Investigating the neurotoxic effects of NM-300K silver nanoparticles: in vitro and in vivo studies

Silver nanoparticles (AgNPs) have gained widespread use in various applications, but their potential neurotoxic effects remain a concern. This study investigates the neurotoxicity of NM-300K AgNPs, which are Representative Manufactured Nanomaterials (RMNs), through in vitro assays using NG108-15 neuronal cells and in vivo experiments with BALB/c and Kunming mice. In vitro results showed an IC₅₀ value of 100 µg mL^-1 for NG108-15 cells, with a sub-lethal concentration of 25 µg mL^-1 selected for further analysis. Proteomic analysis identified 96 significantly upregulated proteins, indicating activation of stress response pathways. Behavioral assessments revealed that mice exposed to 0.5 mg kg^-1 day^-1 AgNPs exhibited cognitive deficits, while those receiving 10 mg kg^-1 day^-1 displayed hyperactivity and increased anxiety-like behaviors. Histopathological examinations indicated neuronal vacuolation and loss in the CA3 region of the hippocampus, correlating with behavioral impairments. Biomarker analysis demonstrated significant oxidative stress, as evidenced by elevated reactive oxygen species (ROS) levels, increased interleukin-6, and increased Nrf2 levels. Exposure to high doses of AgNPs also led to reduced total antioxidant capacity (T-AOC), decreased glutathione (GSH), and elevated tumor necrosis factor-alpha (TNF-α), indicating an inflammatory response and activation of apoptotic pathways (caspase-3), suggesting that exposure to AgNPs can lead to neuronal dysfunction and cell death. These findings contribute to understanding the neurotoxic mechanisms of AgNPs, highlighting the need for thorough risk assessments and regulatory measures to mitigate potential health impacts associated with nanoparticle exposure.