Role of the Abcg2 transporter in plasma, milk, and tissue levels of the anthelmintic monepantel in mice.
Chem Biol Interact
; 398: 111117, 2024 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-38906501
ABSTRACT
Breast cancer resistance protein/ATP-binding cassette subfamily G2 (BCRP/ABCG2) is an ATP-binding cassette efflux (ABC) transporter expressed in the apical membrane of cells in tissues, such as the liver, intestine, kidney, testis, brain, and mammary gland. It is involved in xenobiotic pharmacokinetics, potentially affecting the efficacy and toxicity of many drugs. In this study, the role of ABCG2 in parasiticide monepantel (MNP) and its primary metabolite, monepantel sulfone (MNPSO2)'s systemic distribution and excretion in milk, was tested using female and male wild-type and Abcg2-/- mice. Liquid chromatography coupled with a tandem mass spectrometer (LC-MS/MS) was used for the analysis in a 10-min run time using positive-mode atmospheric pressure electrospray ionization (ESI+) and multiple reaction monitoring (MRM) scanning. For the primary metabolite tested, milk concentrations were 1.8-fold higher in wild-type mice than Abcg2-/- female lactating mice (P = 0.042) after intravenous administration of MNP. Finally, despite the lack of a difference between groups, we investigated potential differences in MNP and MNPSO2's plasma and tissue accumulation levels between wild-type and Abcg2-/- male mice. In this study, we demonstrated that MNPSO2 milk levels were affected by Abcg2, with potential pharmacological and toxicological consequences, contributing to the undesirable xenobiotic residues in milk.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Leche
/
Transportador de Casetes de Unión a ATP, Subfamilia G, Miembro 2
/
Antihelmínticos
Límite:
Animals
Idioma:
En
Revista:
Chem Biol Interact
Año:
2024
Tipo del documento:
Article
Pais de publicación:
Irlanda