Journal
JOURNAL OF NUTRITION
Volume 150, Issue 9, Pages 2353-2363Publisher
ELSEVIER SCIENCE INC
DOI: 10.1093/jn/nxaa144
Keywords
cardio-oncology; flaxseed; heart failure; cardiotoxicity; doxorubicin; murine echocardiography
Categories
Funding
- Research Manitoba
- CancerCare Manitoba
- St. Boniface Hospital Research Centre: Molson'sWomen Heart Health Initiative
- Heart and Stroke Foundation of Canada
- Caroline A. Cope Award for Excellence in Oncology Research
- University of Manitoba Faculty of Graduate Studies Research Completion Scholarship
- Research Manitoba Master's Studentship
- Institute of Cardiovascular Sciences Studentship
- St. Boniface Hospital
Ask authors/readers for more resources
Background: Although the combination of doxorubicin (DOX) and trastuzumab (TRZ) reduces the progression and recurrence of breast cancer, these anticancer drugs are associated with significant cardiotoxic side effects. Objective: We investigated whether prophylactic administration of flaxseed (FLX) and its bioactive components, alpha-linolenic acid (ALA) and secoisolariciresinol diglucoside (SDG), would be cardioprotective against DOX + TRZ-mediated cardiotoxicity in a chronic in vivo female murine model. Methods: Wild-type C57BL/6 female mice (10-12 wk old) received daily prophylactic treatment with one of the following diets: 1) regular control (RC) semi-purified diet; 2) 10% FLX diet; 3) 4.4% ALA diet; or 4) 0.44% SDG diet for a total of 6 wks. Within each arm, mice received 3 weekly injections of 0.9% saline or a combination of DOX [8 mg/(kg.wk)] and TRZ [3 mg/(kg.wk)] starting at the end of week 3. The main outcome was to evaluate the effects of FLX, ALA, and SDG on cardiovascular remodeling and markers of apoptosis, inflammation, and mitochondrial dysfunction. Significance between measurements was determined using a 4 (diet) x 2 (chemotherapy) x 2 (time) mixed factorial design with repeated measures. Results: In the RC + DOX + TRZ-treated mice at week 6 of the study, the left ventricular ejection fraction (LVEF) decreased by 50% compared with the baseline LVEF (P < 0.05). However, the prophylactic administration of the FLX, ALA, or SDG diet was partially cardioprotective, with mice in these treatment groups showing an similar to 68% increase in LVEF compared with the RC + DOX + TRZ-treated group at week 6 (P < 0.05). Although markers of inflammation (nuclear transcription factor kappa B), apoptosis [poly (ADP-ribose) polymerase-1 and the ratio of BCL2-associated X protein to B-cell lymphoma-extra large], and mitochondrial dysfunction (BCL2-interacting protein 3) were significantly elevated by approximately 2-fold following treatment with RC + DOX + TRZ compared with treatment with RC + saline at week 6, prophylactic administration of FLX, ALA, or SDG partially downregulated these signaling pathways. Conclusion: In a chronic in vivo female C57BL/6 mouse model of DOX + TRZ-mediated cardiotoxicity, FLX, ALA, and SDG were partially cardioprotective.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available