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

Abstract

PM_2.5 is a known threat to human health. For example, PM_2.5 can impair brain health by damaging neurons. In this work, a model PM_2.5 particle library was employed to investigate the role of PM_2.5 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 PM_2.5 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 PM_2.5 particles loaded with Al³⁺ at an environmentally relevant concentration.