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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12520%2F18%3A43898752" target="_blank" >RIV/60076658:12520/18:43898752 - isvavai.cz</a>

Result on the web

<a href="https://www.sciencedirect.com/science/article/pii/S0278691518300206" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0278691518300206</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.fct.2018.01.020" target="_blank" >10.1016/j.fct.2018.01.020</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Food and Chemical Toxicology

ISSN

0278-6915

e-ISSN

—

Volume of the periodical

113

Issue of the periodical within the volume

MAR 2018

Country of publishing house

GB - UNITED KINGDOM

Number of pages

5

Pages from-to

14-18

UT code for WoS article

000428498100002

EID of the result in the Scopus database

2-s2.0-85041488246