title: High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance of Intact Zebrafish Embryos Detects Metabolic Changes Following Exposure to Teratogenic Polymethoxyalkenes from Algae.
abstract: Techniques based on nuclear magnetic resonance (NMR) for imaging and chemical analyses of in vivo, or otherwise intact, biological systems are rapidly emerging and finding diverse applications within a wide range of fields. Very recently, several NMR-based techniques have been developed for the zebrafish as a model animal system. In the current study, the novel application of high-resolution magic angle spinning (HR-MAS) NMR is presented as a means of metabolic profiling of intact zebrafish embryos. Toward investigating the utility of HR-MAS NMR as a toxicological tool, these studies specifically examined metabolic changes of embryos exposed to polymethoxy-1-alkenes (PMAs)-a recently identified family of teratogenic compounds from freshwater algae-as emerging environmental contaminants. One-dimensional and two-dimensional HR-MAS NMR analyses were able to effectively identify and quantify diverse metabolites in early-stage (≤36 h postfertilization) embryos. Subsequent comparison of the metabolic profiles between PMA-exposed and control embryos identified several statistically significant metabolic changes associated with subacute exposure to the teratogen, including (1) elevated inositol as a recognized component of signaling pathways involved in embryo development; (2) increases in several metabolites, including inositol, phosphoryl choline, fatty acids, and cholesterol, which are associated with lipid composition of cell membranes; (3) concomitant increase in glucose and decrease in lactate; and (4) decreases in several biochemically related metabolites associated with central nervous system development and function, including γ-aminobutyric acid, glycine, glutamate, and glutamine. A potentially unifying model/hypothesis of PMA teratogenicity based on the data is presented. These findings, taken together, demonstrate that HR-MAS NMR is a promising tool for metabolic profiling in the zebrafish embryo, including toxicological applications.
authors.affiliation: 1 Department of Chemistry and Biochemistry, Florida International University , North Miami, Florida.
authors.forename: John P
authors.initials: JP
authors.lastname: Berry
authors.affiliation: 2 Institute of Medical Physics and Biophysics, University of Leipzig , Leipzig, Germany .|3 Institut für Analytische Chemie, University of Leipzig , Leipzig, Germany .
authors.forename: Upasana
authors.initials: U
authors.lastname: Roy
authors.affiliation: 1 Department of Chemistry and Biochemistry, Florida International University , North Miami, Florida.
authors.forename: Asha
authors.initials: A
authors.lastname: Jaja-Chimedza
authors.affiliation: 1 Department of Chemistry and Biochemistry, Florida International University , North Miami, Florida.
authors.forename: Kristel
authors.initials: K
authors.lastname: Sanchez
authors.affiliation: 3 Institut für Analytische Chemie, University of Leipzig , Leipzig, Germany .
authors.forename: Joerg
authors.initials: J
authors.lastname: Matysik
authors.affiliation: 2 Institute of Medical Physics and Biophysics, University of Leipzig , Leipzig, Germany .|4 Leiden Institute of Chemistry , Leiden, the Netherlands .
authors.forename: A
authors.initials: A
authors.lastname: Alia
mesh_terms: D000475:Alkenes / Q000633:toxicity*; D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013723:Teratogens / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D000475:Alkenes; D013723:Teratogens; D014874:Water Pollutants, Chemical