Dataset Information

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.

SUBMITTER: Huang SC

PROVIDER: S-EPMC5377412 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Publications

Doxorubicin inhibits muscle inflammation after eccentric exercise.

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]

PMID: 27897404

Similar Datasets

Project description:The current consensus in exercise physiology is that the repeated bout effect always appears after few eccentric exercise sessions. This is the first attempt to challenge this tenet, by exploiting specificity in muscle plasticity. More specifically, we examined whether the opposing adaptations in muscle induced after concentric and eccentric exercise can attenuate and/or remove the repeated bout effect. Seventeen young men were randomly assigned into one of the following groups: (1) the alternating eccentric-concentric exercise group; and (2) the eccentric-only exercise group. Both groups performed 8 weeks of resistance exercise using the knee extensors of both legs on an isokinetic dynamometer. The alternating eccentric-concentric exercise group performed an alternating exercise protocol, switching between eccentric-only and concentric-only exercise every 4 weeks, while the eccentric-only group performed eccentric exercise. Evaluation of muscle damage using physiological (isometric torque, delayed onset muscle soreness, and range of movement) and biochemical (creatine kinase) markers and inflammation (C-reactive protein) was performed at weeks 1, 5, and 10. Baseline isometric peak torque was also evaluated at week 14 after another cycle (4 weeks) of alternating or eccentric-only exercise training. In the alternating eccentric-concentric exercise group, the concentric exercise training performed prior to eccentric exercise reduced dramatically the repeated bout effect by reversing muscle back to its unaccustomed state. On the contrary, the eccentric-only exercise group exhibited a typical manifestation of the repeated bout effect. Interestingly, muscle strength was elevated similarly for both alternating and eccentric-only exercise groups after 13 weeks of training. The alternating eccentric-concentric exercise scheme, implemented in the present study, has for the first time successfully overcame the repeated bout effect. The similarity in muscle strength measurements following the two protocols is against the notion that inflammation plays an important role in exercise-induced adaptations in muscle.

Project description:BACKGROUND:Avenanthramides (AVA) are a group of di-phenolic acids found only in oats and have shown antioxidant and anti-inflammatory effects in vitro and in vivo. Eccentric muscle contraction is intimately involved in rigorous exercise that activates systemic and local inflammatory responses. The objective of the study is to evaluate whether chronic AVA supplementation could attenuate peripheral inflammatory and immunological markers in human subjects in response to an acute bout of downhill running (DR). METHODS:Eleven male and thirteen female subjects voluntarily participated in this double-blinded, randomized controlled study and were randomly divided into AVA-supplemented (AVA) or control (C) groups. All subjects conducted a DR protocol at -?10% grade with an intensity equivalent to 75% of their maximal heart rate. Blood samples were collected at rest and various time points (0-72?h) after DR (PRE). After an 8-week washout period, participants received two cookies daily containing either 206?mg/kg (AVA) or 0?mg/kg (C) AVA for 8?weeks. Following the oat supplementation regimen, the DR and blood sampling protocols were repeated (POST). Plasma inflammatory and immunological markers were measured using Multiplex immunoassay and muscle soreness was evaluated with pain rating scale. RESULTS:DR increased plasma creatine kinase (CK) activity (P?<?0.01) during PRE, but the response was reduced at 24 and 48?h during POST vs. PRE regardless of AVA status (P?<?0.05). Neutrophil respiratory burst (NRB) levels were elevated at 4 and 24?h (P?<?0.05) during PRE but were significantly decreased at 0-48?h during POST vs. PRE (P?<?0.05 or 0.01). Granulocyte-colony stimulating factor (G-CSF), the neutrophil stimulating cytokine, was also increased in response to DR but showed lower levels in AVA compared to C during POST vs. PRE (P?<?0.05). Plasma interleukin-6 (IL-6) content showed an increase at 0 and 4?h during PRE and 0?h during POST (P?<?0.01), whereas during POST there was a trend toward a lower IL-6 level in AVA vs. C (P?=?0.082). Plasma levels of anti-inflammatory agent interleukin-1 receptor antagonist (IL-1Ra) showed an increase at 4?h during PRE, and was significantly elevated in AVA vs. C during POST. Both soluble vascular cell adhesion molecule-1 (sVCAM-1) and monocyte chemoattractant protein-1 (MCP-1) contents increased at 0 and 24?h post DR during PRE as well as POST sessions, however, sVCAM-1 content was lower in AVA vs. C during POST (P?<?0.05) and MCP-1 levels were below resting level at 24, 48 and 72?h during POST (P?<?0.05). DR increased muscle pain at all post-DR time points (P?<?0.01), but the pain level was alleviated by oat supplementation at 48 and 72?h during POST regardless of AVA treatment (P?<?0.05). CONCLUSIONS:Oat AVA supplementation reduced circulatory inflammatory cytokines and inhibited expression of chemokines and cell adhesion molecules induced by DR. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT02584946 . Registered 23 October 2015.

Dataset Information

Doxorubicin inhibits muscle inflammation after eccentric exercise.

Background

Methods

Results

Conclusions

Publications

Doxorubicin inhibits muscle inflammation after eccentric exercise.

Similar Datasets

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