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

Abstract

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-κB p65, and IκBα.

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-α 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 IκBα degradation and NF-κB 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-κB signal pathway.

• Authors: Deqing Yang, Dan Xu, Tao Wang, Zhicheng Yuan, Lian Liu, Yongchun Shen, Fuqiang Wen
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 90 Pg. 107149 (Jan 2021) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 33191175 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Cytokines
• Inflammation Mediators
• NF-kappa B
• Organophosphorus Compounds
• Smoke
• Ubiquinone
• mitoquinone

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Cytokines (metabolism)
• Disease Models, Animal
• Inflammation Mediators (metabolism)
• Lung (drug effects, metabolism, pathology)
• Male
• Mice, Inbred C57BL
• Mitochondria (drug effects, metabolism, pathology)
• Mucus (metabolism)
• NF-kappa B (metabolism)
• Organophosphorus Compounds (pharmacology)
• Oxidative Stress (drug effects)
• Pneumonia (etiology, metabolism, pathology, prevention & control)
• Secretory Pathway
• Signal Transduction
• Smoke
• Tobacco Products
• Ubiquinone (analogs & derivatives, pharmacology)
• Mice