Schreiter, Thomas, Sowa, Jan-Peter ORCID: 0000-0003-2943-0015, Schlattjan, Martin, Treckmann, Juergen, Paul, Andreas, Strucksberg, Karl-Heinz, Baba, Hideo A., Odenthal, Margarete, Gieseler, Robert K., Gerken, Guido, Arteel, Gavin E. and Canbay, Ali ORCID: 0000-0001-6069-7899 (2016). Human Ex-Vivo Liver Model for Acetaminophen-induced Liver Damage. Sci Rep, 6. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schreiter, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sowa, Jan-PeterUNSPECIFIEDorcid.org/0000-0003-2943-0015UNSPECIFIED
Schlattjan, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Treckmann, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paul, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Strucksberg, Karl-HeinzUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baba, Hideo A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Odenthal, MargareteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gieseler, Robert K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gerken, GuidoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arteel, Gavin E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Canbay, AliUNSPECIFIEDorcid.org/0000-0001-6069-7899UNSPECIFIED
URN: urn:nbn:de:hbz:38-266376
DOI: 10.1038/srep31916
Journal or Publication Title: Sci Rep
Volume: 6
Date: 2016
Publisher: NATURE PUBLISHING GROUP
Place of Publication: LONDON
ISSN: 2045-2322
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MELD SCORE; FAILURE; INJURY; HEPATOTOXICITY; BIOMARKERS; MICRORNAS; HEPATITIS; TOXICITY; SYSTEMMultiple languages
Multidisciplinary SciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/26637

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