Assessment of cardioprotective effect of deferiprone on doxorubicin-induced cardiac toxicity in a rat model.

Abstract

Introduction: Doxorubicin (DOX)- induced cardiotoxicity is widely- known as the most severe complications of anthracycline based chemotherapy in patients with cancer. It is unknown whether Deferiprone (DFP), could reduce the severity of DOX- induced cardiotoxicity by inhibiting free radical reactions. Thus, this study was performed to assess the protective effect of Deferiprone on DOX-induced cardiotoxicity in a rat model. Methods: The rats were divided into five groups. Group one was control group. Group 2 was DOX (2 mg/kg/day, every other day for 12 days), and Group three to five which receiving DOX as in group 2 and DFP 75,100 and 150 mg/kg/day, for 19 days, respectively. Deferiprone was starting 5 days prior to first DOX injection and two days after the last DOX injection throughout the study. Electrocardiographic and hemodynamic studies, along with histopathological examination were conducted. In addition, serum sample was taken and Malone dialdehyde,lactate dehydrogenase, total anti-oxidant and creatine kinase were assessed. Result: Doxorubicin showed severe cardiotoxicity manifested by changes in ECG and hemodynamic parameters which was further confirmed by histology of heart and decrease in heart weight. These doxorubicin induced changes were attenuated by treatment with deferiprone. Discussion: The results also showed that deferiprone treatment significantly improved DOX-induced heart damage, structural changes in the myocardium and ventricular function. Our data confirm that deferiprone is protective against cardiovascular-related disorders induced by DOX. Clinical studies are needed to be involved to examine these findings in human. This observation revealed that the model adequately trained using 8 data points and could be used as a practical strategy for predicting the solubility of drugs in binary solvent mixtures at various temperatures with acceptable prediction error and using minimum experimental efforts.