Original Article
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World J Gastroenterol. Nov 21, 2014; 20(43): 16203-16214
Published online Nov 21, 2014. doi: 10.3748/wjg.v20.i43.16203
Polyethylene glycol rinse solution: An effective way to prevent ischemia-reperfusion injury
Mohamed Amine Zaouali, Mohamed Bejaoui, Maria Calvo, Emma Folch-Puy, Eirini Pantazi, Gianfranco Pasut, Antoni Rimola, Hassen Ben Abdennebi, René Adam, Joan Roselló-Catafau
Mohamed Amine Zaouali, Mohamed Bejaoui, Emma Folch-Puy, Eirini Pantazi, Joan Roselló-Catafau, Experimental Hepatic Ischemia-Reperfusion Unit, IIBB-CSIC, CSIC-IDIBAPS, 08036 Barcelona, Spain
Maria Calvo, Serveis Cientifico-Tècnics, Universitat de Barcelona, 08036 Barcelona, Spain
Gianfranco Pasut, Pharmaceutical and Pharmacological Department, University of Padova, 35122 Padova, Italy
Antoni Rimola, Joan Roselló-Catafau, Hospital Clínic, Networked Biomedical Research Center of Hepatic and Digestive Diseases (CiberEHD), 08036 Barcelona, Spain
Mohamed Amine Zaouali, Hassen Ben Abdennebi, Molecular Biology and Anthropology Applied to Development and Health (UR12ES11), Faculty of Pharmacy, University of Monastir, 5000 Monastir, Tunisia
René Adam, AP-HP Hôpital Paul Brousse, Centre Hepato-Biliaire, Univ Paris-Sud Villejuif, 75008 Paris, France
Author contributions: Zaouali MA, Bejaoui M, Folch-Puy E, and Pantazi E carried out the experimental work; Zaouali MA and Calvo M carried out the confocal microscopy analysis; Ben Abdennebi H, Pasut G and Rimola A provided protocols and analyzed data; Ben Abdennebi H and Adam R established the animal experimental model and contributed to the critical analyses of the data; Zaouali MA and Roselló-Catafau J designed the study, coordinated the experiments, and wrote the paper.
Supported by The Ministerio de Sanidad y Consumo No. PIO81988 (Madrid, Spain); Eirini Pantazi wishes to thank the Agència de Gestió d’Ajuts Universitaris i de Recerca No.2012FI_B00382; Mohamed Bejaoui thanks CSIC No. I-COOP05 for their fellowships
Correspondence to: Joan Roselló-Catafau, PhD, Experimental Hepatic Ischemia-Reperfusion Unit, IIBB-CSIC, CSIC-IDIBAPS, C/Rosselló 161, 7th floor, 08036 Barcelona, Spain. joan.rosello@iibb.csic.es
Telephone: +34-93-3638333 Fax: +34-93-3638301
Received: February 14, 2014
Revised: May 2, 2014
Accepted: June 12, 2014
Published online: November 21, 2014
Processing time: 279 Days and 1 Hours
Abstract

AIM: To test whether a new rinse solution containing polyethylene glycol 35 (PEG-35) could prevent ischemia-reperfusion injury (IRI) in liver grafts.

METHODS: Sprague-Dawley rat livers were stored in University of Wisconsin preservation solution and then washed with different rinse solutions (Ringer’s lactate solution and a new rinse solution enriched with PEG-35 at either 1 or 5 g/L) before ex vivo perfusion with Krebs-Heinseleit buffer solution. We assessed the following: liver injury (transaminase levels), mitochondrial damage (glutamate dehydrogenase activity), liver function (bile output and vascular resistance), oxidative stress (malondialdehyde), nitric oxide, liver autophagy (Beclin-1 and LCB3) and cytoskeleton integrity (filament and globular actin fraction); as well as levels of metalloproteinases (MMP2 and MMP9), adenosine monophosphate-activated protein kinase (AMPK), heat shock protein 70 (HSP70) and heme oxygenase 1 (HO-1).

RESULTS: When we used the PEG-35 rinse solution, reduced hepatic injury and improved liver function were noted after reperfusion. The PEG-35 rinse solution prevented oxidative stress, mitochondrial damage, and liver autophagy. Further, it increased the expression of cytoprotective heat shock proteins such as HO-1 and HSP70, activated AMPK, and contributed to the restoration of cytoskeleton integrity after IRI.

CONCLUSION: Using the rinse solution containing PEG-35 was effective for decreasing liver graft vulnerability to IRI.

Keywords: Liver washout; Liver transplantation; Rinse solution; Ischemia-reperfusion injury; Polyethylene glycol 35; Nitric oxide; Adenosine monophosphate-activated protein kinase; Heme oxygenase 1; Heat shock protein 70; Metalloproteinases

Core tip: Research into optimal rinse solutions for graft washout is limited, and their clinical application is dependent on surgeon preference. We present a new rinse solution containing polyethylene glycol 35 (PEG-35) that is not only suitable for washing liver grafts after cold preservation, but also provided good graft protection against reperfusion injury. Using PEG-35 in the rinse solution resulted in less hepatic injury, a significant induction of cytoprotective proteins, and the preservation of cytoskeletal integrity. Thus, PEG-35 supplemented rinse solutions may contribute to liver graft protection against ischemia-reperfusion injury.