Xenobiotic metabolism in the zebrafish: a review of the spatiotemporal distribution, modulation and activity of Cytochrome P450 families 1 to 3

The zebrafish (Danio rerio) has been increasingly explored in pharmaceutical research as a promising alternative model for toxicological screens. This necessitates a thorough knowledge on the biotransformation processes for a correct interpretation of pharmacological and toxicological data. Physiolo...

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Bibliographic Details
Published in:Journal of toxicological sciences 2016/02/01, Vol.41(1), pp.1-11
Main Authors: Saad, Moayad, Cavanaugh, Kate, Verbueken, Evy, Pype, Casper, Casteleyn, Christophe, Ginneken, Chris Van, Cruchten, Steven Van
Format: Article
Language:English
Subjects:
Animals
Biotransformation
Cytochrome P-450 Enzyme System - genetics
Cytochrome P-450 Enzyme System - metabolism
Cytochrome P450
Evolution, Molecular
Gene Ontology
Humans
Isoenzymes - genetics
Isoenzymes - metabolism
Ontogeny
Synteny
Xenobiotics
Xenobiotics - metabolism
Zebrafish
Zebrafish - metabolism
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Summary:The zebrafish (Danio rerio) has been increasingly explored in pharmaceutical research as a promising alternative model for toxicological screens. This necessitates a thorough knowledge on the biotransformation processes for a correct interpretation of pharmacological and toxicological data. Physiologically, cytochrome P450 (CYP) enzymes, specifically CYP families 1-3, play a pivotal role in drug metabolism. And yet, information regarding activity of CYP, its isoforms, and conjugation enzymes in zebrafish is either scarce or conflicting. To account for this discrepancy, the available spatiotemporal, modulation and activity data on zebrafish CYP 1-3 families are reviewed in this paper and compared with human CYP data. The CYP genetic features and synteny are well characterized, as is their expression in different organ systems. Moreover, several substrates metabolized by humans also show metabolism in zebrafish, with other CYP isoforms possibly involved. Altogether, the five CYP1 members, 41 CYP2 members and five CYP3 members in zebrafish show distinct evolutionary and orthological similarities with humans.
ISSN:0388-1350
1880-3989
DOI:10.2131/jts.41.1