Comparative neurotoxicities of PFOS and its alternative F-53B based on acetylcholinesterase

The novel perfluorooctane sulfonate (PFOS) alternative, 6:2 chlorinated polyfluorinated ether sulfonate (F-53B) was found in various environments showing even higher levels than PFOS. However, its neurotoxicity and the possible molecular mechanisms remain largely unknown. Acetylcholinesterase (AChE) is a critical enzyme that hydrolyzes the neurotransmitter acetylcholine (ACh) and regulates nerve conduction. With zebrafish as the model animal and AChE as the target, this study comparatively investigated the in vitro and in vivo neurotoxicity of PFOS and F-53B, uncovering possible induced mechanisms. Our results indicated PFOS and F-53B could increase AChE activity to induce neurotoxicity in zebrafish brain, whereas the induced effect of F-53B lasted longer than PFOS. We found that oxidative stress was one of the mechanisms underlying PFOS and F-53B neurotoxicity. PFOS and F-53B loosened the AChE protein skeleton, thereby changing the AChE secondary structure. F-53B exhibited greater effects on the secondary structure content than PFOS. PFOS and F-53B showed approximately one binding site on AChE, spontaneously binding to various AChE amino acid residues through different forces. In contrast, the hydrogen bond distance formed by PFOS was longer, resulting in a weaker binding force to AChE than F-53B The study expands our comprehension of the molecular mechanisms underlying PFOS and F-53B neurotoxicity and offers novel insights into the safety of PFOS substitutes.