Fe.sup.3+ opposes the 1,25.sub.2D.sub.3-induced calcium transport across intestinal epithelium-like Caco-2 monolayer in the presence or absence of ascorbic acid

Although iron is an essential element for hemoglobin and cytochrome synthesis, excessive intestinal iron absorption-as seen in dietary iron supplementation and hereditary disease called thalassemia-could interfere with transepithelial transport of calcium across the intestinal mucosa. The underlying cellular mechanism of iron-induced decrease in intestinal calcium absorption remains elusive, but it has been hypothesized that excess iron probably negates the actions of 1,25-dihydroxyvitamin D [1,25(OH).sub.2 D.sub.3 ]. Herein, we exposed the 1,25(OH).sub.2 D.sub.3 -treated epithelium-like Caco-2 monolayer to FeCl.sub.3 to demonstrate the inhibitory effect of ferric ion on 1,25(OH).sub.2 D.sub.3 -induced transepithelial calcium transport. We found that a 24-h exposure to FeCl.sub.3 on the apical side significantly decreased calcium transport, while increasing the transepithelial resistance (TER) in 1,25(OH).sub.2 D.sub.3 -treated monolayer. The inhibitory action of FeCl.sub.3 was considered rapid since 60-min exposure was sufficient to block the 1,25(OH).sub.2 D.sub.3 -induced decrease in TER and increase in calcium flux. Interestingly, FeCl.sub.3 did not affect the baseline calcium transport in the absence of 1,25(OH).sub.2 D.sub.3 treatment. Furthermore, although ascorbic acid is often administered to maximize calcium solubility and to enhance intestinal calcium absorption, it apparently had no effect on calcium transport across the FeCl.sub.3 - and 1,25(OH).sub.2 D.sub.3 -treated Caco-2 monolayer. In conclusion, apical exposure to ferric ion appeared to negate the 1,25(OH).sub.2 D.sub.3 -stimulated calcium transport across the intestinal epithelium. The present finding has, therefore, provided important information for development of calcium and iron supplement products and treatment protocol for specific groups of individuals, such as thalassemia patients and pregnant women.