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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2015; 21(26): 8021-8031
Published online Jul 14, 2015. doi: 10.3748/wjg.v21.i26.8021
Published online Jul 14, 2015. doi: 10.3748/wjg.v21.i26.8021
Losartan activates sirtuin 1 in rat reduced-size orthotopic liver transplantation
Eirini Pantazi, Mohamed Bejaoui, Mohamed Amine Zaouali, Emma Folch-Puy, Arnau Panisello, Joan Roselló-Catafau, Experimental Pathology Department, Experimental Hepatic Ischemia-Reperfusion Unit, Institute of Biomedical Research of Barcelona (IIBB-CSIC), Barcelona, 08036 Catalonia, Spain
Anabela Pinto Rolo, Carlos Marques Palmeira, Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, 3004-517 Coimbra, Portugal
Anabela Pinto Rolo, Carlos Marques Palmeira, Portugal and Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal
Author contributions: Pantazi E carried out the experimental work; Pantazi E, Bejaoui M and Folch-Puy E provided protocols and analyzed data; Zaouali MA, Bejaoui M and Panisello A established the animal experimental model and injury parameters; Rolo AP and Palmeira CM determinated NAD+, NAMPT levels and contributed to critical analysis of the data and discussion; Pantazi E, Folch-Puy E and Roselló-Catafau J designed the study, coordinated the experiments and wrote the paper.
Supported by Grants from Fondo de Investigaciones Sanitarias, No. FIS PI12/00519; fellowship from Agència de Gestió d’Ajuts Universitaris i de Recerca, No. 2012FI_B00382; Generalitat de Catalunya, Barcelona, Catalonia, Spain (to Pantazi E).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Ethics Committees for Animal Experimentation (CEEA, Directive 400/12), University of Barcelona and all procedures complied with European Union regulations for animal experiments (EU guideline 86/609/EEC).
Conflict-of-interest statement: The authors declare that they have no conflict of interest or any financial interests.
Data sharing statement: Any further information related to technical appendix, statistical code and dataset are available from the corresponding author at jrcbam@iibb.csic.es. The authors 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: Joan Roselló-Catafau, Professor, Experimental Pathology Department, Experimental Hepatic Ischemia-Reperfusion Unit, Institute of Biomedical Research of Barcelona (IIBB-CSIC), C/Rosello 161, 7th floor, 08036 Barcelona, Spain. jrcbam@iibb.csic.es
Telephone: +34-933-638300 Fax: +34-933-638301
Received: January 15, 2015
Peer-review started: January 16, 2015
First decision: February 10, 2015
Revised: February 25, 2015
Accepted: April 3, 2015
Article in press: April 3, 2015
Published online: July 14, 2015
Peer-review started: January 16, 2015
First decision: February 10, 2015
Revised: February 25, 2015
Accepted: April 3, 2015
Article in press: April 3, 2015
Published online: July 14, 2015
Core Tip
Core tip: Losartan is an angiotensin II type 1 receptor (AT1R) antagonist known to protect livers against ischemia-reperfusion injury (IRI). However, the mechanisms underlying this hepatoprotective effect are not fully understood, especially in case of reduced-size orthotopic liver transplantation (ROLT). SIRT1 has recently emerged as an important target to modulate for alleviating IRI. In our study, we describe that AT1R antagonism enhances SIRT1 activity and prevents endoplasmic reticulum stress and liver apoptosis in a rat model of ROLT. Consequently, losartan increases the resistance of ROLT grafts against IRI.