Doxorubicin administration at 12 mg/kg significantly reduced ejection fraction to 50.03% compared to 70.19% in controls, and caused severe ultrastructural myocardial damage in a rat model.
Does doxorubicin induce measurable echocardiographic and ultrastructural cardiotoxicity in a rat model?
Echocardiography and transmission electron microscopy are effective methods for detecting doxorubicin-induced cardiotoxicity in a rat model, which is optimally induced at a cumulative dose of 12 mg/kg without mortality.
Absolute Event Rate: 50.03% vs 70.19%
p-value: p=<0.01
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.
Babaei et al. (2020) studied Doxorubicin-induced cardiotoxicity (n=30). Doxorubicin vs. Normal saline was evaluated on Ejection fraction (p=<0.01). Doxorubicin administration at 12 mg/kg significantly reduced ejection fraction to 50.03% compared to 70.19% in controls, and caused severe ultrastructural myocardial damage in a rat model.
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