Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2005; 11(40): 6322-6329
Published online Oct 28, 2005. doi: 10.3748/wjg.v11.i40.6322
Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, protects pancreas against acute cerulein-induced pancreatitis
Peter C Konturek, Artur Dembinski, Zygmunt Warzecha, Grzegorz Burnat, Piotr Ceranowicz, Eckhart G Hahn, Marcin Dembinski, Romana Tomaszewska, Stanislaw J Konturek
Peter C Konturek, Grzegorz Burnat, Eckhart G Hahn, First Department of Medicine, University Erlangen-Nürnberg, Germany
Artur Dembinski, Zygmunt Warzecha, Piotr Ceranowicz, Marcin Dembinski, Stanislaw J Konturek, Department of Physiology, Jagiellonian University Medical College, Cracow, Poland
Romana Tomaszewska, Department of Pathology, Jagiellonian University Medical College, Cracow, Poland
Author contributions: All authors contributed equally to the work.
Correspondence to: Peter C Konturek, First Department of Medicine, University Erlangen- Nürnberg, Erlangen, Germany. peter.konturek@med1. imed.uni-erlangen.de
Telephone: +49-9131-8535211 Fax: +49-9131-8535212
Received: January 12, 2005
Revised: April 26, 2005
Accepted: April 30, 2005
Published online: October 28, 2005
Abstract

AIM: To determine the effect of pioglitazone, a specific peroxisome proliferator-activated receptor-γ (PPARγ) ligand, on the development of acute pancreatitis (AP) and on the expression of heat shock protein 70 (HSP70) in the pancreas.

METHODS: AP was induced in rats by subcutaneous infusion of cerulein for 5 h. Pancreatic blood flow was measured by laser Doppler flowmetry. Plasma lipase activity, interleukin-1β (IL-1β) and IL-10 were determined. Pancreatic weight and histology were evaluated and pancreatic DNA synthesis and blood flow as well as pancreatic mRNA for IL-1β and HSP70 were assessed in rats treated with pioglitazone alone or in combination with cerulein.

RESULTS: Pioglitazone administered (10-100 mg/kg i.g.) 30 min before cerulein, attenuated dose-dependently the pancreatic tissue damage in cerulein-induced pancreatitis (CIP) as demonstrated by the improvement of pancreatic histology, reduction in plasma lipase activity, plasma concentration of pro-inflammatory IL-1β and its gene expression in the pancreas and attenuation of the pancreatitis-evoked fall in pancreatic blood flow. CIP increased pancreatic HSP70 mRNA and protein expression in the pancreas and this effect was enhanced by pioglitazone treatment.

CONCLUSION: Pioglitazone attenuates CIP and the beneficial effect of this pioglitazone is multifactorial probably due to its anti-inflammatory activities, to the suppression of IL-1β and to the overexpression of HSP70. PPARγ ligands could represent a new therapeutic option in the treatment of AP.

Keywords: Cerulein-induced pancreatitis; PPARγ ligand; Heat shock protein 70