Contribution of Lipophilic Secondary Metabolites to the Toxicity of Strains of Freshwater Cyanobacterial Harmful Algal Blooms, Identified Using the Zebrafish (Danio rerio) Embyo as a Model for Vertebrate Development

Jaja-Chimedza, Asha

doi:10.25148/etd.fi14071128

Cited by 1 publication

(1 citation statement)

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“…It has, in fact, been previously proposed based on 3D modeling that PMAs-and the repetitively polymethoxylated backbone, in particular, which forms a hydrophobic ''corkscrew''-like conformation-might interact with lipids and consequently disrupt membranes. 30 Accordingly, disruption of cell membranes could be postulated to potentiate consequent hydrolysis of phospholipids (through access to phospholipases) and consequent release (i.e., intracellular elevation) of free PC, m-Ins, and FA. Simultaneously, increased synthesis or, alternatively, release from lipoproteins of cholesterol might, in turn, serve a compensatory response to restore membrane integrity.…”

Section: Discussionmentioning

confidence: 99%

High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance of Intact Zebrafish Embryos Detects Metabolic Changes Following Exposure to Teratogenic Polymethoxyalkenes from Algae

et al. 2016

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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 c-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.

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Section: Discussionmentioning

confidence: 99%