Research team
The development of a metabolomics-based in vitro model for human hepatotoxicity
Abstract
In order to comply with the REACH-regulations (Registration Evaluation and Authorization of Chemicals) and to improve animal welfare, a human based in vitro model to investigate the hepatotoxicity of new chemical entities (NCEs) will be developed. The designed model is based on an innovative approach combining in vitro methodology with LC-MS metabolomics, a recent – omics domain that examines alterations in the endogenous metabolic profile of cells and organisms. The basis of our model is the hepatic human HepaRG® cell line, which closely resembles primary hepatocytes in terms of metabolic capacity and toxicological response. In a first phase, the model will be developed by exposing HepaRG cell cultures to well known hepatotoxic compounds, such as acetaminophen, valproic acid, fluoxetine, bosentan and aflatoxine B1; the intracellular profile of the endogenous metabolites will be investigated in an untargeted approach using Liquid Chromatography coupled to High Resolution Mass Spectrometry (LC-QTOF-MS). Differences between the metabolic profiles of exposed and unexposed cells will be examined using bioinformatics tools in order to identify possible biomarkers characteristic for the multiple hepatotoxic modes of action (MoA). A database containing the reference compounds, their MoAs and the corresponding specific biomarkers will be used in a targeted approach to investigate the hepatotoxic MoA of NCEs, including pharmaceutical and/or industrial compounds.Researcher(s)
- Promoter: Covaci Adrian
- Co-promoter: Laukens Kris
- Fellow: Cuykx Matthias
Research team(s)
Project type(s)
- Research Project
The development of a metabolomics-based in vitro model for human hepatotoxicity.
Abstract
In order to comply with the REACH-regulations (Registration Evaluation and Authorization of Chemicals) and to improve animal welfare, a human based in vitro model to investigate the hepatotoxicity of new chemical entities (NCEs) will be developed. The designed model is based on an innovative approach combining in vitro methodology with LC-MS metabolomics, a recent – omics domain that examines alterations in the endogenous metabolic profile of cells and organisms. The basis of our model is the hepatic human HepaRG® cell line, which closely resembles primary hepatocytes in terms of metabolic capacity and toxicological response. In a first phase, the model will be developed by exposing HepaRG cell cultures to well known hepatotoxic compounds, such as acetaminophen, valproic acid, fluoxetine, bosentan and aflatoxine B1; the intracellular profile of the endogenous metabolites will be investigated in an untargeted approach using Liquid Chromatography coupled to High Resolution Mass Spectrometry (LC-QTOF-MS). Differences between the metabolic profiles of exposed and unexposed cells will be examined using bioinformatics tools in order to identify possible biomarkers characteristic for the multiple hepatotoxic modes of action (MoA). A database containing the reference compounds, their MoAs and the corresponding specific biomarkers will be used in a targeted approach to investigate the hepatotoxic MoA of NCEs, including pharmaceutical and/or industrial compounds.Researcher(s)
- Promoter: Covaci Adrian
- Co-promoter: Laukens Kris
- Fellow: Cuykx Matthias
Research team(s)
Project type(s)
- Research Project