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ETHNOPHARMACOLOGICAL RELEVANCE Chromolaena odorata (L) King and Robinson and Tridax procumbens Linn are used in traditional medicine in the treatment of diabetes mellitus and hypertension. AIM OF THE STUDY This study investigated the potential protective role of aqueous leaf-extracts of Chromolaena odorata and Tridax procumbens against cardiotoxicity induced by doxorubicin. MATERIALS AND METHODS To this end, their impact on plasma markers of cardiac integrity, cardiac markers of oxidative stress, cardiac lipids and electrolyte profiles, and activities of cardiac ATPases, lactate dehydrogenase and creatine kinase, were monitored in doxorubicin treated rats. Metformin (250 mg/kg body weight, orally) and both extracts (50, 75 and 100 mg/kg, orally) were daily administered for 14 days; while cardiotoxicity was induced with doxorubicin (15 mg/kg, intra-peritioneally, once on the 12th day of study). RESULTS The plasma activities of creatine kinase, lactate dehydrogenase and AST of Test control were significantly (p<0.05) higher than those of the other groups. Also, the cardiac malondialdehyde, calcium, chloride, sodium, cholesterol and triglyceride concentrations of Test control were significantly (p<0.05) higher than those of the others. However, the cardiac concentrations of ascorbic acid, reduced glutathione, magnesium and potassium, and cardiac activities of catalase, glutathione peroxidase, superoxide dismutase, Ca2+-ATPase, Mg2+-ATPase, Na+,K+-ATPase, creatine kinase and lactate dehydrogenase of Test control were significantly (p<0.05) lower than those of the others. CONCLUSIONS Pre-treatment with the extracts and metformin elicited a cardioprotective effect, as indicated by the prevention of doxorubicin-induced cardiac oxidative stress and prevention of adverse alterations in plasma cardiac markers, cardiac lipids and electrolyte profiles, as well as improvement of the activities of cardiac ATPases, creatine kinase and lactate dehydrogenase.