The iron-loaded gerbil model revisited: effects of deferoxamine and deferiprone treatment.
Although the beneficial effects of deferoxamine (DFO) on iron-associated morbidity and mortality are well documented, the role of deferiprone (L1) in the management of transfusional iron overload is controversial. This debate involves not only the question of efficacy but also of safety, with particular emphasis on the risk of a paradoxical aggravation of iron toxicity by L1. We used the iron-loaded gerbil model introduced by Carthew et al to compare the chelating efficacy of L1, DFO, or both in two gerbil strains treated by means of weekly iron-dextran injections: Psammomys obesus and pathogen-free Mongolian gerbils (Meriones unguiculatus). The difference between the high mortality and advanced hepatocellular necrosis observed in iron-loaded P obesus and the absence of mortality and limited morbidity encountered in pathogen-free Mongolian gerbils is most likely explained by the prevention of coincidental laboratory infections in the latter group. Iron-chelating treatment in all experimental groups resulted in a significant decrease in hepatic iron concentrations and normalization of mitochondrial respiratory enzyme activities, with combined L1 and DFO treatment being the most efficient, followed, in decreasing order, by DFO and L1 as single-drug treatments. Judged by tissue iron concentrations, mitochondrial enzyme activity, and hepatic histology, we could find no evidence of a paradoxical aggravation of iron toxicity by L1 in either of the two series of studies. Although these data appear to be reassuring, the present controversy related to the role of L1 in the development of hepatic cirrhosis should be eventually settled by clinical studies evaluating the effects of long-term iron-chelating treatment.
Hershko
C
C
Department of Medicine, Shaare Zedek Medical Center, Jerusalem, Israel.
Link
G
G
Konijn
A M
AM
Huerta
M
M
Rosenmann
E
E
Reinus
C
C
D000818:Animals; D000077543:Deferiprone; D003676:Deferoxamine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005260:Female; D005849:Gerbillinae; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D011728:Pyridones / Q000627:therapeutic use*
D007502:Iron Chelating Agents; D011728:Pyridones; D000077543:Deferiprone; D003676:Deferoxamine