Detoxification and in part also activation of electrophilic substances occurs through conjugation with glutathione (GSH) by glutathione S-transferases (GSTs). The conjugate is then transformed to the mercapturate in the mercapturic acid pathway (MAP) and excreted. In order to be able to assess the potential impact of electrophiles on health and the environment, it is important to know whether the MAP is functional in model systems.
Zebrafish early life stages and cell lines have been established as good models for the study of bioactive compounds, because of their genetic relation to humans and because powerful analytical and biomolecular tools are available. To be useful for risk assessment, the formation of mercapturates must be demonstrated for these models. For this we have i) successfully demonstrated the expression of cytosolic GSTs on the protein level (Tierbach et al, 2018) and ii) the in vivo formation of the MPA metabolites under exposure to nontoxic concentrations of a model electrophile using mass spectrometry (Tierbach et al, 2020, under review).