Is flaxseed equivalent and/or synergistic with ACE inhibition in the treatment of chemotherapy induced cardiotoxicity?
Bibliographic record
Abstract
Background: 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 about whether flaxseed (FLX) is equivalent to, or synergistic with, angiotensin converting enzyme inhibition (ACEi) in the treatment of DOX+TRZ mediated cardiotoxicity. Objective: The specific aim is to evaluate whether FLX is comparable and/or incremental to standard pharmacological therapy using the ACEi Perindopril (PER) in the treatment of DOX+TRZ mediated cardiotoxicity. Methods: 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 regimen, the mice were randomized to daily consumption of a 10% FLX supplemented diet, administration of PER (3mg/kg) via oral gavage, or a combination of both 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 and plasma. Results: In mice treated with DOX+TRZ, the left ventricular ejection fraction (LVEF) decreased from 74±4% at baseline to 39±5% at week 6. Treatment with either FLX, PER, or FLX+PER improved LVEF to 63±4%, 64±3%, and 65±4%, respectively (p<0.05). 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. Although Bcl-2 interacting protein 3 (Bnip-3) and high mobility group box 1 protein (HMGB1) expression were significantly elevated in mice receiving DOX+TRZ, these markers of mitochondrial damage and cell death were attenuated by treatment with either FLX, PER, or FLX+PER. Finally, oxylipin analysis showed that 18-hydroxy-eicosatetraenoic acid (18-HETE) and 20-carboxy-arachidonic acid (20-COOH-AA) concentrations were significantly elevated in mice receiving DOX+TRZ; increases in concentrations of these oxylipins were attenuated by treatment with either FLX, PER, or FLX+PER. Conclusion: In a chronic in vivo murine model of DOX+TRZ induced cardiotoxicity, FLX was equivalent to PER at improving cardiovascular remodeling, reducing histopathological changes in cardiomyocyte ultrastructure, and reducing biomarkers of inflammation, mitochondrial damage, and cell death in the treatment of cardiotoxicity, but the combination of FLX+PER was not synergistic.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".