Whole-body exercise following doxorubicin administration alters skeletal muscle drug accumulation and amino acid pools
Bibliographic record
Abstract
Doxorubicin is a commonly used chemotherapy that rapidly accumulates within muscle and disrupts nitric oxide formation and amino acid homeostasis. Exercise has been lauded as a potential countermeasure to protect skeletal muscle from the harmful effects of the drug; however, little is known about how exercise impacts these factors following doxorubicin administration. Young, healthy male Sprague-Dawley rats ( n = 36) were randomly assigned to experimental groups. All groups except true control received a 4.5 mg/kg intraperitoneal injection of doxorubicin. Dox24 and Dox48 rats were drug-only controls, harvested at 24 and 48 h post-injection, respectively. The remaining groups performed exercise at 24 h and were sacrificed immediately following (1EXE), exercised at 24 h followed by 24 h of recovery (1EXE + REC), and exercised at both 24 and 48 h (2EXE). Recovery following exercise elevated intramuscular doxorubicin, which was reduced by a secondary bout ( p < 0.05). Intramuscular nitric oxide formation was significantly reduced by doxorubicin, and exercise did not restore levels to that of true control. Essential amino acids were reduced by exercise ( p < 0.05). Glutamate was reduced ( p < 0.05) in all groups except Dox24. Methionine was elevated ( p < 0.05) in all groups compared to true control. The data suggest that multiple bouts of exercise are likely required to continuously remove doxorubicin from muscle. Exercise could not restore impaired nitric oxide production. Depleted glutamate and increased methionine suggest increased metabolism and production to combat oxidative stress and energetic constraints. Depleted essential amino acid pools highlight the importance of dietary intervention in exercise oncology settings.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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".