Effects of dietary and physiological factors on Fe transport and metabolism by human intestinal Caco-2 cells

The Caco-2 human intestinal cell line was selected as a potential model for the study of iron bioavailability and absorption because confluent cultures spontaneously differentiate into polarized, enterocyte-like cells. Initially, the influence of several dietary factors on Fe uptake and transport by Caco-2 intestinal cells were examined. Both the uptake and transport of nonheme Fe were decreased by inositol hexaphosphate and its lesser phosphorylated metabolites. In contrast, ascorbic acid enhanced the cellular acquisition and transport of this micronutrient, even in the presence of inositol phosphates. These and other data support the usefulness of the Caco-2 cell line as an appropriate model for investigating qualitative and quantitative effects of various dietary factors on iron bioavailability for humans

Ascorbic Acid Offsets the Inhibitory Effect of Bioactive Dietary Polyphenolic Compounds on Transepithelial Iron Transport in Caco-2 Intestinal Cells12

We previously reported that (-)-epigallocatechin-3-gallate (EGCG) and grape seed extract (GSE) at high concentration nearly blocked intestinal iron transport across the enterocyte. In this study, we aimed to determine whether small amounts of EGCG, GSE, and green tea extract (GT) are capable of inhibiting iron absorption, to examine if ascorbic acid counteracts the inhibitory action of polyphenols on iron absorption, and to explore the mechanisms of polyphenol-mediated apical iron uptake and basolateral iron release. An55Fe absorption study was conducted by adding various concentrations of EGCG, GSE, and GT using Caco-2 intestinal cells. Polyphenols were found to inhibit the transepithelial 55Fe transport in a dose-dependent manner. The addition of ascorbic acid offset the inhibitory effects of polyphenols on iron transport. Ascorbic acid modulated the transepithelial iron transport without changing the apical iron uptake and the expression of ferroportin-1 protein in the presence of EGCG. The polyphenol-mediated apical iron uptake was inhibited by membrane impermeable Fe2+ chelators (P < 0.001), but at a low temperature (4°C), the apical iron uptake was still higher than the control values at 37°C (P < 0.001). These results suggest that polyphenols enhance the apical iron uptake partially by reducing the conversion of ferric to ferrous ions and possibly by increasing the uptake of polyphenol-iron complexes via the energy-independent pathway. The present results indicate that the inhibitory effects of dietary polyphenols on iron absorption can be offset by ascorbic acid. Further studies are needed to confirm the current findings in vivo