Involvement of breast cancer resistance protein (BCRP1/ABCG2) in the bioavailability and tissue distribution of trans-resveratrol in knockout mice.
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.
Grup de Fisiologia i Nutricio Experimental, Departament de Fisiologia (Farmacia) and Institut de Recerca en Nutricio i Seguretat Alimentaria (INSA), Universitat de Barcelona, Barcelona, Spain. aialvf@unileon.es
Irene
I
Alfaras
Míriam
M
Pérez
Maria Emília
ME
Juan
Gracia
G
Merino
Julio Gabriel
JG
Prieto
Joana Maria
JM
Planas
Ana Isabel
AI
Alvarez
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001682:Biological Availability; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; D013267:Stilbenes; D000077185:Resveratrol