Zebrafish early life stages as alternative model to study 'designer drugs': Concordance with mammals in response to opioids.

Autor: Kirla KT; University of Zurich, Zurich Institute of Forensic Medicine, Department of Forensic Pharmacology and Toxicology, Zurich 8057, Switzerland; Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, Duebendorf 8600, Switzerland., Erhart C; Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, Duebendorf 8600, Switzerland., Groh KJ; Food Packaging Forum Foundation, Zurich 8045, Switzerland., Stadnicka-Michalak J; Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, Duebendorf 8600, Switzerland; EPFL, School of Architecture, Civil and Environmental Engineering, Lausanne 1015, Switzerland., Eggen RIL; Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, Duebendorf 8600, Switzerland; ETHZ, Institute of Biogeochemistry and Pollutant Dynamics, Zurich 8092, Switzerland., Schirmer K; Eawag, Swiss Federal Institute of Aquatic Science and Technology, Department of Environmental Toxicology, Duebendorf 8600, Switzerland; EPFL, School of Architecture, Civil and Environmental Engineering, Lausanne 1015, Switzerland; ETHZ, Institute of Biogeochemistry and Pollutant Dynamics, Zurich 8092, Switzerland. Electronic address: kristin.schirmer@eawag.ch., Kraemer T; University of Zurich, Zurich Institute of Forensic Medicine, Department of Forensic Pharmacology and Toxicology, Zurich 8057, Switzerland.
Jazyk: angličtina
Zdroj: Toxicology and applied pharmacology [Toxicol Appl Pharmacol] 2021 May 15; Vol. 419, pp. 115483. Date of Electronic Publication: 2021 Mar 13.
DOI: 10.1016/j.taap.2021.115483
Abstrakt: The number of new psychoactive substances (NPS) on the illicit drug market increases fast, posing a need to urgently understand their toxicity and behavioural effects. However, with currently available rodent models, NPS assessment is limited to a few substances per year. Therefore, zebrafish (Danio rerio) embryos and larvae have been suggested as an alternative model that would require less time and resources to perform an initial assessment and could help to prioritize substances for subsequent evaluation in rodents. To validate this model, more information on the concordance of zebrafish larvae and mammalian responses to specific classes of NPS is needed. Here, we studied toxicity and behavioural effects of opioids in zebrafish early life stages. Synthetic opioids are a class of NPS that are often used in pain medication but also frequently abused, having caused multiple intoxications and fatalities recently. Our data shows that fentanyl derivatives were the most toxic among the tested opioids, with toxicity in the zebrafish embryo toxicity test decreasing in the following order: butyrfentanyl>3-methylfentanyl>fentanyl>tramadol> O-desmethyltramadol>morphine. Similar to rodents, tramadol as well as fentanyl and its derivatives led to hypoactive behaviour in zebrafish larvae, with 3-methylfentanyl being the most potent. Physico-chemical properties-based predictions of chemicals' uptake into zebrafish embryos and larvae correlated well with the effects observed. Further, the biotransformation pattern of butyrfentanyl in zebrafish larvae was reminiscent of that in humans. Comparison of toxicity and behavioural responses to opioids in zebrafish and rodents supports zebrafish as a suitable alternative model for rapidly testing synthetic opioids.
(Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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