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7-Hydroxylation of warfarin is strongly inhibited by sesamin, but not by episesamin, caffeic and ferulic acids in human hepatic microsomes

Pilipenko, Nadezhda; Rasmussen, Martin Kr�yer; Doran, Olena; Zamaratskaia, Galia

7-Hydroxylation of warfarin is strongly inhibited by sesamin, but not by episesamin, caffeic and ferulic acids in human hepatic microsomes Thumbnail


Authors

Nadezhda Pilipenko

Martin Kr�yer Rasmussen

Olena Doran Olena.Doran@uwe.ac.uk
College Dean of Research and Enterprise

Galia Zamaratskaia



Abstract

© 2018 Elsevier Ltd Warfarin is a commonly used anticoagulant drug and is a derivate of coumarin. Cytochrome P450 2C9 (CYP2C9) plays the key role in transformation of coumarin and thus, influences determination of warfarin dosage. A number of factors including dietary compounds such as sesamin, caffeic acid and ferulic acids can regulate the activity of CYP2C9. The present study tested the hypothesis that sesamin, episesamin, caffeic acid and ferulic acid decreases the rate of warfarin 7-hydroxylation via inhibition of hepatic CYP2C9. The experiments were conducted on hepatic microsomes from human donors. It was demonstrated that the rate of 7-hydroxylation of warfarin was significantly decreased in the presence of sesamin in the range of concentrations from 5 to 500 nM, and was not affected by episesamin, caffeic acid and ferulic acid in the same range of concentrations. The kinetic analysis indicated non-competitive type of inhibition by sesamin with Ki = 202 ± 18 nM. In conclusion, the results of our in vitro study revealed that sesamin was able to inhibit formation of a major metabolite of warfarin, 7-hydroxywarfarin. The potentially negative consequences of the consumption of high amounts of sesamin-containing food or dietary supplements in warfarin-treated patients need to be further studied.

Citation

Pilipenko, N., Rasmussen, M. K., Doran, O., & Zamaratskaia, G. (2018). 7-Hydroxylation of warfarin is strongly inhibited by sesamin, but not by episesamin, caffeic and ferulic acids in human hepatic microsomes. Food and Chemical Toxicology, 113, 14-18. https://doi.org/10.1016/j.fct.2018.01.020

Journal Article Type Article
Acceptance Date Jan 12, 2018
Online Publication Date Jan 17, 2018
Publication Date Mar 1, 2018
Deposit Date Jan 15, 2018
Publicly Available Date Mar 29, 2024
Journal Food and Chemical Toxicology
Print ISSN 0278-6915
Electronic ISSN 1873-6351
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 113
Pages 14-18
DOI https://doi.org/10.1016/j.fct.2018.01.020
Keywords food quality, microsomes, S-7-hydroxywarfarin, Cytochrome P450, In vitro, Food-drug interactions, Detoxification
Public URL https://uwe-repository.worktribe.com/output/875529
Publisher URL https://doi.org/10.1016/j.fct.2018.01.020

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