Aerobic exercise training attenuates detrimental effects of cigarette smoke exposure on peripheral muscle through stimulation of the Nrf2 pathway and cytokines: a time-course study in mice.

Cigarette smoke (CS) exposure reduces skeletal muscle function; however, the mechanisms involved have been poorly investigated. The current study evaluated the temporal effects of aerobic exercise training on oxidant and antioxidant systems as well as inflammatory markers in skeletal muscle of mice exposed to CS. Mice were randomly allocated to control, exercise, smoke, and smoke+exercise groups and 3 time points (4, 8, and 12 weeks; n = 12 per group). Exercise training and CS exposure were performed for 30 min/day, twice a day, 5 days/week for 4, 8, and 12 weeks. Aerobic exercise improved functional capacity and attenuated the increase in the cachexia index induced by CS exposure after 12 weeks. Concomitantly, exercise training downregulated tumor necrosis factor α concentration, glutathione oxidation, and messenger RNA (mRNA) expression of Keap1 (P < 0.01) and upregulated interleukin 10 concentration, total antioxidant capacity, and mRNA expression of Nrf2, Gsr, and Txn1 (P < 0.01) in muscle. Exercise increased mRNA expression of Hmox1 compared with the control after 12 weeks (P < 0.05). There were no significant differences between smoke groups for superoxide dismutase activity and Hmox1 mRNA expression. Exercise training improved the ability of skeletal muscle to adequately upregulate key antioxidant and anti-inflammatory defenses to detoxify electrophilic compounds induced by CS exposure, and these effects were more pronounced after 12 weeks. Novelty Exercise attenuates oxidative stress in skeletal muscle from animals exposed to CS via Nrf2 and glutathione pathways. Exercise is a helpful tool to control the inflammatory balance in skeletal muscle from animals exposed to CS. These beneficial effects were evident after 12 weeks.

The tick-derived rBmTI-A protease inhibitor attenuates the histological and functional changes induced by cigarette smoke exposure.

INTRODUCTION: Smoking is the main risk factor for chronic obstructive pulmonary disease development and cigarette smoke (CS) exposure is considered an important approach to reproduce in rodents this human disease. We have previously shown that in an elastase-induced model of emphysema, the administration of a protease inhibitor (rBmTI-A) prevented and attenuated tissue destruction in mice. Thus, in this study we aimed to verify the effects of rBmTI-A administration on the physiopathological mechanisms of CS-induced emphysema. METHODS: Mice (C57BL/6) were exposed to CS or room air for 12 weeks. In this period, 3 nasal instillations of rBmTI-A inhibitor or its vehicle were performed. After euthanasia, respiratory mechanics were evaluated and lungs removed for analysis of mean linear intercept, volume proportion of collagen and elastic fibers, density of polymorphonuclear cells, macrophages, and density of positive cells for MMP-12, MMP-9, TIMP-1 and gp91phox. RESULTS: The rBmTI-A administration improved tissue elastance, decreased alveolar enlargement and collagen fibers accumulation to control levels and attenuated elastic fibers accumulation in animals exposed to CS. There was an increase of MMP-12, MMP-9 and macrophages in CS groups and the rBmTIA only decreased the number of MMP-12 positive cells. Also, we demonstrated an increase in gp91phox in CS treated group and in TIMP-1 levels in both rBmTI-A treated groups. CONCLUSION: In summary, the rBmTI-A administration attenuated emphysema development by an increase of gp91phox and TIMP-1, accompanied by a decrease in MMP-12 levels.

Time-course effects of aerobic physical training in the prevention of cigarette smoke-induced COPD.

A previous study by our group showed that regular exercise training (ET) attenuated pulmonary injury in an experimental model of chronic exposure to cigarette smoke (CS) in mice, but the time-course effects of the mechanisms involved in this protection remain poorly understood. We evaluated the temporal effects of regular ET in an experimental model of chronic CS exposure. Male C57BL/6 mice were divided into four groups: Control (sedentary + air), Exercise (aerobic training + air), Smoke (sedentary + smoke), and Smoke + Exercise (aerobic training + smoke). Mice were exposed to CS and ET for 4, 8, or 12 wk. Exercise protected mice exposed to CS from emphysema and reductions in tissue damping and tissue elastance after 12 wk (P < 0.01). The total number of inflammatory cells in the bronchoalveolar lavage increased in the Smoke group, mainly due to the recruitment of macrophages after 4 wk, neutrophils and lymphocytes after 8 wk, and lymphocytes and macrophages after 12 wk (P < 0.01). Exercise attenuated this increase in mice exposed to CS. The protection conferred by exercise was mainly observed after exercise adaptation. Exercise increased IL-6 and IL-10 in the quadriceps and lungs (P < 0.05) after 12 wk. Total antioxidant capacity and SOD was increased and TNF-α and oxidants decreased in lungs of mice exposed to CS after 12 wk (P < 0.05). The protective effects of exercise against lung injury induced by cigarette smoke exposure suggests that anti-inflammatory mediators and antioxidant enzymes play important roles in chronic obstructive pulmonary disease development mainly after the exercise adaptation.NEW & NOTEWORTHY These experiments investigated for the first time the temporal effects of regular moderate exercise training in cigarette smoke-induced chronic obstructive pulmonary disease. We demonstrate that aerobic conditioning had a protective effect in emphysema development induced by cigarette smoke exposure. This effect was most likely secondary to an effect of exercise on oxidant-antioxidant balance and anti-inflammatory mediators.