Insulin like growth factor-1 increases fatty liver preservation in IGL-1 solution

Abstract

To investigate the benefits of insulin like growth factor-1 (IGF-1) supplementation to serum-free institut georges lopez-1 (IGL-1) solution to protect fatty liver against cold ischemia reperfusion injury. Steatotic livers were preserved for 24 h in IGL-1 solution supplemented with or without IGF-1 and then perfused "ex vivo" for 2 h at 37degrees C. We examined the effects of IGF-1 on hepatic damage and function (transaminases, percentage of sulfobromophthalein clearance in bile and vascular resistance). We also studied other factors associated with the poor tolerance of fatty livers to cold ischemia reperfusion injury such as mitochondrial damage, oxidative stress, nitric oxide, tumor necrosis factor-α (TNF-α) and mitogen-activated protein kinases. Steatotic livers preserved in IGL-1 solution supplemented with IGF-1 showed lower transaminase levels, increased bile clearance and a reduction in vascular resistance when compared to those preserved in IGL-1 solution alone. These benefits are mediated by activation of AKT and constitutive endothelial nitric oxide synthase (eNOS), as well as the inhibition of inflammatory cytokines such as TNF-α. Mitochondrial damage and oxidative stress were also prevented. IGL-1 enrichment with IGF-1 increased fatty liver graft preservation through AKT and eNOS activation, and prevented TNF-α release during normothermic reperfusion.