Metabolomics for informing adverse outcome pathways: Androgen receptor activation and the pharmaceutical spironolactone.

ABSTRACT: One objective in developing adverse outcome pathways (AOPs) is to connect biological changes that are relevant to risk assessors (i.e., fecundity) to molecular and cellular-level alterations that might be detectable at earlier stages of a chemical exposure. Here, we examined biochemical responses of fathead minnows (Pimephales promelas) to inform an AOP relevant to spironolactone's activation of the androgen receptor, as well as explore other biological impacts possibly unrelated to this receptor. Liquid chromatography with high resolution mass spectrometry (LC-MS) was used to measure changes in endogenous polar metabolites in livers of male and female fish that were exposed to five water concentrations of spironolactone (0, 0.05, 0.5, 5, or 50μgL^-1) for 21days. Metabolite profi

SUBMITTER: Davis JM 

PROVIDER: S-EPMC6145081 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature