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Improved rat steatotic and nonsteatotic liver preservation by the addition of epidermal growth factor and insulin‐like growth factor‐I to University of Wisconsin solution
Author(s) -
Zaouali M. Amine,
PadrissaAltés Susagna,
Ben Mosbah Ismail,
AlfanyFernandez Izabel,
MassipSalcedo Marta,
CasillasRamirez Araní,
BintanelMorcillo María,
Boillot Olivier,
Serafin Anna,
Rimola Antoni,
Rodés Juan,
RosellóCatafau Joan,
Peralta Carmen
Publication year - 2010
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.22126
Subject(s) - medicine , epidermal growth factor , insulin like growth factor , growth factor , endocrinology , receptor
This study examined the effects of epidermal growth factor (EGF) and insulin‐like growth factor‐I (IGF‐I) supplementation to University of Wisconsin solution (UW) in steatotic and nonsteatotic livers during cold storage. Hepatic injury and function were evaluated in livers preserved for 24 hours at 4°C in UW and in UW with EGF and IGF‐I (separately or in combination) and then perfused ex vivo for 2 hours at 37°C. AKT was inhibited pharmacologically. In addition, hepatic injury and survival were evaluated in recipients who underwent transplantation with steatotic and nonsteatotic livers preserved for 6 hours in UW and UW with EGF and IGF‐I (separately or in combination). The results, based on isolated perfused liver, indicated that the addition of EGF and IGF‐I (separately or in combination) to UW reduced hepatic injury and improved function in both liver types. A combination of EGF and IGF‐I resulted in hepatic injury and function parameters in both liver types similar to those obtained by EGF and IGF‐I separately. EGF increased IGF‐I, and both additives up‐regulated AKT in both liver types. This was associated with glycogen synthase kinase‐3β (GSK3 β ) inhibition in nonsteatotic livers and PPARγ overexpression in steatotic livers. When AKT was inhibited, the effects of EGF and IGF‐I on GSK3 β , PPARγ, hepatic injury and function disappeared. The benefits of EGF and IGF‐I as additives in UW solution were also clearly seen in the liver transplantation model, because the presence of EGF and IGF‐I (separately or in combination) in UW solution reduced hepatic injury and improved survival in recipients who underwent transplantation with steatotic and nonsteatotic liver grafts. In conclusion, EGF and IGF‐I may constitute new additives to UW solution in steatotic and nonsteatotic liver preservation, whereas a combination of both seems unnecessary. Liver Transpl 16:1098–1111, 2010. © 2010 AASLD.