Doxorubicin inhibits muscle inflammation after eccentric exercise

• Published in: Journal of cachexia, sarcopenia and muscle sarcopenia and muscle, 2017-04, Vol.8 (2), p.277-284
• Main Authors: Huang, Sheng‐Chih, Wu, Jin‐Fu, Saovieng, Suchada, Chien, Wei‐Horng, Hsu, Ming‐Fen, Li, Xiao‐Fei, Lee, Shin‐Da, Huang, Chih‐Yang, Kuo, Chia‐Hua
• Format: Article
• Language: English
• Subjects: Adriamycin; Animals; Anti-Inflammatory Agents - pharmacology; Cancer therapies; CD163; CD68; Chemotherapy; Clinical trials; Doxorubicin - pharmacology; Eccentric exercise; Experiments; Fitness equipment; Histology; Inflammation; Interleukin-10 - genetics; Laboratories; Macrophage; Macrophages - drug effects; Macrophages - immunology; Male; Medical research; Mitochondria; Mitochondrial DNA; Mortality; Muscle atrophy; Muscle contraction; Muscle, Skeletal - anatomy & histology; Muscle, Skeletal - drug effects; Muscle, Skeletal - immunology; Muscle, Skeletal - metabolism; Musculoskeletal system; Original; Physical Conditioning, Animal; Proteins; Rats, Sprague-Dawley; RNA, Messenger - metabolism; Running; Sarcopenia; Skeletal muscle; Studies; Tumor Necrosis Factor-alpha - genetics; Tumor necrosis factor-TNF; Tyrosine - analogs & derivatives; Tyrosine - metabolism
• ISSN: 2190-5991; 2190-6009
• DOI: 10.1002/jcsm.12148

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.