Jiménez-Castro MB, Negrete-Sánchez E, Casillas-Ramírez A et al.
Transplant Biomedicals S.L., Barcelona, 08042, Spain.
Clinical science (London, England : 1979). Feb 2017.
In this 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 upregulation 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 downregulated in steatotic liver grafts. Exogenous administration of cortisol negatively affected hepatic damage and survival rate in non-steatotic liver transplantation; however, cortisol treatment upregulated the PI3K-PKC pathway, resulting in protection against the deleterious effects of brain-dead donors on damage and inflammatory response in steatotic liver transplantation as well as in increased survival of recipients. This 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.