Effects of Lercanidipine on Fe2+-Induced Mitochondrial Lipid Peroxidation

Cardiac mitochondria were incubated with ferrous ion as catalyst of lipid peroxidation. Ferrous ions induced an increase in malondialdehyde (MDA) formation (from 1.24 ± 0.51 to 7.84 ± 1.66 nmol/mg protein; p < 0.01), and a significant reduction (p < 0.001) in mitochondrial oxygen consumption and calcium transporting capacity. Lercanidipine was used at two concentrations; 10−7 and 10−8M. Administration of lercanidipine at 10−8M failed to significantly prevent lipid peroxidation and mitochondrial damage, despite a trend toward protection. At the higher concentration of 10−7M, lercanidipine exerted significant protection because it reduced the formation of MDA (from 7.84 ± 1.66 to 4.19 ± 1.15 nmol/mg protein; p < 0.01), significantly improved all indices of mitochondrial function (RCI, QO2/3, QO2/4, and ADP/O), and prevented the ironmediated changes in mitochondrial calcium accumulation and retention capacity. These data indicate that lercanidipine at submicromolar concentrations prevents heart mitochondrial damage induced by lipid peroxidation.