Publication
Title
From mRNA expression of drug disposition genes to in vivo assessment of CYP-mediated biotransformation during zebrafish embryonic and larval development
Author
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 CYP1except CYP1Aand SULT1ST1 were shown to be already mature in early embryonic development
Language
English
Source (journal)
International journal of molecular sciences
Publication
2018
ISSN
1422-0067
1661-6596
Volume/pages
19 :12 (2018) , 30 p.
Article Reference
3976
ISI
000455323500278
Pubmed ID
30544719
Medium
E-only publicatie
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Project info
Equipment for high-speed refrigerated, preparative ultracentrifugation, automated gradient formation and fraction collection and analysis.
The impact of endocrine disruption on vertebrate embryonic and larval development.
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 18.12.2018
Last edited 21.10.2021
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