ABSTRACT
The usefulness of doxorubicin [DOX], a highly effective antitumor drug, is limited by the risk of developing cardiomyopathy. Subcellular changes leading to this toxicity are suggested to be mediated through a drug-induced increase in free radicals and lipid peroxidation. The present study was undertaken to investigate the possible protection that simvastatin [SIM], a lipid-lowering drug, can offer against DOX induced cardiotoxicity. DOX was administered to male Swiss albino rats in 6 equal interaperitoneal injections over a period of 2 weeks [cumulative dose, 15 mg/kg]. Protection from doxorubicin-oxidative injury was investigated by administration of SIM [cumulative dose, 60 mg /kg] in 12 equal oral doses over a period of 4 weeks [2 weeks before and 2 weeks concurrent with doxorubicin]. At the end of treatment, ECG was performed; myocardial antioxidants and lipid peroxidation were assayed. In addition, body weight changes during the experiment, mortality%, and histopathological examination of the heart tissue were performed. DOX treatment increased peritoneal fluid, myocardial oxidative damage and decreased survival. Myocardial antioxidants including reduced glutathione [GSH], glutathione-S-transferase [GST], and DT-diaphorase activities were reduced, while lipid peroxidation was increased. Administration of SIM before and concurrent with DOX significantly reduced the oxidative myocardial changes-induced by DOX treatment. It also decreased mortality, and eliminated ascites. Histopathological observations were in correlation with the biochemical parameters. This indicates that SIM provide protection from DOX-induced cardiac injury in terms of oxidative stress