Abstract

The efflux transporter breast cancer resistance protein (BCRP/ABCG2) decrease intestinal absorption of many food toxicants. Oleic acid increases absorption of the specific BCRP substrate mitoxantrone (MXR), and also BCRP gene expression in human intestinal Caco-2 cells, suggesting that oleic acid affect the BCRP function. Here, we investigated the effect of oleic acid on intestinal absorption of MXR in mice. Mice were orally dosed with 2.4 g oleic acid/kg b.w. and 1 mg MXR/kg b.w., and sacrificed 30, 60, 90 or 120 min after exposure, or were exposed to 0.6, 2.4 or 4.8 g oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 90 min after exposure. Mice were also treated with Ko143 together with MXR and sacrificed after 60 min, as a positive control of BCRP-mediated effects on MXR absorption. Absorption of MXR increased after exposure to oleic acid at all doses, and also after exposure to Ko143. Intestinal BCRP gene expression tended to increase 120 min after oleic acid exposure. Our results in mice demonstrate that oleic acid decreases BCRP-mediated efflux, causing increased intestinal MXR absorption in mice. These findings may have implications in humans, concomitantly exposed to oleic acid and food contaminants that, similarly as MXR, are substrates of BCRP. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Keywords

Oleic acid; BCRP; Mitoxantrone; FVB mice; Intestinal absorption

Published in

Toxicology Letters
2015, Volume: 237, number: 2, pages: 133-139
Publisher: ELSEVIER IRELAND LTD

SLU Authors

• Tallkvist, Jonas

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

Sustainable Development Goals

SDG3 Ensure healthy lives and promote well-being for all at all ages


UKÄ Subject classification

Pharmacology and Toxicology


Publication identifier

DOI: https://doi.org/10.1016/j.toxlet.2015.06.009

Permanent link to this page (URI)

https://res.slu.se/id/publ/75493