Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Schreiter, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Sowa, Jan-Peter UNSPECIFIED orcid.org/0000-0003-2943-0015 UNSPECIFIED Schlattjan, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Treckmann, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Paul, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Strucksberg, Karl-Heinz UNSPECIFIED UNSPECIFIED UNSPECIFIED Baba, Hideo A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Odenthal, Margarete UNSPECIFIED UNSPECIFIED UNSPECIFIED Gieseler, Robert K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gerken, Guido UNSPECIFIED UNSPECIFIED UNSPECIFIED Arteel, Gavin E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Canbay, Ali UNSPECIFIED orcid.org/0000-0001-6069-7899 UNSPECIFIED
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:	Keywords Language MELD SCORE; FAILURE; INJURY; HEPATOTOXICITY; BIOMARKERS; MICRORNAS; HEPATITIS; TOXICITY; SYSTEM Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26637