Details zur Publikation

Kategorie Textpublikation
Referenztyp Zeitschriften
DOI 10.1021/acs.chemrestox.1c00371
Titel (primär) Zebrafish Oatp1d1 acts as a cellular efflux transporter of the anionic herbicide bromoxynil
Autor Halbach, K.; Aulhorn, S.; Lechtenfeld, O.J. ORCID logo ; Lecluse, M.; Leippe, S.; Reemtsma, T.; Seiwert, B.; Wagner, S.; König, J.; Luckenbach, T. ORCID logo
Quelle Chemical Research in Toxicology
Erscheinungsjahr 2022
Department BIOTOX; ANA
Band/Volume 35
Heft 2
Seite von 315
Seite bis 325
Sprache englisch
Topic T9 Healthy Planet
Abstract Toxicokinetics (TK) of ionic compounds in the toxico-/pharmacological model zebrafish embryo (Danio rerio) depend on absorption, distribution, metabolism, and elimination (ADME) processes. Previous research indicated involvement of transport proteins in the TK of the anionic pesticide bromoxynil in zebrafish embryos. We here explored the interaction of bromoxynil with the organic anion-transporting polypeptide zebrafish Oatp1d1. Mass spectrometry imaging revealed accumulation of bromoxynil in the gastrointestinal tract of zebrafish embryos, a tissue known to express Oatp1d1. In contrast to the Oatp1d1 reference substrate bromosulfophthalein (BSP), which is actively taken up by transfected HEK293 cells overexpressing zebrafish Oatp1d1, those cells accumulated less bromoxynil than empty vector-transfected control cells. This indicates cellular efflux of bromoxynil by Oatp1d1. This was also seen for diclofenac but not for carbamazepine, examined for comparison. Correspondingly, internal concentrations of bromoxynil and diclofenac in the zebrafish embryo were increased when coexposed with BSP, inhibiting the activities of various transporter proteins, including Oatp1d1. The effect of BSP on accumulation of bromoxynil and diclofenac was enhanced in further advanced embryo stages, indicating increased efflux activity in those stages. An action of Oatp1d1 as an efflux transporter of ionic environmental compounds in zebrafish embryos should be considered in future TK assessments.
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Halbach, K., Aulhorn, S., Lechtenfeld, O.J., Lecluse, M., Leippe, S., Reemtsma, T., Seiwert, B., Wagner, S., König, J., Luckenbach, T. (2022):
Zebrafish Oatp1d1 acts as a cellular efflux transporter of the anionic herbicide bromoxynil
Chem. Res. Toxicol. 35 (2), 315 - 325 10.1021/acs.chemrestox.1c00371