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.
Madro
A
A
Department of Gastroenterology with Endoscopic Unit, Medical University of Lublin, Poland. agnieszka.madro@wp.pl
Korolczuk
A
A
Czechowska
G
G
Celiński
K
K
Słomka
M
M
Prozorow-Król
B
B
Korobowicz
E
E
D000199:Actins / Q000378:metabolism; D000450:Aldosterone / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002216:Captopril / Q000494:pharmacology / Q000627:therapeutic use; D049109:Cell Proliferation / Q000187:drug effects*; D004656:Enalapril / Q000494:pharmacology / Q000627:therapeutic use; D007150:Immunohistochemistry; D017706:Lisinopril / Q000494:pharmacology / Q000627:therapeutic use; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009947:Organotin Compounds; D010179:Pancreas / Q000187:drug effects* / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control; D051381:Rats; D011917:Rats, Inbred Lew; D012084:Renin-Angiotensin System / Q000187:drug effects*
D000199:Actins; D000450:Aldosterone; D002216:Captopril; D004656:Enalapril; D017706:Lisinopril; D019808:Losartan; D009947:Organotin Compounds; C498862:Acta2 protein, rat; C020735:dibutyldichlorotin