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: Sheng-Chih Huang, Jin-Fu Wu, Suchada Saovieng, Wei-Horng Chien, Ming-Fen Hsu, Xiao-Fei Li, Shin-Da Lee, Chih-Yang Huang, Chih-Yang Huang, Chia-Hua Kuo
• Journal: Journal of cachexia, sarcopenia and muscle (J Cachexia Sarcopenia Muscle) Vol. 8 Issue 2 Pg. 277-284 (Apr 2017) ISSN: 2190-6009 [Electronic] Germany
• PMID: 27897404 (Publication Type: Journal Article)
• Copyright: © 2016 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Chemical References

• Anti-Inflammatory Agents
• RNA, Messenger
• Tumor Necrosis Factor-alpha
• Interleukin-10
• 3-nitrotyrosine
• Tyrosine
• Doxorubicin

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Doxorubicin (pharmacology)
• Interleukin-10 (genetics)
• Macrophages (drug effects, immunology)
• Male
• Muscle, Skeletal (anatomy & histology, drug effects, immunology, metabolism)
• Physical Conditioning, Animal
• RNA, Messenger (metabolism)
• Rats, Sprague-Dawley
• Tumor Necrosis Factor-alpha (genetics)
• Tyrosine (analogs & derivatives, metabolism)