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Norfluoxetine Is the Only Metabolite of Fluoxetine in Zebrafish (Danio rerio) Embryos That Accumulates at Environmentally Relevant Exposure Scenarios

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Heidelberg, den 13. 3. 2020

Fluoxetine has been recognized as one of the most toxic pharmaceuticals in the aquatic environment. Since there is growing evidence that the toxic potential of fluoxetine in surface waters is markedly influenced by its own metabolism in aquatic species, this study investigated the biotransformation of fluoxetine in the zebrafish embryo – an aquatic model organism of intermediate complexity.

Zebrafish embryos were exposed to 0.1, 1.0, 10, 50, and 5000 ?g/L of fluoxetine from 48 to 120 h post-fertilization (hpf), and the accumulation of fluoxetine and its metabolites was analyzed over time. Additionally, depuration of fluoxetine and its metabolites from 96 to 120 hpf was investigated, and autoinhibitory effects of fluoxetine on phase I biotransformation were analyzed.

Exposure to 5000 ?g/L fluoxetine resulted in elevated 7-ethoxyresorufin-O-deethylase (EROD) activity of cytochrome P450 enzymes and continuous accumulation of fluoxetine and 11 fluoxetine metabolites. Embryos exposed to 10 and 50 ?g/L fluoxetine were able to reduce fluoxetine accumulation from 94 to 120 hpf. During depuration, accumulation of fluoxetine and most metabolites was clearly reduced, and biotransformation shifted in favor of norfluoxetine, the primary fluoxetine metabolite in humans.

Findings demonstrated that norfluoxetine is the only metabolite of fluoxetine that accumulates in zebrafish embryos at environmentally relevant exposure scenarios.

Read the complete article here:

Florian Zindler, Selina Tisler, Ann-Kathrin Loerracher, Christian Zwiener, and Thomas Braunbeck: Norfluoxetine Is the Only Metabolite of Fluoxetine in Zebrafish (Danio rerio) Embryos That Accumulates at Environmentally Relevant Exposure Scenarios
Environmental Science & Technology 2020 54 (7), 4200-4209
https://doi.org/10.1021/acs.est.9b07618

Kontakt

Prof. Dr. Thomas Braunbeck
Aquatic Ecology & Toxicology
COS - Centre for Organismal Studies

University of Heidelberg
Im Neuenheimer Feld 504
D-69120 Heidelberg

braunbeck@uni-hd.de
Tel.: +49-(0)62 21-54 56 68