Quercetin inhibits intestinal iron absorption and ferroportin transporter expression in vivo and in vitro.

Marija Lesjak,Marija Lesjak,Marija Lesjak,Sara Balesaria,Sara Balesaria,Edward S Debnam,Paul A Sharp,Surjit K S Srai,Surjit K S Srai,Vernon Skinner,Rukshana Hoque,Vernon Skinner,James F Collins

doi:10.1371/journal.pone.0102900

Abstract

Balancing systemic iron levels within narrow limits is critical for maintaining human health. There are no known pathways to eliminate excess iron from the body and therefore iron homeostasis is maintained by modifying dietary absorption so that it matches daily obligatory losses. Several dietary factors can modify iron absorption. Polyphenols are plentiful in human diet and many compounds, including quercetin – the most abundant dietary polyphenol – are potent iron chelators. The aim of this study was to investigate the acute and longer-term effects of quercetin on intestinal iron metabolism. Acute exposure of rat duodenal mucosa to quercetin increased apical iron uptake but decreased subsequent basolateral iron efflux into the circulation. Quercetin binds iron between its 3-hydroxyl and 4-carbonyl groups and methylation of the 3-hydroxyl group negated both the increase in apical uptake and the inhibition of basolateral iron release, suggesting that the acute effects of quercetin on iron transport were due to iron chelation. In longer-term studies, rats were administered quercetin by a single gavage and iron transporter expression measured 18 h later. Duodenal FPN expression was decreased in quercetin-treated rats. This effect was recapitulated in Caco-2 cells exposed to quercetin for 18 h. Reporter assays in Caco-2 cells indicated that repression of FPN by quercetin was not a transcriptional event but might be mediated by miRNA interaction with the FPN 3′UTR. Our study highlights a novel mechanism for the regulation of iron bioavailability by dietary polyphenols. Potentially, diets rich in polyphenols might be beneficial for patients groups at risk of iron loading by limiting the rate of intestinal iron absorption.

Highlights

Iron is an essential transition metal that plays an important role in all mammalian organisms
Based on the data from our current study we discuss four possible mechanisms that might underlie the inhibitory effects of quercetin on intestinal iron transport: 1. Iron chelation; 2
We argued that iron chelation by quercetin could play important role in this phenomenon

Summary

Introduction

Iron is an essential transition metal that plays an important role in all mammalian organisms It is incorporated into a diverse array of proteins, including the oxygen carriers haemoglobin and myoglobin, cytochrome complexes involved in electron transfer in the mitochondria, and enzymes participating in nucleic acid processing such as ribonucleotide reductase [1,2]. Non-haem iron is present almost entirely in the ferric (Fe3+) form; to be bioavailable it must first be reduced to ferrous (Fe2+). This is achieved by the combined action of duodenal cytochrome b (Dcytb), a ferri-reductase which resides on the apical membrane of duodenal enterocytes [5,6], or exogenous dietary reducing agents, such as ascorbic acid (reviewed in [4]). Ferrous iron is transferred across the basolateral membrane of the enterocyte via the iron exporter, ferroportin (FPN) [8,9,10] and re-oxidized by ferroxidase hephaestin [11] on the basolateral surface, prior to loading onto transferrin

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