Expert Reviews in Molecular Medicine: http://www.expertreviews.org/
Accession information: Vol. 8; Issue 10; 9 May 2006 Abstract
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Factors that can contribute to, and those that can ameliorate, iron overload in the thalassaemias

Fabrizia Urbinati, Catherine Madigan and Punam Malik

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Figure 1. Factors that can contribute to, and those that can ameliorate, iron overload in the thalassaemias. (a) The three major causes of iron overload in thalassaemic patients are ineffective erythropoiesis and red blood cell (RBC) transfusion [both resulting in release of iron from degradation of haeme and haemoglobin (haeme degradation)] and increased gastrointestinal (GI) iron absorption as a result of the chronic anaemia. The plasma (pale blue area) transferrin (pink cylinder) becomes saturated and the non-transferrin-bound iron (NTBI; red circle) increases. NTBI affects parenchymal tissues (mainly the heart, liver, pancreas and the pituitary gland) through the formation of toxic free radicals, causing tissue damage. (b) Iron overload can be countered by iron-chelating agents [desferrioxamine (DFO), deferasirox and deferiprone]. Each molecule of DFO, deferasirox and deferiprone binds iron molecules in a molar ratio of 1:1, 2:1 and 3:1, respectively, and removes it from plasma through excretion in stool and urine. Hepcidin (purple circle) is a physiological peptide produced by the liver that has recently been found to be a major regulator of iron absorption. High levels of hepcidin cause hypoferraemia by decreasing intestinal iron absorption, blocking iron efflux from intestinal cells to plasma or from the macrophage to the erythron, and, by causing internalisation of ferroportin (green cylinder), trapping iron inside cells.