Medaka embryos as a model for metabolism of anabolic steroids

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

Abstract

In anti-doping science, the knowledge of drug metabolism is a prerequisite to identify analytical targets for the detection of misused prohibited substances. As the most obvious way to study xenobiotic metabolism, the administration to human volunteers, faces ethical concerns, there is a need for model systems. In the present study, we investigated whether Oryzias latipes (medaka) embryos might be an alternative, non-animal test model to study human-like metabolism. In the present study, we exposed medaka embryos at the morula stage to the anabolic steroid metandienone (10 µM or 50 µM) for a period of 2 or 8 days. According to the fish embryo toxicity test (OECD test), we assessed the developmental status of the embryos. We further investigated metandienone metabolites by high-performance liquid chromatography- and gas chromatography-mass spectrometry. Medaka embryos produced three mono-hydroxylated and one reduced metabolite known from human biotransformation. Developmental malformations were observed for the exposition to 50 µM metandienone, while a significant elevation of the heart beat was also present in those individuals exposed to the lower dose for 8 days. The present study demonstrates that the medaka embryo represents a promising model to study human-like metabolism. Moreover, the judgement of developmental parameters of the fish embryos enables for the simultaneous assessment of toxicity.

Details

OriginalspracheEnglisch
Aufsatznummer819
Seiten (von - bis)1963-1974
Seitenumfang12
FachzeitschriftArchives of toxicology
Jahrgang96
Ausgabenummer7
Frühes Online-Datum30 März 2022
PublikationsstatusVeröffentlicht - 30 März 2022
Peer-Review-StatusJa

Externe IDs

Scopus 85127284830
unpaywall 10.1007/s00204-022-03284-4
Mendeley be95aa5c-8ea2-3b67-bcec-2b100d66daad
WOS 000774728100001
ORCID /0000-0002-2157-4711/work/142251661
ORCID /0000-0001-9326-7967/work/142252304

Schlagworte

DFG-Fachsystematik nach Fachkollegium

Schlagwörter

  • Biotransformation, Doping analysis, Fish embryo toxicity, Mass spectrometry, Metandienone, Oryzias latipes, Humans, Embryo, Nonmammalian/metabolism, Oryzias/metabolism, Animals, Chromatography, High Pressure Liquid/methods, Testosterone Congeners, Methandrostenolone/metabolism

Bibliotheksschlagworte