The effect of cortisol in rat steatotic and non-steatotic liver transplantation from brain-dead donors Jiménez Castro, Mónica B. Negrete-Sánchez, Elsa Casillas-Ramírez, Araní Gulfo, Jose Álvarez Mercado, Ana Isabel Cornide Petronio, María Eugenia Gracia-Sancho, Jordi Rodés, Juan Peralta, Carmen Brain death Cortisol Ischemia-reperfusion This research was supported by the Ministerio de Economía y Competitividad (MINECO) (Project grant SAF2015-64857-R) Madrid, Spain; by the European Union (Fondos FEDER, “una manera de hacer Europa”); by CERCA Program/Generalitat de Catalunya and by the Secretaria d'Universitats i Recerca del Departament d'Economia i Coneixement (project grant 2014_SGR_144) Barcelona, Spain; Jiménez-Castro M.B. has a contract from the Programa de Promoción del talento y su empleabilidad - Ministerio de Economía y Competitividad (Grant EMP-TU-2015-4167) Madrid, Spain; Cornide-Petronio M.E. has received a Sara Borrell postdoctoral contract from the Instituto de Salud Carlos III (Grant CD15/00129), Madrid, Spain and Gracia-Sancho J. has a contract from the Programa Ramón y Cajal-Ministerio de Economía y Competitividad, Madrid, Spain. In the present study, we examined the effects of cortisol on steatotic and non-steatotic liver grafts from brain-dead donors and characterized the underlying mechanisms involved. Non-steatotic liver grafts showed reduced cortisol and increased cortisone levels in association with up-regulation of enzymes that inactivate cortisol. Conversely, steatotic liver grafts exhibited increased cortisol and reduced cortisone levels. The enzymes involved in cortisol generation were overexpressed, and those involved in cortisol inactivation or clearance were down-regulated in steatotic liver grafts. Exogenous administration of cortisol negatively affected hepatic damage and survival rate in non-steatotic liver transplantation (LT); however, cortisol treatment up-regulated the phosphoinositide 3-kinase (PI3K)–protein kinase C (PKC) pathway, resulting in protection against the deleterious effects of brain-dead donors on damage and inflammatory response in steatotic LT as well as in increased survival of recipients. The present study highlights the differences in the role of cortisol and hepatic mechanisms that regulate cortisol levels based on the type of liver. Our findings suggest that cortisol treatment is a feasible and highly protective strategy to reduce the adverse effects of brain-dead donor livers in order to ultimately improve liver graft quality in the presence of steatosis, whereas cortisol treatment would not be recommended for non-steatotic liver grafts. 2026-01-23T09:59:16Z 2026-01-23T09:59:16Z 2017-04-25 journal article Published version: Mónica B. Jiménez-Castro, Elsa Negrete-Sánchez, Araní Casillas-Ramírez, Jose Gulfo, Ana I. Álvarez-Mercado, María Eugenia Cornide-Petronio, Jordi Gracia-Sancho, Juan Rodés, Carmen Peralta; The effect of cortisol in rat steatotic and non-steatotic liver transplantation from brain-dead donors. Clin Sci (Lond) 25 April 2017; 131 (8): 733–746. https://doi.org/10.1042/CS20160676 https://hdl.handle.net/10481/110126 10.1042/CS20160676 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License Attribution-NonCommercial-NoDerivatives 4.0 Internacional Portland Press