Resistance exercise attenuates skeletal muscle oxidative stress, systemic pro-inflammatory state, and cachexia in Walker-256 tumor-bearing rats

Appl Physiol Nutr Metab. 2017 Sep;42(9):916-923. doi: 10.1139/apnm-2016-0436. Epub 2017 May 5.

Abstract

The aim of this study was to investigate the effects of resistance exercise training (RET) on oxidative stress, systemic inflammatory markers, and muscle wasting in Walker-256 tumor-bearing rats. Male (Wistar) rats were divided into 4 groups: sedentary controls (n = 9), tumor-bearing (n = 9), exercised (n = 9), and tumor-bearing exercised (n = 10). Exercised and tumor-bearing exercised rats were exposed to resistance exercise of climbing a ladder apparatus with weights tied to their tails for 6 weeks. The physical activity of control and tumor-bearing rats was confined to the space of the cage. After this period, tumor-bearing and tumor-bearing exercised animals were inoculated subcutaneously with Walker-256 tumor cells (11.0 × 107 cells in 0.5 mL of phosphate-buffered saline) while control and exercised rats were injected with vehicle. Following inoculation, rats maintained resistance exercise training (exercised and tumor-bearing exercised) or sedentary behavior (control and tumor-bearing) for 12 more days, after which they were euthanized. Results showed muscle wasting in the tumor-bearing group, with body weight loss, increased systemic leukocytes, and inflammatory interleukins as well as muscular oxidative stress and reduced mTOR signaling. In contrast, RET in the tumor-bearing exercised group was able to mitigate the reduced body weight and muscle wasting with the attenuation of muscle oxidative stress and systemic inflammatory markers. RET also prevented loss of muscle strength associated with tumor development. RET, however, did not prevent the muscle proteolysis signaling via FBXO32 gene messenger RNA expression in the tumor-bearing group. In conclusion, RET performed prior tumor implantation prevents cachexia development by attenuating tumor-induced systemic pro-inflammatory condition with muscle oxidative stress and muscle damage.

Keywords: dommage oxydatif; entraînement à la force; fonte musculaire; interleukines; interleukins; muscle proteolysis; muscle wasting; oxidative damage; protéolyse musculaire; strength training.

MeSH terms

  • Animals
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Cachexia / etiology
  • Cachexia / immunology
  • Cachexia / prevention & control*
  • Carcinoma 256, Walker / metabolism
  • Carcinoma 256, Walker / pathology
  • Carcinoma 256, Walker / physiopathology
  • Carcinoma 256, Walker / therapy*
  • Cytokines / blood
  • Gene Expression Regulation, Neoplastic
  • Inflammation Mediators / blood
  • Leukocytosis / etiology
  • Leukocytosis / immunology
  • Leukocytosis / prevention & control*
  • Male
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Muscle Weakness / etiology
  • Muscle Weakness / immunology
  • Muscle Weakness / prevention & control*
  • Muscle, Skeletal / immunology
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology*
  • Oxidative Stress*
  • Physical Conditioning, Animal*
  • Random Allocation
  • Rats, Wistar
  • SKP Cullin F-Box Protein Ligases / genetics
  • SKP Cullin F-Box Protein Ligases / metabolism
  • TOR Serine-Threonine Kinases / genetics
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Burden
  • Weight Gain
  • Weight Loss

Substances

  • Biomarkers
  • Cytokines
  • Inflammation Mediators
  • Muscle Proteins
  • Fbxo32 protein, rat
  • SKP Cullin F-Box Protein Ligases
  • mTOR protein, rat
  • TOR Serine-Threonine Kinases