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


METHODS
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.


RESULTS
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.


CONCLUSIONS
IGL-1 enrichment with IGF-1 increased fatty liver graft preservation through AKT and eNOS activation, and prevented TNF-α release during normothermic reperfusion.
Experimental Hepatic Ischemia-Reperfusion Unit, Institut d'Investigacions Biomèdiques de Barcelona, Consejo Superior de Investigaciones Científicas, 08036 Barcelona, Spain. jrcbam@iibb.csic.es
Mohamed Amine
MA
Zaouali
Susagna
S
Padrissa-Altés
Ismail
I
Ben Mosbah
Hassen
H
Ben Abdennebi
Olivier
O
Boillot
Antoni
A
Rimola
Dalila
D
Saidane-Mosbahi
Joan
J
Roselló-Catafau
D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001646:Bile / Q000378:metabolism; D050377:Cold Ischemia / Q000009:adverse effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014655:Vascular Resistance; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C504757:IGL-1 solution; D019188:Organ Preservation Solutions; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007334:Insulin-Like Growth Factor I; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases