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Pathophysiology of iron toxicity

Britton, R.S., Ramm, G.A., Olynyk, J., Singh, R., O’Neill, R. and Bacon, B.R. (1994) Pathophysiology of iron toxicity. In: Hershko, C., Konijin, A.M. and Aisen, P., (eds.) Progress in Iron Research. Springer US, New York, USA, pp. 239-253.

Link to Published Version: http://dx.doi.org/10.1007/978-1-4615-2554-7_26
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Abstract

It has been shown that approximately 1 in 250–300 individuals of European descent are homozygous for the hemochromatosis gene, 1 thus identifying hereditary hemochromatosis as one of the most common inherited disorders. In both hereditary hemochromatosis and in the various forms of secondary iron overload, there is a pathologic expansion of body iron stores, due mainly to an increase in absorption of dietary iron. 2,3 Cellular uptake of circulating excess iron results in increased formation of ferritin and hemosiderin found in highest concentration in the parenchymal tissues of several organs (e.g., liver, heart, pancreas). At high tissue iron levels, fibrogenesis occurs in these organs accompanied by functional insufficiency. 2-6 Although best studied in the liver, pathological studies support this association in other organs affected in iron overload as well. Thus, clinical evidence for toxicity and fibrosis in hepatic iron overload has been provided by studies of patients with hereditary hemochromatosis, 4,5 African iron overload, 7 and secondary iron overload due to ß-thalassemia8 in which a correlation between hepatic iron concentration and the occurrence of liver damage has been demonstrated or in which therapeutic reduction of hepatic iron by either phlebotomy or chelation therapy has resulted in clinical improvement. Despite clinical evidence for the cellular and tissue toxicity of excess iron, the specific pathophysiologic mechanisms of tissue injury and fibrogenesis in chronic iron overload are still poorly understood.

Publication Type: Book Chapter
Publisher: Springer US
Copyright: Plenum Press
Notes: Series title: Advances in Experimental Medicine and Biology; No. 356
URI: http://researchrepository.murdoch.edu.au/id/eprint/19944
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