Enantioselective effects of chiral prothioconazole and its metabolites: Oxidative stress in HepG2 cells and lysozyme activity

Chiral pesticides may exhibit enantioselectivity in terms of bioconcentration, environmental fate, and reproductive toxicity. Here, chiral prothioconazole and its metabolites were selected to thoroughly investigate their enantioselective toxicity and mechanisms at the molecular and cellular levels. Multispectral techniques revealed that the interaction between chiral PTC/PTCD and lysozyme resulted in the formation of a complex, leading to a change in the conformation of lysozyme. Meanwhile, the effect of different conformations of PTC/PTCD on the conformation of lysozyme differed, and its metabolites were able to exert a greater effect on lysozyme compared to prothioconazole. Moreover, the S-configuration of PTCD interacted most strongly with lysozyme. This conclusion was further verified by DFT calculations and molecular docking as well. Furthermore, the oxidative stress indicators within HepG2 cells were also affected by chiral prothioconazole and its metabolites. Specifically, S-PTCD induced more substantial perturbation of the normal oxidative stress processes in HepG2 cells, and the magnitude of the perturbation varied significantly among different configurations (P > 0.05). Overall, chiral prothioconazole and its metabolites exhibit enantioselective effects on lysozyme conformation and oxidative stress processes in HepG2 cells. This work provides a scientific basis for a more comprehensive risk assessment of the environmental behaviors and effects caused by chiral pesticides, as well as for the screening of highly efficient and less biotoxic enantiomeric monomers.