| Doxorubicin (DOX) is one of the secondary metabolites of Streptomyces peucetius var. caesius. It is a common
and effective chemotherapeutic agent used for the treatment of different diseases, including lymphoma,
leukemia, breast cancer, and solid tumors. However, this medicine causes cardiotoxic side effects, which limit
its clinical application. The present study examined the cardiomyopathy induced by DOX via echocardiography
and transmission electron microscopy (TEM). The main objective was to evaluate the capacity of
echocardiography and TEM as diagnostic tools for DOX-induced cardiotoxicity. Moreover, the correlation
between intracellular and functional changes due to cardiotoxicity was assessed in a rat model. Cardiomyopathy
was induced in rats by two cumulative doses of DOX. Group I received DOX 12 [i.e., 12 mg/kg, intraperitoneal
(IP)] and group II received DOX 15 (i.e., 15 mg/kg, IP) in six equal doses over two weeks. Group III as the
control (Ctrl) group received normal saline as a vehicle. Mortality during the study was only observed in the
DOX 15 group. The echocardiographic assessments revealed significant changes in ejection fraction, fractional
shortening, and heart rate in the groups which received DOX. In addition, severe cardiac arrhythmia was evident
in DOX-treated groups. Remarkable adverse effects, such as moderately degenerated cells and inflated
mitochondria were observed in the TEM analysis of rat hearts in the DOX groups. The present study indicated
that rat models are suitable for investigating DOX-induced cardiomyopathy, especially at the dose of 12 mg/kg.
Furthermore, echocardiography and TEM examinations were found to be valuable methods for the
determination of cardiotoxicity in rats due to DOX. |