Aluminum and ABC transporter activity

• Published in: Environmental toxicology and pharmacology Vol. 108; p. 104451
• Main Authors: Oezen, Goezde, Kraus, Lisa, Schentarra, Eva-Maria, Bolten, Jan Stephan, Huwyler, Joerg, Fricker, Gert
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2024
• Subjects: ABC-transporter; Aluminum; Aluminum - toxicity; Animals; ATP Binding Cassette Transporter, Subfamily G, Member 2 - genetics; ATP Binding Cassette Transporter, Subfamily G, Member 2 - metabolism; ATP-Binding Cassette Transporters - metabolism; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Cell Line; Dogs; Fundulidae; Humans; Kidney function; Killifish; Madin Darby Canine Kidney Cells; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins - genetics; Multidrug Resistance-Associated Proteins - metabolism; Neoplasm Proteins - metabolism; Zinc Compounds; Killifish; ABC-transporter; Aluminum; Kidney function
• ISSN: 1382-6689; 1872-7077
• DOI: 10.1016/j.etap.2024.104451

Aluminum is the third most common element on Earth´s crust and despite its wide use in our workaday life it has been associated with several health risks after overexposure. In the present study the impact of aluminum salts upon ABC transporter activity was studied in the P-GP-expressing human blood-brain barrier cell line hCMEC/D3, in MDCKII cells overexpressing BCRP and MRP2, respectively, and in freshly isolated, functionally intact kidney tubules from Atlantic killifish (Fundulus heteroclitus), which express the analog ABC transporters, P-gp, Bcrp and Mrp2. In contrast to previous findings with heavy metals salts (cadmium(II) chloride or mercury(II) chloride), which have a strong inhibitory effect on ABC transporter activity, or zinc(II) chloride and sodium arsenite, which have a stimulatory effect upon ABC transport function, the results indicate no modulatory effect of aluminum salts on the efflux activity of the human ABC transporters P-GP, BCRP and MRP2 nor on the analog transporters P-gp, Bcrp and Mrp2. •Aluminum has no impact on ABC transporters in human blood brain barrier cells hCMEC/D3 and overexpressing MDCKII cells.•In isolated, functionally intact kidney tubules from killifish no effect of aluminum chloride upon P-gp, Mrp2 and Bcrp was observed.•This is in contrast to effects by cadmium and mercury (transporter inhibition) or arsenite and zinc (transporter stimulation)