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World J Gastroenterol. Dec 28, 2010; 16(48): 6058-6067
Published online Dec 28, 2010. doi: 10.3748/wjg.v16.i48.6058
Molecular mechanisms of liver preconditioning
Elisa Alchera, Caterina Dal Ponte, Chiara Imarisio, Emanuele Albano, Rita Carini
Elisa Alchera, Caterina Dal Ponte, Chiara Imarisio, Emanuele Albano, Rita Carini, Department of Medical Sciences, University of East Piedmont “A. Avogadro”, Via Solaroli 17, 28100 Novara, Italy
Author contributions: Alchera E, Dal Ponte C, Imarisio C and Carini R performed the research and analyzed the data; Albano E and Carini R designed the research; Albano E critically revised the paper; Carini R wrote the paper.
Supported by The Regional Government of Piedmont, Italy (Carini, Fondi Ricerca Sanitaria Finalizzata, 2006, 2007; 2008, 2008 bis, 2009; Alchera, Fondi Ricerca Sanitaria Finalizzata, 2008 bis, 2009); and by the University “Amedeo Avogadro”
Correspondence to: Dr. Rita Carini, Department of Medical Sciences, University of East Piedmont “A. Avogadro”, Via Solaroli 17, 28100 Novara, Italy. carini@med.unipmn.it
Telephone: +39-321-660685 Fax: +39-321-620421
Received: June 28, 2010
Revised: November 3, 2010
Accepted: November 10, 2010
Published online: December 28, 2010
Abstract

Ischemia/reperfusion (I/R) injury still represents an important cause of morbidity following hepatic surgery and limits the use of marginal livers in hepatic transplantation. Transient blood flow interruption followed by reperfusion protects tissues against damage induced by subsequent I/R. This process known as ischemic preconditioning (IP) depends upon intrinsic cytoprotective systems whose activation can inhibit the progression of irreversible tissue damage. Compared to other organs, liver IP has additional features as it reduces inflammation and promotes hepatic regeneration. Our present understanding of the molecular mechanisms involved in liver IP is still largely incomplete. Experimental studies have shown that the protective effects of liver IP are triggered by the release of adenosine and nitric oxide and the subsequent activation of signal networks involving protein kinases such as phosphatidylinositol 3-kinase, protein kinase C δ/ε and p38 MAP kinase, and transcription factors such as signal transducer and activator of transcription 3, nuclear factor-κB and hypoxia-inducible factor 1. This article offers an overview of the molecular events underlying the preconditioning effects in the liver and points to the possibility of developing pharmacological approaches aimed at activating the intrinsic protective systems in patients undergoing liver surgery.

Keywords: Apoptosis; Hepatocyte; Hypoxia; Ischemia/reperfusion; Liver surgery; Necrosis; Pharmacological preconditioning; Preconditioning; Survival pathways