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Oleic acid increases intestinal absorption of the BCRP/ABCG2 substrate, mitoxantrone, in mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Microbiology and Infectious Medicine.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
2015 (English)In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 237, no 2, 133-139 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2015. Vol. 237, no 2, 133-139 p.
Keyword [en]
Oleic acid, BCRP, Mitoxantrone, FVB mice, Intestinal absorption
National Category
Pharmacology and Toxicology
URN: urn:nbn:se:uu:diva-259082DOI: 10.1016/j.toxlet.2015.06.009ISI: 000357391500008PubMedID: 26071310OAI: oai:DiVA.org:uu-259082DiVA: diva2:843521
Available from: 2015-07-29 Created: 2015-07-27 Last updated: 2015-07-29Bibliographically approved

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Ilbäck, Nils-Gunnar
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