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Int. J. Mol. Sci. 2018, 19(2), 348;

Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK

Experimental Hepatic Ischemia-Reperfusion Unit, Institut d’Investigacions Biomèdiques de Barcelona (IIBB), Spanish National Research Council (CSIC), 08036 Barcelona, Catalonia, Spain
Department of Cell Biology, Physiology and Immunology, Universitat de Barcelona, Barcelona, 08028 Catalonia, Spain
Centre Hépato-Biliaire, AP-PH, Hôpital Paul Brousse, 94800 Villejuif, France
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Catalonia, Spain
Center for Neuroscience and Cell Biology, Universidade Coimbra, 3000-370 Coimbra, Portugal
Author to whom correspondence should be addressed.
Received: 29 November 2017 / Revised: 16 January 2018 / Accepted: 19 January 2018 / Published: 24 January 2018
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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. View Full-Text
Keywords: cold ischemia injury; liver; IGL-1 solution; HTK solution; mTOR; autophagy and apoptosis cold ischemia injury; liver; IGL-1 solution; HTK solution; mTOR; autophagy and apoptosis

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Panisello-Roselló, A.; Verde, E.; Lopez, A.; Flores, M.; Folch-Puy, E.; Rolo, A.; Palmeira, C.; Hotter, G.; Carbonell, T.; Adam, R.; Roselló-Catafau, J. Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK. Int. J. Mol. Sci. 2018, 19, 348.

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