Universität zu Köln

Rodrigues, Robim M., Heymans, Anja, De Boe, Veerle, Sachinidis, Agapios, Chaudhari, Umesh ORCID: 0000-0002-7743-4371, Govaere, Olivier ORCID: 0000-0002-4426-6930, Roskams, Tania, Vanhaecke, Tamara ORCID: 0000-0002-6685-7299, Rogiers, Vera ORCID: 0000-0003-0635-7740 and De Kock, Joery ORCID: 0000-0002-4078-4896 (2016). Toxicogenomics-based prediction of acetaminophen-induced liver injury using human hepatic cell systems. Toxicol. Lett., 240 (1). S. 50 - 60. CLARE: ELSEVIER IRELAND LTD. ISSN 1879-3169

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Abstract

Primary human hepatocytes (hHEP), human HepaRG and HepG2 cell lines are the most used human liver-based in vitro models for hepatotoxicity testing, including screening of drug-induced liver injury (DILI)-inducing compounds. hHEP are the reference hepatic in vitro system, but their availability is limited and the cells available for toxicology studies are often of poor quality. Hepatic cell lines on the other hand are highly proliferative and represent an inexhaustible hepatic cell source. However, these hepatoma-derived cells do not represent the population diversity and display reduced hepatic metabolism. Alternatively, stem cell-derived hepatic cells, which can be produced in high numbers and can differentiate into multiple cell lineages, are also being evaluated as a cell source for in vitro hepatotoxicity studies. Human skin-derived precursors (hSKP) are post-natal stem cells that, after conversion towards hepatic cells (hSKP-HPC), respond to hepatotoxic compounds in a comparable way as hHEP. In the current study, four different human hepatic cell systems (hSKP-HPC, hHEP, HepaRG and HepG2) are evaluated for their capacity to predict hepatic toxicity. Their hepatotoxic response to acetaminophen (APAP) exposure is compared to data obtained from patients suffering from APAP-induced acute liver failure (ALF). The results indicate that hHEP, HepaRG and hSKP-HPC identify comparable APAP-induced hepatotoxic functions and that HepG2 cells show the slightest hepatotoxic response. Pathway analyses further points out that HepaRG cells show the highest predicted activation of the functional genes related to 'damage of liver', followed by hSKP-HPC and hHEP cells that generated similar results. HepG2 did not show any activation of this function. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rodrigues, Robim M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heymans, Anja UNSPECIFIED UNSPECIFIED UNSPECIFIED De Boe, Veerle UNSPECIFIED UNSPECIFIED UNSPECIFIED Sachinidis, Agapios UNSPECIFIED UNSPECIFIED UNSPECIFIED Chaudhari, Umesh UNSPECIFIED orcid.org/0000-0002-7743-4371 UNSPECIFIED Govaere, Olivier UNSPECIFIED orcid.org/0000-0002-4426-6930 UNSPECIFIED Roskams, Tania UNSPECIFIED UNSPECIFIED UNSPECIFIED Vanhaecke, Tamara UNSPECIFIED orcid.org/0000-0002-6685-7299 UNSPECIFIED Rogiers, Vera UNSPECIFIED orcid.org/0000-0003-0635-7740 UNSPECIFIED De Kock, Joery UNSPECIFIED orcid.org/0000-0002-4078-4896 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-287622
DOI:	10.1016/j.toxlet.2015.10.014
Journal or Publication Title:	Toxicol. Lett.
Volume:	240
Number:	1
Page Range:	S. 50 - 60
Date:	2016
Publisher:	ELSEVIER IRELAND LTD
Place of Publication:	CLARE
ISSN:	1879-3169
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DRUG-METABOLISM; STEM-CELLS; HEPATOTOXICITY; TOXICITY; DATABASE; FAILURE; MODEL Multiple languages Toxicology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/28762