Differential effects of endothelins on histological and ultrastructural changes and trypsinogen activation in the secretagogue-induced acute pancreatitis in rats

Exp Toxicol Pathol. 2011 May;63(4):371-8. doi: 10.1016/j.etp.2010.02.013. Epub 2010 Mar 20.


The role of endothelins in acute pancreatitis remains obscure. To assess the effects of endothelins (ETs) in early (4 h) caerulein-induced acute pancreatitis (AP) in rats, ET-1, ET-2 and ET-3 (0.5 or 1.0 nmol/kg) were applied twice with i.p. caerulein (2×40 μg/kg) at 1h interval. Histological and ultrastructural examinations of pancreases and the assay of trypsinogen activation in whole homogenate were performed. All ETs, especially ET-1 at the higher dose, decreased inflammatory cell infiltration despite an increase in the edema score. The vacuolization and necrosis of acinar cells were slightly increased after the lower dose of ET-1 and ET-2. Ultrastructural changes were generally improved after the higher dose of ETs. Trypsinogen activation increased from 4.8±1.3% in control to 18.4±3.8% in AP (p<0.01). It was attenuated to 6.4±1.3% (p<0.01) by the higher dose of ET-1 and to 8.8±1.5% (p<0.05) by the lower dose of ET-3. In summary, ETs, especially ET-1 at the higher dose, were found to have some beneficial effects on morphological changes and trypsinogen activation in the pancreas in early caerulein-induced AP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ceruletide / toxicity
  • Dose-Response Relationship, Drug
  • Endothelins / pharmacology*
  • Enzyme Activation / drug effects*
  • Enzyme Activation / physiology
  • Male
  • Microscopy, Electron, Transmission
  • Pancreatitis / chemically induced
  • Pancreatitis / enzymology*
  • Pancreatitis / pathology*
  • Rats
  • Rats, Wistar
  • Trypsinogen / metabolism*


  • Endothelins
  • Ceruletide
  • Trypsinogen