Cytotoxic and metabolic effects of organic extracts from airborne fine particulate matter (PM2.5) in neuronal cells

Airborne fine particulate matter (PM_2.5) has been linked to neurological diseases, but its cellular and metabolic effects remain incompletely understood. This study assessed the cytotoxic and metabolic impact of PM_2.5 samples from São Paulo, Brazil, on SH-SY5Y neuroblastoma cells. Even at low toxicity levels (IC₁₀–IC₃₀), PM_2.5 organic extracts induced apoptosis, increased TNF-α secretion, and triggered moderate oxidative responses. Metabolomic analyses revealed a downregulation of energy-producing pathways, including glycolysis and the TCA cycle, along with decreased ATP and phosphocreatine levels. Compensatory adaptations were evident, such as increased proline oxidation, lipid accumulation, and activation of the creatine-phosphocreatine system. One-carbon metabolism was also affected, with changes suggesting suppression of the folate and methionine cycles. Elevated glutathione levels indicated an enhanced antioxidant response. These findings highlight how PM_2.5 disrupts neuronal energy homeostasis and redox balance, offering new insights into the cellular mechanisms of air pollution-related neurotoxicity.