Effect of exercise on neuromuscular toxicity in oxaliplatin‐treated mice

• Published in: Muscle & nerve 2021-08, Vol.64 (2), p.225-234
• Main Authors: Lees, Justin G., Abdulla, Munawwar, Barkl‐Luke, Mallory E., Livni, Lital, Keating, Brooke A., Hayes, Jessica, Fiore, Nathan T., Park, Susanna B., Moalem‐Taylor, Gila, Goldstein, David
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Chemotherapy; Disease Models, Animal; Euthanasia; exercise; Exploratory behavior; Gastrocnemius muscle; Gene expression; Hyperalgesia - chemically induced; Hyperalgesia - therapy; Male; Mechanical properties; Mice; Mice, Inbred C57BL; Morphology; muscle wasting; Muscles; neuromuscular; Organs; Oxaliplatin; Oxaliplatin - pharmacology; Pain perception; Pain Threshold - drug effects; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - therapy; Peripheral neuropathy; Physical Conditioning, Animal - physiology; Toxicity; Weight reduction
• ISSN: 0148-639X; 1097-4598
• DOI: 10.1002/mus.27329

Introduction/Aims Clinically, the chemotherapeutic agent oxaliplatin can cause peripheral neuropathy, impaired balance, and muscle wastage. Using a preclinical model, we investigated whether exercise intervention could improve these adverse conditions. Methods Mice were chronically treated with oxaliplatin alone or in conjunction with exercise. Behavioral studies, including mechanical allodynia, rotarod, open‐field, and grip‐strength tests, were performed. After euthanasia, multiple organs and four different muscle types were dissected and weighed. The cross‐sectional area (CSA) of muscle fibers in the gastrocnemius muscle was assessed and gene expression analysis performed on the forelimb triceps muscle. Results Oxaliplatin‐treated mice displayed reduced weight gain, mechanical allodynia, and exploratory behavior deficits that were not significantly improved by exercise. Oxaliplatin‐treated exercised mice showed modest evidence of reduced muscle wastage compared with mice treated with oxaliplatin alone, and exercised mice demonstrated evidence of a mild increase in CSA of muscle fibers. Discussion Exercise intervention did not improve signs of peripheral neuropathy but moderately reduced the negative impact of oxaliplatin chemotherapy related to muscle morphology, suggesting the potential for exploring the impact of exercise on reducing oxaliplatin‐induced neuromuscular toxicity in cancer patients.