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Title: Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach
Authors: Bardallo, Raquel G.
Silva, Rui Teixeira da 
Carbonell, Teresa 
Folch-Puy, Emma
Palmeira, Carlos 
Roselló-Catafau, Joan 
Pirenne, Jacques
Adam, René 
Panisello-Roselló, Arnau
Keywords: fatty liver; PEG35; IGL-1 solution; ALDH2; 4-HNE; nitric oxide
Issue Date: 19-May-2021
Publisher: MDPI
Project: Instituto de Salud Carlos III through FIS project PI 15/00110 co-funded by FEDER from Regional Development European Funds (European Union) 
FOIE GRAS project, which has received funding from the European Union’s Horizon 2020 Research 
Innovation program under the Marie Sklodowska-Curie Grant (Agreement No. 722619) 
Serial title, monograph or event: International Journal of Molecular Sciences
Volume: 22
Issue: 10
Abstract: The total damage inflicted on the liver before transplantation is associated with several surgical manipulations, such as organ recovery, washout of the graft, cold conservation in organ preservation solutions (UW, Celsior, HTK, IGL-1), and rinsing of the organ before implantation. Polyethylene glycol 35 (PEG35) is the oncotic agent present in the IGL-1 solution, which is an alternative to UW and Celsior solutions in liver clinical transplantation. In a model of cold preservation in rats (4 °C; 24 h), we evaluated the effects induced by PEG35 on detoxifying enzymes and nitric oxide, comparing IGL-1 to IGL-0 (which is the same as IGL-1 without PEG). The benefits were also assessed in a new IGL-2 solution characterized by increased concentrations of PEG35 (from 1 g/L to 5 g/L) and glutathione (from 3 mmol/L to 9 mmol/L) compared to IGL-1. We demonstrated that PEG35 promoted the mitochondrial enzyme ALDH2, and in combination with glutathione, prevented the formation of toxic aldehyde adducts (measured as 4-hydroxynonenal) and oxidized proteins (AOPP). In addition, PEG35 promoted the vasodilator factor nitric oxide, which may improve the microcirculatory disturbances in steatotic grafts during preservation and revascularization. All of these results lead to a reduction in damage inflicted on the fatty liver graft during the cold storage preservation. In this communication, we report on the benefits of IGL-2 in hypothermic static preservation, which has already been proved to confer benefits in hypothermic oxygenated dynamic preservation. Hence, the data reported here reinforce the fact that IGL-2 is a suitable alternative to be used as a unique solution/perfusate when hypothermic static and preservation strategies are used, either separately or combined, easing the logistics and avoiding the mixture of different solutions/perfusates, especially when fatty liver grafts are used. Further research regarding new therapeutic and pharmacological insights is needed to explore the underlying mitochondrial mechanisms exerted by PEG35 in static and dynamic graft preservation strategies for clinical liver transplantation purposes.
ISSN: 1422-0067
DOI: 10.3390/ijms22105332
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais

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