1. Doxorubicin inhibits muscle inflammation after eccentric exercise
- Author
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Wei Horng Chien, Chih Yang Huang, Shin-Da Lee, Chia-Hua Kuo, Suchada Saovieng, Xiao Fei Li, Sheng Chih Huang, Ming Fen Hsu, and Jin Fu Wu
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0301 basic medicine ,medicine.medical_specialty ,Inflammation ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,medicine ,Orthopedics and Sports Medicine ,Doxorubicin ,Soleus muscle ,business.industry ,Nitrotyrosine ,Skeletal muscle ,M2 Macrophage ,Muscle atrophy ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,chemistry ,030220 oncology & carcinogenesis ,medicine.symptom ,business ,CD163 ,medicine.drug - 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.
- Published
- 2016
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