PMID- 33191175
OWN - NLM
STAT- MEDLINE
DCOM- 20210526
LR  - 20240226
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 90
DP  - 2021 Jan
TI  - Mitoquinone ameliorates cigarette smoke-induced airway inflammation and mucus 
      hypersecretion in mice.
PG  - 107149
LID - S1567-5769(20)33616-X [pii]
LID - 10.1016/j.intimp.2020.107149 [doi]
AB  - 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-kappaB p65, and IkappaBalpha. 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 IkappaBalpha degradation and NF-kappaB 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-kappaB signal pathway.
CI  - Copyright (c) 2020 Elsevier B.V. All rights reserved.
FAU - Yang, Deqing
AU  - Yang D
AD  - Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and 
      Department of Respiratory and Critical Care Medicine, West China Hospital of 
      Sichuan University, Chengdu, China.
FAU - Xu, Dan
AU  - Xu D
AD  - Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and 
      Department of Respiratory and Critical Care Medicine, West China Hospital of 
      Sichuan University, Chengdu, China.
FAU - Wang, Tao
AU  - Wang T
AD  - Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and 
      Department of Respiratory and Critical Care Medicine, West China Hospital of 
      Sichuan University, Chengdu, China.
FAU - Yuan, Zhicheng
AU  - Yuan Z
AD  - Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and 
      Department of Respiratory and Critical Care Medicine, West China Hospital of 
      Sichuan University, Chengdu, China.
FAU - Liu, Lian
AU  - Liu L
AD  - Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and 
      Department of Respiratory and Critical Care Medicine, West China Hospital of 
      Sichuan University, Chengdu, China.
FAU - Shen, Yongchun
AU  - Shen Y
AD  - Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and 
      Department of Respiratory and Critical Care Medicine, West China Hospital of 
      Sichuan University, Chengdu, China. Electronic address: shen_yongchun@126.com.
FAU - Wen, Fuqiang
AU  - Wen F
AD  - Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and 
      Department of Respiratory and Critical Care Medicine, West China Hospital of 
      Sichuan University, Chengdu, China. Electronic address: wenfuqiang@scu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20201112
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (NF-kappa B)
RN  - 0 (Organophosphorus Compounds)
RN  - 0 (Smoke)
RN  - 1339-63-5 (Ubiquinone)
RN  - 47BYS17IY0 (mitoquinone)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Antioxidants/pharmacology
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Inflammation Mediators/metabolism
MH  - Lung/*drug effects/metabolism/pathology
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mitochondria/*drug effects/metabolism/pathology
MH  - Mucus/*metabolism
MH  - NF-kappa B/metabolism
MH  - Organophosphorus Compounds/*pharmacology
MH  - Oxidative Stress/drug effects
MH  - Pneumonia/etiology/metabolism/pathology/*prevention & control
MH  - Secretory Pathway
MH  - Signal Transduction
MH  - Smoke
MH  - Tobacco Products
MH  - Ubiquinone/*analogs & derivatives/pharmacology
MH  - Mice
OTO - NOTNLM
OT  - Cigarette smoke
OT  - Inflammation
OT  - Mitoquinone
OT  - Mucus hypersecretion
OT  - Oxidative stress
EDAT- 2020/11/17 06:00
MHDA- 2021/05/27 06:00
CRDT- 2020/11/16 05:32
PHST- 2020/07/07 00:00 [received]
PHST- 2020/10/19 00:00 [revised]
PHST- 2020/10/20 00:00 [accepted]
PHST- 2020/11/17 06:00 [pubmed]
PHST- 2021/05/27 06:00 [medline]
PHST- 2020/11/16 05:32 [entrez]
AID - S1567-5769(20)33616-X [pii]
AID - 10.1016/j.intimp.2020.107149 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2021 Jan;90:107149. doi: 10.1016/j.intimp.2020.107149. Epub 
      2020 Nov 12.