Key result
Prophylactic treatment with flaxseed, perindopril, or both preserved left ventricular ejection fraction (61%, 62%, and 64%, respectively) compared to control (37%) in mice receiving DOX + TRZ.
Why the study?
Flaxseed and perindopril have been studied individually, but whether prophylactic flaxseed is comparable and/or synergistic with perindopril in preventing doxorubicin and trastuzumab cardiotoxicity was unknown.
Does prophylactic flaxseed or perindopril prevent doxorubicin and trastuzumab-induced cardiotoxicity in a murine model?
RCT (n=81)
randomized
Does prophylactic flaxseed or perindopril prevent doxorubicin and trastuzumab-induced cardiotoxicity in a murine model?
Absolute Event Rate: 61% vs 37%
Flaxseed supplementation was equivalent to perindopril in partially preventing doxorubicin and trastuzumab-induced left ventricular systolic dysfunction in a murine model.
Flaxseed equivalent to perindopril in murine model; leaves open human translation and prospective trials.
BACKGROUND: Two anti-cancer agents, doxorubicin (DOX) and trastuzumab (TRZ), are commonly used in the management of breast cancer in women. Despite their efficacy in reducing the morbidity and mortality of individuals with breast cancer, the use of these agents is limited by adverse cardiotoxic side effects. Both the nutraceutical agent flaxseed (FLX) and the pharmaceutical drug perindopril (PER) have been studied individually in the prevention of chemotherapy-mediated cardiac dysfunction. The objective of this study was to determine whether the prophylactic administration of FLX is comparable and/or synergistic with PER in preventing DOX + TRZ-induced cardiotoxicity. METHODS: Over a six-week period, 81 wild-type C57Bl/6 female mice (8-12 weeks old) were randomized to receive regular chow (RC) or 10% FLX-supplemented diets with or without PER (3 mg/kg/week; oral gavage). Starting at week 4, mice were randomized to receive a weekly injection of saline or DOX (8 mg/kg) + TRZ (3 mg/kg). Serial echocardiography was conducted weekly and histological and biochemical analyses were performed at the end of the study. RESULTS: In mice treated with RC + DOX + TRZ, left ventricular ejection (LVEF) decreased from 75 ± 2% at baseline to 37 ± 3% at week 6. However, prophylactic treatment with either FLX, PER, or FLX + PER partially preserved left ventricular systolic function with LVEF values of 61 ± 2%, 62 ± 2%, and 64 ± 2%, respectively. The administration of FLX, PER, or FLX + PER was also partially cardioprotective in preserving cardiomyocyte integrity and attenuating the expression of the inflammatory biomarker NF-κB due to DOX + TRZ administration. CONCLUSION: FLX was equivalent to PER at preventing DOX + TRZ-induced cardiotoxicity in a chronic in vivo murine model.
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Eekhoudt et al. (2022) conducted an RCT in Doxorubicin and Trastuzumab-Induced Cardiotoxicity (n=81). Flaxseed (FLX) and/or Perindopril (PER) vs. Regular chow (RC) was evaluated on Left ventricular ejection fraction (LVEF) at week 6. Prophylactic treatment with flaxseed, perindopril, or both preserved left ventricular ejection fraction (61%, 62%, and 64%, respectively) compared to control (37%) in mice receiving DOX + TRZ.
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