The effect of co-administered flavonoids on the metabolism of hesperetin and the disposition of its metabolites in Caco-2 cell monolayers

W. Brand, B. Padilla, P.J. van Bladeren, G. Williamson, I. Rietjens

Research output: Contribution to journalArticleAcademicpeer-review

35 Citations (Scopus)

Abstract

Metabolism by phase II enzymes and transport from intestinal cells back into the lumen by ATP binding cassette (ABC) transporters limits the bioavailability of the flavanone hesperetin, the aglycone of hesperidin. This study investigates to what extent other flavonoids modulate the metabolism and transport of hesperetin by characterizing the effect of co-administrating a series of flavonoids using Caco-2 cell monolayers in a two-compartment transwell system. Flavonoids may interfere with hesperetin metabolism and can also inhibit the apically located ABC transporter breast cancer resistance protein (ABCG2) which was previously shown to be responsible for the apical transport of hesperetin metabolites. Co-exposure of Caco-2 cell monolayers to hesperetin with specific flavonoids reduced the ratio of apical efflux to basolateral transport of hesperetin metabolites, and in some cases, also reduced the amount of hesperetin metabolites detected extracellularly. As intracellular accumulation of hesperetin metabolites did not account for this decrease, inhibition of metabolism of hesperetin is likely the underlying mechanism for the reduced metabolite formation and excretion. In spite of the reduction in metabolism the amount of hesperetin metabolites transported to the basolateral side significantly increased upon co-exposure with specific flavonoids and therefore co-administration of specific flavonoids could be a strategy to improve the bioavailability of hesperetin
Original languageEnglish
Pages (from-to)851-860
JournalMolecular Nutrition & Food Research
Volume54
Issue number6
DOIs
Publication statusPublished - 2010

Keywords

  • cancer resistance protein
  • dependent glucose-transporter
  • line caco-2
  • multidrug-resistance
  • orange juice
  • (abcg2)-mediated transport
  • intestinal-absorption
  • mediated inhibition
  • abc transporters
  • biochanin-a

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