Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach
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 glyc...
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/10/5332 |
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| author | Raquel G. Bardallo Rui Teixeira da Silva Teresa Carbonell Emma Folch-Puy Carlos Palmeira Joan Roselló-Catafau Jacques Pirenne René Adam Arnau Panisello-Roselló |
| author_facet | Raquel G. Bardallo Rui Teixeira da Silva Teresa Carbonell Emma Folch-Puy Carlos Palmeira Joan Roselló-Catafau Jacques Pirenne René Adam Arnau Panisello-Roselló |
| author_sort | Raquel G. Bardallo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T11:17:15Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T11:17:15Z |
| publishDate | 2021-05-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-947d47c9f56a4443bcb17245dc629c822023-11-21T20:22:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012210533210.3390/ijms22105332Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 ApproachRaquel G. Bardallo0Rui Teixeira da Silva1Teresa Carbonell2Emma Folch-Puy3Carlos Palmeira4Joan Roselló-Catafau5Jacques Pirenne6René Adam7Arnau Panisello-Roselló8Experimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB), CSIC-IDIBAPS, 08036 Barcelona, SpainExperimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB), CSIC-IDIBAPS, 08036 Barcelona, SpainDepartment of Physiology, Faculty of Biology, Universitat de Barcelona, 08028 Barcelona, SpainExperimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB), CSIC-IDIBAPS, 08036 Barcelona, SpainCenter for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, PortugalExperimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB), CSIC-IDIBAPS, 08036 Barcelona, SpainDepartment of Abdominal Transplant Surgery, University Hospitals Leuven, 3000 Leuven, BelgiumAP-HP Hôpital Paul Brousse, UR, Chronothérapie, Cancers et Transplantation, Université Paris-Saclay, Villejuif, 91190 Paris, FranceExperimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB), CSIC-IDIBAPS, 08036 Barcelona, SpainThe 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.https://www.mdpi.com/1422-0067/22/10/5332fatty liverPEG35IGL-1 solutionALDH24-HNEnitric oxide |
| spellingShingle | Raquel G. Bardallo Rui Teixeira da Silva Teresa Carbonell Emma Folch-Puy Carlos Palmeira Joan Roselló-Catafau Jacques Pirenne René Adam Arnau Panisello-Roselló Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach International Journal of Molecular Sciences fatty liver PEG35 IGL-1 solution ALDH2 4-HNE nitric oxide |
| title | Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach |
| title_full | Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach |
| title_fullStr | Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach |
| title_full_unstemmed | Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach |
| title_short | Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach |
| title_sort | role of peg35 mitochondrial aldh2 and glutathione in cold fatty liver graft preservation an igl 2 approach |
| topic | fatty liver PEG35 IGL-1 solution ALDH2 4-HNE nitric oxide |
| url | https://www.mdpi.com/1422-0067/22/10/5332 |
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