SELENIUM SUPPLEMENTATION DECREASES THE PROOXIDANT AND CARDIOTOXICITY EFFECTS OF ADRIAMYCIN IN THE RAT

Adriamycin (doxorubicin; ADR) is an antineoplastic drug used to treat various cancers; however, its chronic use is unfortunately accompanied by cardiotoxicity. Previous results suggested that a free radical mec hanism may contribute to ADR toxicity. Because it is often reported th at cancer patients are deficient in selenium (Se), we hypothesised tha t ADR toxicity might be reduced by antioxidant agents such as vitamin E and Se. ADR-induced cardiotoxicity was examined in rats maintained o n a Se-supplemented diet. The animals were kept on either a standard ( 0.22 mg/kg) or a Se-supplemented (2.5 mg/kg) diet starting 4 weeks pri or to the first ADR treatment. ADR, or its excipient, was administered intraperitoneally in six equal injections over a period of 3 weeks gi ving a cumulative dose of 15 mg/kg body weight. Blood was collected in the thoracic cavity and the heart was subjected to a sequence of perf usion/partial ischemia/reperfusion ex vivo. Se status, GPx activities, vitamins E and C and MDA contents were determined on RBC and cardiac homogenates. ADR-treated rats showed a significant decrease in RBC Se (-29%) and in RBC Se-GPx (-34%) compared to the placebo group, and a s ignificant increase in RBC MDA content (+2000%). This latter increase was attenuated by the Se supplementation (+1600%). In parallel, RBC vi tamin E decreased markedly in the ADR-treated group (-50%) and was tot ally restored by the Se supplementation. Cardiac biochemical analyses confirmed the blood results. The present data confirm that a free radi cal mechanism does contribute to ADR toxicity, and show the importance of balancing the Se levels in ADR-treated subjects to limit its harmf ul myocardial action. A decrease in ADR toxicity with no concomitant d ecrease in its antineoplastic activity would be of considerable value by improving the therapeutic benefit of the drug.