Amlodipine Decreases Iron Uptake and Oxygen Free Radical Production in the Heart of Chronically Iron Overloaded Mice

Abstract

Hereditary hemochromatosis is a disorder of iron metabolism, which is currently the most prevalent autosomal recessive disorder in the world, with an expression of the homozygous form occurring in approximately 1 in 200 individuals of European descent. Approximately one third of patients with hemochromatosis die of iron-induced cardiac complications. Although the exact mechanism is not known, it is believed that the toxicity of excess iron in biological systems is due to its ability to catalyze the generation of harmful reactive oxygen free radical species (ROS), which can damage proteins, lipids, and DNA. There is preliminary evidence to suggest that nontransferrinbound iron uptake in the myocardium may occur through voltage-dependent L-type calcium channels, and that calcium channel blockers (CCBs) may possess antioxidant properties. Accordingly, the authors hypothesized that the administration of amlodipine besylate would (1) decrease iron uptake in the myocardium and (2) decrease oxygen free radical production as measured by cytotoxic aldehyde–derived peroxidation products in a murine model of iron overload cardiomyopathy. The findings show that the CCB amlodipine is partially effective in limiting iron uptake in the heart and significantly inhibits the production of ROS in chronically iron-loaded mice. These are important preliminary findings because they suggest that CCBs may have significance in the clinical management of genetic disorders of iron metabolism.