Electroacupuncture Alleviates Chemotherapy- Associated Cancer-Related Fatigue by Restoring Mitochondrial Homeostasis

ObjectiveCancer-related fatigue (CRF) is a persistent and debilitating symptom commonly associated with cancer cachexia and impaired physical function, yet effective therapeutic strategies remain limited. This study aimed to evaluate the anti-fatigue effects of electroacupuncture (EA) and to explore its underlying mechanisms.MethodsA CRF mouse model was established by 5-fluorouracil (5-FU) administration. EA was applied at ST36. Fatigue-related behaviors were assessed using rotarod, grip strength, swimming, and open-field tests. Skeletal muscle morphology was evaluated by histological staining, and mitochondrial ultrastructure was examined by transmission electron microscopy. Mitochondrial function and oxidative stress were assessed by measuring membrane potential (ΔΨm), mtDNA content, reactive oxygen species (ROS), and superoxide dismutase (SOD) activity. The expression of mitochondrial dynamics-related genes was analyzed by RT-qPCR.ResultsEA significantly alleviated fatigue-like behaviors, improving muscle strength, endurance, and locomotor activity in CRF mice. EA preserved muscle fiber morphology and increased cross-sectional area. Mitochondrial structural damage induced by 5-FU was markedly attenuated by EA. Furthermore, EA restored mitochondrial membrane potential and mtDNA content, reduced ROS levels, and enhanced SOD activity. The dysregulated expression of mitochondrial dynamics-related genes was also normalized by EA.ConclusionsEA can alleviate CRF by regulating mitochondrial dynamics and reducing oxidative stress in skeletal muscle, highlighting its potential as a novel intervention for CRF treatment.