Pathways Contributing to Chemotherapy-Induced Myotoxicity Are Attenuated by EPA + DHA in a Clinically Relevant Model of Colorectal Cancer.
Level 5 - mechanism / opinion, no new human data
Animal research (rat model)
PubMed 41243421 · doi:10.1002/jcsm.70110
What was done
Fischer 344 rats bearing Ward colon tumours were assigned to three groups: standard diet (TUMOUR STD), standard diet with chemotherapy comprising irinotecan plus 5-fluorouracil (CHEMO STD), or a fish oil-supplemented diet (2.3 g/100 g diet providing EPA and DHA) initiated alongside chemotherapy (CHEMO FO). Following two cycles of chemotherapy, gastrocnemius muscle transcriptomes were profiled via next-generation RNA sequencing. Differentially expressed genes were identified using DESeq2 (fold-change cut-off ≥ 1.5, p < 0.05), followed by Ingenuity Pathway Analysis for canonical pathway and upstream regulator profiling.
What was found
Compared with TUMOUR STD, CHEMO STD altered 272 genes (55% upregulated, 45% downregulated), significantly affecting pathways for muscle cell proliferation (p < 10^-7), connective tissue disorder (p < 10^-6), apoptosis (p < 10^-3), and neurodevelopmental disorders (p < 10^-3), with predicted inhibition of transcription factors regulating myogenic regeneration. Compared with CHEMO STD, CHEMO FO differentially expressed 274 genes (73% upregulated, 27% downregulated), exclusively altering immune functions with notable downregulation of leukocyte extravasation (-log p-value 5.92, z-score -2.83) and predicted inhibition of inflammatory cytokines.
Why it matters
The findings identify transcriptomic pathways involved in chemotherapy-induced muscle toxicity and show that dietary EPA and DHA suppress inflammatory leukocyte infiltration signalling in muscle.
Limits
The study was conducted in a rodent model, limiting direct generalisability to human patients. The abstract does not state the total number of animals (n) or report functional or morphological endpoints such as muscle mass, fibre cross-sectional area, or contractile force.
Cited by
- supports Research by Vera Mazurak in rodent models demonstrates that feeding omega-3 fatty acids protects against chemotherapy-induced muscle atrophy.