PUBLICATION
From mRNA Expression of Drug Disposition Genes to In Vivo Assessment of CYP-Mediated Biotransformation during Zebrafish Embryonic and Larval Development
- Authors
- Verbueken, E., Bars, C., Ball, J.S., Periz-Stanacev, J., Marei, W.F.A., Tochwin, A., Gabriëls, I.J., Michiels, E.D.G., Stinckens, E., Vergauwen, L., Knapen, D., Van Ginneken, C.J., Van Cruchten, S.J.
- ID
- ZDB-PUB-181215-14
- Date
- 2018
- Source
- International Journal of Molecular Sciences 19(12): (Journal)
- Registered Authors
- Knapen, Dries, Van Cruchten, Steven, Verbueken, Evy, Vergauwen, Lucia
- Keywords
- activity, and expression, biotransformation, cytochrome P450, development, drug transporter, embryo, larva, phase II, zebrafish
- MeSH Terms
-
- ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism
- Animals
- Biotransformation/genetics
- Cytochrome P-450 Enzyme System/metabolism*
- Embryo, Nonmammalian/metabolism
- Embryonic Development/genetics*
- Gene Expression Regulation, Developmental*
- Larva/genetics
- Oxazines/metabolism
- Pharmaceutical Preparations/metabolism*
- RNA, Messenger/genetics
- RNA, Messenger/metabolism
- Zebrafish/embryology*
- Zebrafish/genetics*
- PubMed
- 30544719 Full text @ Int. J. Mol. Sci.
Citation
Verbueken, E., Bars, C., Ball, J.S., Periz-Stanacev, J., Marei, W.F.A., Tochwin, A., Gabriëls, I.J., Michiels, E.D.G., Stinckens, E., Vergauwen, L., Knapen, D., Van Ginneken, C.J., Van Cruchten, S.J. (2018) From mRNA Expression of Drug Disposition Genes to In Vivo Assessment of CYP-Mediated Biotransformation during Zebrafish Embryonic and Larval Development. International Journal of Molecular Sciences. 19(12).
Abstract
The zebrafish (Danio rerio) embryo is currently explored as an alternative for developmental toxicity testing. As maternal metabolism is lacking in this model, knowledge of the disposition of xenobiotics during zebrafish organogenesis is pivotal in order to correctly interpret the outcome of teratogenicity assays. Therefore, the aim of this study was to assess cytochrome P450 (CYP) activity in zebrafish embryos and larvae until 14 d post-fertilization (dpf) by using a non-specific CYP substrate, i.e., benzyloxy-methyl-resorufin (BOMR) and a CYP1-specific substrate, i.e., 7-ethoxyresorufin (ER). Moreover, the constitutive mRNA expression of CYP1A, CYP1B1, CYP1C1, CYP1C2, CYP2K6, CYP3A65, CYP3C1, phase II enzymes uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) and sulfotransferase 1st1 (SULT1ST1), and an ATP-binding cassette (ABC) drug transporter, i.e., abcb4, was assessed during zebrafish development until 32 dpf by means of quantitative PCR (qPCR). The present study showed that trancripts and/or the activity of these proteins involved in disposition of xenobiotics are generally low to undetectable before 72 h post-fertilization (hpf), which has to be taken into account in teratogenicity testing. Full capacity appears to be reached by the end of organogenesis (i.e., 120 hpf), although CYP1-except CYP1A-and SULT1ST1 were shown to be already mature in early embryonic development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping