Metabolome analysis of zebrafish embryo exposed to perfluorobutane sulfonate

Abstract

Biomolecular mechanism underlying neurotoxicity of short-chain per- and polyfluoroalkyl substances (PFAS) is largely unknown. The aim of this study is to compare the difference in toxicity of perfluorooctanesulfonic acid (PFOS) and perfluorobutanesulfonic acid (PFBS), with respect to neurotoxicity using integrated multi-omics analysis. Zebrafish embryos were exposed to 0-100 μM PFOS and 0-50000 μM PFBS at 4-120 hours-post fertilization (hpf), and developmental neurotoxicity was evaluated. Biomolecules (i.e. transcriptome, proteome, and metabolome) of zebrafish embryos were profiled at 120 hpf. Data-driven and knowledge-based integration of multi-omics were applied to uncover biomolecular impact of PFOS and PFBS. The toxicity assessment demonstrated that 10 μM PFOS and 7000 μM PFBS showed the analogous toxic potency based on benchmark dose of mortality and similar neurobehavioral effect. Biomolecular profiles showed the similarities between PFOS and PFBS in oxidative stress, immune response, lipid metabolism and energy metabolism. Likewise, the integrated multi-omics analysis showed dysregulation of various signaling pathways, lipids metabolism, energy metabolism, oxidative stress, calcium ion transport, peroxisome and synapse. In particular, the integrated multi-omics analysis suggested that the biomolecular mechanism underlying neurotoxicity of PFAS is briefly interlinked regardless of chain-length, including perturbation of Ca2+, synapse dysfunction and lipid metabolism with peroxisome. These findings demonstrated the toxicological similarities between PFOS and PFBS with the integration of multi-omics, and broaden the biomolecular understanding of PFAS-induced neurotoxicity in zebrafish embryos.