Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 14, 2015; 21(14): 4159-4168
Published online Apr 14, 2015. doi: 10.3748/wjg.v21.i14.4159
Effects of Institut Georges Lopez-1 and Celsior preservation solutions on liver graft injury
Donia Tabka, Mohamed Bejaoui, James Javellaud, Joan Roselló-Catafau, Jean-Michel Achard, Hassen Ben Abdennebi
Donia Tabka, Hassen Ben Abdennebi, Unité de recherche “Biologie et anthropologie moléculaire appliquées au développement et à la santé” (UR12ES11), University of Monastir, Faculty of Pharmacy, Monastir 5000, Tunisia
Mohamed Bejaoui, Joan Roselló-Catafau, Experimental Hepatic Ischemia-Reperfusion Unit, Institut d’Investigacions Biomèdiques de Barcelona-Consejo Superior de Investigaciones Cientificas, 08036 Barcelona, Spain
James Javellaud, Jean-Michel Achard, INSERM, Unité Mixte de Recherche S-850, 8000 Limoges, France
Author contributions: Tabka D and Bejaoui M performed the animal experiments, interpreted the data and wrote the article; Javellaud J did the teaching work and participated in the surgery required for the rat hepatic artery rings model; Roselló-Catafau J contributed to the critical revision of the article; Achard JM and Abdennebi HB designed the study and wrote the article; all the authors have read and approved the final manuscript.
Supported by Tunisian Ministry of Higher Education and Scientific Research, No.UR12ES11.
Institutional animal care and use committee: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Comité Regional D’Ethique pour L’Expérimentation Animale du Limousin (No.33).
Conflict-of-interest: There is no conflict of interest with any financial organization regarding the material discussed in the manuscript.
Data sharing: Technical appendix, statistical code and dataset are available from the corresponding author at (hbenabdennebi@yahoo.fr); all participants gave informed consent for data sharing.
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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hassen Ben Abdennebi, Professor, Department of Physiology, Unité de Recherche “Biologie et anthropologie moléculaire appliquées au développement et à la santé” (UR12ES11), University of Monastir, Faculty of Pharmacy, Rue Avicenne, Monastir 5000, Tunisia. hbenabdennebi@yahoo.fr
Telephone: +216-73-461000
Received: November 6, 2014
Peer-review started: November 9, 2014
First decision: December 11, 2014
Revised: December 30, 2014
Accepted: January 30, 2015
Article in press: January 30, 2015
Published online: April 14, 2015
Processing time: 160 Days and 1.4 Hours
Abstract

AIM: To compare Institut Georges Lopez (IGL-1) and Celsior preservation solutions for hepatic endothelium relaxation and liver cold ischemia reperfusion injury (IRI).

METHODS: Two experimental models were used. In the first one, acetylcholine-induced endothelium-dependent relaxation (EDR) was measured in isolated ring preparations of rat hepatic arteries preserved or not in IGL-1 or Celsior solutions (24 h at 4 °C). To determine nitric oxide (NO) and cyclooxygenase EDR, hepatic arteries were incubated with L-NG-nitroarginine methyl ester (L-NAME), an inhibitor of endothelium nitric oxide synthase (eNOS), or with L-NAME plus indomethacin, an inhibitor of cyclooxygenase. In the second experiment, rat livers were cold-stored in IGL-1 or Celsior solutions for 24 h at 4 °C and then perfused “ex vivo” for 2 h at 37 °C. Liver injury was assessed by transaminase measurements, liver function by bile production and bromosulfophthalein clearance, oxidative stress by malondialdehyde levels and catalase activity and alterations in cell signaling pathways by pAkt, pAMPK, eNOS and MAPKs proteins level.

RESULTS: After cold storage for 24 h with either Celsior or IGL-1, EDR was only slightly altered. In freshly isolated arteries, EDR was exclusively mediated by NO. However, cold-stored arteries showed NO- and COX-dependent relaxation. The decrease in NO-dependent relaxation after cold storage was significantly more marked with Celsior. The second study indicated that IGL-1 solution obtained better liver preservation and protection against IRI than Celsior. Liver injury was reduced, function was improved and there was less oxidative stress. IGL-1 solution activated Akt and AMPK, which was concomitant with increased eNOS expression and nitrite/nitrate levels. Furthermore, MAPKs kinases were regulated in livers preserved with IGL-1 solution since reductions in p-p38, p-ERK and p-JNK protein levels were observed.

CONCLUSION: IGL-1 solution preserved NO-dependent relaxation better than Celsior storage solution and enhanced liver graft preservation.

Keywords: Organ preservation solutions; Institut Georges Lopez solution; Celsior; Reperfusion injury; Endothelium-dependent relaxing factors; Nitric oxide

Core tip: Vascular endothelium dysfunction plays an important role in various pathophysiological conditions. Protection of the vascular endothelium is a critical factor in organ preservation. This evaluation of the endothelium-dependent relaxation of rat hepatic artery after preservation in Celsior and Institut Georges Lopez (IGL-1) solutions provides the first head-to-head comparison of these two storage solutions. Our results show that cold storage of the hepatic artery with IGL-1 preserves nitric oxide-dependent endothelium-mediated relaxation better than cold storage with Celsior solution. In addition, we provide evidence that IGL-1 is more efficient than Celsior for liver preservation using an isolated perfused rat liver model.