Environ Int. 2026 Jan 24;208:110102. doi: 10.1016/j.envint.2026.110102. Online ahead of print.
ABSTRACT
Perfluorooctanoic acid (PFOA) and perfluorobutyric acid (PFBA), as representative long-chain and short-chain per- and polyfluoroalkyl substances (PFAS), are widely distributed in the environment. These compounds can interact with nanoplastics (NPs) to form complex mixed pollutants, posing potential threats to aquatic organisms and human health. The nervous system, characterized by high sensitivity and energy dependence, is particularly vulnerable to such pollutants. However, the mechanisms underlying neurological toxicity induced by co-exposure to PFOA, PFBA, and NPs remain largely unclear. In this study, zebrafish larvae and human neuroblastoma SH-SY5Y cells were employed as model systems to systematically evaluate the effects of PFOA and PFBA, alone or in combination with NPs, on neural development, behavior, cell viability, mitochondrial function, and autophagy. The results demonstrated that NPs exhibited a significantly higher adsorption capacity for PFOA than for PFBA, and that co-exposure exacerbated neurodevelopmental impairments, behavioral abnormalities, and reductions in cell viability. At the molecular level, co-exposure markedly inhibited the PINK1/Parkin-mediated mitophagy pathway, resulting in mitochondrial damage accumulation, disruption of energy metabolism, and blockade of autophagic flux. Through PINK1 overexpression and pharmacological activation experiments, the pivotal role of the PINK1/Parkin-mediated mitophagy pathway in mitigating neurotoxicity was functionally validated. Collectively, this study elucidates the molecular mechanism by which co-exposure to PFOA, PFBA, and NPs induces neurotoxicity via suppression of mitophagy. These findings identify a potential molecular target for the prevention and treatment of PFAS- and NPs-induced neurological injury and provide valuable theoretical and experimental evidence for evaluating the neurotoxic risks of mixed environmental pollutants.
PMID:41616538 | DOI:10.1016/j.envint.2026.110102