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

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Abstract
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 chemihuninescence and malonaldehyde formation were measured in mouse heart homogenates. Control mice showed a maximal photoemission of 52 ± 2 (×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 chemihuninescence 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.

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