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. 2019 Mar 15;9:4620. doi: 10.1038/s41598-019-40995-8

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Inhibition of atRA metabolism by specific CYP inhibitors. Panel A shows the inhibition of 4-OH-RA formation by CYP3A7 inhibitor fluconazole (fluc, 300 μM) and the CYP26 inhibitor talarozole (tal, 200 nM). atRA concentrations were 10 μM and 500 nM in the CYP3A7 and CYP26 incubations. Panels B and C show the percentage inhibition of 4-OH-RA (B) and 4-OH-RA + 4-oxo-RA (C) formation in four representative human fetal livers (hFL, numbers correspond to sample identifiers) by fluconazole (black bars), talarozole (grey bars), and ketoconazole (striped bars) in comparison to vehicle controls (white bars). The stars (***) indicate a significant difference between the incubations with the indicated inhibitor and vehicle control. The numbers indicate the donor codes for the fetal liver donors.