title: Human Ex-Vivo Liver Model for Acetaminophen-induced Liver Damage.
abstract: Reliable test systems to identify hepatotoxicity are essential to predict unexpected drug-related liver injury. Here we present a human ex-vivo liver model to investigate acetaminophen-induced liver injury. Human liver tissue was perfused over a 30 hour period with hourly sampling from the perfusate for measurement of general metabolism and clinical parameters. Liver function was assessed by clearance of indocyanine green (ICG) at 4, 20 and 28 hours. Six pieces of untreated human liver specimen maintained stable liver function over the entire perfusion period. Three liver sections incubated with low-dose acetaminophen revealed strong damage, with ICG half-lives significantly higher than in non-treated livers. In addition, the release of microRNA-122 was significantly higher in acetaminophen-treated than in non-treated livers. Thus, this model allows for investigation of hepatotoxicity in human liver tissue upon applying drug concentrations relevant in patients.
authors.affiliation: Department for Gastroenterology and Hepatology, Center for Internal Medicine, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schreiter
authors.affiliation: Department for Gastroenterology and Hepatology, Center for Internal Medicine, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Jan-Peter
authors.initials: JP
authors.lastname: Sowa
authors.affiliation: Department for Gastroenterology and Hepatology, Center for Internal Medicine, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Schlattjan
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Treckmann
authors.affiliation: Department of General, Visceral and Transplantation Surgery, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Paul
authors.affiliation: Department of Clinical Chemistry, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Strucksberg
authors.affiliation: Institute of Pathology, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Hideo A
authors.initials: HA
authors.lastname: Baba
authors.affiliation: Institute of Pathology, University Hospital Cologne, Cologne, Germany.
authors.forename: Margarete
authors.initials: M
authors.lastname: Odenthal
authors.affiliation: Rodos BioTarget GmbH, Medical Park Hannover, Hannover, Germany.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Gieseler
authors.affiliation: Department for Gastroenterology and Hepatology, Center for Internal Medicine, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.affiliation: University of Louisville Health Sciences Center, Louisville, Kentucky, USA.
authors.forename: Gavin E
authors.initials: GE
authors.lastname: Arteel
authors.affiliation: Department for Gastroenterology and Hepatology, Center for Internal Medicine, University Hospital, University Duisburg-Essen, Essen, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: Canbay
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000235:genetics; D005260:Female; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D008954:Models, Biological; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D004272:DNA, Mitochondrial; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D000082:Acetaminophen