Ultrastructural aspects of acute pancreatitis induced by 2, 2'-azobis (2-amidinopropane) dihydrochloride (AAPH) in rats

Abstract

Background. Pathophysiology of acute pancreatitis (AP) has not been clearly established, nevertheless accumulating evidence implicates highly reactive oxygen species (ROS) as important mediators of exocrine tissue damage.

Methods. In this study, we used a water-soluble radical initiator, 2,2'-azobis-(2-amidinopropane) dihydrochloride (AAPH), to investigate consequences of oxidative stress insult to rats pancreas. Detailed ultrastructural characterization of exocrine pancreatic changes that involved a time course of AAPH (40 mg/1kg body weight) induction from 3 to 24 hours was performed.

Results. Considerable damage to the mitochondria in acinar cells manifested by increased translucence of the matrix, partial destruction of cristae and formation of myelin figures were noted. At the same time, focal dilation, degranulation of rough endoplasmic reticulum (RER), and reduced number of zymogen granules was observed. The most prominent ultrastructural feature was accumulation of highly polymorphic cytoplasmic vacuoles in acinar cells. Different in size and shape double membrane-bound autophagosomes with sequestered organelles, autophagolisosomes, and also large, empty, single-membrane-bound vacuoles were observed within the cytoplasm.

Conclusions. The results indicate that intensive but impaired autophagy mediates pathological accumulation of vacuoles in acinar cells. Rat model of acute pancreatitis induced by AAPH  is useful to investigate the early events of oxidative stress insult to pancreas.