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


OBJECTIVE
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.
Raja
K B
KB
Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London.
Pountney
D
D
Bomford
A
A
Przemioslo
R
R
Sherman
D
D
Simpson
R J
RJ
Williams
R
R
Peters
T J
TJ
D000704:Analysis of Variance; D001706:Biopsy; D016022:Case-Control Studies; D004386:Duodenum / Q000378:metabolism*; D005290:Ferric Compounds / Q000378:metabolism*; D005292:Ferricyanides / Q000008:administration & dosage; D005297:Ferrozine / Q000008:administration & dosage; D006432:Hemochromatosis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D007413:Intestinal Mucosa / Q000378:metabolism*; D007504:Iron Radioisotopes; D008875:Middle Aged; D010084:Oxidation-Reduction
D005290:Ferric Compounds; D005292:Ferricyanides; D007504:Iron Radioisotopes; D005297:Ferrozine