Abstract

Flavonoids are known to have effects on cytochrome P450 enzymatic activity. However, little effort has been made to examine species differences and the relevance of studies on mammalian and fish microsomes so that extrapolations can be made to humans. Therefore, the effects of several naturally occurring flavonoids on the activity of CYP3A-dependent 7-benzyloxy-4-trifluoromethylcoumarin O-debenzylase (BFCOD) were evaluated in human, pig, mouse, and juvenile rainbow trout sources of hepatic microsomes. Each was exposed to three concentrations (1, 10, and 100 mu M) of diosmin, naringin, and naringenin. Naringenin competitively inhibited BFCOD activity (K-i values were 24.6 mu M in human, 15.6 mu M in pig, and 19.6 mu M in mouse microsomes). In fish, BFCOD activity was inhibited in a noncompetitive manner (K-i = 7 mu M). Neither diosmin nor naringenin affected BFCOD activity in hepatic microsomes from the studied model organisms. These results suggest that dietary flavonoids potentially inhibit the metabolism of clinical drugs. (C) 2016 Elsevier Inc. All rights reserved.

Keywords

CYP3A; Inhibition; Diosmin; Naringin; Naringenin

Published in

Biochemical Pharmacology
2016, Volume: 110-111, pages: 109-116
Publisher: PERGAMON-ELSEVIER SCIENCE LTD

SLU Authors

• Zamaratskaia, Galia

  • Department of Molecular Sciences, Swedish University of Agricultural Sciences
    
  • University of South Bohemia in České Budějovice

UKÄ Subject classification

Biochemistry and Molecular Biology


Publication identifier

DOI: https://doi.org/10.1016/j.bcp.2016.04.011

Permanent link to this page (URI)

https://res.slu.se/id/publ/77968