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.
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Research Article|
June 30 2014
A novel form of the human manganese superoxide dismutase protects rat and human livers undergoing ischaemia and reperfusion injury
Diana Hide;
Diana Hide
*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
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Martí Ortega-Ribera;
Martí Ortega-Ribera
*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
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Anabel Fernández-Iglesias;
Anabel Fernández-Iglesias
†Nutrigenomics Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Spain
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Constantino Fondevila;
Constantino Fondevila
‡Liver Surgery and Transplantation Unit, IDIBAPS, Hospital Clínic de Barcelona, CIBERehd, Universitat de Barcelona, Spain
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M. Josepa Salvadó;
M. Josepa Salvadó
†Nutrigenomics Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Spain
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Lluís Arola;
Lluís Arola
†Nutrigenomics Group, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Tarragona, Spain
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Juan Carlos García-Pagán;
Juan Carlos García-Pagán
*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
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Aldo Mancini;
Aldo Mancini
§Molecular Biology and Viral Oncogenesis, National Cancer Institute, Naples, Italy
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Jaime Bosch;
Jaime Bosch
*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
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Jordi Gracia-Sancho
*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
Correspondence: Dr Jordi Gracia-Sancho (email [email protected]).
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Publisher: Portland Press Ltd
Received:
February 19 2014
Revision Received:
April 09 2014
Accepted:
April 22 2014
Accepted Manuscript online:
April 22 2014
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2014 Biochemical Society
2014
Clin Sci (Lond) (2014) 127 (8): 527–537.
Article history
Received:
February 19 2014
Revision Received:
April 09 2014
Accepted:
April 22 2014
Accepted Manuscript online:
April 22 2014
Citation
Diana Hide, Martí Ortega-Ribera, Anabel Fernández-Iglesias, Constantino Fondevila, M. Josepa Salvadó, Lluís Arola, Juan Carlos García-Pagán, Aldo Mancini, Jaime Bosch, Jordi Gracia-Sancho; A novel form of the human manganese superoxide dismutase protects rat and human livers undergoing ischaemia and reperfusion injury. Clin Sci (Lond) 1 October 2014; 127 (8): 527–537. doi: https://doi.org/10.1042/CS20140125
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