Plant polyphenols and multidrug resistance: effects of dietary flavonoids on drug transporters in Caco-2 and MDCKII-MDR1 cell transport models

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
R Rodriguez-ProteauD R Buhler

Abstract

The hypothesis tested was that specific flavonoids such as epicatechin gallate, epigallocatechin gallate, genistein, genistin, naringenin, naringin, quercetin and xanthohumol will modulate cellular uptake and permeability (P(e)) of multidrug-resistant substrates, cyclosporin A (CSA) and digoxin, across Caco-2 and MDCKII-MDR1 cell transport models. (3)H-CSA/(3)H-digoxin transport and uptake experiments were performed with and without co-exposure of the flavonoids. Aglycone flavonoids reduced the P(e) of CSA to a greater extent than glycosylated flavonoids with 30 microM xanthohumol producing the greatest effect (7.2 x 10(-6) to 6.6 x 10(-7) and 17.9 x 10(-6) to 4.02 x 10(-6) cm s(-1) in Caco-2 and MDCKII-MDR1 cells, respectively); while no measurable effects were seen with digoxin. Xanthohumol significantly demonstrated (1) saturable efflux, (2) increased uptake of (3)H-digoxin and (3) decreased uptake of (3)H-CSA in the Caco-2 cells. The transport data suggests that xanthohumol effects transport of CSA in a manner that is distinct from the digoxin efflux pathway and suggests that intestinal transport of these MDR1 substrates is more complex than previously reported.

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Citations

Jan 17, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Y Fan, R Rodriguez-Proteau
Oct 28, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·J-S Taur, R Rodriguez-Proteau
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