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

摘要

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 frans-resveratrol and its metabolites after the oral administration of 60 mg/kg in Bcrp1~(-/-) mice. frans-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 frans-resveratrol was found. In conclusion, Bcrpl plays an important role in the efflux of resveratrol conjugates, contributing to their bioavailability, tissue distribution and elimination.