Desferri‐Exochelin, A Lipid Soluble Iron Chelator Effectively Removes Tissue Iron

Abstract

Chronic iron-overload is damaging to organs including the heart and liver. Better iron chelators are needed to treat this serious medical condition. We studied the uptake and distribution of the lipid-soluble, hexadentate iron chelator desferri-Exochelin (D-Exo) and its efficacy in removing iron from tissue in rodent models. 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 minutes. Uptake was high in the heart and liver, two organs especially susceptible to damage from clinical iron overload. To assess actual decreases in cardiac and hepatic iron in response to D-Exo, we studied mice loaded intraperitoneally (i.p.) with 42 mg of iron dextran (2100 mg/kg). 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 i.p. 4 days/wk for 8 wks (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 hr 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 i.p. rapidly diffuses into multiple organs, including the heart and liver, and effectively removes iron without apparent toxicity. Supported by NIH Grant HL55291