title: The effect of cortisol in rat steatotic and non-steatotic liver transplantation from brain-dead donors.
abstract: 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.
authors.affiliation: Transplant Biomedicals S.L.
authors.forename: Mónica B
authors.initials: MB
authors.lastname: Jiménez-Castro
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS).
authors.forename: Elsa
authors.initials: E
authors.lastname: Negrete-Sánchez
authors.affiliation: Hospital Regional de Alta Especialidad de Ciudad Victoria, México.|Facultad de Medicina e Ingeniería en Sistemas Computacionales de Matamoros, Universidad Autónoma de Tamaulipas, México.
authors.forename: Araní
authors.initials: A
authors.lastname: Casillas-Ramírez
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS).|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
authors.forename: Jose
authors.initials: J
authors.lastname: Gulfo
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS).
authors.forename: Ana I
authors.initials: AI
authors.lastname: Álvarez-Mercado
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS).
authors.forename: María Eugenia
authors.initials: ME
authors.lastname: Cornide-Petronio
authors.affiliation: Barcelona Hepatic Hemodynamic Laboratory, IDIBAPS, CIBEREHD, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Gracia-Sancho
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS).|Liver Transplant Unit, Hospital Clínic, Universitat de Barcelona, IDIBAPS, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Rodés
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) cperalta@clinic.ub.es.|Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Barcelona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Peralta
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001926:Brain Death; D003348:Cortisone / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005234:Fatty Liver / Q000378:metabolism* / Q000473:pathology; D006854:Hydrocortisone / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D016031:Liver Transplantation / Q000009:adverse effects / Q000379:methods*; D058539:Phosphatidylinositol 3-Kinase / Q000096:biosynthesis; D011493:Protein Kinase C / Q000096:biosynthesis; D011924:Rats, Zucker; D015398:Signal Transduction / Q000187:drug effects; D015996:Survival Rate; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D000324:Adrenocorticotropic Hormone; D058539:Phosphatidylinositol 3-Kinase; D011493:Protein Kinase C; D003348:Cortisone; D006854:Hydrocortisone
keywords: brain death; cortisol; ischemia-reperfusion; liver transplantation; steatotic liver grafts