Ontology highlight
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
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]