Mitoquinone ameliorates cigarette smoke-induced airway inflammation and mucus hypersecretion in mice

Background: Cigarette smoking, which induces airway inflammation and mucus hypersecretion, is a major risk factor for the development of cigarette smoke (CS)-induced airway disorders. In this study, we investigated the effects and mechanisms of mitoquinone (MitoQ), a mitochondria-targeted antioxidant, on CS-induced airway inflammation and mucus hypersecretion in mice. Methods: C57BL/6J mice were exposed to CS for 75 min twice daily, 5 days per week for 4 weeks. MitoQ (2.5, 5 mg/kg/day) was administered intraperitoneally 1 h before CS exposure. Bronchoalveolar lavage fluid (BALF) was obtained for cell counting and determination of pro-inflammatory cytokine levels. Lung tissue was collected for histological examination; Western blotting was used to measure levels of Mfn2, Drp1, cytochrome c, NF-kappa B p65, and I kappa B alpha. Results: Pretreatment with MitoQ significantly attenuated CS-induced thickening of the airway epithelium, peribronchial inflammatory cell infiltration, goblet cell hyperplasia and Muc5ac staining. The numbers of total cells, neutrophils and macrophages, as well as levels of TNF-alpha and IL-6 in BALF were remarkably decreased by MitoQ in a dose-dependent manner. MitoQ attenuated oxidative stress by preventing the CS-induced increase in malondialdehyde level and decrease in superoxide dismutase activity and GSH/GSSG ratio. MitoQ decreased the expression of mitochondrial fission protein Drp1 and increased that of mitochondrial fusion protein Mfn2, as well as reduced cytochrome c release into the cytosol. Furthermore, MitoQ suppressed I kappa B alpha degradation and NF-kappa B p65 nuclear translocation. Conclusions: MitoQ attenuates inflammation, mucus hypersecretion, and oxidative stress induced by CS. It may exert these effects in part by modulating mitochondrial function and the NF-kappa B signal pathway.