Vitamin E deficiency accentuates adriamycin-induced cardiomyopathy and cell surface changes.
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.
Singal
P K
PK
Cardiovascular Sciences Division, St. Boniface General Hospital Research Center, Winnipeg, Canada.
Tong
J G
JG
D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects; D004317:Doxorubicin / Q000633:toxicity*; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008854:Microscopy, Electron; D009206:Myocardium / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000648:ultrastructure; D012794:Sialic Acids / Q000032:analysis; D014811:Vitamin E Deficiency / Q000378:metabolism*
D012794:Sialic Acids; D008315:Malondialdehyde; D004317:Doxorubicin