Molecular Factors and Mechanisms Affecting Iron and Other Metal Excretion or Absorption in Health and Disease. The Role of Natural and Synthetic Chelators

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Abstract:

The maintenance of iron and other essential metal ion balance in humans is based on the presence of homeostatic mechanisms of regulatory absorption, storage, re-utilisation and excretion. There are a number of factors and mechanisms that can affect the level of iron excretion or absorption and overall body iron stores. Net iron loss due to increased iron excretion by comparison to dietary iron absorption is considered as one of the causes of iron deficiency anaemia. Body iron loss greater than normal has been shown in many other conditions. These include the increase in urinary iron excretion observed in iron loaded patients, the substantial reduction in serum ferritin and liver iron of ex-thalassaemia patients several years following bone marrow transplantation and the increase in iron excretion in normal individuals following long term sport activities. There are differences in the metabolism, mode of action, interactions with the iron pools and routes of iron excretion, of the iron chelating drugs deferiprone (L1), deferoxamine and other experimental chelators such as ICL670 in iron-loaded patients. Naturally occurring chelators and some synthetic drugs are known to bind iron and affect iron absorption and excretion. The molecular characteristics of naturally occurring or synthetic chelators can influence other aspects of iron metabolism in addition to iron absorption or excretion. Similar mechanisms and factors can affect the metabolism of other essential metals. The understanding of the mechanisms involved in iron excretion and their overall effects on body iron levels can facilitate the design of new chelators and improved therapeutic protocols for the treatment of conditions of iron and other metal metabolic imbalance and toxicity.

Keywords: chelators; deferiprone; iron absorption; iron deficiency; iron excretion; iron overload; metal ions; thalassaemia; toxicity

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/092986705774463030

Affiliations: Postgraduate Research Institute of Science, Technology, Environment and Medicine, 3, Ammochostou Street, Limassol 3021, Cyprus.

Publication date: November 1, 2005

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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