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© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

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.

Details

Title
Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach
Author
Bardallo, Raquel G 1   VIAFID ORCID Logo  ; Rui Teixeira da Silva 2 ; Carbonell, Teresa 3   VIAFID ORCID Logo  ; Folch-Puy, Emma 4   VIAFID ORCID Logo  ; Palmeira, Carlos 5 ; Roselló-Catafau, Joan 4 ; Pirenne, Jacques 6   VIAFID ORCID Logo  ; Adam, René 7 ; Panisello-Roselló, Arnau 4 

 Experimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB), CSIC-IDIBAPS, 08036 Barcelona, Spain; [email protected] (R.G.B.); [email protected] (R.T.d.S.); [email protected] (E.F.-P.); [email protected] (A.P.-R.); Department of Physiology, Faculty of Biology, Universitat de Barcelona, 08028 Barcelona, Spain; [email protected] 
 Experimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB), CSIC-IDIBAPS, 08036 Barcelona, Spain; [email protected] (R.G.B.); [email protected] (R.T.d.S.); [email protected] (E.F.-P.); [email protected] (A.P.-R.); Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; [email protected] 
 Department of Physiology, Faculty of Biology, Universitat de Barcelona, 08028 Barcelona, Spain; [email protected] 
 Experimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB), CSIC-IDIBAPS, 08036 Barcelona, Spain; [email protected] (R.G.B.); [email protected] (R.T.d.S.); [email protected] (E.F.-P.); [email protected] (A.P.-R.) 
 Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal; [email protected]; Department of Life Sciences, University of Coimbra, 3004-517 Coimbra, Portugal 
 Department of Abdominal Transplant Surgery, University Hospitals Leuven, 3000 Leuven, Belgium; [email protected] 
 AP-HP Hôpital Paul Brousse, UR, Chronothérapie, Cancers et Transplantation, Université Paris-Saclay, Villejuif, 91190 Paris, France; [email protected] 
First page
5332
Publication year
2021
Publication date
2021
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2532581770
Copyright
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.