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. 1996 May;38(5):765–769. doi: 10.1136/gut.38.5.765

A duodenal mucosal abnormality in the reduction of Fe(III) in patients with genetic haemochromatosis.

K B Raja 1, D Pountney 1, A Bomford 1, R Przemioslo 1, D Sherman 1, R J Simpson 1, R Williams 1, T J Peters 1
PMCID: PMC1383162  PMID: 8707126

Abstract

BACKGROUND--Previous in vitro studies have shown that the uptake of Fe(III) by freshly isolated duodenal mucosal biopsy specimens is increased in patients with genetic haemochromatosis. Moreover, in the mouse it has recently been found that reduction of Fe(III) to Fe(II) is a prerequisite for iron uptake by the proximal intestine. AIMS/METHODS--This study used the in vitro technique to investigate the rates of reduction and uptake of 59Fe(III) by duodenal mucosal biopsy specimens obtained at endoscopy from treated and untreated patients with genetic haemochromatosis. RESULTS--The rate of reduction of iron in the medium was proportional to the incubation time and was not caused by the release of reducing factors from the tissue fragments. Ferrozine, a specific Fe(II) chelator and ferricyanide, a non-permeable oxidising agent, inhibited uptake of 59Fe showing that reduction of Fe(III) precedes uptake. The rates (all values given as pmol/mg/min) of reduction (152 (49) v 92 (23)) and uptake (8.3 (4.0) v 3.6 (1.3), mean (SD)), were significantly increased in biopsy specimens from the untreated group (n = 6) compared with those from 10 control subjects (p < 0.04). Furthermore, the reduction and uptake rates were still increased in five patients in whom iron stores were normal after venesection treatment. CONCLUSIONS--These results show that there is a persistent abnormality in the reduction and uptake of iron by the intestine in genetic haemochromatosis.

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Selected References

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  1. Adams P. C., Kertesz A. E., Valberg L. S. Rate of iron reaccumulation following iron depletion in hereditary hemochromatosis. Implications for venesection therapy. J Clin Gastroenterol. 1993 Apr;16(3):207–210. doi: 10.1097/00004836-199304000-00008. [DOI] [PubMed] [Google Scholar]
  2. Boender C. A., Verloop M. C. Iron absorption, iron loss and iron retention in man: studies after oral administration of a tracer dose of 59FeSO4 and 131-BaSO4. Br J Haematol. 1969 Jul;17(1):45–58. doi: 10.1111/j.1365-2141.1969.tb05663.x. [DOI] [PubMed] [Google Scholar]
  3. CROSBY W. H. THE CONTROL OF IRON BALANCE BY THE INTESTINAL MUCOSA. Blood. 1963 Oct;22:441–449. [PubMed] [Google Scholar]
  4. Chidambaram M. V., Reddy M. B., Thompson J. L., Bates G. W. In vitro studies of iron bioavailability. Probing the concentration and oxidation-reduction of pinto bean iron with ferrous chromogens. Biol Trace Elem Res. 1989 Jan-Feb;19(1-2):25–40. doi: 10.1007/BF02925447. [DOI] [PubMed] [Google Scholar]
  5. Cowart R. E., Singleton F. L., Hind J. S. A comparison of bathophenanthrolinedisulfonic acid and ferrozine as chelators of iron(II) in reduction reactions. Anal Biochem. 1993 May 15;211(1):151–155. doi: 10.1006/abio.1993.1246. [DOI] [PubMed] [Google Scholar]
  6. Cox T. M. Haemochromatosis. Blood Rev. 1990 Jun;4(2):75–87. doi: 10.1016/0268-960x(90)90030-v. [DOI] [PubMed] [Google Scholar]
  7. Cox T. M., Peters T. J. Uptake of iron by duodenal biopsy specimens from patients with iron-deficiency anaemia and primary haemochromatosis. Lancet. 1978 Jan 21;1(8056):123–124. doi: 10.1016/s0140-6736(78)90420-8. [DOI] [PubMed] [Google Scholar]
  8. Dancis A., Klausner R. D., Hinnebusch A. G., Barriocanal J. G. Genetic evidence that ferric reductase is required for iron uptake in Saccharomyces cerevisiae. Mol Cell Biol. 1990 May;10(5):2294–2301. doi: 10.1128/mcb.10.5.2294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Edwards C. Q., Dadone M. M., Skolnick M. H., Kushner J. P. Hereditary haemochromatosis. Clin Haematol. 1982 Jun;11(2):411–435. [PubMed] [Google Scholar]
  10. Forth W., Rummel W. Iron absorption. Physiol Rev. 1973 Jul;53(3):724–792. doi: 10.1152/physrev.1973.53.3.724. [DOI] [PubMed] [Google Scholar]
  11. Francanzani A. L., Fargion S., Romano R., Piperno A., Arosio P., Ruggeri G., Ronchi G., Fiorelli G. Immunohistochemical evidence for a lack of ferritin in duodenal absorptive epithelial cells in idiopathic hemochromatosis. Gastroenterology. 1989 Apr;96(4):1071–1078. doi: 10.1016/0016-5085(89)91625-9. [DOI] [PubMed] [Google Scholar]
  12. Grebing C., Crane F. L., Löw H., Hall K. A transmembranous NADH-dehydrogenase in human erythrocyte membranes. J Bioenerg Biomembr. 1984 Dec;16(5-6):517–533. doi: 10.1007/BF00743243. [DOI] [PubMed] [Google Scholar]
  13. Lombard M., Bomford A. B., Polson R. J., Bellingham A. J., Williams R. Differential expression of transferrin receptor in duodenal mucosa in iron overload. Evidence for a site-specific defect in genetic hemochromatosis. Gastroenterology. 1990 Apr;98(4):976–984. doi: 10.1016/0016-5085(90)90022-s. [DOI] [PubMed] [Google Scholar]
  14. Lombard M., Bomford A., Hynes M., Naoumov N. V., Roberts S., Crowe J., Williams R. Regulation of the hepatic transferrin receptor in hereditary hemochromatosis. Hepatology. 1989 Jan;9(1):1–5. doi: 10.1002/hep.1840090102. [DOI] [PubMed] [Google Scholar]
  15. Marx J. J. Mucosal uptake, mucosal transfer and retention of iron, measured by whole-body counting. Scand J Haematol. 1979 Oct;23(4):293–302. doi: 10.1111/j.1600-0609.1979.tb02864.x. [DOI] [PubMed] [Google Scholar]
  16. Mueller S., Simpson R. J. Photoreduction of iron at physiological pH: effect of biological buffers. Biochem Soc Trans. 1994 May;22(2):93S–93S. doi: 10.1042/bst022093s. [DOI] [PubMed] [Google Scholar]
  17. Olynyk J. K. Genetic haemochromatosis--preventable rust. Aust N Z J Med. 1994 Dec;24(6):711–716. doi: 10.1111/j.1445-5994.1994.tb01789.x. [DOI] [PubMed] [Google Scholar]
  18. PIRZIO-BIROLI G., FINCH C. A. Iron absorption. III. The influence of iron stores on iron absorption in the normal subject. J Lab Clin Med. 1960 Feb;55:216–220. [PubMed] [Google Scholar]
  19. Pietrangelo A., Rocchi E., Casalgrandi G., Rigo G., Ferrari A., Perini M., Ventura E., Cairo G. Regulation of transferrin, transferrin receptor, and ferritin genes in human duodenum. Gastroenterology. 1992 Mar;102(3):802–809. doi: 10.1016/0016-5085(92)90161-q. [DOI] [PubMed] [Google Scholar]
  20. Pountney D. J., Simpson R. J. Mucosal surface ferricyanide reductase in mouse duodenum. Biochem Soc Trans. 1993 May;21(2):204S–204S. doi: 10.1042/bst021204s. [DOI] [PubMed] [Google Scholar]
  21. Powell L. A., Halliday J. W. Iron absorption and iron overload. Clin Gastroenterol. 1981 Sep;10(3):707–735. [PubMed] [Google Scholar]
  22. Powell L. W., Bassett M. L., Halliday J. W. Hemochromatosis: 1980 update. Gastroenterology. 1980 Feb;78(2):374–381. [PubMed] [Google Scholar]
  23. Powell L. W., Campbell C. B., Wilson E. Intestinal mucosal uptake of iron and iron retention in idiopathic haemochromatosis as evidence for a mucosal abnormality. Gut. 1970 Sep;11(9):727–731. doi: 10.1136/gut.11.9.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Raja K. B., Duane P., Snape S. D., Simpson R. J., Papasavvas G., Peters T. J. In vitro duodenal iron uptake and serum and mucosal iron protein levels, with special reference to rheumatoid arthritis. Br J Rheumatol. 1995 Nov;34(11):1041–1047. doi: 10.1093/rheumatology/34.11.1041. [DOI] [PubMed] [Google Scholar]
  25. Raja K. B., Simpson R. J., Peters T. J. Investigation of a role for reduction in ferric iron uptake by mouse duodenum. Biochim Biophys Acta. 1992 Jun 10;1135(2):141–146. doi: 10.1016/0167-4889(92)90129-y. [DOI] [PubMed] [Google Scholar]
  26. Sallee V. L., Wilson F. A., Dietschy J. M. Determination of unidirectional uptake rates for lipids across the intestinal brush border. J Lipid Res. 1972 Mar;13(2):184–192. [PubMed] [Google Scholar]
  27. Whittaker P., Skikne B. S., Covell A. M., Flowers C., Cooke A., Lynch S. R., Cook J. D. Duodenal iron proteins in idiopathic hemochromatosis. J Clin Invest. 1989 Jan;83(1):261–267. doi: 10.1172/JCI113868. [DOI] [PMC free article] [PubMed] [Google Scholar]

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