The impact of chemosensitisation on bioaccumulation and sediment toxicity

Cellular multixenobiotic resistance (MXR) transport proteins enhance the efflux of numerous organic pollutants. However, MXR proteins may be blocked or saturated by xenobiotic compounds, acting as inhibitors - also called chemosensitisers. Although effective on a cellular level, the environmental relevance of chemosensitisers has not been conclusively demonstrated. Since sediments are an important source of bioaccumulating compounds in aquatic ecosystems, sediments and sediment-associated hydrophobic pollutants were investigated for their potential to increase exposure and toxicity in the presence of chemosensitisation. In this study, we address this issue by (1) comparing the net uptake of 17 hydrophobic environmental pollutants by zebrafish (Danio rerio) embryos in the presence and absence of the model chemosensitiser verapamil and (2) investigating the impact of verapamil on the dose-dependent effect on zebrafish embryos exposed to polluted sediment extracts. None of the 17 pollutants showed a reproducible increase in bioaccumulation upon chemosensitisation with verapamil. Instead, internal concentrations were subject to intra-species variation by a factor of approximately two. However, a significant increase in toxicity was observed upon embryo co-exposure to verapamil for one of three sediment extracts. In contrast, another sediment extract exhibited less toxicity when combined with verapamil. In general, the results indicate only a minor impact of verapamil on the uptake of moderately hydrophobic chemicals in zebrafish embryos.