Metabolomics analysis of the toxicity pathways of triphenyl phosphate in HepaRG cells and comparison to oxidative stress mechanisms caused by acetaminophen

Toxicology in Vitro : an International Journal Published in Association with BIBRA
Nele Van den EedeTamara Vanhaecke

Abstract

Since the publication of REACH guidelines, the need for in vitro tools for toxicity testing has increased. We present here the development of a hepatotoxicity testing tool using human HepaRG cell cultures and metabolomics. HepaRG cells were exposed to either 4mM acetaminophen (APAP) as reference toxicant for oxidative stress or 50 μM triphenyl phosphate (TPHP) as toxicant with unknown toxicity pathways (TPs). After 72 h exposure, cells were subjected to quenching and liquid-liquid extraction which resulted in a polar and an apolar fraction. Analysis of fractions was performed by ultrahigh performance liquid chromatography-high resolution tandem mass spectrometry (UHPLC-QTOF-MS). Significantly up or down regulated metabolites were selected by univariate statistics prior to identification. In order to obtain robust and specific TP biomarkers, the experiment was also repeated using a different culture medium composition to assess which metabolites show consistent changes. Potential biomarkers belonging to different TPs were found for APAP and TPHP. For APAP, the biomarkers were related to a decrease in unsaturated phospholipids, and for TPHP to an accumulation of phosphoglycerolipids and increase of palmitoyl lysophosphatidylcholi...Continue Reading

References

Jan 1, 1988·Archives of Toxicology·T Nishimaki-MogamiM Sato
Feb 13, 2001·Journal of Clinical Epidemiology·E Skovlund, G U Fenstad
Jul 18, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Stefan WilkeningAugustinus Bader
Jan 13, 2006·Therapeutic Drug Monitoring·Colin A SmithGary Siuzdak
Jan 24, 2007·Chemico-biological Interactions·André GuillouzoChristiane Guguen-Guillouzo
Jun 23, 2007·Nucleic Acids Research·Eoin FahyShankar Subramaniam
Oct 24, 2007·Journal of Lipid Research·Myoung Sook HanMyung-Shik Lee
Oct 30, 2007·Analytical Biochemistry·Huifeng WuMark R Viant
Feb 25, 2009·The Analyst·Helen M ParsonsMark R Viant
Dec 19, 2009·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Sébastien AnthérieuAndré Guillouzo
Mar 24, 2010·BMC Bioinformatics·Sebastian WolfSteffen Neumann
May 13, 2010·Journal of Pharmacological and Toxicological Methods·Marc LübberstedtKatrin Zeilinger
Jul 28, 2010·Toxicology and Applied Pharmacology·Vidya V IyerMarianthi G Ierapetritou
Sep 8, 2010·Environmental Toxicology and Chemistry·Gerald T AnkleyDaniel L Villeneuve
Feb 15, 2011·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Mitchell R McGillHartmut Jaeschke
Jan 17, 2012·Analytical Chemistry·Laetitia ShintuMarc-Emmanuel Dumas
Feb 15, 2012·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Daniel MuellerFozia Noor
May 31, 2012·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Sébastien AnthérieuAndré Guillouzo
Jun 1, 2013·Journal of Applied Toxicology : JAT·Mounir BouhifdLiang Zhao
Sep 3, 2013·Journal of Chemical Information and Modeling·Lochana C MenikarachchiDavid F Grant
May 9, 2014·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Johannes EichnerRainer Lehmann

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Citations

Oct 22, 2016·Environmental Science & Technology·Nele Van den EedeAdrian Covaci
Jul 13, 2018·Metallomics : Integrated Biometal Science·Qixiao ZhaiWei Chen
Mar 8, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sabine U VorrinkVolker M Lauschke
Aug 30, 2018·Archives of Toxicology·Matthias CuykxAdrian Covaci
Mar 20, 2021·Analytica Chimica Acta·M Hernández-MesaG Dervilly
Aug 28, 2020·Neurotoxicology and Teratology·Mathan RameshSathisaran Umamaheswari

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