Chemical effects on dye efflux activity in live zebrafish embryos and on zebrafish Abcb4 ATPase activity

ATP‐binding cassette (ABC) transporter proteins include efflux pumps that confer multixenobiotic resistance to zebrafish embryos, a valuable toxico/pharmacological model. Here, we established an automated microscopy‐based rhodamine B dye accumulation assay in which enhanced dye accumulation in live zebrafish embryos indicates inhibition of multixenobiotic efflux transporter activity. Twenty structurally divergent known substrates and/or inhibitors of human ABC transporters and environmentally relevant compounds were examined using this assay and the ATPase activity of recombinant zebrafish Abcb4 as readouts. These two assays confirmed that Abcb4 functions as an efflux transporter in zebrafish, whereas they gave discordant results for some of the tested substances. The dye accumulation assay in zebrafish embryos could be useful to screen environmental pollutants and other chemicals for efflux transporter interaction in a medium‐throughput fashion.Fil: Bieczynski, Flavia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Confluencia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Confluencia. Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue. Instituto de Biotecnología Agropecuaria del Comahue | Universidad Nacional del Comahue. Facultad de Ciencias Agrarias. Centro de Investigaciones en Toxicología Ambiental y Agrobiotecnología del Comahue. Instituto de Biotecnología Agropecuaria del Comahue; ArgentinaFil: Burkhardt Medicke, Kathleen. Universitat Leipzig; Alemania. Helmholtz Centre for Environmental Research; AlemaniaFil: Luquet, Carlos Marcelo. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnologico Conicet - Patagonia Norte. Instituto de Investigaciones En Biodiversidad y Medioambiente. Subsede Junín de Los Andes-inibioma-centro de Ecología Aplicada del Neuquén (cean) | Universidad Nacional del Comahue. Centro Regional Universitario Bariloche. Instituto de Investigaciones En Biodiversidad y Medioambiente. Subsede Junín de Los Andes-inibioma-centro de Ecología Aplicada del Neuquén (cean).; ArgentinaFil: Scholz, Stefan. Universitat Leipzig; Alemania. Helmholtz Centre for Environmental Research; AlemaniaFil: Luckenbach, Till. Universitat Leipzig; Alemania. Helmholtz Centre for Environmental Research; Alemani