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Title: Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK
Authors: Panisello-Roselló, Arnau
Verde, Eva
Lopez, Alexandre 
Flores, Marta
Folch-Puy, Emma
Rolo, Anabela 
Palmeira, Carlos 
Hotter, Georgina
Carbonell, Teresa 
Adam, René 
Roselló-Catafau, Joan 
Keywords: cold ischemia injury; liver; IGL-1 solution; HTK solution; mTOR; autophagy and apoptosis
Issue Date: 24-Jan-2018
Publisher: MDPI
Project: Instituto de Salud Carlos III through FIS project PI 12/0056 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 and Innovation programme under the Marie Sklodowska-Curie Grant (Agreement No. 722619) 
Serial title, monograph or event: International Journal of Molecular Sciences
Volume: 19
Issue: 2
Abstract: Institute Goeorges Lopez 1 (IGL-1) and Histidine-Tryptophan-Ketoglutarate (HTK) preservation solutions are regularly used in clinical for liver transplantation besides University of Wisconsin (UW) solution 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; especially 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 preservation solutions. After organ recovery and rinsing of fatty liver grafts with Ringer Lactate solution, we measured the changes in mechanistic target of rapamycin (mTOR) signaling activation, liver autophagy markers (Beclin-1, Beclin-2, LC3B and ATG7) and apoptotic markers (caspase 3, caspase 9 and TUNEL). These determinations were correlated with the prevention of liver injury (aspartate and alanine aminostransferase (AST/ALT), histology) and mitochondrial damage (glutamate dehydrogenase (GLDH) and confocal microscopy findings). Liver grafts preserved in IGL-1 solution showed a marked reduction on p-TOR/mTOR ratio when compared to HTK. This was concomitant with significant increased cyto-protective autophagy and prevention of liver apoptosis, including inflammatory cytokines such as HMGB1. Together, our results revealed that IGL-1 preservation solution better protected fatty liver grafts against cold ischemia damage than HTK solution. IGL-1 protection was associated with a reduced liver damage, higher induced autophagy and decreased apoptosis. All these effects would contribute to limit the subsequent extension of reperfusion injury after graft revascularization in liver transplantation procedures.
ISSN: 1422-0067
DOI: 10.3390/ijms19020348
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais

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