title: A novel form of the human manganese superoxide dismutase protects rat and human livers undergoing ischaemia and reperfusion injury.
abstract: Hepatic microcirculatory dysfunction due to cold storage and warm reperfusion (CS+WR) injury during liver transplantation is partly mediated by oxidative stress and may lead to graft dysfunction. This is especially relevant when steatotic donors are considered. Using primary cultured liver sinusoidal endothelial cells (LSECs), liver grafts from healthy and steatotic rats, and human liver samples, we aimed to characterize the effects of a new recombinant form of human manganese superoxide dismutase (rMnSOD) on hepatic CS+WR injury. After CS+WR, the liver endothelium exhibited accumulation of superoxide anion (O2-) and diminished levels of nitric oxide (NO); these detrimental effects were prevented by rMnSOD. CS+WR control and steatotic rat livers exhibited markedly deteriorated microcirculation and acute endothelial dysfunction, together with liver damage, inflammation, oxidative stress, and low NO. rMnSOD markedly blunted oxidative stress, which was associated with a global improvement in liver damage and microcirculatory derangements. The addition of rMnSOD to CS solution maintained its antioxidant capability, protecting rat and human liver tissues. In conclusion, rMnSOD represents a new and highly effective therapy to significantly upgrade liver procurement for transplantation.
authors.affiliation: *Barcelona Hepatic Hemodynamic Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Hide
authors.affiliation: *Barcelona Hepatic Hemodynamic Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Martí
authors.initials: M
authors.lastname: Ortega-Ribera
authors.affiliation: †Nutrigenomics Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Anabel
authors.initials: A
authors.lastname: Fernández-Iglesias
authors.affiliation: ‡Liver Surgery and Transplantation Unit, IDIBAPS, Hospital Clínic de Barcelona, CIBERehd, Universitat de Barcelona, Spain.
authors.forename: Constantino
authors.initials: C
authors.lastname: Fondevila
authors.affiliation: †Nutrigenomics Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: M Josepa
authors.initials: MJ
authors.lastname: Salvadó
authors.affiliation: †Nutrigenomics Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Arola
authors.affiliation: *Barcelona Hepatic Hemodynamic Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: García-Pagán
authors.affiliation: §Molecular Biology and Viral Oncogenesis, National Cancer Institute, Naples, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Mancini
authors.affiliation: *Barcelona Hepatic Hemodynamic Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Bosch
authors.affiliation: *Barcelona Hepatic Hemodynamic Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic de Barcelona, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Gracia-Sancho
mesh_terms: D000818:Animals; D005234:Fatty Liver / Q000628:therapy; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D015427:Reperfusion Injury / Q000188:drug therapy*; D013482:Superoxide Dismutase / Q000494:pharmacology*; D000099156:Superoxide Dismutase 2
chemical_list: D009569:Nitric Oxide; D011994:Recombinant Proteins; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2