Enhanced iron removal from liver parenchymal cells in experimental iron overload: liposome encapsulation of HBED and phenobarbital administration.
The effectiveness of N,N'-bis[2-hydroxybenzyl]-ethylene-diamine-N,N'-diacetic acid (HBED) in removing radioiron introduced into the parenchymal cells of mouse liver as 59Fe-ferritin has been investigated. The effectiveness of HBED, an iron chelator of low water solubility, has also been compared with that of desferrioxamine (DF), an iron chelator of high water solubility and currently in clinical use for treatment of transfusional iron overload. Using the 59Fe excretion as the measure of effectiveness of chelation therapy and a standardized single chelator dose of 25 mg/kg, we have found that: (1) a saline suspension of HBED, prepared by sonication and given intraperitoneally to mice, promotes a small but significant increase in excretion of radioiron compared to the untreated controls, whereas DF, in its free form, is ineffective; (2) HBED encapsulated in lipid bilayers of liposomes and given intravenously is superior to nonencapsulated HBED; (3) DF encapsulated in small unilamellar liposomes is ineffective in removing iron given in the form of ferritin; (4) administration of phenobarbital in drinking water, at a concentration of 1 g/liter, induces a 30%-55% increase of iron excretion from untreated control mice and also from mice given HBED either in liposome-encapsulated or nonencapsulated form. We have demonstrated that HBED is superior to DF for removal of storage iron from liver parenchymal cells and that liposomes are useful carriers for iron chelators of low water solubility.
D000818:Animals; D003676:Deferoxamine / Q000494:pharmacology; D004492:Edetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005243:Feces / Q000032:analysis; D005293:Ferritins / Q000008:administration & dosage*; D007501:Iron / Q000302:isolation & purification* / Q000378:metabolism; D008081:Liposomes / Q000008:administration & dosage*; D008099:Liver / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D010634:Phenobarbital / Q000008:administration & dosage / Q000494:pharmacology*
D008081:Liposomes; C037740:N,N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid; D005293:Ferritins; D004492:Edetic Acid; D007501:Iron; D003676:Deferoxamine; D010634:Phenobarbital