Comparison of Lipid Peroxidation and Myocardial Damage Induced by Adriamycin and 4′-Epiadriamycin in Mice

Adriamycin (ADM) and 4'-epiadriamycin (4'-ADM) were given to mice in a single dose of 15 mg/kg body weight (i.p.). Twenty-five mice were alloted to 3 groups. One group (Group I; n = 8) was given ADM; another group (Group II; n = 9) was similarly treated with 4'-ADM, and a control group (n = 8) received an equivalent volume of 0.9% NaCl solution. Mice were sacrificed 4 days after the described treatment. A complete autopsy was carried out in each animal. Hydroperoxide-initiated chemiluminescence and malonaldehyde formation were measured in mouse heart homogenates. Control mice showed a maximal photoemission of 52 +/- 2 (X 10(-3)) (mean values +/- S.E.M.) cpm/mg protein and a formation of 20 +/- 4 nmol malonaldehyde/g organ after a 2 hr-incubation. The ADM-treated mice showed a 24% enhanced hydroperoxide-initiated photoemission and a 370% increased malonaldehyde formation. The 4'-ADM-treated mice showed a 15% increased hydroperoxide-stimulated chemiluminescence and an 85% increased malonaldehyde formation. Vitamin A (5000 IU), vitamin E (85 IU) and vitamins A and E (same doses as before) given as a single dose i.p. 1 day before doxorubicin administration were able to decrease the hydroperoxide-initiated chemiluminescence by 24%, 26% and 44%, respectively. Microscopically, only scarce isolated microvacuolated subendocardial fibers were found in the ADM-treated animals. Our data showing that 4'-ADM lacks a statistically significant effect in increasing heart peroxidation as compared to ADM may explain its lower myocardial toxicity.