Co-administration of resveratrol with doxorubicin in young mice attenuates detrimental late-occurring cardiovascular changes
Bibliographic record
Abstract
Aims: Doxorubicin (DOX) is among the most effective chemotherapies used in paediatric cancer patients. However, the clinical utility of DOX is offset by its well-known cardiotoxicity, which often does not appear until later in life. Since hypertension significantly increases the risk of late-onset heart failure in childhood cancer survivors, we investigated whether juvenile DOX exposure impairs the ability to adapt to angiotensin II (Ang II)-induced hypertension later in life and tested a treatment that could prevent this. Methods and results: Five-week-old male mice were administered a low dose of DOX (4 mg/kg) or saline once a week for 3 weeks and then allowed to recover for 5 weeks. Following the 5-week recovery period, mice were infused with Ang II or saline for 2 weeks. In another cohort, mice were fed chow containing 0.4% resveratrol 1 week before, during, and 1 week after the DOX administrations. One week after the last DOX administration, p38 mitogen-activated protein kinase (MAPK) was activated in hearts of DOX-treated mice demonstrating molecular signs of cardiac stress; yet, there was no change in cardiac function between groups. However, DOX-treated mice failed to develop compensatory cardiac hypertrophy in response to Ang II-induced hypertension later in life. Of importance, mice receiving DOX with resveratrol co-administration displayed normalization in p38 MAPK activation in the heart and a restored capacity for cardiac hypertrophy in response to Ang II-induced hypertension. Conclusion: We have developed a juvenile mouse model of DOX-induced cardiotoxicity that displays no immediate overt physiological dysfunction; but, leads to an impaired ability of the heart to adapt to hypertension later in life. We also show that co-administration of resveratrol during DOX treatment was sufficient to normalize molecular markers of cardiotoxicity and restore the ability of the heart to undergo adaptive remodelling in response to hypertension later in life.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".