ArticleBiomolecules & therapeutics2026
Mechanistic Insights into Nrf2 Activation and Oxidative Stress Responses of Per- and Polyfluoroalkyl Substances (PFAS) in Human Keratinocytes.
Article in Biomolecules & therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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3 authors.
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Abstract
Per- and polyfluoroalkyl substances (PFAS) are widely used in consumer products for their hydrophobic and chemical stability, yet their dermatotoxicological effects remain underexplored. This study investigated the ability of representative PFAS (PFBS, PFBA, PFHpA, PFOA, PFNA, PFDA, 4:2 FTOH, and 6:2 FTOH) to activate the Nrf2-Keap1-ARE signaling pathway and induce oxidative stress in human keratinocytes. Results revealed that PFOA and PFHpA tested positive for the KeratinoSens™ assay, while PFNA showed borderline activity. PFNA and 6:2 FTOH produced the highest ROS increases at sub-cytotoxic levels, decreasing at higher doses, suggesting cytotoxic stress. PFHpA, PFOA, PFBS, PFBA, 4:2 FTOH and PFDA induced relatively minor fluctuations in ROS across all concentrations. Although previously reported as negative in the murine Local Lymph Node Assay (LLNA), PFOA tested positive in both KeratinoSens™ and ROS assays, indicating activation of oxidative stress-driven cellular pathways distinct from classical immune sensitization mechanisms.
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