Quercetin inhibits intestinal non-haem iron absorption by regulating iron metabolism genes in the tissues

Marija Lesjak,Edward S. Debnam,Vernon Skinner,Sara Balesaria,Surjit Kaila S. Srai

doi:10.1007/s00394-018-1680-7

Abstract

PurposeThere is general agreement that some dietary polyphenols block non-haem iron uptake, but the mechanisms by which they achieve this action are poorly understood. Since the polyphenol quercetin is ingested daily in significant amounts, we have investigated the effect of quercetin on duodenal non-haem iron absorption in vivo, as well as its effect on factors known to be involved in systemic iron metabolism.MethodsRats were subject to gastric gavage and systemic quercetin administration. Treatments were followed with uptake studies using radiolabeled iron, serum iron and transferrin saturation measurements, LC-MS/MS analysis of quercetin metabolites in serum, determination of tissue non-haem iron content and analysis of gene expression of iron-related proteins.ResultsBoth oral and intraperitoneal (IP) quercetin caused serum and tissue iron depletion by two means, first by increasing mucosal iron uptake and inhibiting iron efflux from duodenal mucosa, and second by decreasing levels of duodenal DMT1, Dcytb and FPN. Additionally, IP quercetin induced highly significant increased liver expression of hepcidin, a hormone known to inhibit intestinal iron uptake.ConclusionsOral quercetin significantly inhibited iron absorption, while IP quercetin significantly affected iron-related genes. These results could lead to development of new effective ways of preventing and treating iron deficiency anaemia, the most widespread nutritional disorder in the world.

Highlights

Maintaining systemic iron levels within narrow limits is important for human health
The main aim of the gavage experiments was to investigate whether intake of quercetin influences non-haem iron absorption in the duodenum 5 or 18 h after administration of the polyphenol
For animals twice-gavaged with quercetin, 18 and 5 h before the uptake experiment, the effect on iron absorption was even more pronounced compared with that seen after single gavage

Summary

Introduction

Maintaining systemic iron levels within narrow limits is important for human health. Iron homeostasis is maintained by regulating the iron levels in plasma (transferrin-bound iron), which is maintained by four coordinated processes: duodenal iron absorption, macrophage iron recycling, hepatic iron storage and erythropoiesis [1]. Since there is no known physiological mechanism for controlling iron excretion and that macrophage-mediated iron recycling cannot be sufficient for maintaining erythropoiesis over the long term, especially during periods of growth and pregnancy, efficient duodenal absorption of dietary iron is critical for body iron homeostasis [1, 2]. Non-haem iron is mainly present in the diet as Fe3+ This must be reduced to the Fe2+ form to be available for absorption. By binding to FPN, hepcidin controls the main supply routes of iron into the circulation, such as iron absorbed from the diet in duodenal enterocytes, iron from macrophages liberated during recycling of senescent erythrocytes and iron which is stored in hepatocytes [6]. It was considered worthwhile to further investigate the effect of quercetin on duodenal non-haem iron absorption in vivo as well as its effect on systemic iron metabolism

Materials and methods

Results

Discussion

Compliance with ethical standards