Neonicotinoid insecticides (NNIs) are ubiquitously detected in the environment, yet their comparative neurotoxicity and mechanisms remain insufficiently characterized. This study systematically evaluated the neurotoxic potential of eight common NNIs (imidacloprid, acetamiprid, thiacloprid, thiamethoxam, clothianidin, flonicamid, sulfoxaflor, and imidaclothiz) using human SH-SY5Y cells. Results demonstrated that all tested NNIs significantly reduced cell viability. Mechanistically, NNI exposure triggered excessive reactive oxygen species (ROS) production, inhibited superoxide dismutase (SOD) activity, and elevated malondialdehyde (MDA) levels, indicating severe oxidative stress. Notably, Exposure to NNIs caused a dissipation of mitochondrial membrane potential (MMP) and profoundly disrupted mitochondrial bioenergetics. Analysis of energy metabolism revealed that NNIs suppressed both the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), suggesting an impairment of oxidative phosphorylation and glycolysis. These findings suggested that NNIs induced neurotoxicity through coordinated oxidative stress and mitochondrial dysfunction, resulting in global bioenergetic suppression characterized by concurrent impairment of oxidative phosphorylation and glycolysis. This study provides critical toxicological evidence for the environmental risk assessment of NNIs and underscores their potential impact on human neurological health.
Insecticide resistance in pest control poses a threat to agricultural production and human health. Numerous insect species express genes coding for detoxification enzymes that have broad substrate promiscuity thus conferring resistance to various insecticides. However, whether the homologs of these genes play similar roles in resistance phenotypes of closely related species remains largely unclear. Therefore, this study compares the resistance profiles of three major rice planthopper species (Delphacidae) ( Laodelphax striatellus , Nilaparvata lugens , and Sogatella furcifera ) based on the metabolic activity of their cytochrome P450s. Genome-wide analyses resulted in 68, 70, and 64 P450 genes in L. striatellus , N. lugens , and S. furcifera , respectively. Phylogenetic analyses among these genes found that most resistance-related genes in one species had homologs in other planthopper species. The most resistance-relevant orthogroup ( CYP6ER s) showed higher evolutionary instability than most other groups. RNAi and in vitro metabolism assays revealed that CYP6ER s confers more divergent insecticide resistance profiles among planthopper species than the other two major resistance-related P450 subfamilies ( CYP6AY s and CYP4C61 s). Alphafold-based structural predictions and alignments suggested that P450 orthogroups with higher phylogenetic instability tended to have less structural similarities, resulting in more divergent metabolic profiles. This relationship was also in silico validated on Aphidae aphids and Lepidoptera noctuids. This study proposes combined phylogenetic and toxicogenomic analyses for understanding CYPome-based insecticide resistance convergency and divergency among closely related pests. These findings may improve the accuracy and rationality of chemical pest control.
危险品化学品经营许可证（带存储）