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Journal of Immunology Research
Volume 2018, Article ID 9807139, 14 pages
https://doi.org/10.1155/2018/9807139
Research Article

Alda-1 Ameliorates Liver Ischemia-Reperfusion Injury by Activating Aldehyde Dehydrogenase 2 and Enhancing Autophagy in Mice

1Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
2Shanghai Key Laboratory for Molecular Imaging, Collaborative Research Center, Shanghai University of Medicine & Health Science, Shanghai, China

Correspondence should be addressed to Hailong Wu; nc.moc.liamtoh@2gnoliahuw, Xiaoni Kong; moc.621@gnok-inoaix, and Qiang Xia; nc.ude.umshs@gnaiqaix

Received 26 March 2018; Revised 14 July 2018; Accepted 7 August 2018; Published 24 December 2018

Academic Editor: Peirong Jiao

Copyright © 2018 Meng Li et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme for metabolism of reactive aldehydes, but its role during liver ischemia-reperfusion injury (IRI) remains unclear. In the present study, we investigated the effects of the ALDH2 activator, Alda-1, in liver IRI and elucidated the underlying mechanisms. Mice were pretreated with Alda-1 and subjected to a 90 min hepatic 70% ischemia model, and liver tissues or serum samples were collected at indicated time points after reperfusion. We demonstrated that Alda-1 pretreatment had a hepatoprotective role in liver IRI as evidenced by decreased liver necrotic areas, serum ALT/AST levels, and liver inflammatory responses. Mechanistically, Alda-1 treatment enhanced ALDH2 activity and subsequently reduced the accumulation of reactive aldehydes and toxic protein adducts, which result in decreased hepatocyte apoptosis and mitochondrial dysfunction. We further demonstrated that Alda-1 treatment could activate AMPK and autophagy and that AMPK activation was required for Alda-1-mediated autophagy enhancement. These findings collectively indicate that Alda-1-mediated ALDH2 activation could be a promising strategy to improve liver IRI by clearance of reactive aldehydes and enhancement of autophagy.