A unique rodent model for both the cardiotoxic and hepatotoxic effects of prolonged iron overload.
BACKGROUND
Hemochromatosis is a disease of excessive iron storage leading to tissue damage and fibrosis. Both genetic hemochromatosis, which can affect 1 in 500 of some populations, and the form of this disease which occurs as a secondary consequence of the hemoglobinopathy, homozygous beta-thalassemia, with 40 million carriers worldwide, have a common pathology. The cardiotoxicity and hepatotoxicity, which occurs with this disease, have never been produced experimentally in other species.


METHODS
Using a regimen of iron dextran administered subcutaneously to gerbils on a weekly basis for 7 weeks, we have produced severe hemosiderosis, especially of the liver and heart. By examining gerbils at 1, 2 and 3 months after the final iron injections we followed the subsequent development of hemochromatosis in the hearts and livers of iron overloaded animals.


RESULTS
Hemochromatosis of the liver was evident as a scarring fibrosis in all cases between 1 and 3 months after iron dextran administration to gerbils. The iron burden in the cardiac myocytes of gerbils gradually increased between 1 and 3 months, resulting in hemochromatosis of the heart 2 and 3 months after the final iron dextran injections.


CONCLUSIONS
Repeated parenteral injections of iron dextran to gerbils resulted in hemochromatosis affecting the liver and heart with a pathology which is the same as occurs in the end-stage disease in man. This model will allow the detailed study of the mechanism of iron induced, free radical tissue damage, which is though to be the cause of these lesions and will also be useful in the evaluation of iron chelating therapies to determine whether the hepatic and cardiac pathology of iron overload can be modulated over a long period.
Carthew
P
P
MRC Toxicology Unit, University of Leicester, United Kingdom.
Dorman
B M
BM
Edwards
R E
RE
Francis
J E
JE
Smith
A G
AG
D000818:Animals; D003911:Dextrans; D004195:Disease Models, Animal; D005355:Fibrosis; D005849:Gerbillinae; D006321:Heart / Q000187:drug effects*; D006432:Hemochromatosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D007501:Iron / Q000378:metabolism* / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D009206:Myocardium / Q000473:pathology; D009336:Necrosis
D003911:Dextrans; D007501:Iron