An in silico structural approach to characterize human and rainbow trout estrogenicity of mycotoxins: Proof of concept study using zearalenone and alternariol

The mycotoxins zearalenone and alternariol may contaminate food and feed raising toxicological concerns due to their estrogenicity. Inter-species differences in their toxicokinetics and toxicodynamics may occur depending on evolution of taxa-specific traits. As a proof of principle, this manuscript investigates the comparative toxicodynamics of zearalenone, its metabolites (alpha-zearalenol and beta-zearalenol), and alternariol with regards to estrogenicity in humans and rainbow trout. An in silico structural approach based on docking simulations, pharmacophore modeling and molecular dynamics was applied and computational results were analyzed in comparison with available experimental data. The differences of estrogenicity among species of zearalenone and its metabolites have been structurally explained. Also, the low estrogenicity of alternariol in trout has been characterized here for the first time. This approach can provide a powerful tool for the characterization of interspecies differences in mycotoxin toxicity for a range of protein targets and relevant compounds for the food- and feed-safety area.