Is flaxseed equivalent and/or synergistic with ACE inhibition in the prevention of chemotherapy-mediated cardiotoxicity?
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Date
2021-08
Authors
Bortuluzzi, Tessa
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Abstract
Background: Two commonly used anti-cancer agents for patients with breast cancer are Doxorubicin (DOX) and Trastuzumab (TRZ). Despite their efficacy in reducing the morbidity and mortality of individuals with breast cancer, the use of these agents is associated with an increased risk of cardiotoxicity. The pharmaceutical agent, perindopril (PER), and the nutraceutical agent, flaxseed (FLX), have both been shown to attenuate adverse cardiac changes associated with DOX+TRZ treatment when administered as monotherapy. However, little is known regarding the prophylactic role of the combination of FLX and PER in the prevention of DOX+TRZ-mediated cardiotoxicity.
Objective: To evaluate whether the prophylactic use of FLX will be comparable and/or incremental to standard pharmacological therapy using PER in preventing DOX+TRZ mediated cardiotoxicity in a chronic in vivo murine model.
Methods: A total of 200 female mice were randomized to prophylactically receive either regular chow (RC), PER, 10% FLX-supplemented diet or FLX+PER for 6 weeks. After the 3-week prophylactic period, mice were further randomized to receive intraperitoneal injections of either: i) 0.9% saline; ii) DOX (8mg/kg/wk); iii) TRZ (3mg/kg/wk); or iv) DOX+TRZ. Weekly echocardiography was performed to assess for cardiovascular remodeling. At study endpoint, biochemical and histological analyses were performed using harvested cardiac tissue.
Results: The prophylactic administration of PER and FLX was cardioprotective in: i) preventing adverse cardiovascular remodeling; ii) attenuating histological injury; and iii) reducing inflammatory biomarkers associated with DOX+TRZ treatment.
Conclusion: Although FLX was comparable to PER when administered alone in preventing the cardiotoxic effects of DOX+TRZ, they were not synergistic.
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Keywords
cardiotoxicity, flaxseed