Potentiation of iron accumulation in cardiac myocytes during the treatment of iron overload in gerbils with the hydroxypyridinone iron chelator CP94.
Gerbils administered iron dextran are the only animal species which have been shown to develop hemochromatosis of the liver and heart in the same manner as transfusion dependent homozygous thalassemics. The iron chelating hydroxypyridinone, CP94, has been administered prophylactically to iron overloaded gerbils in a dosing regime which favors the formation of bidentate chelated iron, to examine the possibility of additional toxicity being caused to the liver and heart by the bidentate chelated iron complex. Hepatic iron accumulation was inhibited by CP94 administration for up to 6 weeks, but not after 20 weeks. Iron accumulation in the heart was increased significantly after 6 and 20 weeks of chelator treatment. Pathological changes in both organs were markedly more severe after 20 weeks in chelator treated animals. There was a higher incidence of cardiofibrosis and more extensive liver fibrosis in iron overloaded, chelator treated animals after 20 weeks.
Carthew
P
P
MRC Toxicology Unit, University of Leicester, UK.
Smith
A G
AG
Hider
R C
RC
Dorman
B
B
Edwards
R E
RE
Francis
J E
JE
D000818:Animals; D005849:Gerbillinae; D007501:Iron / Q000032:analysis* / Q000378:metabolism; D007505:Iron-Dextran Complex / Q000633:toxicity*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011728:Pyridones / Q000633:toxicity*
D011728:Pyridones; C068543:1,2-diethyl-3-hydroxypyridin-4-one; D007505:Iron-Dextran Complex; D007501:Iron