Desferri-Exochelin, a lipid-soluble, hexadentate iron chelator, effectively removes tissue iron

Yvonne K. Hodges; Howard D. Weinberger; Janet Stephens; Marcus A. Horwitz; Lawrence D. Horwitz

doi:10.1016/j.trsl.2006.03.003

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Desferri-Exochelin, a lipid-soluble, hexadentate iron chelator, effectively removes tissue iron

Journal article

Peer reviewed

Desferri-Exochelin, a lipid-soluble, hexadentate iron chelator, effectively removes tissue iron

Yvonne K. Hodges, Howard D. Weinberger, Janet Stephens, Marcus A. Horwitz and Lawrence D. Horwitz

Translational research : the journal of laboratory and clinical medicine, Vol.148(2), pp.63-71

08/01/2006

DOI: 10.1016/j.trsl.2006.03.003

PMID: 16890146

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Abstract

Chronic iron-overload is damaging to the heart, liver, and other organs. Better iron chelators are needed to treat this serious medical condition. The uptake and distribution of the lipid-soluble, hexadentate iron chelator desferri-Exochelin 772SM (D-Exo) is studied and its efficacy in removing iron from tissue in rodent models is evaluated. After an intravenous bolus of tritiated D-Exo to rats, counts rapidly disappeared from the blood and rapidly appeared in 15 organs studied, usually peaking within 15 min. There was considerable uptake in the heart and liver, 2 organs especially susceptible to damage from clinical iron overload. To assess actual decreases in cardiac and hepatic iron in response to D-Exo, mice loaded with 42 mg of iron dextran (2100 mg/kg) were studied. Untreated, iron-loaded mice sacrificed 9 weeks later had a 4-fold increase in cardiac iron and a 20-fold increase in hepatic iron compared with controls that were not iron-loaded. In iron-loaded mice treated with 7 mg of D-Exo intraperitoneally (i.p.) 4 days/week for 8 weeks (total 224 mg), tissue iron, measured by atomic absorption, was reduced by 20% in the liver and 25% in the heart ( P < 0.01 for each organ). During the first 8 h after a D-Exo dose, iron was excreted in the urine. Mice treated with D-Exo gained weight normally and showed no evidence of toxicity. In conclusion, in this iron-overload mouse model, D-Exo administered intravenously or i.p. rapidly diffuses into multiple organs, including the heart and liver, and effectively removes iron without apparent toxicity.

D-Exo

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Details

Title: Subtitle: Desferri-Exochelin, a lipid-soluble, hexadentate iron chelator, effectively removes tissue iron
Creators: Yvonne K. Hodges - University of Colorado Health
Howard D. Weinberger - Department of Cardiology, Colorado Health Sciences Center, Denver, Colo
Janet Stephens - Department of Pathology, Exempla St. Joseph Hospital, Denver, Colo
Marcus A. Horwitz - University of California, Los Angeles
Lawrence D. Horwitz - Department of Cardiology, Colorado Health Sciences Center, Denver, Colo
Resource Type: Journal article
Publication Details: Translational research : the journal of laboratory and clinical medicine, Vol.148(2), pp.63-71
DOI: 10.1016/j.trsl.2006.03.003
PMID: 16890146
NLM abbreviation: Transl Res
ISSN: 1931-5244
eISSN: 1878-1810
Publisher: Mosby, Inc
Language: English
Date published: 08/01/2006
Academic Unit: Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984656528002771

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