RT info:eu-repo/semantics/article
T1 Secretion into Milk of the Main Metabolites of the Anthelmintic Albendazole Is Mediated by the ABCG2/BCRP Transporter
A1 Blanco Paniagua, Esther
A1 Álvarez Fernández, Laura
A1 Gracia Lino, Alba
A1 Álvarez de Felipe, Ana Isabel
A1 Merino Peláez, Gracia
A2 Fisiologia
K1 Fisiología
K1 Veterinaria
K1 ABCG2
K1 Albendazole
K1 Metabolites
K1 Substrates
K1 Milk
K1 2411 Fisiología Humana
K1 2401.13 Fisiología Animal
AB Albendazole (ABZ) is an anthelmintic with a broad-spectrum activity, widely used in human and veterinary medicine. ABZ is metabolized in all mammalian species to albendazole sulfoxide (ABZSO), albendazole sulfone (ABZSO2) and albendazole 2-aminosulphone (ABZSO2-NH2). ABZSO and ABZSO2 are the main metabolites detected in plasma and all three are detected in milk. The ATP-binding cassette transporter G2 (ABCG2) is an efflux transporter that is involved in the active secretion of several compounds into milk. Previous studies have reported that ABZSO was in vitro transported by ABCG2. The aim of this work is to correlate the in vitro interaction between ABCG2 and the other ABZ metabolites with their secretion into milk by this transporter. Using in vitro transepithelial assays with cells transduced with murine Abcg2 and human ABCG2, we show that ABZSO2 and ABZSO2-NH2 are in vitro substrates of both. In vivo assays carried out with wild-type and Abcg2−/− lactating female mice demonstrated that secretion into milk of these ABZ metabolites was mediated by Abcg2. Milk concentrations and milk-to-plasma ratio were higher in wild-type compared to Abcg2−/− mice for all the metabolites tested. We conclude that ABZ metabolites are undoubtedly in vitro substrates of ABCG2 and actively secreted into milk by ABCG2.
PB American Society for Microbiology
SN 0066-4804
LK http://hdl.handle.net/10612/15134
UL http://hdl.handle.net/10612/15134
NO Blanco-Paniagua, E., Álvarez- Fernández, L., Garcia-Lino, A. M., Álvarez, A. I., & Merino, G. (2022). Secretion into Milk of the Main Metabolites of the Anthelmintic Albendazole Is Mediated by the ABCG2/BCRP Transporter. Antimicrobial Agents and Chemotherapy, 66(7). https://doi.org/10.1128/AAC.00062-22
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 27-abr-2024