Basic Research
Copyright ©The Author(s) 2005. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2005; 11(38): 5958-5965
Published online Oct 14, 2005. doi: 10.3748/wjg.v11.i38.5958
Ischemic preconditioning inhibits development of edematous cerulein-induced pancreatitis: Involvement of cyclooxygenases and heat shock protein 70
Zygmunt Warzecha, Artur Dembinski, Piotr Ceranowicz, Stanislaw J Konturek, Marcin Dembinski, Wieslaw W Pawlik, Romana Tomaszewska, Jerzy Stachura, Beata Kusnierz-Cabala, Jerzy W Naskalski, Peter C Konturek
Zygmunt Warzecha, Artur Dembinski, Piotr Ceranowicz, Stanislaw J Konturek, Marcin Dembinski, Wieslaw W Pawlik, Department of Physiology, Jagiellonian University Medical College, Krakow, Poland
Romana Tomaszewska, Jerzy Stachura, Department of Pathology, Jagiellonian University Medical College, Krakow, Poland
Beata Kusnierz-Cabala, Jerzy W Naskalski, Department of Clinical Biochemistry, Jagiellonian University Medical College, Krakow, Poland
Peter C Konturek, Department of Internal Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany
Author contributions: All authors contributed equally to the work.
Correspondence to: Professor Artur Dembinski, MD, PhD, Department of Physiology, Jagiellonian University Medical College, ul. Grzegózecka 16, Krakow 31-531,Poland. mpdembin@cyf-kr.edu.pl
Telephone: +48-12-4211006 Fax: +48-12-4225478
Received: December 17, 2004
Revised: March 15, 2005
Accepted: March 21, 2005
Published online: October 14, 2005
Abstract

AIM: To determine whether ischemic preconditioning (IP) affects the development of edematous cerulein-induced pancreatitis and to assess the role of cyclooxygenase-1 (COX-1), COX-2, and heat shock protein 70 (HSP 70) in this process.

METHODS: In male Wistar rats, IP was performed by clamping of celiac artery (twice for 5 min at 5-min intervals). Thirty minutes after IP or sham operation, acute pancreatitis was induced by cerulein. Activity of COX-1 or COX-2 was inhibited by resveratrol or rofecoxib, respectively (10 mg/kg).

RESULTS: IP significantly reduced pancreatic damage in cerulein-induced pancreatitis as demonstrated by the improvement of pancreas histology, reduction in serum lipase and poly-C ribonuclease activity, and serum concentration of pro-inflammatory interleukin (IL)-1β. Also, IP attenuated the pancreatitis-evoked fall in pancreatic blood flow and pancreatic DNA synthesis. Serum level of anti-inflammatory IL-10 was not affected by IP. Cerulein-induced pancreatitis and IP increased the content of HSP 70 in the pancreas. Maximal increase in HSP 70 was observed when IP was combined with cerulein-induced pancreatitis. Inhibition of COXs, especially COX-2, reduced the protective effect of IP in edematous pancreatitis.

CONCLUSION: Our results indicate that IP reduces pancreatic damage in cerulein-induced pancreatitis and this effect, at least in part, depends on the activity of COXs and pancreatic production of HSP 70.

Keywords: Acute pancreatitis; Ischemic preconditioning; Cyclooxygenase-2; Interleukin-1β; Heat shock protein-70