STIMULATION OF MYOGLOBIN-DEPENDENT LIPID-PEROXIDATION BY ADRIAMYCIN

The objective of this investigation was to determine whether myoglobin can serve as a physiological source of iron in the catalysis of Adria mycin-stimulated lipid peroxidation. In vitro peroxidation of arachido nic acid was stimulated 2-fold by 50 mu M Adriamycin, the extent of li pid peroxidation being dependent on the duration of incubation and the concentrations of both Adriamycin and myoglobin. Differential inhibit ion studies suggest that hydroxyl radicals are involved in and is reac tion; however, superoxide and hydrogen peroxide were not implicated. T he results demonstrate a potentially important stimulation by Adriamyc in of myoglobin-dependent membrane-lipid peroxidation. In light of the abundance of myoglobin and the deficiency of oxygen radical detoxifyi ng enzymes in the heart, this interaction may be a significant determi nant of the cardioselective toxicity of Adriamycin. (C) 1994 Academic Press, Inc.