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 2.4g
oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 30, 60, 90 or 120min after exposure, or were exposed to 0.6, 2.4 or 4.8g
oleic acid/kg b.w. and 1mg MXR/kg b.w., and sacrificed 90min after exposure. Mice were also treated with Ko143 together with MXR and sacrificed after 60min, 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 120min 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.