Daily intake of antioxidants ameliorates PM(2.5)-induced neuronal injury in mice.

OBJECTIVE: Fine particulate matter (PM(2.5)) within polluted air is a significant health risk and a strong oxidant. Even exposure to low-level PM(2.5) (at or below the WHO standard) is linked to neuroinflammatory, oxidative stress and the development of neurological disorders in the long term. This study aimed to investigate the prophylactic effects of antioxidant supplementation on mitigating sub-chronic exposure to low-level PM(2.5)-induced brain pathology in mice. MATERIALS AND METHODS: Mice were exposed to traffic-derived PM(2.5) (5 μg/day) collected from a highway in Sydney, Australia, once daily for 3 weeks, while receiving antioxidant, vitamin C (10 mM) or N-acetylcysteine (NAC, 40 mM), via drinking water. Oxidative stress and neuronal loss were assessed across different brain regions. In vitro experiments were conducted to evaluate neuronal integrity and mitochondrial function by VC and NAC treatment in PM(2.5)-exposed primary neurons. RESULTS: Sub-chronic PM(2.5) exposure increased lipid peroxidation and reduced neurofilament density in the cortex, hippocampus, and thalamus, which were mitigated by VC and NAC supplementation. Although oxidative stress (ROS accumulation and increase in 4-HNE) was prevented in all brain regions by VC and NAC, neurofilament loss remained. In vitro, VC and NAC reduced mitochondrial ROS production, which in turn improved neuronal and synaptic survival, suggesting mitochondria-dependent oxidative stress plays a central role in PM(2.5)-induced neurotoxicity at least in the cortex and hippocampus. CONCLUSION: Mitochondria-dependent oxidative stress is a key mechanism underlying PM(2.5)-induced neurotoxicity, which can be attenuated by VC and NAC supplementation. This highlights a potential prophylactic strategy to partially protect the brain from polluted air.