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Copper and Selenium Deficiencies Do Not Enhance the Cardiotoxicity in Rats Due to Chronic Doxorubicin Treatment^1,2,

Joan G. Fischer, Randall L. Tackett^*, E. W. Howerth and Mary Ann Johnson³

Department of Foods and Nutrition ^* Department of Pharmacology and Toxicology Department of Pathology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602

This study tests the hypothesis that Cu and Se deficiencies enhance doxorubicin-induced cardiotoxicity and anemia. Male Sprague-Dawley rats (n = 48) were fed Cu and Se-adequate (+Cu+Se), Cu-deficient (-Cu), Se-deficient (-Se) or Cu and Se-deficient (-Cu-Se) diets for 5.5 wk. Doxorubicin (4 mg/kg body wt) or saline was administered once weekly for the last 4 wk of the study. Copper deficiency was confirmed by 79% lower liver Cu, 67% lower liver Cu,Zn superoxide dismutase (Cu,Zn SOD) activity and 76% lower erythrocyte Cu,Zn SOD activity. Selenium deficiency was confirmed by 90% lower liver glutathione peroxidase activity. Rats fed the -Cu diet had greater reductions in hematocrit than did those fed the +Cu diet after administration of doxorubicin. Doxorubicin, Cu deficiency and Se deficiency all produced electrocardiographic abnormalities and ultrastructural anatomical lesions. However, the dietary deficiencies did not enhance doxorubicin-induced cardiotoxicity. Doxorubicin, but not Cu or Se deficiency, raised lipid peroxidation 16% in liver (P < 0.01) and 18% in heart (not significant). These data suggest that the cardiomyopathies caused by doxorubicin and Cu and Se deficiencies have some similarities, but cardiac changes may be related to mechanisms other than lipid peroxidation.

KEY WORDS: • doxorubicin • copper • rats • selenium • heart

¹ Presented in part at the Annual Meeting of the Federation of American Societies for Experimental Biology, April 1991, Atlanta GA (Fischer, J., Tackett, R. & Johnson, M. A. (1991) Interactions between copper deficiency, selenium deficiency and adriamycin toxicity. FASEB J. 4: A6281 (abs.)].

² Funded in part by International Life Sciences Institute-Nutrition Foundation, Future Leaders Award (MAJ); University of Georgia Experiment Station, Hatch Project #H630 (MAJ); and The University of Georgia Graduate School (JF).

³ To whom correspondence should be addressed.

Manuscript received 13 April 1992. Revision accepted 7 July 1992.