Protective Role of m-TOR System in Fatty Liver Grafts Preserved in IGL-1 and HTK Solutions

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Abstract

IGL-1 and HTK preservation solutions are regularly used in clinical for liver transplantation besides UW and Celsior. Several clinical trials and experimental works have been carried out comparing all the solutions, however the comparative IGL-1 and HTK appraisals are poor; specially when they deal with the underlying protection mechanisms of the fatty liver graft during cold storage. Fatty livers from male obese Zücker rats were conserved for 24 h at 4°C in IGL-1 or HTK solutions. After torgan recovery and rinsing of fatty liver grafts with Ringer Lactate solution, we measured the changes in the expression levels of m-TOR, phosphorylated m-TOR, in liver autophagy markers (Beclin 1, Beclin 2 and LC3B) and apoptosis (caspase 3 and caspase 9 activity). These determinations were correlated with the prevention of liver injury (AST/ALT, histology) and mitochondrial damage (GLDH and confocal microscopy findings). Liver grafts preserved in IGL-1 solution showed a marked reduction on p-TOR/m-TOR expression when compared to HTK. This was concomitant with significant increased cyto-protective autophagy and prevention of liver apoptosis. Together, our results revealed the importance of m-TOR system to modulate autophagy and apoptosis during static cold storage of fatty liver. m-TOR inhibition permit to explain how IGL-1 solution better protected fatty liver grafts against cold ischemia damage contributing thus, to limit the subsequent extension of reperfusion injury after graft revascularization in liver transplantation procedures.

This work was supported by Instituto de Salud Carlos III (ISCIII) through the FIS project PI12/0056, co-funded by FEDER from Regional Development European Funds (European Union).

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