Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2016; 22(28): 6501-6508
Published online Jul 28, 2016. doi: 10.3748/wjg.v22.i28.6501
Polyethylene glycols: An effective strategy for limiting liver ischemia reperfusion injury
Gianfranco Pasut, Arnau Panisello, Emma Folch-Puy, Alexandre Lopez, Carlos Castro-Benítez, Maria Calvo, Teresa Carbonell, Agustín García-Gil, René Adam, Joan Roselló-Catafau
Gianfranco Pasut, Department of Pharmaceutical and Pharmacological, University of Padova and Veneto Institute of Oncology, IRCCS, 35128 Padova, Italy
Arnau Panisello, Emma Folch-Puy, Joan Roselló-Catafau, Experimental Pathology Department, Institute of Biomedical Research of Barcelona, 08036 Barcelona, Spain
Alexandre Lopez, Carlos Castro-Benítez, René Adam, Centre Hépatobiliaire, AP-HP Hôpital Paul Brousse, Inserm U935, Université Paris-Sud, Villejuif, 75008 Paris, France
Maria Calvo, Unitat de Microscòpia Òptic Avançada, CCiTUB, Centre Científics i Tecnològics, Faculty of Medicine, University of Barcelona, 08036 Barcelona, Spain
Teresa Carbonell, Physiology Department, Faculty of Biology, Universitat de Barcelona, 08036 Barcelona, Spain
Agustín García-Gil, Hospital Clinico de Zaragoza, 50009 Zaragoza, Spain
Author contributions: All authors contributed equally to the writing of the manuscript and approved the final version.
Supported by Fondo de Investigaciones Sanitarias, Ministerio de Economía y Competitividad (Madrid, Spain), No. PI15/00110.
Conflict-of-interest statement: The authors have no conflict of interests to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Joan Roselló-Catafau, PhD, Experimental Pathology Department, Institute of Biomedical Research of Barcelona, Rosselló 161, 08036-Barcelona, Catalonia, Spain.
Telephone: +34-93-3638333 Fax: +34-93-3638301
Received: March 9, 2016
Peer-review started: March 10, 2016
First decision: April 14, 2016
Revised: May 4, 2016
Accepted: June 2, 2016
Article in press: June 2, 2016
Published online: July 28, 2016

Liver ischemia-reperfusion injury (IRI) is an inherent feature of liver surgery and liver transplantation in which damage to a hypoxic organ (ischemia) is exacerbated following the return of oxygen delivery (reperfusion). IRI is a major cause of primary non-function after transplantation and may lead to graft rejection, regardless of immunological considerations. The immediate response involves the disruption of cellular mitochondrial oxidative phosphorylation and the accumulation of metabolic intermediates during the ischemic period, and oxidative stress during blood flow restoration. Moreover, a complex cascade of inflammatory mediators is generated during reperfusion, contributing to the extension of the damage and finally to organ failure. A variety of pharmacological interventions (antioxidants, anti-cytokines, etc.) have been proposed to alleviate graft injury but their usefulness is limited by the local and specific action of the drugs and by their potential undesirable toxic effects. Polyethylene glycols (PEGs), which are non-toxic water-soluble compounds approved by the FDA, have been widely used as a vehicle or a base in food, cosmetics and pharmaceuticals, and also as adjuvants for ameliorating drug pharmacokinetics. Some PEGs are also currently used as additives in organ preservation solutions prior to transplantation in order to limit the damage associated with cold ischemia reperfusion. More recently, the administration of PEGs of different molecular weights by intravenous injection has emerged as a new therapeutic tool to protect liver grafts from IRI. In this review, we summarize the current knowledge concerning the use of PEGs as a useful target for limiting liver IRI.

Keywords: Ischemia reperfusion injury, Polyethylene glycol, Liver preconditioning, Liver transplantation, UW solution, IGL-1 solution, SCOT solution, PEG rinse solution, Machine perfusion

Core tip: Pharmacological treatments for preventing liver ischemia reperfusion injury are limited, due to the complex pathophysiology of this condition. The drugs currently used for preventing ischemia-reperfusion injury (IRI) all have local and specific activity with potentially damaging side effects. This review focuses on the current understanding of polyethylene glycols, which are non-toxic polymers, as new emerging agents for limiting liver IRI, and proposes directions for future investigations.