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From mRNA Expression of Drug Disposition Genes to In Vivo Assessment of CYP-Mediated Biotransformation during Zebrafish Embryonic and Larval Development.
Verbueken, Evy; Bars, Chloé; Ball, Jonathan S; Periz-Stanacev, Jelena; Marei, Waleed F A; Tochwin, Anna; Gabriëls, Isabelle J; Michiels, Ellen D G; Stinckens, Evelyn; Vergauwen, Lucia; Knapen, Dries; Van Ginneken, Chris J; Van Cruchten, Steven J.
Afiliación
  • Verbueken E; Applied Veterinary Morphology, Department of Veterinary Sciences, University of Antwerp, Wilrijk 2610, Antwerp, Belgium. evy.verbueken@uantwerpen.be.
  • Bars C; Applied Veterinary Morphology, Department of Veterinary Sciences, University of Antwerp, Wilrijk 2610, Antwerp, Belgium. chloe.bars@uantwerpen.be.
  • Ball JS; Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, UK. J.Ball@exeter.ac.uk.
  • Periz-Stanacev J; Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk 2610, Antwerp, Belgium. Jelena.perizstanacev@uantwerpen.be.
  • Marei WFA; Gamete Research Centre, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk 2610, Antwerp, Belgium. waleed.marei@uantwerpen.be.
  • Tochwin A; Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter EX4 4QD, UK. A.Tochwin@exeter.ac.uk.
  • Gabriëls IJ; Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk 2610, Antwerp, Belgium. Isabelle.gabriels@uantwerpen.be.
  • Michiels EDG; Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk 2610, Antwerp, Belgium. ellen.michiels@uantwerpen.be.
  • Stinckens E; Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk 2610, Antwerp, Belgium. evelyn.stinckens@uantwerpen.be.
  • Vergauwen L; Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk 2610, Antwerp, Belgium. lucia.vergauwen@uantwerpen.be.
  • Knapen D; Systemic Physiological and Ecotoxicological Research (SPHERE), Department of Biology, University of Antwerp, Antwerp 2020, Belgium. lucia.vergauwen@uantwerpen.be.
  • Van Ginneken CJ; Zebrafishlab, Veterinary Physiology and Biochemistry, Department of Veterinary Sciences, University of Antwerp, Wilrijk 2610, Antwerp, Belgium. dries.knapen@uantwerpen.be.
  • Van Cruchten SJ; Applied Veterinary Morphology, Department of Veterinary Sciences, University of Antwerp, Wilrijk 2610, Antwerp, Belgium. chris.vanginneken@uantwerpen.be.
Int J Mol Sci ; 19(12)2018 Dec 10.
Article en En | MEDLINE | ID: mdl-30544719
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Preparaciones Farmacéuticas / Regulación del Desarrollo de la Expresión Génica / Sistema Enzimático del Citocromo P-450 / Desarrollo Embrionario Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2018 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Pez Cebra / Preparaciones Farmacéuticas / Regulación del Desarrollo de la Expresión Génica / Sistema Enzimático del Citocromo P-450 / Desarrollo Embrionario Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2018 Tipo del documento: Article País de afiliación: Bélgica Pais de publicación: Suiza