Different cellular mechanism of imidacloprid and acetamiprid by a combined targeted lipidomics and metabolomics approach in Neuro-2a cells.

As commonly used neonicotinoid insecticides for pest control, imidacloprid (IMI) and acetamiprid (ACE) posed neurotoxicity effects on living organisms. However, researches of the differences in toxicity mechanism between these two neonicotinoid insecticides are still limited. In this study, different cellular metabolism perturbations and redox homeostasis damages induced by IMI and ACE exposure in Neuro-2a cells were investigated. Distinct elevation of lactate dehydrogenase (LDH) activity and caspase 7 level demonstrated the influences on necrosis and apoptosis. There were 21 and 12 metabolites screened out as potential biomarkers after IMI and ACE exposure, including lipids and amino acids. Remarkable decrease of lipid hydroperoxides (LOOH) and increase of reactive oxygen species (ROS) generation were found only in the ACE20 group. Interference with glutathione metabolism pathway was further validated by detecting GPx (glutathion peroxidase), GSH (reduced glutathione) and GSSG (oxidized glutathione) levels. Taken together, the metabolic interferences and oxidative damages in ACE20 group were significantly different from the other three exposure groups. These results help to explore the toxicity mechanism of neonicotinoid insecticides from multiple perspectives. This study provides scientific basis for evaluating toxicity of different neonicotinoid insecticides.