New grapefruit cultivars exhibit low cytochrome P4503A4-Inhibition activity

Yelena Guttman, Iris Yedidia, Adi Nudel, Yuliya Zhmykhova, Zohar Kerem*, Nir Carmi

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Furanocoumarins are the main compounds responsible for the food–drug interactions known as the grapefruit effect, which is caused by the inhibition of CYP3A4-mediated drug metabolism. We evaluated the effects of two new, low-furanocoumarin grapefruit cultivars on CYP3A4 activity and the roles of different furanocoumarins, individually and together with other juice compounds, in the inhibition of CYP3A4 by grapefruit. Whereas a standard grapefruit cultivar inhibited CYP3A4 activity in a dose-dependent manner, neither of the two examined low-furanocoumarin cultivars had an inhibitory effect. Despite the fact that bergamottin and 6′,7′-dihydroxybergamottin are weak inhibitors of CYP3A4, their relatively high levels in grapefruit make them the leading cause of the grapefruit effect. We found that furanocoumarins together with other juice compounds inhibit CYP3A4 in an additive manner. In silico docking simulation was employed, and differentiated between high- and low-potency inhibitors, suggesting that modeling may be useful for identifying potentially harmful food–drug interactions.

Original languageAmerican English
Article number111135
JournalFood and Chemical Toxicology
Volume137
DOIs
StatePublished - Mar 2020

Bibliographical note

Publisher Copyright:
© 2020

Keywords

  • CYP3A4
  • Docking
  • Food–drug interactions
  • Furanocoumarins
  • Grapefruit juice

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