Antagonistic role of Al3+ against PM2.5-induced neurotoxicity via suppression of NADPH oxidase-triggered oxidative stress

PM2.5 is a known threat to human health. For example, PM2.5 can impair brain health by damaging neurons. In this work, a model PM2.5 particle library was employed to investigate the role of PM2.5 compositions in regulating neurotoxicity using the mouse hippocampal neuron cell line HT22 and the human neuroblastoma cell line SH-SY5Y as in vitro models. Our results demonstrated that while Pb2+, Cr(vi) and As(iii) at environmentally relevant concentrations all contributed to neurotoxicity when loaded onto model PM2.5 particles, the loading of Al3+ played an antagonistic role. We further revealed that this antagonistic effect was mediated via suppression of NADPH oxidase-induced cellular reactive oxygen species when cells were exposed to model PM2.5 particles loaded with Al3+ at an environmentally relevant concentration.