Heart cells in culture: A model of myocardial iron overload and chelation

The effect of iron loading and chelation was studied in heart cell cultures obtained from newborn rats. Radioactive iron uptake per 2 × 10⁶ cells/24 hr was 3.8% for ⁵⁹Fe-transferrin, 15.8% for ⁵⁹Fe-ferric ammonium citrate (FeAC) at 20 μg Fe/ml in 20% serum, and 37.1% for ⁵⁹FeAC at 20 μg Fe/ml in serum-free medium. About one third of the cellular radioactive iron was in ferritin and the rest in an insoluble lysosomal fraction. Iron uptake was almost completely inhibited by reducing the incubation temperature from 37 °C to 10 °C. Intracellular concentrations of malonyldialdehyde (MDA) were doubled after 15 minutes of iron loading and reached maximal concentrations at 3 hours. Conversely, iron mobilization by deferoxamine at concentrations ranging from 0.025 mmol/L to 0.3 mmol/L resulted in normalization of cellular MDA concentrations, in direct proportion to the amounts of iron removed. These findings indicate that cultured myocardial cells are able to assimilate large amounts of nontransferrin iron and that iron uptake and mobilization are associated with striking changes in lipid peroxidation as manifested by the respective increase and decrease in cellular MDA concentrations.