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Doxorubicin (DOX) is a potent anticancer drug used in the treatment of various cancer, but its clinical use is limited for its marked cardiotoxicity. The aim of this study was to investigate the possible protective effect of wheat germ oil (WGO) on doxorubicin-induced cardiotoxicity and its impact on oxidative stress and lipid peroxidation. Wheat germ oil (WGO) contains richest amount of tocopherols among all vegetable oils and also polyphenols. Incorporation of WGO in our diet is the best way to ameliorate the DOX-induced cardiotoxicity and for enhancing its clinical use. DOX in a single dose (10 mg/kg i.p.) was used to produce oxidative stress and lipid peroxidation. Pretreatment with WGO was initiated in dose-dependent (125 mg/kg, 250 mg/kg and 500 mg/kg) and time-dependent (15 days, 30 days and 45 days) manner to evaluate the cardioprotective activity. DOX produced elevation in heart malodialdehyde (MDA) levels, decreased the levels of glutathione (GSH), lactate dehydrogenase (LDH), total proteins and decreased the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px). Plasma levels of aspartate amino transferase (AST), alanine amino transferase (ALT), nitric oxide (NO) increased and serum levels of creatine kinase isoenzyme MB (CK-MB) were also increased. All doses of WGO were capable of preventing oxidative stress and lipid peroxidation. Cardiac histopathological changes were observed in the DOX alone treated group as compared to the control group. In contrast, these histopathological changes appeared nearly normal in the groups pretreated with WGO. The ameliorating effect of WGO is possibly due to the presence of tocopherols, polyphenols, linolenic acid, linoleic acid, octacosanol and polycosanol.