Ultrastructural and Echocardiographic Assessment of Chronic Doxorubicin-Induced Cardiotoxicity in Rats

Abstract Doxorubicin (DOX) is one of the secondary metabolites of Streptomyces peucetius var. caesius. It is a common and effective chemotherapeutic drug; used for the treatment of different diseases, including lymphoma, leukemia, breast cancer, and solid tumors, even though it causes cardiotoxic side effects, which limit its clinical application. The present study examined cardiomyopathy induced by DOX via echocardiography and transmission electron microscopy (TEM). The main objective was to analyze the capacity of echocardiography and TEM as diagnostic tools for DOX-induced cardiotoxicity and to assess the correlation between intracellular and functional changes due to cardiotoxicity in a rat model. Cardiomyopathy was induced in rats by 2 cumulative doses of DOX. Group I received DOX 12 (12 mg/kg, IP) and group II received DOX 15 (15 mg/kg, IP) in 6 equal doses over 2 weeks. Group III was the control (Ctrl) group and received normal saline as vehicle. Mortality was only observed in the DOX 15 group (15 mg/kg, IP) during the study. The echocardiography assessments revealed significant changes in ejection fraction, fractional shortening, and heart rate; moreover, severe cardiac arrhythmia was evident in DOX-treated groups. Remarkable adverse effects, including moderately degenerated cells and inflated mitochondria, were observed in TEM analysis of rat hearts in the DOX groups. The present study indicated that rat models are suitable for the study of cardiomyopathy induced by DOX (12 mg/kg). Also, echocardiography and TEM examinations could be valuable methods for determination of DOX-induced cardiotoxicity in rats. Keywords: Cardiomyopathy, Doxorubicin, Echocardiography, Electron Microscopy, Rat Heart