Suitability of human HepaRG cells and liver spheroids as in vitro model to investigate the bioactivation of the organothiophosphate pesticide parathion

Toxicol In Vitro. 2024 Mar 21:105811. doi: 10.1016/j.tiv.2024.105811. Online ahead of print.ABSTRACTOrganophosphorus compounds (OP) constitute a large group of chemicals including pesticides and nerve agents. Organothiophosphate pesticides require cytochrome P450-mediated oxidative desulphuration in the liver to form corresponding oxons, which are potent inhibitors of the enzyme acetylcholinesterase (AChE). Human HepaRG cells are a promising tool to study liver-specific functions and have been shown to maintain drug metabolizing enzymes. This research describes for the first time the in vitro metabolic activation of an organothiophosphate to its active oxon by two different HepaRG cell-based models. Monolayer cultures and liver spheroids were exposed to the model OP parathion and the quantification of the corresponding oxon was performed with an AChE inhibition assay. Our results showed a time- and dose-dependent cytochrome P450 catalyzed bioactivation and a superior metabolism capacity of the monolayer HepaRG model in comparison with the liver spheroids. Finally, HepaRG cells can be assessed as a metabolically competent cell model intermediate between cell-free preparations and intact animals and as suitable to study OP metabolism in the human liver.PMID:38521251 | DOI:10.1016/j.tiv.2024.105811
Source: Toxicology in Vitro - Category: Toxicology Authors: Source Type: research