Journal of Cachexia, Sarcopenia and Muscle (JCSM) - Abstract


Doxorubicin inhibits muscle inflammation after eccentric exercise

Sheng-Chih Huang, Jin-Fu Wu, Suchada Saovieng, Wei-Horng Chien, Ming-Fen Hsu, Xiao-Fei Li, Shin-Da Lee, Chih-Yang Huang, Chih-Yang Huang, Chia-Hua Kuo

 

Background

Doxorubicin, a widely used anti-tumour drug, is known to cause muscle loss in cancer patients.

Methods

Following an acute dose of doxorubicin injection (2.5 mg/kg per body weight), we examined macrophage distribution in rat soleus muscle challenged by eccentric exercise (downhill running). Long-term doxorubicin treatment (one injection every 3 days) on muscle mass and survival were also determined.

Results

Under non-exercised condition, increased tumour necrosis factor (TNF)-alpha mRNA and decreased IL-10 mRNA were observed in soleus muscle of doxorubicin-treated rats, compared with saline-treated control rats. However, increases in inflammation score (leukocyte infiltration), nitrotyrosine level, and M1 macrophage (CD68+) invasion in exercised soleus muscle were absent in doxorubicin-treated rats, whereas increased M2 macrophage (CD163+) localization in exercised muscle was less affected by doxorubicin. Despites coenzyme Q (Q10) supplementation significantly elevated TNF-alpha mRNA, nitrotyrosine, and anti-oxidant gamma-glutamylcysteine synthetase (GCS) levels in non-exercised soleus muscle, these pro-inflammatory responses were also abolished in doxorubicin-treated rats. Results from long-term doxorubicin treatment show a significant muscle loss followed by an accelerated death, which cannot be reversed by Q10 supplementation.

Conclusions

(i) Doxorubicin impairs inflammation mechanism by depleting M1 macrophage in exercised skeletal muscle; (ii) Muscle loss and accelerated death during prolonged doxorubicin treatment cannot be reversed by Q10 supplementation.

 

Huang, S. -C., Wu, J. -F., Saovieng, S., Chien, W. -H., Hsu, M. -F., Li, X. -F., Lee, S. -D., Huang, C. -Y., Huang, C. -Y., and Kuo, C. -H. (2016) Doxorubicin inhibits muscle inflammation after eccentric exercise. Journal of Cachexia, Sarcopenia and Muscle, 8; 277–284. doi: 10.1002/jcsm.12148.