A comprehensive untargeted metabolomics study in zebrafish embryos exposed to perfluorohexane sulfonate (PFHxS)

Perfluorohexane sulfonate (PFHxS) is one of the short-chain perfluoroalkyl substances (PFASs), and frequently de-tected in the environment, humans, and wildlife, but a detailed mechanism of toxicity has been not studied yet. In this study, a comprehensive set of polar metabolites was determined in i) the developing zebrafish embryo (4, 24, 48, 72, and 120 h post fertilization (hpf)), and ii) in the developing zebrafish after exposure to four concentrations of PFHxS (0.3, 1, 3, and 10 mu M) from 24to 120 hpf. The temporal (developmental stages) distribution of individual me-tabolites (541 metabolites) in zebrafish provided comprehensive information about the biological roles of various me-tabolites in developing vertebrates such as genetic processes, energy metabolism, protein metabolism, and glycerophospholipid metabolism. PFHxS in zebrafish embryo showed time-and concentration-dependent bioaccumu-lation, and no baseline toxicity was expected at the test concentrations. However, effects on many metabolites were already observed at the lowest tested concentration (0.3 mu M), and these effects were more pronounced at later stages of developmental (72 and 120 hpf). In addition to oxidative stress, the effects of PFHxS on zebrafish embryos were re-lated to the disruption of the fatty acid oxidation (FAO), sugar metabolism, and other metabolic pathways. This study gave new and comprehensive information on the underlying mechanism of the toxicity of PFHxS.

Automated summary

This study provides detailed insights into the toxic mechanism of PFHxS, showing time and concentration-dependent bioaccumulation in zebrafish embryos and adverse effects on fatty acid oxidation, sugar metabolism, and other metabolic pathways.