Lesjak, M; (2015) Role of polyphenols in iron homeostasis. Doctoral thesis , UCL (University College London).

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Abstract

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

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