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Research article2017Peer reviewed

In vitro inhibition of human CYP2E1 and CYP3A by quercetin and myricetin in hepatic microsomes is not gender dependent

Ostlund, Johanna; Zlabek, Vladimir; Zamaratskaia, Galia

Abstract

This is the first in vitro study to investigate gender-related differences in the regulation of human cytochrome P450 by the flavonoids. Activities of CYP2E1 and CYP3A were measured in the presence of quercetin, myricetin, or isorhamnetin in hepatic microsomal pools from male and female donors. Hydroxylation of p-nitrophenol (PNPH) was measured to determine CYP2E1 activity, and O-dealkylation of 7-benzyloxy-4-trifluoromethylcoumarin (BFC) was measured to determine CYP3A activity. Quercetin, but not myricetin or isorhamnetin, competitively inhibited PNPH activity in human recombinant cDNAexpressed CYP2E1 with the Ki = 52.1 +/- 6.31 mu M. In the human microsomes, slight inhibition of PNPH activity by quercetin was not considered as physiologically relevant. Quercetin inhibited BFC activity in human recombinant cDNA-expressed CYP3A4 competitively with the Ki = 15.4 +/- 1.52 mu M, and myricetin noncompetitively with the Ki = 74.6 +/- 7.99 mu M. The degree of inhibition by quercetin was similar between genders. Myricetin showed somewhat stronger inhibition in female pools, but the Ki values were higher than physiologically relevant concentrations. Isorhamnetin did not affect either PNPH or BFC activity. We concluded that observed inhibition of CYP2E1 and CYP3A by some flavonols were not gender dependent. (C) 2017 Elsevier B.V. All rights reserved.

Keywords

Flavonols; Cytochrome P450; Hepatic microsomes; Males; Females

Published in

Toxicology
2017, Volume: 381, pages: 10-18
Publisher: ELSEVIER IRELAND LTD

      SLU Authors

        • Sustainable Development Goals

        Achieve gender equality and empower all women and girls

        UKÄ Subject classification

        Pharmacology and Toxicology

        Publication identifier

        DOI: https://doi.org/10.1016/j.tox.2017.02.012

        Permanent link to this page (URI)

        https://res.slu.se/id/publ/94196