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Forms of soluble iron in mouse stomach and duodenal lumen: significance for mucosal uptake

Published online by Cambridge University Press:  09 March 2007

Robert J. Simpson  and
T. J. Peters
Robert J. Simpson
Affiliation:
Division of Clinical Cell Biology, Clinical Research Centre, Watford Road, Harrow, Middlesex HA1 3UJ
T. J. Peters
Affiliation:
Division of Clinical Cell Biology, Clinical Research Centre, Watford Road, Harrow, Middlesex HA1 3UJ
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Abstract

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Stomach contents of mice fed on a standard rodent breeding diet contained 29–733 pM-soluble non-haem-iron. A very variable percentage (3–100, mean 49·3 (se 4·7), n 37) of this Fe was rapidly (half-life < 1–2 s) available for chelation by the strong Fe(II) chelator ferrozine, with little or no further Fe being available on addition of ascorbate. Ferrozine-available Fe could be detected in the duodenal lumen at concentrations up to 60 μM in vivo and after in vitro neutralization of stomach contents. No significant changes in quantity of stomach ferrozine-available Fe or soluble non-haem-Fe occurred in mice with adaptive enhancement of Fe absorption induced by chronic hypoxia. Electron paramagnetic resonance (e.p.r.) spectroscopy of the soluble portion of mouse stomach contents demonstrated a g = 4·3 signal (rhombic Fe(III)) equivalent to up to 20 % of soluble non-haem-Fe. The signal was unaffected by addition of excess ferrozine and increased on subsequent neutralization, suggesting redistribution of Fe from other e.p.r.-silent species. Solutions of Fe-nitrilotriacetate (NTA) (a synthetic Fe chelate used as a bioavailable, model Fe solution) were found to contain both rapidly and slowly ferrozine-available Fe (after addition of ascorbate) depending on pH, NTA:Fe ratio and the presence of Ca(II) ions. Fe-ascorbate mixtures (a model solution for Fe absorption studies) also contained ferrozine-available Fe. These results suggest the presence of Fe(II), rhombic Fe(III) and other e.p.r.-silent Fe species in the soluble fraction of mouse stomach contents. The ferrozine-available (Fe(II)) fraction is not limited by the reducing power in the diet, but by binding to ligands. Neutralization with bicarbonate leads to a loss of ferrozine-available Fe and increase in rhombic Fe(III) at the expense of both ferrozine-available and other e.p.r.-silent Fe species. The ferrozine-available Fe in mouse stomach and duodenal lumen can be related to Fe species present in model solutions used for in vitro studies of mucosal uptake mechanisms.

Keywords

Duodenal iron uptakeIron availabilityMouse
Type
Mineral Nutrition
Information
British Journal of Nutrition , Volume 63 , Issue 1 , January 1990 , pp. 79 - 89
Copyright
Copyright © The Nutrition Society 1990

References

REFERENCES

Barton, J.C., Conrad, M.E. & Parmley, R.T. (1983). Calcium inhibition of inorganic iron absorption in rats. Gastroenterology 84, 90–101.CrossRefGoogle ScholarPubMed
Becker, G., Huebers, H. & Rummel, W. (1979). Intestinal absorption of cobalt and iron: mode of interaction and subcellular distribution. Blut 38, 397–406.CrossRefGoogle ScholarPubMed
Berner, L.A., Miller, D.D. & Van Campen, D. (1986). Absorption of iron from ferric hydroxide polymers introduced into ligated rat duodenal segments. Journal of Nutrition 116, 259–264.CrossRefGoogle ScholarPubMed
Conrad, M.E., Foy, A.L., Williams, H.L. & Knospe, W.H. (1967). Effect of starvation and protein depletion on ferrokinetics and iron absorption. American Journal of Physiology 213, 557–565.CrossRefGoogle ScholarPubMed
Cox, T.M. & O'Donnell, M.W. (1981). Studies of the binding of iron by rabbit intestinal microvillus membranes. Biochemical Journal 194, 753–759.CrossRefGoogle ScholarPubMed
Cox, T.M. & Peters, T.J. (1979). The kinetics of iron uptake in vitro by human duodenal mucosa: studies in normal subjects. Journal of Physiology 289, 469–478.CrossRefGoogle ScholarPubMed
Davis, P.S., Luke, C.G. & Deller, D.J. (1967). Gastric iron binding protein in iron chelation by gastric juice. Nature 214, 1126.CrossRefGoogle ScholarPubMed
Dorey, C., Dickson, D.P.E., St Pierre, T.G., Pollard, R.K., Gibson, J.F., Simpson, R.J. & Peters, T.J. (1987). Iron species in iron ascorbate solutions at physiological pH. Biochemical Society Transactions 15, 688.CrossRefGoogle Scholar
Eastham, E.J., Bell, J.I. & Douglas, A.P. (1977). Iron-transport characteristics of vesicles of brush border and basolateral plasma membrane from the rat enterocyte. Biochemical Journal 164, 289–294.CrossRefGoogle ScholarPubMed
Forth, W. & Rummel, W. (1973). Iron absorption. Physiology Reviews 53, 724–792.CrossRefGoogle ScholarPubMed
Forth, W. & Schafer, S.G. (1987). Absorption of di- and trivalent iron. Experimental evidence. Arzneim- Forschung/Drug Research 37, 96–100.Google ScholarPubMed
Foy, A.L., Williams, H.L., Cortell, S. & Conrad, M.E. (1967). A modified procedure for the determination of non-haem iron in tissue. Analytical Biochemistry 18, 559–563.CrossRefGoogle Scholar
Glover, J. & Jacobs, A. (1971). Observations on iron in the jejunal lumen after a standard meal. Gut 12, 369–371.CrossRefGoogle ScholarPubMed
Greenberger, N.J., Ruppert, R.D. & Cuppage, E.E. (1967). Inhibition of intestinal iron transport induced by tetracycline. Gastroenterology 53, 590–599.CrossRefGoogle ScholarPubMed
Helbock, H.L. & Saltman, P. (1967). The transport of iron by rat intestine. Biochimica et Biophysica Acta 135, 979–990.CrossRefGoogle ScholarPubMed
Hopping, J.M. & Ruliffson, W.S. (1963). Effects of chelating agents on radioiron absorption and distribution in rats in vivo. American Journal of Physiology 205, 885–889.CrossRefGoogle ScholarPubMed
Huebers, H., Huebers, E. & Rummel, W. (1974). Dependence of increased iron absorption by iron-deficient rats on an elutable component of jejunal mucosa. Hoppe-Seyler's Zeitschrift für Physiologische Chemie 355, 1159–1161.Google Scholar
Hungerford, D.M. & Linder, M.C. (1983). Interactions of pH and ascorbate in intestinal iron absorption. Journal of Nutrition 113, 2615–2622.CrossRefGoogle ScholarPubMed
Jacobs, A. & Greenman, D.A. (1969). Availability of food iron. British Medical Journal i, 673–676.CrossRefGoogle Scholar
James, A.H. & Pickering, G.W. (1949). The role of gastric acidity in the pathogenesis of peptic ulcer. Clinical Science 8, 181–210.Google ScholarPubMed
Johnson, G., Jacobs, P. & Purves, L.R. (1983). Iron binding proteins of iron-absorbing rat intestinal mucosa. Journal of Clinical Investigation 71, 1467–1476.CrossRefGoogle ScholarPubMed
Kohler, G.D., Elvehjem, C.A. & Hart, E.B. (1936). Modifications of the bipyridine method for available iron. Journal of Biological Chemistry 113, 49–53.CrossRefGoogle Scholar
Lock, S. & Bender, A.E. (1980). Measurement of chemically-available iron in foods by incubation with human gastric juice in vitro. British Journal of Nutrition 43, 413–420.CrossRefGoogle ScholarPubMed
Manis, J.G. & Schachter, D. (1964). Active transport of iron by intestine mucosal iron pools. American Journal of Physiology 207, 893–900.CrossRefGoogle ScholarPubMed
Marx, J.J.M. & Aisen, P. (1981). Iron uptake by rabbit intestinal mucosal membrane vesicles. Biochimica et Biophysica Acta 649, 297–304.CrossRefGoogle ScholarPubMed
Muir, W.A., Hopfer, U. & King, M. (1984). Iron transport across brush border membranes from normal and iron-deficient mouse upper small intestine. Journal of Biological Chemistry 259, 4896–4903.CrossRefGoogle ScholarPubMed
Narasinga Rao, B.S. & Prabhavathi, T. (1978). An in vitro method for predicting the bioavailability of iron from foods. American Journal of Clinical Nutrition 31, 169–175.CrossRefGoogle Scholar
Pearson, W.N., Reich, M., Frank, H. & Salamat, L. (1967). Effects of dietary iron level on gut iron levels and iron absorption in the rat. Journal of Nutrition 92, 53–65.CrossRefGoogle ScholarPubMed
Peters, T.J., Raja, K.B., Simpson, R.J. & Snape, S. (1988). Mechanisms and regulation of intestinal iron absorption. Annals of the New York Academy of Sciences 526, 141–147.CrossRefGoogle ScholarPubMed
Raja, K.B., Simpson, R.J. & Peters, T.J. (1987a). Comparison of 59Fe3+ uptake in vitro and in vivo by mouse duodenum. Biochimica et Biophysica Acta 901, 52–60.CrossRefGoogle ScholarPubMed
Raja, K.B., Simpson, R.J. & Peters, T.J. (1987b). Effect of Ca2+ and Mg2+ on the uptake of Fe3+ by mouse intestinal mucosa. Biochimica et Biophysica Acta 923, 46–51.CrossRefGoogle ScholarPubMed
Reddy, M.B., Chidambaram, M.V., Fonseca, J. & Bates, G.W. (1986). Potential role of in vitro iron bioavailability studies in combatting iron deficiency: a study of the effects of phosvitin on iron mobilisation from pinto beans. Clinical Physiology and Biochemistry 4, 78–86.Google ScholarPubMed
Royston, J.P. (1983). Some techniques for assessing multivariate normality based on the Shapiro-Wilk W. Journal of the Royal Statistical Society 32C, 121–133.Google Scholar
Ruliffson, W.S. & Hopping, J.M. (1963). Maturation, iron deficiency and ligands in enteric iron absorption. American Journal of Physiology 207, 893–900.Google Scholar
Sanford, R. (1960). Release of iron from conjugates in food. Nature 185, 533–534.CrossRefGoogle Scholar
Savin, M.A. & Cook, J.D. (1980). Mucosal iron transport by rat intestine. Blood 56, 1029–1035.CrossRefGoogle ScholarPubMed
Shackleton, L. & McCance, R.A. (1936). The ionizable iron in foods. Biochemical Journal 30, 582–591.CrossRefGoogle Scholar
Simpson, R.J., Moore, R. & Peters, T.J. (1988). Significance of non-esterified fatty acids in iron uptake by intestinal brush border membrane vesicles. Biochimica et Biophysica Acta 941, 39–47.CrossRefGoogle ScholarPubMed
Simpson, R.J. & Peters, T.J. (1984). Studies of Fe3+ transport across intestinal brush border membrane of the mouse. Biochimica et Biophysica Acta 772, 220–226.CrossRefGoogle ScholarPubMed
Simpson, R.J. & Peters, T.J. (1985). Fe2+ uptake by intestinal brush border membrane of the mouse. Biochimica et Biophysica Acta 814, 381–388.CrossRefGoogle Scholar
Simpson, R.J. & Peters, T.J. (1986). Mouse intestinal Fe3+ uptake kinetics in vivo. The significance of brush-border membrane vesicle transport in the mechanism of mucosal Fe3+ uptake. Biochimica et Biophysica Acta 856, 115–122.CrossRefGoogle ScholarPubMed
Simpson, R.J. & Peters, T.J. (1987). Transport of Fe2+ across lipid bilayers: possible role of free fatty acids. Biochimica et Biophysica Acta 898, 187–195.CrossRefGoogle ScholarPubMed
Simpson, R.J., Raja, K.B. & Peters, T.J. (1986). Fe2+ uptake by mouse intestinal mucosa in vivo and by isolated intestinal brush border membrane vesicles. Biochimica et Biophysica Acta 860, 229–235.CrossRefGoogle ScholarPubMed
Stremmel, W., Lotz, G., Niederau, C., Teschke, R. & Strohmeyer, G. (1987). Iron uptake by rat duodenal microvillus membrane vesicles: evidence for a carrier mediated process. European Journal of Clinical Investigation 17, 136–145.CrossRefGoogle Scholar
Terato, K., Kiramatsu, Y. & Yoshino, Y. (1973). Studies on iron absorption. II. Transport mechanism of low molecular weight iron chelate in rat intestine. Digestive Diseases 18, 129–134.CrossRefGoogle ScholarPubMed
Thomson, A.B.R. & Valberg, L.S. (1971). Kinetics of intestinal iron absorption in the rat: effect of cobalt. American Journal of Physiology 220, 1080–1085.CrossRefGoogle ScholarPubMed
Webb, J., Multani, J.S., Saltman, P. & Gray, H.B. (1973). Spectroscopic and magnetic studies of iron(III) gastroferrin. Biochemistry 12, 265–267.CrossRefGoogle Scholar
Wetherill, G.B. (1967). Elementary Statistical Methods. London: Methuen and Co. Ltd.Google Scholar
Wheby, M.S. & Crosby, W.H. (1963). The gastrointestinal tract and iron absorption. Blood 22, 416–428.CrossRefGoogle ScholarPubMed
Wynter, C.V.A. & Williams, R. (1968). Iron-binding properties of gastric juice in idiopathic haemochromatosis. Lancet i, 534–537.CrossRefGoogle Scholar