title: Protective Effect of Intravenous High Molecular Weight Polyethylene Glycol on Fatty Liver Preservation.
abstract: Ischemia reperfusion injury (IRI) leads to significant tissue damage in liver surgery. Polyethylene glycols (PEGs) are water soluble nontoxic polymers that have proved their effectiveness against IRI. The objective of our study was to investigate the potential protective effects of intravenous administration of a high molecular weight PEG of 35 kDa (PEG 35) in steatotic livers subjected to cold ischemia reperfusion. In this study, we used isolated perfused rat liver model to assess the effects of PEG 35 intravenous administration after prolonged cold ischemia (24 h, 4°C) and after reperfusion (2 h, 37°C). Liver injury was measured by transaminases levels and mitochondrial damage was determined by confocal microscopy assessing mitochondrial polarization (after cold storage) and by measuring glutamate dehydrogenase activity (after reperfusion). Also, cell signaling pathways involved in the physiopathology of IRI were assessed by western blot technique. Our results show that intravenous administration of PEG 35 at 10 mg/kg ameliorated liver injury and protected the mitochondria. Moreover, PEG 35 administration induced a significant phosphorylation of prosurvival protein kinase B (Akt) and activation of cytoprotective factors e-NOS and AMPK. In conclusion, intravenous PEG 35 efficiently protects steatotic livers exposed to cold IRI.
authors.affiliation: Experimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB-CSIC), 08036 Barcelona, Catalonia, Spain.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bejaoui
authors.affiliation: Experimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB-CSIC), 08036 Barcelona, Catalonia, Spain.
authors.forename: Eirini
authors.initials: E
authors.lastname: Pantazi
authors.affiliation: Experimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB-CSIC), 08036 Barcelona, Catalonia, Spain.
authors.forename: Emma
authors.initials: E
authors.lastname: Folch-Puy
authors.affiliation: Experimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB-CSIC), 08036 Barcelona, Catalonia, Spain.
authors.forename: Arnau
authors.initials: A
authors.lastname: Panisello
authors.affiliation: Serveis Cientifico-Tècnics, Universitat de Barcelona, 08036 Barcelona, Catalonia, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Calvo
authors.affiliation: Pharmaceutical and Pharmacological Sciences Department, University of Padova, 35122 Padova, Italy.
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Pasut
authors.affiliation: Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, 08036 Barcelona, Catalonia, Spain ; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Catalonia, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Rimola
authors.affiliation: Liver Unit, Hospital Clinic Barcelona, IDIBAPS, University of Barcelona, 08036 Barcelona, Catalonia, Spain ; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Catalonia, Spain.
authors.forename: Miquel
authors.initials: M
authors.lastname: Navasa
authors.affiliation: Centre Hepato-Biliaire, AP-P-HP Hôpital Paul Brousse, Inserm U776, Université Paris Sud, Villejuif, 75008 Paris, France.
authors.forename: René
authors.initials: R
authors.lastname: Adam
authors.affiliation: Experimental Pathology Department, Institute of Biomedical Research of Barcelona (IIBB-CSIC), 08036 Barcelona, Catalonia, Spain ; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Catalonia, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Roselló-Catafau
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D050377:Cold Ischemia; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008930:Mitochondria, Liver / Q000473:pathology* / Q000648:ultrastructure; D008970:Molecular Weight; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D000637:Transaminases / Q000378:metabolism
chemical_list: D011092:Polyethylene Glycols; D000637:Transaminases