A UNIQUE RODENT MODEL FOR BOTH THE CARDIOTOXIC AND HEPATOTOXIC EFFECTS OF PROLONGED IRON OVERLOAD

BACKGROUND: Hemochromatosis is a disease of excessive iron storage lea ding to tissue damage and fibrosis. Both genetic hemochromatosis, whic h can affect 1 in 500 of some populations, and the form of this diseas e which occurs as a secondary consequence of the hemoglobinopathy, hom ozygous beta-thalassemia, with 40 million carriers worldwide, have a c ommon pathology. The cardiotoxicity and hepatotoxicity, which occurs w ith this disease, have never been produced experimentally in other spe cies. EXPERIMENTAL DESIGN: Using a regime of iron dextran administered subcutaneously to gerbils on a weekly basis for 7 weeks, we have prod uced severe hemosiderosis, especially of the liver and heart. By exami ning gerbils at 1, 2 and 3 months after the final iron injections we f ollowed the subsequent development of hemochromatosis in the hearts an d livers of iron overloaded animals. RESULTS: Hemochromatosis of the l iver was evident as a scarring fibrosis in all cases between 1 and 3 m onths after iron dextran administration to gerbils. The iron burden in the cardiac myocytes of gerbils gradually increased between 1 and 3 m onths, resulting in hemochromatosis of the heart 2 and 3 months after the final iron dextran injections. CONCLUSIONS: Repeated parenteral in jections of iron dextran to gerbils resulted in hemochromatosis affect ing the liver and heart with a pathology which is the same as occurs i n the end-stage disease in man. This model will allow the detailed stu dy of the mechanism of iron induced, free radical tissue damage, which is thought to be the cause of these lesions and will also be useful i n the evaluation of iron chelating therapies to determine whether the hepatic and cardiac pathology of iron overload can be modulated over a long period.