Imperial College London
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ProfessorHectorKeun

Faculty of Medicine, Department of Surgery & Cancer

Professor of Biochemistry
 
 
 
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Contact

 

+44 (0)20 7594 3161h.keun

 
 
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Location

 

officesInstitute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Rodrigues:2018:10.1007/s00204-018-2214-z,
author = {Rodrigues, RM and Kollipara, L and Chaudhari, U and Sachinidis, A and Zahedi, RP and Sickmann, A and Kopp-Schneider, A and Jiang, X and Keun, H and Hengstler, J and Oorts, M and Annaert, P and Hoeben, E and Gijbels, E and De, Kock J and Vanhaecke, T and Rogiers, V and Vinken, M},
doi = {10.1007/s00204-018-2214-z},
journal = {Archives of Toxicology},
pages = {1939--1952},
title = {Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures},
url = {http://dx.doi.org/10.1007/s00204-018-2214-z},
volume = {92},
year = {2018}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Bosentan is well known to induce cholestatic liver toxicity in humans. The present study was set up to characterize the hepatotoxic effects of this drug at the transcriptomic, proteomic, and metabolomic levels. For this purpose, human hepatoma-derived HepaRG cells were exposed to a number of concentrations of bosentan during different periods of time. Bosentan was found to functionally and transcriptionally suppress the bile salt export pump as well as to alter bile acid levels. Pathway analysis of both transcriptomics and proteomics data identified cholestasis as a major toxicological event. Transcriptomics results further showed several gene changes related to the activation of the nuclear farnesoid X receptor. Induction of oxidative stress and inflammation were also observed. Metabolomics analysis indicated changes in the abundance of specific endogenous metabolites related to mitochondrial impairment. The outcome of this study may assist in the further optimization of adverse outcome pathway constructs that mechanistically describe the processes involved in cholestatic liver injury.
AU  - Rodrigues,RM
AU  - Kollipara,L
AU  - Chaudhari,U
AU  - Sachinidis,A
AU  - Zahedi,RP
AU  - Sickmann,A
AU  - Kopp-Schneider,A
AU  - Jiang,X
AU  - Keun,H
AU  - Hengstler,J
AU  - Oorts,M
AU  - Annaert,P
AU  - Hoeben,E
AU  - Gijbels,E
AU  - De,Kock J
AU  - Vanhaecke,T
AU  - Rogiers,V
AU  - Vinken,M
DO  - 10.1007/s00204-018-2214-z
EP  - 1952
PY  - 2018///
SN  - 0340-5761
SP  - 1939
TI  - Omics-based responses induced by bosentan in human hepatoma HepaRG cell cultures
T2  - Archives of Toxicology
UR  - http://dx.doi.org/10.1007/s00204-018-2214-z
UR  - https://www.ncbi.nlm.nih.gov/pubmed/29761207
UR  - http://hdl.handle.net/10044/1/60716
VL  - 92
ER  -
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