Young adult New Zealand White rabbits were used to investigate the protective effect of vitamin E against Adriamycininduced toxicity. The animal trials were based upon the observation that the dose-dependent oxidation of reduced glutathione by Adriamycin can be prevented by the addition of adequate amounts of vitamin E.

Rabbits given an injection of a single i.v. dose of Adriamycin (7 mg/kg) showed significant oxidation of reduced glutathione in erythrocytes and cardiac tissues. Rabbit heart has low activities of glutathione peroxidase and catalase. Changes in electrocardiography were observed in three fourths of the animals. All rabbits receiving this dose of the anthracycline died within 1 week. Animals treated with 200 mg of vitamin E i.m. daily for 4 days or more prior to the Adriamycin injection showed protection against adverse effects. With four consecutive daily i.m. vitamin E injections, serum α-tocopherol levels reached 2 to 4 times base-line levels with a concomitant 2-fold increase of cardiac α-tocopherol level. This amount of vitamin E concentration does not prevent the drug-induced marrow suppression or alter the pharmacokinetics of Adriamycin. The animals showed no decrease in reduced glutathione levels in their erythrocytes and cardiac tissue. The serum creatine phosphokinase level and isoenzyme patterns were normal. There was no abnormality discernible in the electrocardiogram. Four of 11 rabbits lived when vitamin E therapy was given 4 days prior to Adriamycin, and four out of six rabbits survived with 14 days of vitamin E prior to Adriamycin. The data suggest that the oxidation of free sulfhydryl groups represents a peroxidative insult induced by the drug and that vitamin E protects rabbits from early Adriamycin cardiac toxicity. Light and electron microscopy studies support this conclusion.

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Presented in part at the 1978 Annual Meeting of the American Society for Cancer Research held April 5 to 8, 1978, at Washington, D. C. (13). This study was supported in part by USPHS Biomedical Research Grant RR-5511 and a grant from Hoffmann-La Roche Inc., Nutley, N. J.

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