Role of polyphenols in iron homeostasis

Abstract

<p>Balancing systemic iron levels within narrow limits is critical for human health, as both<br />iron deficiency and overload lead to serious disorders. There are no known<br />physiologically controlled pathways to eliminate iron from the body and therefore iron<br />homeostasis is maintained by modifying dietary iron absorption. Several dietary factors,<br />such as polyphenols, are known to greatly affect iron absorption. Furthermore, it is<br />proposed that polyphenols can affect iron status by regulating expression and activity of<br />proteins involved in either the systemic regulation of iron metabolism or iron<br />absorption. To reveal how polyphenols affect iron metabolism, experiments which<br />included intraperitoneal (IP) or forced feeding (gavage) treatment of Sprague Dawley<br />rats with quercetin, polyphenol which is plentiful in the diet, were performed. These<br />treatments were followed by the evaluation of iron-related genes and iron content in<br />duodenum, liver, spleen, kidney and serum. Results revealed that quercetin treatment,<br />IP or gavage, provoked iron deficiency. Oral treatment mainly affected iron absorption,<br />mostly by changing the expression of iron transporters. Additionally, with in vivo<br />uptake studies it was shown that quercetin reduces duodenal iron uptake by direct<br />chelation of iron consequently increasing apical iron uptake and decreasing basolateral<br />iron release from enterocyte. IP treatment mainly affected systemic iron homeostasis,<br />mainly through up-regulation of hepcidin expression in liver and kidney. Additionally,<br />in in vitro studies quercetin metabolites and other polyphenols showed a notable effect<br />on hepcidin expression in human liver HepG2 cells, as well as on inflammatory and<br />iron-related genes in THP1 cells. Results showed that polyphenols have multiple effects<br />on iron homeostasis. Thus, polyphenols may have important consequences for<br />conditions that are low in iron such as anaemia. Alternatively, polyphenols have<br />therapeutic potential for iron overload diseases, potentially as a part of chelato-therapy.</p>