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Exercise stimulates beneficial adaptations to diminish doxorubicin-induced cellular toxicity.

Doxorubicin (DOX) is a highly effective antitumor agent used for the treatment of a wide range of cancers. Unfortunately, DOX treatment results in cytotoxic side effects due to its accumulation within off-target tissues. DOX-induced cellular toxicity occurs as a result of increased oxidative damage, resulting in apoptosis and cell death. While there is currently no standard of care practice to prevent DOX-induced toxicity to healthy organs, exercise has been shown to prevent cellular dysfunction when combined with DOX chemotherapy. Endurance exercise stimulates numerous biochemical adaptations that promote a healthy phenotype in several vulnerable tissues, without affecting the antineoplastic properties of DOX. Therefore, determining the appropriate exercise regimen to prescribe to cancer patients receiving DOX therapy, and understanding the mechanisms responsible for exercise-induced protection against DOX toxicity to non-cancer cells is important to developing an effective strategy to combat the pathological effects of DOX. This review summarizes the cytotoxic effects of DOX on the heart, skeletal muscle, liver and kidneys and discusses the current understanding of the clinical benefits of regular physical activity and the potential mechanisms mediating the positive effects of exercise on each organ system.