Role of Quercetin on iron homeostasis

Iron is crucial in processes such as oxygen binding in haemoglobin, electron transport in mitochondria, cell proliferation and differentiation, etc. Insufficient iron regulation can lead to either accumulation of iron that enhances oxidative stress or iron deficiency leading to altered cell growth and metabolism. As there is no regulated physiological mechanism for excretion of iron, iron homeostasis is maintained primarily by regulating iron absorption. Dietary iron content and other dietary constituents can have a major impact on iron homeostasis. Flavonoids are a group of compounds found in the diet either naturally or added as food additives. Therefore interaction of these compounds with iron is of interest. Quercetin, one of the most abundant flavonols in the diet, is an effective iron chelator and also acts as an antioxidant by modulating expression of antioxidant enzymes. Both of these properties of quercetin therefore can have an effect on iron absorption. The aim of this work was to elucidate the effect of quercetin administered by gavage or intraperitionally (IP) on iron uptake. Sprague Dawley male rats, fed on an iron deficient or iron replete diet for two weeks, were used as the animal model. Gene expression of selected intestinal proteins (DMT1, FPN, Dcytb, GLUT1 and SGLT1) was quantitated by Real-time PCR. Intestinal iron absorption was measured in another group of animals using the in situ loop method and radioactive iron. Additionally, levels of iron and transferrin saturation in serum, and nonheme iron in duodenum, liver and spleen, were determined. Results were obtained during 13 different treatments on animal models. Study showed that quercetin affects iron homeostasis by changing expression of proteins involved in iron absorption in greater amount when administrated orally than IP. Furthermore, after longer oral treatment with quercetin, animals became iron deficient as both liver and spleen iron levels decreased significantly, 1.2 and 1.1 fold, respectively. These results confirmed negative effects of polyphenols on iron adsorption when consumed in a diet for a longer time. Additionally, when administrated orally, quercetin significantly upregulated SGLT1 transporter, namely 1.8 and 1.6 fold, 18 hours and 5 hours before being sacrificed. These results indicate that quercetin is probably transported by SGLT1 in the duodenum. Moreover, in uptake experiments where quercetin was introduced into the duodenum together with radioactive iron, there was a significant difference in levels of radioactive iron accumulated by duodenal mucosa (increase 2.7 fold) or transferred to serum (decrease 7.3 fold), compared to controls. The most probable explanation is that quercetin chelates iron, and that the complex is transported into enterocytes, but is not further transported into circulation. However, other uptake experiments showed no change in concentration of absorbed iron. Bearing in mind our results and the fact that there was no change in concentration of absorbed iron in the mucosa and circulation during uptake studies, further experiments are needed in order to get a more complete picture of how quercetin affects iron absorption.

Acknowledgements:

This study was carried out in the Laboratory of Professor Surjit Kaila Singh Srai, supported by a BBSRC project grant awarded to Professor Srai, UCL, London UK. This work was kindly supported by Dr. Willmar Schwabe Research Scholarship for Young Scientists awarded by the Society for Medicinal Plant and Natural Product Research and by the Ministry of Education and Sciences Republic of Serbia (Grant No. 172058).