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Breast cancer is a major public health concern in Canada. Although the current combination of surgery, radiation, and chemotherapy may lead to a cure in the breast cancer setting, the administration of the anti-cancer drugs Doxorubicin and Trastuzumab (DOX+TRZ) is associated with an increased risk of developing heart failure. Little is known, however, on whether flaxseed (FLX) is equivalent to angiotensin converting enzyme inhibition (ACEi) in the treatment of DOX+TRZ mediated cardiotoxicity.
Methods and Results
In a chronic in vivo murine model of chemotherapy mediated cardiotoxicity, DOX+TRZ (8mg/kg and 3mg/kg, respectively) were administered weekly for a total of 3 weeks. Following this, mice were randomized to daily treatment with a 10% FLX supplemented diet, Perindopril (PER) (3mg/kg) via oral gavage, or a combination treatment of FLX+PER for an additional 3 weeks. Serial echocardiography was performed weekly. At the end of week 6, the mice were euthanized, and histological and biochemical analyses were performed on cardiac tissue. In mice treated with DOX+TRZ, the left ventricular ejection fraction (LVEF) decreased from 72±4% at baseline to 30±2% at week 6. Treatment with either FLX, PER, or FLX+PER improved LVEF to 52±4%, 54±4%, and 55±3%, respectively (P < 0.05) (Figure 1). Histological analyses confirmed significant disruption of myofibrils, vacuolization, and loss of sarcomere integrity in the DOX+TRZ treated mice. Treatment with FLX, PER, or FLX+PER, however, improved myofibril integrity at week 6 in mice receiving DOX+TRZ.
In a chronic in vivo murine model of DOX+TRZ induced cardiotoxicity, although FLX was equivalent to PER in the treatment of adverse LV remodeling, the combination of FLX and PER was not synergistic.