Skeletal muscle as a possible compartment for the sequestering of Doxorubicin following administration
Bibliographic record
Abstract
Doxorubicin (DOX) is an anti‐cancer chemotherapeutic and although widely used, its accumulation over time in skeletal muscle tissue has attracted little attention. The purpose of this research was to study intracellular DOX concentrations in skeletal muscle following its administration in the rat. A bolus injection of 1.5 and 4.5 mg/kg of DOX was administered intraperitoneally in Sprague Dawley rats, and medial gastrocnemius samples were collected 24 and 96 hrs post injection. Intramuscular DOX concentrations were elevated (P<0.05) as compared to control at all time points. Following the 1.5 and 4.5 mg/kg dose, intramuscular concentrations decreased (P<0.05) from 0.24±0.05 and 0.83±0.18 nmol/g at 24 hrs to 0.04±0.01 and 0.40±0.10 nmol/g at 96 hrs, respectively. Although there was a decrease in the intramuscular concentration of DOX over time, these levels remained higher (P<0.05) in the 4.5 mg/kg rats as compared to those administered the 1.5 mg/kg dose. Interestingly, at the lower dose, the intramuscular DOX levels had decreased 83% between 24–96 hrs, while at the larger dose this decrease was only 52%. These data clearly demonstrate that DOX accumulates in skeletal muscle in a dose dependant manner. Furthermore, it appears that the rate of removal or degradation of the intramuscular DOX is slower at increasing doses. These findings have clinical implications as skeletal muscle may be an important compartment for the sequestering of DOX from the circulation, hence limiting its therapeutic impact. This intramuscular accumulation may also have an effect on long‐term function as its metabolite has been shown to be cytotoxic. Supported by NSERC.
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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 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".