Vitamin E deficiency accentuates adriamycin-induced cardiomyopathy and cell surface changes

Abstract

Free radicals have been suggested to play a role in adriamycin-induced cardiomyopathy. Adriamycin-induced myocardial effects were examined in rats maintained on a vitamin E deficient diet. Animals were divided into four groups: I, control; II, adriamycin-treated; III, vitamin E deficient diet; IV, vitamin E deficient diet plus adriamycin treatment. Adriamycin-treated animals (groups II and IV) were given six injections (i.p.) over two weeks for producing a cumulative dose of 15 mg/kg. Animals in groups III and IV were placed on vitamin E deficient diet starting two weeks prior to the first injection of adriamycin or vehicle. Myocardial tissue analysis were performed on animals sacrificed 1 week after the last injection. Mortality was significantly higher in group IV which also showed doubling of myocardial malondialdehyde content relative to the non-adriamycin-treated vitamin E deficient group (III). Myocardial cell damage in group IV was characterized by separation of the external lamina, subsarcolemmal changes, mitochondrial swelling and myofibril dropout. Group II hearts showed only a mild dilation of the sarcotubules and swelling of the mitochondria. Total sialic acid content of the sarcolemma in groups II, III and IV was 55, 90 and 24% of the control values in group I. These data show a characteristic sarcolemmal injury produced by adriamycin in hearts of animals with reduced antioxidant capacity which is probably mediated by increased free radical activity as well as lipid peroxidation.