Enhanced iron removal from liver parenchymal cells in experimental iron
overload: liposome encapsulation of HBED and phenobarbital administration
YE Rahman, EA Cerny, EH Lau and BA Carnes
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.
Volume 62,
Issue 1,
pp. 209-213,
07/01/1983
Copyright © 1983 by The American Society of Hematology
