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 ha ve been shown to develop hemochromatosis of the liver and heart in the same manner as transfusion dependent homozygous thalassemics. The iro n chelating hydroxypyridinone, CP94, has been administered prophylacti cally to iron overloaded gerbils in a dosing regime which favors the f ormation of bidentate chelated iron, to examine the possibility of add itional 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 accumu lation in the heart was increased significantly after 6 and 20 weeks o f chelator treatment. Pathological changes in both organs were markedl y more severe after 20 weeks in chelator treated animals. There was a higher incidence of cardiofibrosis and more extensive liver fibrosis i n iron overloaded, chelator treated animals after 20 weeks.