A metabolomic analysis of zebrafish embryos exposed to PFOS inducing neurotoxicity

다국어 초록 (Multilingual Abstract)

Perfluorooctanesulfonic acid (PFOS) is a persistent organic pollutant that has been widely used in consumer products. Recent studies revealed that PFOS disrupts or penetrates the blood-brain barrier, but the mode of action is still unclear. In this work, the mechanism of PFOS induced neurotoxicity was investigated using zebrafish (Danio rerio) as a model organism and liquid chromatography-mass spectrometry (LC-MS) based metabolomics. Zebrafish embryos are divided into four groups, which consist of a single control group and three exposure groups at concentrations of 1, 5, 10 μM PFOS. Identified and quantified metabolites by LC-MS were subjected to partial least-squares discriminant analysis (PLS-DA) and hierarchical clustering. Control and exposure groups were separated in PLS-DA, and hierarchical clustering classified metabolites into three clusters according to their concentration change. Annotation of affected biological pathways using KEGG database revealed that the arachidonic acid metabolism, tryptophan metabolism, and alanine, aspartate, glutamate metabolism are affected by PFOS exposure. Disruption of the arachidonic acid and tryptophan metabolisms by PFOS induces the inflammatory reactions that may damage the neural system. Also, impact on the alanine, aspartate, glutamate metabolism can lead to neurotoxicity by abnormal regulation of important neurotransmitters, glutamic acid and γ -aminobutyric acid. Overall, this study showed that neurotoxicity of PFOS can be exerted by neuroinflammation and disruption of the neurotransmitter pathways.