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Applying high resolution mass spectrometry and network analysis to assess exposure to a novel androgen, spironolactone, on metabolic pathways in fish
Citation:
Davis, J., D. Ekman, D. Skelton, C. LaLone, G. Ankley, J. Cavallin, Dan Villeneuve, AND Tim Collette. Applying high resolution mass spectrometry and network analysis to assess exposure to a novel androgen, spironolactone, on metabolic pathways in fish. SETAC North America 36th Annual Meeting, Salt Lake City, UT, November 01 - 06, 2015.
Impact/Purpose:
Presented at SETAC North America 36th Annual Meeting
Description:
Although metabolomics can successfully detect effects from overall contaminant exposure, its ability to elucidate specific metabolic pathways impacted by those exposures can be hindered by bottlenecks in metabolite identification. However, improved analytical approaches that combine untargeted high-resolution mass spectrometry and network analysis can facilitate rapid inference of biochemical pathways affected by contaminant exposure. Accordingly, we present results from a laboratory-based study that applied such a metabolomics-based approach to discern biochemical responses of fathead minnows (Pimephales promelas) exposed to spironolactone, a synthetic androgen receptor agonist that has exhibited androgenic properties in aquatic biota. Male and female fish were exposed for 21-days to 5 different concentrations of spironolactone (0, 0.05, 0.5, 5, and 50 µg/L). Endogenous polar metabolites in liver tissue were then analyzed using high resolution mass spectrometry (LC-MS). Results from the multivariate analyses showed that profiles of endogenous metabolites in female fish were significantly impacted at higher concentrations (5 and 50 µg/L), but not at lower concentrations of spironolactone. Metabolite profiles in male fish were only significantly impacted at the highest spironolactone concentration (50 µg/L) tested. Network analysis identified several endogenous metabolites involved in glutamate, tryptophan, and amino acid metabolism that were significantly affected by spironolactone exposure. These results largely agree with previous results showing that females exposed to high concentrations of spironolactone exhibited significantly lower fecundity and plasma vitellogenin (VTG) levels. Thus, this overall study further demonstrates the utility of high resolution mass spectrometry for discerning biochemical responses to chemical exposure and linking them to contaminant modes of action.
