Involvement of Breast Cancer Resistance Protein (BCRP1/ABCG2) in the Bioavailability and Tissue Distribution of trans-Resveratrol in Knockout Mice

• Published in: Journal of agricultural and food chemistry Vol. 58; no. 7; pp. 4523 - 4528
• Main Authors: Alfaras, Irene, Pérez, Míriam, Juan, Maria Emília, Merino, Gracia, Prieto, Julio Gabriel, Planas, Joana Maria, Álvarez, Ana Isabel
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 14-04-2010
• Subjects: animal models; animal proteins; Animals; ATP Binding Cassette Transporter, Sub-Family G, Member 2; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; bioavailability; Biological and medical sciences; Biological Availability; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Disease Models, Animal; Feeding. Feeding behavior; Female; Food industries; Fundamental and applied biological sciences. Psychology; human nutrition; Humans; intestinal absorption; knockout mutants; metabolites; Mice; Mice, Knockout; Molecular Nutrition; nutrition physiology; phytochemicals; polyphenols; resveratrol; Stilbenes - administration & dosage; Stilbenes - chemistry; Stilbenes - pharmacokinetics; Tissue Distribution; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Bioavailability; Bcrp1−/− mice; HPLC-DAD; distribution; trans-resveratrol; Bcrp1; Rodentia; HPLC chromatography; Malignant tumor; mice; Protein; Resistance; Tissue; Vertebrata; Mammalia; Mouse; Distribution; Resveratrol; Mutation; Cancer
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf9042858

trans-Resveratrol undergoes extensive metabolism in the intestinal cells, which leads to the formation of glucuronide and sulfate conjugates. Given the important role of the breast cancer resistance protein (ABCG2/BCRP) in the efflux of conjugated forms, the present study investigates the bioavailability and tissue distribution of trans-resveratrol and its metabolites after the oral administration of 60 mg/kg in Bcrp1−/− mice. trans-Resveratrol and its metabolites were measured in intestinal content, plasma and tissues by HPLC. At 30 min after administration, intestinal content showed decreases of 71% and 97% of resveratrol glucuronide and sulfate, respectively, in Bcrp1−/−, indicating a lower efflux from the enterocytes. Furthermore, the area under plasma concentration curves (AUC) of these metabolites increased by 34% and 392%, respectively, whereas a decrease in the AUC of trans-resveratrol was found. In conclusion, Bcrp1 plays an important role in the efflux of resveratrol conjugates, contributing to their bioavailability, tissue distribution and elimination.