title: The Effect of High-Mobility Group Box 1 in Rat Steatotic and Nonsteatotic Liver Transplantation From Donors After Brain Death.
abstract: High-mobility group box 1 (HMGB1) has been described in different inflammatory disorders, and the deleterious effects of brain death (BD) may counteract the protection conferred by ischemic preconditioning (IP), the only surgical strategy that is being applied in clinical liver transplantation. Our study examined how HMGB1 may affect preconditioned and unpreconditioned steatotic and nonsteatotic liver grafts from donors after BD (DBDs) for transplantation. HMGB1 was pharmacologically modulated in liver grafts from DBDs, and HMGB1-underlying mechanisms were characterized. We found that BD decreased HMGB1 in preconditioned and unpreconditioned livers and was associated with inflammation and damage. Exogenous HMGB1 in DBDs activates phosphoinositide-3-kinase and Akt and reduces hepatic inflammation and damage, increasing the survival of recipients. Combination of IP and exogenous HMGB1 shows additional benefits compared with HMGB1 alone. This study provides new mechanistic insights into the pathophysiology of BD-derived liver graft damage and contributes to the development of novel and efficient strategies to ultimately improve liver graft quality.
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
authors.forename: M E
authors.initials: ME
authors.lastname: Cornide-Petronio
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Negrete-Sánchez
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Mendes-Braz
authors.affiliation: Hospital Regional de Alta Especialidad de Ciudad Victoria, Ciudad Victoria, México.
authors.forename: A
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 (CIBEREHD), Barcelona, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Bujaldon
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Meroño
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
authors.forename: L
authors.initials: L
authors.lastname: Martínez-Carreres
authors.affiliation: Barcelona Hepatic Hemodynamic Laboratory, IDIBAPS, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Gracia-Sancho
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.|Liver Unit, Hospital Clínic, Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Rodés
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
authors.forename: M B
authors.initials: MB
authors.lastname: Jiménez-Castro
authors.affiliation: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Peralta
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001926:Brain Death / Q000503:physiopathology*; D005234:Fatty Liver / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D024243:HMGB1 Protein / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D019194:Ischemic Preconditioning; D016031:Liver Transplantation; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker; D015427:Reperfusion Injury; D013851:Thinness / Q000503:physiopathology*; D014019:Tissue Donors
chemical_list: D024243:HMGB1 Protein; C104200:Hbp1 protein, rat
keywords: animal models: murine; basic (laboratory) research/science; cell death; donors and donation: donation after brain death (DBD); graft survival; ischemia reperfusion injury (IRI); liver transplantation/hepatology