Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2005; 11(8): 1115-1121
Published online Feb 28, 2005. doi: 10.3748/wjg.v11.i8.1115
Effect of endothelin-1 receptor antagonists on histological and ultrastructural changes in the pancreas and trypsinogen activation in the early course of caerulein-induced acute pancreatitis in rats
Anna Andrzejewska, Jan W. Dlugosz, Albert Augustynowicz
Anna Andrzejewska, Albert Augustynowicz, Department of Medical Pathomorphology, Medical University of Bialystok, Bialystok, Poland
Jan W. Dlugosz, Department of Gastroenterology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland
Author contributions: All authors contributed equally to the work.
Supported by the Medical University of Bialystok within the Project # 3-12770
Correspondence to: Professor Anna Andrzejewska M.D., Department of Medical Pathomorphology, Medical University of Bialystok, Waszygton Str. 13, 15-269 Bialystok, Poland.
Telephone: +48-85-7485989 Fax: +48-85-7485989
Received: July 17, 2004
Revised: July 20, 2004
Accepted: September 19, 2004
Published online: February 28, 2005

AIM: To assess the effect of non-selective ETA/B (LU 302872) and selective ETA (LU 302146) antagonist on pancreatic histology and ultrastructure of acinar cells in connection with trypsinogen activation in early caerulein-induced AP.

METHODS: Male Wistar rats with caerulein-induced AP, lasting 4 h, were treated i.p. with 10 and 20 mg/kg b.w. of each antagonist. Edema, inflammatory infiltration, necrosis and vacuolization of acinar cells in the pancreas were scored at 0-3 scale. Free active trypsin (FAT), total potential trypsin (TPT) after activation with enterokinase, and index of trypsinogen activation (%FAT/TPT) were assayed in pancreatic homogenates.

RESULTS: In untreated AP, the edema, inflammatory infiltration, necrosis and vacuolization increased as compared to control healthy rats (P<0.01). None of the treatment exerted any meaningful effect on the edema and inflammatory infiltration. The selective antagonist increased slightly the necrosis score to 0.82±0.06 at higher dose (P<0.05) vs 0.58±0.06 in untreated AP. The non-selective antagonist increased slightly the vacuolization score to 2.41±0.07 at higher dose (P<0.01) vs 1.88±0.08 in untreated AP. The decrease in the number of zymogen granules, disorganization of endoplasmic reticulum, autophagosomes and cytoplasmic vacuoles were more prominent in treated AP than in untreated AP groups. %FAT/TPT in untreated AP increased about four times (18.4±3.8 vs 4.8±1.3 in control group without AP, P<0.001). Treatment of AP with both antagonists did not affect significantly augmented trypsinogen activation.

CONCLUSION: The treatment with endothelin-1 receptors (non-selective ETA/B and selective ETA) antagonists has essential effect neither on the edema and inflammatory infiltration nor on trypsinogen activation observed in the early course of caerulein-induced AP. Nevertheless a slight increase of the necrosis and vacuolization score and some of the ultrastructural data could suggest the possibility of their undesired effects in caerulein-induced AP at investigated doses.

Keywords: Acute pancreatitis, Caerulein, Endothelin-1 receptors antagonists, Ultrastructure, Trypsin