Assessing biological effects of fluoxetine in developing zebrafish embryos using gas chromatography-mass spectrometry based metabolomics. (December 2017)

• Record Type: Journal Article
• Authors: Mishra, Priti; Gong, Zhiyuan; Kelly, Barry C.
• Is Part Of: Chemosphere. Volume 188(2017)
• Page Start: 157
• Page End: 167
• Publication Date: 2017-12
• Subjects: GC-MS -- Metabolomics -- Fluoxetine -- Zebrafish embryos -- Amino acid metabolism; Pollution -- Periodicals; Pollution -- Physiological effect -- Periodicals; Environmental sciences -- Periodicals; Atmospheric chemistry -- Periodicals; 551.511
• DOI: 10.1016/j.chemosphere.2017.08.149
• Languages: English
• ISSNs: 0045-6535

Abstract

Abstract: Continuous low-dose exposure of pharmaceutically active compounds (PhACs) in aquatic ecosystems is a concern worldwide. In this study, we utilized a gas chromatography mass spectrometry (GC-MS) based metabolomics approach to assess endogenous metabolite changes in developing zebrafish embryos exposed to different concentrations of the widely used antidepressant, fluoxetine. Embryos were exposed from 2 h post fertilization (hpf) until 96 hpf. Using the Fiehn GC-MS library, a total of 31 metabolites were positively identified in embryos. Statistical analyses revealed significant dysregulation of 11 metabolites in fluoxetine exposed embryos. Metabolite classes that were significantly altered included, amino acids, monosaccharides, glycerophosphates, fatty acids, carboxylic acid derivatives and sugars. Concentrations of amino acids, maltose, d -malic acid, 3-phosphoglycerate andd -glucose were significantly reduced in exposed embryos. Conversely, concentrations of citric acid were in some cases significantly elevated in exposed embryos. Metabolic pathway analysis revealed perturbation of five main pathways, including (i) alanine, aspartate and glutamate metabolism, (ii) phenylalanine, tyrosine and tryptophan biosynthesis, (iii) phenylalanine metabolism. (iv) tyrosine metabolism and (v) starch and sucrose metabolism. The results indicate fluoxetine exposure causes perturbation of energy and amino acid metabolism, which may adversely impact embryogenesis due to depletion of energy reserves during this period. Also, the observed alterations in aspartic acid, phenylalanine and tyrosine in fluoxetine exposed embryos suggests potential disruption of normal neurobehavioral and liver function. The results further demonstrate that GC-MS based metabolomics is an effective approach for assessing toxicodynamics and threshold effect levels of environmental pollutants in aquatic organisms. Highlights: GC-MS based metabolomics was used to assess fluoxetine toxicity in zebrafish embryos. 31 endogenous metabolites were positively identified. 11 metabolites were significantly altered in fluoxetine exposed embryos. Amino acids, fatty acids and glucose were downregulated in exposed embryos. Citric acid was upregulated in exposed embryos. Pathway analysis revealed perturbation of energy and amino acid metabolism.