Neonicotinoid insecticides induced neurotoxicity in SH-SY5Y cells via oxidative stress and mitochondrial dysfunction

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.