Intestinal breast cancer resistance protein (BCRP)/Bcrp1 and multidrug resistance protein 3 (MRP3)/Mrp3 are involved in the pharmacokinetics of resveratrol

Molecular Pharmacology
Koen van de WeteringPiet Borst

Abstract

The phytoestrogen resveratrol has putative health-promoting effects and is present in several dietary constituents. Resveratrol is metabolized extensively in the gut epithelium, resulting in the formation of hydrophilic glucuronic acid and sulfate conjugates. These polar resveratrol conjugates need specific transporters to cross the cell membrane. We show here that vectorial transport of some of these metabolites is mediated by multidrug resistance protein 3 (MRP3, ABCC3) and/or breast cancer resistance protein (BCRP, ABCG2) located in the basolateral and apical membranes of enterocytes, respectively. In vitro, MRP3 transports resveratrol-glucuronide (Res-3-G). The absence of Mrp3 in mice results in altered disposition of Res-3-G and its parent compound resveratrol, leading to a reduced percentage of resveratrol being excreted via the urine in Mrp3(-/-) mice. Circumstantial evidence suggests that circulating resveratrol is formed by deglucuronidating Res-3-G in vivo, providing a possible explanation for the health beneficial effects of resveratrol in vivo, despite its rapid and extensive conjugation. BCRP transports Res-3-G and resveratrol sulfates in vitro, and its absence in mice results in high plasma levels of resveratrol-d...Continue Reading

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