Pathways Contributing to Chemotherapy‐Induced Myotoxicity Are Attenuated by EPA + DHA in a Clinically Relevant Model of Colorectal Cancer
Bibliographic record
Abstract
BACKGROUND: Skeletal muscle loss is a well-recognized consequence of cancer, and chemotherapy exacerbates myotoxicity through multiple mechanisms. Retaining muscle mass improves tumour response to therapies and tolerance to chemotherapy; hence, interventions to mitigate myotoxicity warrant investigations. This study aimed to investigate the protective effects of dietary eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) provided in the form of fish oil on chemotherapy-induced myotoxicity using next-generation RNA sequencing (NGS). METHODS: Fischer 344 rats were fed either a standard diet (STD) for the entire study or switched to a diet containing fish oil (2.3 g/100 g of diet) when chemotherapy (irinotecan + 5-fluorouracil) was initiated. All rats received the Ward colon tumour and tumours were allowed to grow for 2 weeks. Comparisons were made between (1) tumour-bearing rats on a standard diet (TUMOUR STD), (2) tumour-bearing rats that received chemotherapy on a standard diet (CHEMO STD) and (3) tumour-bearing rats that received chemotherapy on a fish oil diet (CHEMO FO). After two cycles of chemotherapy, NGS was performed on gastrocnemius muscle. Differential expression of genes was performed using DEseq2, with a fold-change cut-off ≥ 1.5 and p value < 0.05. Ingenuity pathway analysis (IPA) was used for functional annotation, canonical pathways and upstream regulators analysis. RESULTS: ). In the CHEMO FO versus CHEMO STD comparison, 274 genes were differentially expressed (73% upregulated and 27% downregulated). Dietary fish oil exclusively altered immune-related functions, notably downregulating several genes in the leukocyte extravasation pathway (-logp value 5.92, z score -2.83). Upstream regulatory molecules after chemotherapy were predicted to inhibit transcription factors involved in myogenic regeneration, while those fed a diet containing fish oil showed inhibition of inflammation-related cytokines. CONCLUSION: Chemotherapy negatively impacts processes involved in muscle homeostasis, including muscle cell proliferation and regeneration. The provision of fish oil primarily showed protective effects from pro-inflammatory mediators by downregulating genes involved in the leukocyte extravasation pathway. Our findings provide novel insights into the molecular mechanisms underlying chemotherapy-induced myotoxicity and the potential therapeutic benefits of dietary EPA + DHA to restore muscle homeostasis in cancer.
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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| 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 | 0.000 | 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".