Deferasirox and deferiprone remove cardiac iron in the iron-overloaded gerbil.
BACKGROUND
Deferasirox effectively controls liver iron concentration; however, little is known regarding its ability to remove stored cardiac iron. Deferiprone seems to have increased cardiac efficacy compared with traditional deferoxamine therapy. Therefore, the relative efficacy of deferasirox and deferiprone were compared in removing cardiac iron from iron-loaded gerbils.


METHODS
Twenty-nine 8- to 10-week-old female gerbils underwent 10 weekly iron dextran injections of 200 mg/kg/week. Prechelation iron levels were assessed in 5 animals, and the remainder received deferasirox 100 mg/kg/D po QD (n = 8), deferiprone 375 mg/kg/D po divided TID (n = 8), or sham chelation (n = 8), 5 days/week for 12 weeks.


RESULTS
Deferasirox reduced cardiac iron content 20.5%. No changes occurred in cardiac weight, myocyte hypertrophy, fibrosis, or weight-to-dry weight ratio. Deferasirox treatment reduced liver iron content 51%. Deferiprone produced comparable reductions in cardiac iron content (18.6% reduction). Deferiprone-treated hearts had greater mass (16.5% increase) and increased myocyte hypertrophy. Deferiprone decreased liver iron content 24.9% but was associated with an increase in liver weight and water content.


CONCLUSIONS
Deferasirox and deferiprone were equally effective in removing stored cardiac iron in a gerbil animal model, but deferasirox removed more hepatic iron for a given cardiac iron burden.
Wood
John C
JC
Division of Cardiology, Childrens Hospital of Los Angeles, CA 90027-0034, USA. jwood@chla.usc.edu
Otto-Duessel
Maya
M
Gonzalez
Ignacio
I
Aguilar
Michelle I
MI
Shimada
Hiro
H
Nick
Hanspeter
H
Nelson
Marvin
M
Moats
Rex
R
D000818:Animals; D001565:Benzoates / Q000627:therapeutic use*; D000077588:Deferasirox; D000077543:Deferiprone; D004195:Disease Models, Animal; D005260:Female; D005849:Gerbillinae; D006321:Heart / Q000187:drug effects; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D019190:Iron Overload / Q000188:drug therapy* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011728:Pyridones / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use*
D001565:Benzoates; D007502:Iron Chelating Agents; D011728:Pyridones; D014230:Triazoles; D000077543:Deferiprone; D007501:Iron; D000077588:Deferasirox