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Effect of Selenium Deficiency on the Chronic Toxicity of Adriamycin in Rats^1,2,

Xiaoshu Chen, Anna Xue, Virginia C. Morris^*, Victor J. Ferrans, Eugene H. Herman, Antoine El-Hage and Orville A. Levander^3,*

Institute of Health, China National Center for Preventive Medicine, Beijing, China ^* Vitamin and Mineral Nutrition Laboratory, USDA-ARS, Beltsville Human Nutrition Research Center, Beltsville, MD 20705 Pathology Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892 Division of Drug Biology, Food and Drug Administration, Washington, DC 20204

The effect of selenium deficiency on the chronic toxicity of adriamycin was examined in rats fed diets adequate in vitamin E. Selenium-deficient and selenium-supplemented diets were fed to rats for 10 wk, after which groups of 10 rats fed each diet were given weekly intravenous injections of adriamycin in saline at doses of 0, 0.5 or 1.0 mg/kg body weight for 12 wk. All rats were killed at 24 wk. Even though the cardiac glutathione peroxidase activity in the selenium-deficient group was less than 1% of that of the selenium-supplemented group, the severity of the adriamycin-induced cardiomyopathy was similar in both groups. However, the selenium-deficient rats were more sensitive to the growth-inhibiting effect of the higher dose of adriamycin than the selenium-supplemented rats. Moreover, the lower dose of adriamycin caused a mild nephropathy in 70% of the deficient rats but affected only 10% of the supplemented rats. Selenium status may have to be considered when adriamycin is used as a chemotherapeutic agent.

KEY WORDS: • selenium deficiency • glutathione peroxidase • adriamycin toxicity • cardiomyopathy • Keshan disease • vitamin E

¹ X. Chen and A. Xue were supported in the laboratories of V. J. Ferrans and O. A. Levander during the academic year 1981–1982 by fellowships from Emory University funded in part by the Evans County Heart Research Foundation, Inc., U.S. Public Health Service grant HL03341, and the China Division of the Coca-Cola Bottling Company, Mr. Peter Lee, Director.

² Some of these data were presented at the Federation of American Societies for Experimental Biology Meeting in St. Louis, MO, April 1984. Morris, V. C., Chen, X., Xue, A., Ferrans, V. J., Herman, E. H., El-Hage, A. & Levander, O. A. (1984) Effect of selenium (Se) deficiency on the chronic toxicity of adriamycin (ADR) in rats. Fed. Proc. 43, 791 (abs. 2958).

³ To whom reprint requests should be addressed.

Manuscript received 7 March 1986. Revision accepted 17 July 1986.