Inhibition of adriamycin‐induced human platelet lipid peroxidation by vitamin E

Abstract Adriamycin® is an important cancer chemotherapeutic agent whose clinical use is compromised by potentially lethal cardiotoxicity. In the mouse, cardiotoxicity is related to the peroxidation of cardiac lipids. Both phenomena, however, can be reduced by pretreatment of the animal with vitamin E. Using the platelet as our model we have demonstrated that Adriamycin induces lipid peroxidation of human platelets in a dose‐dependent manner. Platelet malonyldialdehyde (MDA) production was used as an indicator of lipid peroxidation. Adriamycin at 5, 10, 50, and 100 μg/ml produced 1.40 ± 0.2 (1 SD), 2.23 ± 0.41, 4.23 ± 0.4, and 6.13 ± 0.43 nmoies MDA per 10 9 platelets, respectively. Vitamin E both in vitro and in vivo inhibited this lipid peroxidation. In vitro, vitamin E at concentrations of 0.01, 0.05, and 0.1 mg/ml inhibited platelet MDA formation by 14 ± 2, 29 ± 5, and 38 ± 6%, respectively. In six controls who ingested 1,600 units vitamin E daily for two weeks, platelet MDA formation induced by N‐ethyl maleimide, thrombin, and Adriamycin was decreased by 11‐20%. In similar studies, the ingestion of 10 grains acelyl salicylic acid (ASA) also inhibited platelet lipid peroxidation induced by these same agents. ASA and vitamin E were not additive in their inhibition of MDA formation induced by N‐ethyl maleimide or thrombin. They were additive, however, in their inhibition of Adriamycin‐induced lipid peroxidation, which suggests that the effect of vitamin E on Adriamycin‐induced platelet lipid peroxidation is not due to inhibition of platelet cyclooxygenase. In the light of these observations on the inhibitory effect of vitamin E on lipid peroxidation in human platelets, further studies appear warranted on the clinical effects of E in inhibiting cardiac lipid peroxidation and concomitant cardiotoxicity in humans on Adriamycin therapy.