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Title: Aldehyde Dehydrogenase 2 (ALDH2) in Rat Fatty Liver Cold Ischemia Injury
Authors: Panisello-Roselló, Arnau
Alva, Norma
Flores, Marta
Lopez, Alexandre 
Castro Benítez, Carlos
Folch-Puy, Emma
Rolo, Anabela 
Palmeira, Carlos 
Adam, René 
Carbonell, Teresa 
Roselló-Catafau, Joan 
Keywords: ALDH2; MDA; 4-hydroxynonenal (4-HNE); caspases 3; apoptosis; IGL-1; UW; HTK
Issue Date: 22-Aug-2018
Publisher: MDPI
Project: This research was funded by Instituto de Salud Carlos III through FIS project PI 15/00110 co-funded by FEDER from Regional Development European Funds (European Union) and the FOIE GRAS project, which has received funding from the European Union’s Horizon 2020 Research and Innovation programme under the Marie Sklodowska-Curie Grant (Agreement No. 722619) 
Serial title, monograph or event: International Journal of Molecular Sciences
Volume: 19
Issue: 9
Abstract: Institut George Lopez-1 (IGL-1) and Histidine-tryptophan-ketoglutarate (HTK) solutions are proposed as alternatives to UW (gold standard) in liver preservation. Their composition differs in terms of the presence/absence of oncotic agents such as HES or PEG, and is decisive for graft conservation before transplantation. This is especially so when fatty (steatotic) livers are used since these grafts are more vulnerable to ischemia insult during conservation. Their composition determines the extent of the subsequent reperfusion injury after transplantation. Aldehyde dehydrogenase-2 (ALDH2), a mitochondrial enzyme, has been reported to play a protective role in warm ischemia-reperfusion injury (IRI), but its potential in fatty liver cold ischemic injury has not yet been investigated. We evaluated the relevance of ALDH2 activity in cold ischemia injury when fatty liver grafts from Zucker Obese rats were preserved in UW, HTK, and IGL-1 solutions, in order to study the mechanisms involved. ALDH2 upregulation was highest in livers preserved in IGL-1. It was accompanied by a decrease in transaminases, apoptosis (Caspase 3 and TUNEL assay), and lipoperoxidation, which was concomitant with the effective clearance of toxic aldehydes such as 4-hydroxy-nonenal. Variations in ATP levels were also determined. The results were consistent with levels of NF-E2 p45-related factor 2 (Nrf2), an antioxidant factor. Here we report for the first time the relevance of mitochondrial ALDH2 in fatty liver cold preservation and suggest that ALDH2 could be considered a potential therapeutic target or regulator in clinical transplantation.
ISSN: 1422-0067
DOI: 10.3390/ijms19092479
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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