Comparing Flaxseed and Perindopril in the Prevention of Doxorubicin and Trastuzumab-Induced Cardiotoxicity in C57Bl/6 Mice

Current Oncology

Harold M. Aukema¹  James Thliveris²  Skyler Eastman³  Pawan K. Singal³  Amir Ravandi³  Davinder S. Jassal³  Sonu S. Varghese³  David Y. C. Cheung³  Ishika Mittal³  J. Alejandro Austria³  Tessa Bortoluzzi³  Cameron R. Eekhoudt³  Simon Christie⁴ 

[1] Canadian Centre for Agri-Food Research in Health and Medicine, Department of Food and Human Nutritional Sciences, University of Manitoba, Room W573 Duff Roblin Building, Winnipeg, MB R3T 2N2, Canada;Department of Human Anatomy and Cell Sciences, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, 130 Basic Medical Science Building, 745 Bannatyne Avenue, Winnipeg, MB R3E 0J9, Canada;Institute of Cardiovascular Sciences, Department of Physiology and Pathophysiology, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, 432 Basic Medical Sciences Building, 745 Bannatyne Avenue, Winnipeg, MB R3E 0J9, Canada;Section of Cardiology, Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Room GC430, Health Sciences Centre 820 Sherbrook Street, Winnipeg, MB R3A 1R9, Canada;

关键词: breast cancer;    cardiotoxicity;    flaxseed;    perindopril;    prevention;    cardiovascular remodeling;   

DOI  :  10.3390/curroncol29050241

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown