Abstract
Doxorubicin (Dox) is one of the most effective chemotherapeutic agents; however, it causes dose-dependent cardiotoxicity. Evaluation of left ventricular function relies on measurements based on M-mode echocardiography. A new technique based on quantification of myocardial motion and deformation, strain echocardiography, has been showed promising profile for early detection of cardiac dysfunction. Different therapy strategies, such as flavonoid plant extracts and stem cells, have been investigated to improve heart function in toxic cardiomyopathy. This work aimed to assess early cardiac function improvement after treatments with either flavonoid extract from Camellia sinensis or mesenchymal stem cells in Dox cardiotoxicity using strain echocardiography. Twenty Wistar rats were randomly assigned to four groups. They received water (control, Dox, Dox + stem cells) or 100 mg/kg C. sinensis extract (Dox + C. sinensis) via gavage, daily, for four weeks. Animals also received saline (control) or 5 mg/kg doxorubicin (Dox, Dox + C. sinensis, Dox + stem cells) via intraperitoneal injection, weekly, for four weeks. Stem cells were injected (3 × 106 cells) through tail vein prior the beginning of the experiment (Dox + stem cells). Animals were evaluated by hematological, electrocardiography, echocardiography, and histopathological examinations. Dox cardiotoxicity was only diagnosed with strain echocardiography, detecting a decrease in ventricular function. C. sinensis extract did not prevent ventricular dysfunction induced by Dox. However, strain echocardiography examination revealed that Dox cardiotoxicity was significantly suppressed in rats treated with stem cells. In conclusion, strain echocardiography was able to detect precocity signs of heart failure and stem cell therapy showed cardioprotection effect against Dox cardiotoxicity.
Highlights
One of the most effective chemotherapeutic agents used for treatment of hematological and solid tumors is doxorubicin (Dox) [1]
Regarding such potential causes for cardiotoxicity it is possible to infer that flavonoids which have been studied and showed free radical scavenging properties [9,10] and mesenchymal stem cell (MSC) transplantation replacing injuried cells and due to its paracrine effects and multipotent properties to produce cells with some cardiomyocytes characteristics [11,12] may have beneficial effects toward heart function improvement
Six of the 20 animals died through the experimental period: Dox group (n=2), Dox + C. sinensis group (n=2) and Dox + MSC group (n=2)
Summary
One of the most effective chemotherapeutic agents used for treatment of hematological and solid tumors is doxorubicin (Dox) [1]. Production of reactive oxygen species, calcium imbalance, mitochondrial damage, and apoptosis are considered in Dox cardiotoxicity condition [2,68]. Regarding such potential causes for cardiotoxicity it is possible to infer that flavonoids which have been studied and showed free radical scavenging properties [9,10] and mesenchymal stem cell (MSC) transplantation replacing injuried cells and due to its paracrine effects and multipotent properties to produce cells with some cardiomyocytes characteristics [11,12] may have beneficial effects toward heart function improvement. Strain echocardiography has provided quantification of regional myocardial systolic function objectively and is less influenced by tethering effects and cardiac translational artifact than Doppler tissue imaging [14]. Other examinations as electrocardiography (ECG), radiography, computed tomography, magnetic resonance imaging, measurement of serum cardiac biomarkers including C-reactive protein (CRP), N-terminal pro-B-type natriuretic peptide (nt-proBNP), troponin T (TnT), creatine kinase MB (CK-MB), and lactate dehydrogenase (LDH) are important diagnostic tools in the evaluation of cardiac function [16-
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