Assessing the role of the ABCG2 transporter in plasma levels and secretion into milk of aflatoxins B2 and G1

[EN] Aflatoxins are highly toxic food contaminants frequently detected in cereals and animal–derived products, with milk representing a relevant route of exposure for both animals and humans. Although milk safety assessments have predominantly focused on aflatoxin M1 (AFM1), aflatoxins B2 (AFB2) and...

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Detalles Bibliográficos
Autores: Álvarez Fernández, Laura, Millán García, Alicia, Blanco Paniagua, Esther, López García, Álvaro, Merino Peláez, Gracia
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Universidad de León
Repositorio:BULERIA. Repositorio Institucional de la Universidad de León
OAI Identifier:oai:buleria.unileon.es:10612/27810
Acceso en línea:https://hdl.handle.net/10612/27810
Access Level:acceso abierto
Palabra clave:Fisiología
ABCG2
Aflatoxin B2
Aflatoxin G1
Milk
Mycotoxins
Transport
2410.10 Fisiología Humana
Descripción
Sumario:[EN] Aflatoxins are highly toxic food contaminants frequently detected in cereals and animal–derived products, with milk representing a relevant route of exposure for both animals and humans. Although milk safety assessments have predominantly focused on aflatoxin M1 (AFM1), aflatoxins B2 (AFB2) and G1 (AFG1) have been detected in dairy products and human breast milk. However, the physiological mechanisms governing their biodistribution and secretion into milk remain poorly characterized. Given the central role of ABCG2 in xenobiotic disposition, and the previous evidence of ABCG2–mediated transport of aflatoxin B1 (AFB1) and AFM1, we investigated the contribution of this transporter to the in vitro transport, plasma levels and milk secretion of AFB2 and AFG1. Transepithelial transport assays were conducted using polarized MDCK–II cells overexpressing species–specific ABCG2 variants, followed by in vivo lactation studies in wild–type and Abcg2−/− mice. In vitro, both AFB2 and AFG1 exhibited pronounced basolateral–to–apical transport, with up to 40–fold higher relative efflux ratios in ABCG2–expressing subclones, confirming them as ABCG2 substrates across murine, ovine, bovine, and human variants. In vivo, Abcg2 deficiency resulted in significantly reduced milk concentrations and milk–to–plasma ratios of both aflatoxins, accompanied by increased plasma levels. For AFB2, milk concentrations were approximately two–fold higher and milk–to–plasma ratios three–fold higher in wild–type compared with Abcg2−/− mice, with comparable trends observed for AFG1. Together, these results identify ABCG2 as a key determinant of AFB2 and AFG1 plasma levels and transfer into milk, providing novel mechanistic insight into the active transport of aflatoxins across biological barriers, particularly the mammary gland.