The ABCG2 protein in vitro transports the xenobiotic thiabendazole and increases the appearance of its residues in milk

• Published in: Environmental toxicology and pharmacology 2024-04, Vol.107, p.104421-104421, Article 104421
• Main Authors: Álvarez–Fernández, Laura, Blanco–Paniagua, Esther, Millán–García, Alicia, Velasco-Díez, Miriam, Álvarez, Ana I., Merino, Gracia
• Format: Article
• Language: English
• Subjects: ABCG2; Animals; ATP Binding Cassette Transporter, Subfamily G, Member 2 - genetics; ATP Binding Cassette Transporter, Subfamily G, Member 2 - metabolism; Cell culture; Dogs; Female; Lactation; MDCK–II; Mice; Milk - metabolism; Milk secretion; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Thiabendazole; Thiabendazole - chemistry; Thiabendazole - metabolism; Xenobiotics
• ISSN: 1382-6689; 1872-7077
• DOI: 10.1016/j.etap.2024.104421

Thiabendazole (TBZ) is a broad–spectrum anthelmintic and fungicide used in humans, animals, and agricultural commodities. TBZ residues are present in crops and animal products, including milk, posing a risk to food safety and public health. ABCG2 is a membrane transporter which affects bioavailability and milk secretion of xenobiotics. Therefore, the aim of this work was to characterize the role of ABCG2 in the in vitro transport and secretion into milk of 5–hydroxythiabendazole (5OH–TBZ), the main TBZ metabolite. Using MDCK–II polarized cells transduced with several species variants of ABCG2, we first demonstrated that 5OH–TBZ is efficiently in vitro transported by ABCG2. Subsequently, using Abcg2 knockout mice, we demonstrated that 5OH–TBZ secretion into milk was affected by Abcg2, with a more than 2–fold higher milk concentration and milk to plasma ratio in wild–type mice compared to their Abcg2–/– counterpart. •5OH-thiabendazole is in vitro transported by murine, human, ovine, and bovine ABCG2.•In vitro transport of 5OH-thiabendazole is affected by the bovine Y581S SNP.•ABCG2 transporter increases milk secretion of 5OH-thiabendazole.