Exploring the "iron shuttle" hypothesis in chelation therapy: Effects of combined deferoxamine and deferiprone treatment in hypertransfused rats with labeled iron stores and in iron-loaded rat heart cells in culture

Gabriela Link, Abraham M. Konijn, William Breuer, Z. Ioav Cabantchik, Chaim Hershko*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

92 Scopus citations

Abstract

Although iron chelation therapy results in a significant improvement in well-being and life expectancy of thalassemic patients with transfusional iron overload, failure to achieve these goals in a substantial proportion of patients underlines the need for improved methods of treatment. In the present studies we used selective radioactive iron probes of hepatocellular and reticuloendothelial (RE) iron stores in hypertransfused rats and iron-loaded heart cells to compare the source of iron chelated in vivo by deferoxamine (DFO) or by deferiprone (L1) and its mode of excretion, to examine the ability of DFO and L1 to remove iron directly from iron-loaded myocardial cells, and to examine the mechanism of their combined interaction through a possible additive or synergistic effect. Our results indicate that L1 given orally is 1.6 to 1.9 times more effective in rats, on a weight-per-weight basis, than parenteral DFO in promoting the excretion of storage iron from parenchymal iron stores but shows no advantage over DFO in promoting RE iron excretion. Simultaneous administration of DFO and L1 results in an increase in chelating effect that is additive but not synergistic. The magnitude of this additive effect is identical to an increase in the equivalent (weight or molar) dose of DFO alone rather than the sum of the separate effects of L1 and DFO. This finding is most probably the result of a transfer of chelated iron from L1 to DFO. These observations may have practical implications for current efforts to design better therapeutic strategies for the management of transfusional iron overload.

Original languageAmerican English
Pages (from-to)130-138
Number of pages9
JournalJournal of Laboratory and Clinical Medicine
Volume138
Issue number2
DOIs
StatePublished - 2001

Bibliographical note

Funding Information:
Supported by grant DK54199 from the National Institute of Diabetes and Digestive and Kidney Diseases and by grant 197/99-2 from the Israel Science Foundation.

Fingerprint

Dive into the research topics of 'Exploring the "iron shuttle" hypothesis in chelation therapy: Effects of combined deferoxamine and deferiprone treatment in hypertransfused rats with labeled iron stores and in iron-loaded rat heart cells in culture'. Together they form a unique fingerprint.

Cite this