Key result
Endurance exercise postconditioning provided protective effects against chronic doxorubicin-induced myotoxicity by improving myofiber integrity and regulating FOXO3a activity in mice.
Why the study?
Doxorubicin has severe myotoxicity due to accumulation, while endurance exercise improves pathological features and contributes to muscle homeostasis.
Does endurance exercise training mitigate chronic doxorubicin-induced myotoxicity in mice?
Does endurance exercise training mitigate chronic doxorubicin-induced myotoxicity in mice?
p-value: p=<0.05
Endurance exercise postconditioning provides protective effects against chronic doxorubicin-induced skeletal muscle myotoxicity in a mouse model.
May support exercise against doxorubicin myotoxicity in mice; hypothesis-generating and should not change clinical practice.
PURPOSE: Doxorubicin (DOX) is a potent anti-cancer drug that appears to have severe myotoxicity due to accumulation. The skeletal muscle has a regeneration capacity through satellite cell activation when exposed to extracellular stimulus or damage. Endurance exercise (EXE) is a therapeutic strategy that improves pathological features and contributes to muscle homeostasis. Thus, this study investigated the effect of EXE training in mitigating chronic DOX-induced myotoxicity. METHODS: Male C57BL/6J mice were housed and allowed to acclimatize with free access to food and water. All the mice were randomly divided into four groups: sedentary control (CON, n=9), exercise training (EXE, n=9), doxorubicin treatment (DOX, n=9), doxorubicin treatment and exercise training (DOX+EXE, n=9) groups. The animals were intraperitoneally injected with 5 mg/kg/week of DOX treatment for 4 weeks, and EXE training was initiated for treadmill adaptation for 1 week and then performed for 4 weeks. Both sides of the soleus (SOL) muscle tissues were dissected and weighed after 24 hours of the last training sessions. RESULTS: DOX chemotherapy induced an abnormal myofiber's phenotype and transition of myosin heavy chain (MHC) isoforms. The paired box 7 (PAX7) and myoblast determination protein 1 (MYOD) protein levels were triggered by DOX, while no alterations were shown for the myogenin (MYOG). DOX remarkably impaired the a-actinin (ACTN) protein, but the EXE training seems to repair it. DOX-induced myotoxicity stimulated the expression of the forkhead box O3 (FOXO3a) protein, which was accurately controlled and adjusted by the EXE training. However, the FOXO3a-mediated downstream markers were not associated with DOX and EXE. CONCLUSION: EXE postconditioning provides protective effects against chronic DOX-induced myotoxicity, and should be recommended to alleviate cancer chemotherapy-induced late-onset myotoxicity.
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Insu Kwon (2020) studied Doxorubicin-induced myotoxicity (n=36). Endurance exercise training vs. Sedentary control and doxorubicin without exercise was evaluated on Skeletal muscle regeneration capacity and myofiber integrity (p=<0.05). Endurance exercise postconditioning provided protective effects against chronic doxorubicin-induced myotoxicity by improving myofiber integrity and regulating FOXO3a activity in mice.
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