Role of PEG35, Mitochondrial ALDH2, and Glutathione in Cold Fatty Liver Graft Preservation: An IGL-2 Approach.

Abstract

The total damage inflicted on the liver before transplantation is associated with severalsurgical manipulations, such as organ recovery, washout of the graft, cold conservation in organpreservation 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 alterna-tive to UW and Celsior solutions in liver clinical transplantation. In a model of cold preservation inrats (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 assessedin 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 PEG35promoted the mitochondrial enzyme ALDH2, and in combination with glutathione, prevented theformation 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 microcircu-latory disturbances in steatotic grafts during preservation and revascularization. All of these resultslead 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, whichhas 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 uniquesolution/perfusate when hypothermic static and preservation strategies are used, either separately orcombined, easing the logistics and avoiding the mixture of different solutions/perfusates, especiallywhen fatty liver grafts are used. Further research regarding new therapeutic and pharmacologicalinsights is needed to explore the underlying mitochondrial mechanisms exerted by PEG35 in staticand dynamic graft preservation strategies for clinical liver transplantation purpose