title: 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.
authors.affiliation: Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan.
authors.forename: Sheng-Chih
authors.initials: SC
authors.lastname: Huang
authors.affiliation: Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan.
authors.forename: Jin-Fu
authors.initials: JF
authors.lastname: Wu
authors.affiliation: Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan.
authors.forename: Suchada
authors.initials: S
authors.lastname: Saovieng
authors.affiliation: Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan.
authors.forename: Wei-Horng
authors.initials: WH
authors.lastname: Chien
authors.affiliation: Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan.
authors.forename: Ming-Fen
authors.initials: MF
authors.lastname: Hsu
authors.affiliation: Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan.
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Li
authors.affiliation: Graduate Institute of Physical Therapy and Rehabilitation Science, China Medical University, Taichung, Taiwan.
authors.forename: Shin-Da
authors.initials: SD
authors.lastname: Lee
authors.affiliation: Translation Research Core, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Department of Healthcare Administration, Asia University, Taichung, Taiwan.|Graduate Institute of Basic Medical Science, China Medical University, Taichung City, Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
authors.affiliation: Laboratory of Exercise Biochemistry, University of Taipei, Taipei, Taiwan.|Graduate Institute of Physical Therapy and Rehabilitation Science, China Medical University, Taichung, Taiwan.
authors.forename: Chia-Hua
authors.initials: CH
authors.lastname: Kuo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D016753:Interleukin-10 / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D018482:Muscle, Skeletal / Q000033:anatomy & histology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C002744:3-nitrotyrosine; D014443:Tyrosine; D004317:Doxorubicin
keywords: Adriamycin; CD163; CD68; Chemotherapy; Eccentric exercise; Macrophage; Muscle atrophy; Skeletal muscle