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Doxorubicin inhibits muscle inflammation after eccentric exercise.


ABSTRACT:

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.

SUBMITTER: Huang SC 

PROVIDER: S-EPMC5377412 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Publications

Doxorubicin inhibits muscle inflammation after eccentric exercise.

Huang Sheng-Chih SC   Wu Jin-Fu JF   Saovieng Suchada S   Chien Wei-Horng WH   Hsu Ming-Fen MF   Li Xiao-Fei XF   Lee Shin-Da SD   Huang Chih-Yang CY   Huang Chih-Yang CY   Kuo Chia-Hua CH  

Journal of cachexia, sarcopenia and muscle 20161010 2


<h4>Background</h4>Doxorubicin, a widely used anti-tumour drug, is known to cause muscle loss in cancer patients.<h4>Methods</h4>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.<h4>Results</h4>Under non-exercised condition, increased tumour necrosis  ...[more]

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