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

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 al...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855570/
https://www.ncbi.nlm.nih.gov/pubmed/29364854
http://dx.doi.org/10.3390/ijms19020348
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author 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
author_facet 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
author_sort Panisello-Roselló, Arnau
collection PubMed
description 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.
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spelling pubmed-58555702018-03-20 Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK 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 Int J Mol Sci Article 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. MDPI 2018-01-24 /pmc/articles/PMC5855570/ /pubmed/29364854 http://dx.doi.org/10.3390/ijms19020348 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK
title Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK
title_full Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK
title_fullStr Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK
title_full_unstemmed Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK
title_short Cytoprotective Mechanisms in Fatty Liver Preservation against Cold Ischemia Injury: A Comparison between IGL-1 and HTK
title_sort cytoprotective mechanisms in fatty liver preservation against cold ischemia injury: a comparison between igl-1 and htk
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5855570/
https://www.ncbi.nlm.nih.gov/pubmed/29364854
http://dx.doi.org/10.3390/ijms19020348
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