Polystyrene modulation of perfluorooctanoic acid toxicity in zebrafish: Transcriptomic and toxicological insights

Perfluorooctanoic acid (PFOA) and microplastics are widespread aquatic pollutants, yet their combined toxicological effects remain unclear. This study investigates how polystyrene (PS) microplastics influence the toxicity of PFOA in zebrafish, focusing on transcriptomic, toxicological, and molecular dynamics insights. Zebrafish were exposed to PFOA alone or with PS of varying sizes (0.2, 2, and 20 μm). PFOA disrupted neurotransmitter release pathways, while PS modulated toxicity in a size-dependent manner. Specifically, 0.2 PS enhanced PFOA-induced inhibition of neurotransmission via activation of G protein-gated potassium channels and inhibition of calcium channels. 2 PS exacerbated disruptions in amino acid metabolism, including histidine, glycine, and arginine pathways. Survival rates decreased with increasing PFOA, and PS-particularly 2 PS and 20 PS-further reduced survival and increased PFOA accumulation. Histopathology revealed significant gut and muscle damage under high PFOA exposure, worsened by PS. Molecular simulations showed that PS increased binding energies and altered protein flexibility, weakening ligand-receptor interactions critical to metabolism and detoxification. Moreover, 20 PS amplified PFOA-induced inhibition of phase II conjugation pathways. Overall, PS significantly alters PFOA bioaccumulation and toxicity, underscoring the environmental risks associated with the co-occurrence of microplastics and persistent organic pollutants in aquatic ecosystems.