Using 3D HepaRG cultures to assess hepatic metabolism

The Cell Biology and In Vitro Toxicology group is happy to share its latest publication from a collaborative project between the FHNW Institute for Chemistry and Bioanalytics and Unisanté Lausanne (Group of Nancy Hopf), supported by the Swiss Centre for Applied Human Toxicology (SCAHT).

The team demonstrated the potential of in vitro liver models to predict hepatic clearance of chemicals in the context of neurotoxicity assessment.

First, the team confirmed the presence of the relevant enzymes alcohol dehydrogenase (ADH1A/B/C) and aldehyde dehydrogenase (ALDH2) in the cell model. Furthermore, they showed active solvent metabolization by 3D HepaRG using LC-MS/MS quantification.

3D HepaRG were stained for ADH1A/B/C(green), ALDH2 (red), and counterstained with DAPI (blue). Scale bar representing 100 μm.

Lastly, they integrated the measured in vitro intrinsic hepatic clearance into a toxicokinetic model, whereby the predicted results were comparable to existing experimental data from human exposure studies.

Integration into toxicokinetic model

The in vitro model helps close the knowledge gap in metabolism and systemic toxicity of glycol ethers and may support the safety assessment of solvents with relevant occupational exposures. 

The work was published in the journal of Pharmacology Research & Perspectives.