group IIA as compared to EAP untreated after 6 and 24 h. No significant effect of both treatments on serum lipase was noted. The administration of CGS 21680 resulted in favorable decrease of the inflammatory cell infiltration, hemorrhagic changes, necrosis and vacuolization of acinar cells, without an evident effect on the edema of the interstitial tissue. The administration of ZM 241385 did not affect the scores of necro-hemorrhagic changes and inflammatory infiltration, whereas it decreased the scores of vacuolization and edema. In all groups the expression of A2a receptors was similar. CONCLUSIONS: Our findings suggest, that A2a adenosine receptors are involved in the course of sodium taurocholate EAP. It is probable that the modulation of some subgroups of adenosine receptors could alleviate the course of severe experimental AP.