666 INHIBITION OF ADRIAMYCIN (ADR) INDUCED LIPID PEROXIDATION BY α-TOCOPHEROL (α-T) AND ACETYL SALICYLIC ACID (ASA)

Abstract

ADR induces cardiac toxicity by peroxidation of cardiac lipids. Cardiac toxicity and lipid peroxidation are reduced by α-T in the animal model. Malonyldialdehyde (MDA) formation was measured in human platelet rich plasma (PRP) as a measure of lipid peroxidation. There was a relationship between the concentration of ADR and the amount of MDA produced, i.e., ADR at 5, 50 and 100 μg/ml produced 1.55 ± 0.13 (1 S.D.), 4.09 ± 0.41, and 5.72 ± 0.76, n moles of MDA per 109 platelets. The addition of α-T to PRP prior to ADR decreased MDA formation, the % inhibition being dependent on the concentration of α-T. At final concentration of α-T of 0.01, 0.05, and 0.1 mgm/ml, inhibition of platelet MDA was 14 ± 2%, 27 ± 4%, and 39 ± 5%, and was independent of the ADR concentration. ASA in vivo and vitro caused inhibition of platelet MDA induced by ADR. However, unlike the >90% inhibition of MDA by ASA in the presence of the aggregating agents epinephrine and thrombin, inhibition of ADR induced platelet MDA formation was only 60 ± 4%. α-T (0.1 mg/ml) increased this inhibitory effect of ASA by an additional 24 ± 3%. Platelet lipid peroxidation induced by ADR is inhibited independently by α-T and ASA. Although the effect of ASA appears greater than α-T, both agents are additive. The effect of ASA on ADR induced platelet MDA does not appear to be consistent with its previously known effect on platelet cyclo-oxygenase.