Transport of 14C-deferiprone in normal, thalassaemic and sickle red blood cells.
The transport of deferiprone (L1) in normal (N), sickle (S) and thalassaemic (T) red blood cells (RBC) was determined by incubation with 14C-L1 at 37 degrees C. Following incubation with 0.5 mM 14C-L1 for 4 h, the intracellular concentration of L1 in T RBC was 3 times higher than was found extracellularly. In contrast, no concentration gradient across N and S RBC membranes was detected. Efflux studies showed that T RBC released only 17 +/- 2% of 14C-L1 into the extracellular space. We hypothesize that L1 accumulation in T RBC results from their high content of chelatable iron and formation of large, hydrophilic L1-Fe(III) complexes trapped within the cytosol.
Shalev
O
O
Department of Medicine, Hadassah University Hospital, Jerusalem, Israel. odeds@cc.huji.ac.il
Hileti
D
D
Nortey
P
P
Hebbel
R P
RP
Hoffbrand
V A
VA
D000328:Adult; D000755:Anemia, Sickle Cell / Q000378:metabolism*; D001692:Biological Transport; D000077543:Deferiprone; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D007502:Iron Chelating Agents / Q000493:pharmacokinetics*; D011728:Pyridones / Q000493:pharmacokinetics*; D013789:Thalassemia / Q000378:metabolism*
D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone