PUBLICATION
Antioxidants reduce reactive oxygen species but not embryotoxicity in the metabolic Danio rerio test (mDarT)
- Authors
- Pype, C., Verbueken, E., Saad, M.A., Bars, C., Van Ginneken, C.J., Knapen, D., Van Cruchten, S.J.
- ID
- ZDB-PUB-170701-7
- Date
- 2017
- Source
- Reproductive toxicology (Elmsford, N.Y.) 72: 62-73 (Journal)
- Registered Authors
- Knapen, Dries, Van Cruchten, Steven, Verbueken, Evy
- Keywords
- Embryo, Microsomes, Reactive oxygen species, Toxicity, Zebrafish
- MeSH Terms
-
- Activation, Metabolic
- Animals
- Anticonvulsants/toxicity
- Antioxidants/pharmacology*
- Embryo, Nonmammalian*
- Embryonic Development/drug effects
- Gallic Acid/pharmacology
- NADP/toxicity
- Reactive Oxygen Species/metabolism
- Teratogens/toxicity*
- Toxicity Tests/methods*
- Trimethadione/toxicity
- Zebrafish*
- PubMed
- 28663077 Full text @ Reprod. Toxicol.
Citation
Pype, C., Verbueken, E., Saad, M.A., Bars, C., Van Ginneken, C.J., Knapen, D., Van Cruchten, S.J. (2017) Antioxidants reduce reactive oxygen species but not embryotoxicity in the metabolic Danio rerio test (mDarT). Reproductive toxicology (Elmsford, N.Y.). 72:62-73.
Abstract
Mammalian liver microsomes are occasionally used as a metabolic activation system (MAS) to compensate for the low CYP-mediated bioactivation of drugs in zebrafish embryos, in the so-called mDarT. However, this MAS is embryotoxic and consequently zebrafish embryos are only exposed during a very limited developmental window. The main aim of this study was to try to reduce the embryotoxic properties of MAS in order to extend the exposure window in the mDarT. Removing the microsomes from the incubation medium prior to exposure of the zebrafish embryos did not reduce embryotoxicity. Free radicals (ROS) in the incubation medium were successfully reduced by antioxidants, but the medium remained embryotoxic. Single dosing of NADPH or omitting toxic components from the MAS preparation did also not reduce embryotoxicity. In conclusion, the exposure window in the mDarT could not be extended by reducing ROS levels, single dosing of NADPH or modifications of the MAS preparation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping