<p>Exercise Ameliorates Emphysema Of Cigarette Smoke-Induced COPD In Mice Through The Exercise-Irisin-Nrf2 Axis</p>

Abstract

Background: Oxidative stress is one of the important mechanisms underlying the pathogenesis of chronic obstructive pulmonary disease (COPD). Irisin is a type of myokine secreted from the muscle during exercise and acts against oxidative stress via nuclear factor erythroid 2-related factor 2 (Nrf2), a transcription factor with antioxidant properties. Here, we examined the emphysema suppressive effects of the exercise-irisin-Nrf2 axis in mice. Methods: Mice were divided into three groups, namely, the control, smoking, and exercise + smoking groups. All mice from the smoking and exercise + smoking groups were exposed to cigarette smoke once a day. The mice from the exercise + smoking group were adapted to a treadmill once a day. To investigate the Nrf2 cascade, after 12 weeks, serum irisin concentration and Nrf2 and heme oxygenase-1 (HO-1) expression in the lung homogenate were determined. To evaluate cigarette smoke-induced COPD, the number of inflammatory cells in bronchoalveolar lavage fluid (BALF), mean linear intercept (MLI), and destructive index in the lung tissue were examined. Results: Serum irisin concentration and the expression levels of Nrf2 and HO-1 in the lung homogenate were significantly higher in mice from the exercise + smoking group than in those from the control and smoking groups. The proportion of neutrophils in the BALF was significantly lower in the exercise + smoking group than in the smoking group. The MLI and destructive index were also significantly smaller in mice from the exercise + smoking group than mice from the smoking group. Conclusion: Irisin secreted from the muscle during exercise may exert protective effects against oxidative stress via Nrf2 and HO-1, and ameliorate emphysema of cigarette smokeinduced COPD. The exercise-irisin-Nrf2 axis may serve as a novel target for COPD treatment.

<p>Ninjin’yoeito Ameliorates Skeletal Muscle Complications in COPD Model Mice by Upregulating Peroxisome Proliferator-Activated Receptor γ Coactivator-1α Expression</p>

“…The cigarette smoke-exposed mice showed less weight gain, increased inflammatory cell infiltration in BALF, and development of emphysema characterized by alveolar enlargement and greater destruction of alveoli, similar to mice in a previous report. 23,33,34 Our results showed a discrepancy regarding the effect of NYT on smokinginduced change in pulmonary morphology: NYT induced partial recovery of alveolar damage as indicated by the DI; however, NYT did not reduce air space enlargement as indicated by the MLI. Some reports showed that the DI is a more sensitive parameter of pulmonary destruction than the MLI, 30,35 whereas others revealed a correlation between the MLI and loss of elastic recoil.…”

“…Bronchoalveolar lavage (BAL) was performed, and the BAL fluid (BALF) was collected as previously described. 23 After BAL, the left lung was dissected and immediately soaked in 10% formalin. The gastrocnemius and soleus muscles were dissected from the right leg of each mouse for muscle analysis.…”

“…The recovered BALF was treated as previously described. 23 Briefly, the BALF was centrifuged (1200 × g, 4°C, 10 min), and the cell pellet was resuspended in 1 mL phosphate-buffered saline and subjected to a cytospin procedure using a Shandon Cytospin 3 centrifuge (Shandon Scientific Co., London, England). The slides were stained with Diff-Quik (Sysmex, Kobe, Japan) for cell counts (total cells and neutrophils).…”

“… 22 Furthermore, we showed that an exercise-based intervention increases serum irisin levels and consequently ameliorates cigarette smoke-induced emphysema in COPD model mice through the irisin-accelerated antioxidation pathway. 23 Considering these data, the PGC-1α-related pathway is potent and has a favorable effect not only on muscle fibers but also on lung tissue damaged by smoking.…”

The Effect of Acute Aerobic Exercise on Redox Homeostasis and Mitochondrial Function of Rat White Adipose Tissue

“…Several studies have shown that chronic exposure to exercise results in enhanced cytoprotection and antioxidant defenses in different tissues, such as skeletal muscle [ 10 ], heart [ 39 ], brain [ 40 ], and others [ 41 ]. This physiological adaptation is related to the induction of low levels of ROS in each single bout of exercise [ 38 ].…”