Polyphenol‐Rich Beverages Enhance Zinc Uptake and Metallothionein Expression in Caco‐2 Cells

Kilari, Sreenivasulu; Pullakhandam, Raghu; Nair, K. Madhavan

doi:10.1111/j.1750-3841.2010.01582.x

Cited by 52 publications

(44 citation statements)

References 28 publications

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“…Another possible explanation for this behavior is based on the metal chelating ability of polyphenols, which is related to the presence of ortho-dihydroxy polyphenol, i.e., molecules bearing catechol or galloyl groups and condensed tannins; the possibility of occurrence of chelation in physiological pH also supports the physiological significance of this phenomenon [23]. In tune with our finding, in an in vitro study, polyphenol-rich beverages such as red wine, red grape juice, and green tea or certain specific polyphenols (tannic acid and quercetin) have the ability to enhance the uptake of zinc in Caco-2 cells [24]. Luminal interactions with ligands have drastic consequences for the bioavailability of metals.…”

Section: Discussionsupporting

confidence: 59%

Effects of Long-Term Use of Flavonoids on the Absorption and Tissue Distribution of Orally Administered Doses of Trace Elements in Rats

Jaccob¹,

Hussain²

2012

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The risk of pharmacokinetic polyphenols-trace elements interaction may undesirable therapeutic outcomes. We evaluate the long-term use of silibinin, epigallocatechin (ECGC), quercetin and rutin on the absorption and tissue distribution of zinc, copper and iron after single oral doses in rats. Five groups of rats received either with olive oil as control or one of the polyphenols silibinin, EPGC, quercetin or rutin, administered orally as oily solutions for 30 days. At day 30, a solution contains sulphate salt of zinc, copper and iron was administered orally; 3 hrs later blood samples, tissues of brain, kidney and liver were obtained for evaluation of the elements levels. The results showed that the polyphenols increased both serum and tissue levels of these elements compared with controls. This effect was relatively varied according to the structural differences among flavonoids. In conclusion, long-term use of supraphysiological doses of flavonoids increase absorption of Zn, Cu and Fe and their tissue availability in brain, kidney and liver; this effect seems to be different with variations in structural features.

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Section: Discussionsupporting

confidence: 59%

Effects of Long-Term Use of Flavonoids on the Absorption and Tissue Distribution of Orally Administered Doses of Trace Elements in Rats

Jaccob¹,

Hussain²

2012

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“…28 More recently, QCT was shown to enhance zinc uptake by Caco-2 cells, increasing total zinc accumulation and MT expression. 29 In contrast, grape seed flavonoids, produced a reduction in apical zinc uptake in Caco-2 cells, similar to that produced by phytate, whereas EGCG did not alter zinc absorption. 30 In prostate cancer cells, EGCG accelerated the accumulation of total zinc in the cytosol and mitochondria.…”

Section: Introductionmentioning

confidence: 83%

Zinc Ionophore Activity of Quercetin and Epigallocatechin-gallate: From Hepa 1-6 Cells to a Liposome Model

Dabbagh-Bazarbachi¹,

Clergeaud²,

Quesada

et al. 2014

J. Agric. Food Chem.

100

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Labile zinc, a tiny fraction of total intracellular zinc that is loosely bound to proteins and easily interchangeable, modulates the activity of numerous signaling and metabolic pathways. Dietary plant polyphenols such as the flavonoids quercetin (QCT) and epigallocatechin-gallate act as antioxidants and as signaling molecules. Remarkably, the activities of numerous enzymes that are targeted by polyphenols are dependent on zinc. We have previously shown that these polyphenols chelate zinc cations and hypothesized that these flavonoids might be also acting as zinc ionophores, transporting zinc cations through the plasma membrane. To prove this hypothesis, herein, we have demonstrated the capacity of QCT and epigallocatechin-gallate to rapidly increase labile zinc in mouse hepatocarcinoma Hepa 1-6 cells as well as, for the first time, in liposomes. In order to confirm that the polyphenols transport zinc cations across the plasma membrane independently of plasma membrane zinc transporters, QCT, epigallocatechin-gallate, or clioquinol (CQ), alone and combined with zinc, were added to unilamellar dipalmitoylphosphocholine/cholesterol liposomes loaded with membrane-impermeant FluoZin-3. Only the combinations of the chelators with zinc triggered a rapid increase of FluoZin-3 fluorescence within the liposomes, thus demonstrating the ionophore action of QCT, epigallocatechin-gallate, and CQ on lipid membrane systems. The ionophore activity of dietary polyphenols may underlay the raising of labile zinc levels triggered in cells by polyphenols and thus many of their biological actions.

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“…Similarly, the results of our current study also showed that GT had no effect on the transepithelial transport and apical uptake of 65 Zn in fully differentiated Caco-2 cells grown on microporous membrane inserts. Interestingly, a recent study proposed that green tea might enhance zinc absorption (14). The addition of green tea stimulated apical zinc uptake in intestinal Caco-2 cells grown in a 6-well plate and incubated for 3 h (14).…”

Section: Discussionmentioning

confidence: 99%

“…While bioactive dietary polyphenols are known to have no effect on zinc absorption in animals and humans (8–11), some studies indicated that dietary polyphenols decrease zinc absorption in animals (12–13). In addition, a recent study suggested that some polyphenol-rich beverages, such as green tea, red wine and red grape juice, could enhance zinc absorption by increasing apical zinc uptake (14). Thus, while it is not clear whether dietary polyphenols affect zinc absorption, these previous studies have suggested that some dietary polyphenols may modulate intestinal zinc absorption and metabolism.…”

Section: Introductionmentioning

confidence: 99%

“…On confluence, these cells spontaneously differentiate to exhibit many of the morphological and functional features of normal mature small intestinal enterocytes and have been widely used as a model of normal human intestinal epithelium (20–21). In particular, fully differentiated Caco-2 cells are a well-established in vitro model of human intestinal zinc absorption and metabolism (14, 22–24)…”

Section: Introductionmentioning

confidence: 99%

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Effect of Bioactive Dietary Polyphenols on Zinc Transport across the Intestinal Caco-2 Cell Monolayers

Kim

Pai

Han

2011

J. Agric. Food Chem.

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Polyphenolic compounds are known to possess many beneficial health effects, including the antioxidative activities of scavenging reactive oxygen species and chelating metals, such as iron and zinc. Tea and red wine are thought to be important sources of these compounds. However, some polyphenolic compounds can also reduce the absorption of iron, and possibly other trace metals, when included in a diet. There is very little information on the effect of dietary polyphenolic compounds on the status of trace elements other than iron. We examined the effects of epigallocatechin-3-gallate (EGCG), green tea extract (GT) and grape seed extract (GSE) on the absorption of 65Zn and compared them with their effects on 55Fe absorption in human intestinal Caco-2 cells grown on microporous membrane inserts. The levels of EGCG, GT and GSE used in this study were within the physiological ranges and did not affect the integrity of the Caco-2 cell monolayers. GSE significantly (P < 0.05) reduced zinc transport across the cell monolayer, and the decreased zinc transport was associated with a reduction in apical zinc uptake. However, EGCG and GT did not alter zinc absorption. In contrast, the polyphenolic compounds in EGCG, GT and GSE almost completely blocked transepithelial iron transport across the cell monolayer. The effect of GSE on zinc absorption was very different from that on iron absorption. While GSE decreased zinc absorption by reducing apical zinc uptake, the polyphenolic compounds inhibited iron absorption by enhancing apical iron uptake. GSE inhibited zinc absorption similarly to that observed for phytate. Phytate significantly (P < 0.05) decreased transepithelial zinc transport by reducing apical zinc uptake. The inhibition of zinc absorption may be due to the presence of procyanidins in GSE, which bind zinc with high affinity and block the transport of zinc across the apical membrane of enterocytes. Further research on the absorption of zinc as zinc-polyphenol complexes and free zinc should provide further insight into the process of dietary zinc absorption in the presence of GSE and other bioactive dietary polyphenols. The present study suggests that some individuals should consider their zinc status if they regularly consume procyanidin-containing foods in their diet. However, further studies, especially in vivo studies, are needed to confirm these results.

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Polyphenol‐Rich Beverages Enhance Zinc Uptake and Metallothionein Expression in Caco‐2 Cells

Cited by 52 publications

References 28 publications

Effects of Long-Term Use of Flavonoids on the Absorption and Tissue Distribution of Orally Administered Doses of Trace Elements in Rats

Effects of Long-Term Use of Flavonoids on the Absorption and Tissue Distribution of Orally Administered Doses of Trace Elements in Rats

Zinc Ionophore Activity of Quercetin and Epigallocatechin-gallate: From Hepa 1-6 Cells to a Liposome Model

Effect of Bioactive Dietary Polyphenols on Zinc Transport across the Intestinal Caco-2 Cell Monolayers

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