PMID- 36288647
OWN - NLM
STAT- MEDLINE
DCOM- 20221202
LR  - 20221202
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 113
IP  - Pt A
DP  - 2022 Dec
TI  - Mitoquinone alleviates bleomycin-induced acute lung injury via inhibiting 
      mitochondrial ROS-dependent pulmonary epithelial ferroptosis.
PG  - 109359
LID - S1567-5769(22)00843-8 [pii]
LID - 10.1016/j.intimp.2022.109359 [doi]
AB  - Numerous studies demonstrated that bleomycin (BLM) caused acute lung injury 
      (ALI). This study explored the role of mitochondrial reactive oxygen species 
      (ROS) on BLM-induced ALI and pulmonary epithelial ferroptosis. Male C57BL/6J mice 
      were intratracheally injected with BLM (3.0 mg/kg). BEAS-2B cells, human 
      bronchial epithelial cells, were cultured with BLM (10 mug/ml). Pulmonary MDA and 
      4-HNE, two markers of lipid peroxidation, were elevated in BLM-exposed mice. 
      Oxidized lipids were upregulated in BLM-exposed BEAS-2B cells. 
      Ferroptosis-characteristic ultrastructure, mainly disappearance of mitochondrial 
      bilayer membrane structure and cristae, was observed in BLM-exposed pulmonary 
      epithelium. Ferrostatin-1, a specific inhibitor of ferroptosis, attenuated 
      BLM-evoked pulmonary lipid peroxidation, ferroptosis-characteristic mitochondrial 
      ultrastructure and pulmonary epithelial death. The in vitro experiments showed 
      that mitochondrial membrane potentials (MMPs) were decreased and mitochondrial 
      ROS were increased in BLM-exposed BEAS-2B cells. Mitoquinone (MitoQ), a 
      mitochondria-targeted antioxidant, prevented BLM-induced MMP reduction and 
      mitochondrial ROS elevation in BEAS-2B cells. The in vivo experiment found that 
      MitoQ attenuated BLM-evoked GSH depletion and lipid peroxidation in mouse lungs. 
      Moreover, MitoQ prevented BLM-induced ferroptosis-characteristic mitochondrial 
      changes, pulmonary epithelial death and ALI. In conclusion, mitochondrial ROS are 
      an initiator of BLM-induced pulmonary epithelial ferroptosis. 
      Mitochondria-targeted antioxidants may be used as potential therapeutic agents 
      for BLM-induced ALI.
CI  - Copyright (c) 2022. Published by Elsevier B.V.
FAU - Zhan, Ping
AU  - Zhan P
AD  - Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital 
      of Anhui Medical University, Hefei, Anhui 230601, China.
FAU - Lu, Xue
AU  - Lu X
AD  - Department of Toxicology, Anhui Medical University, Hefei, Anhui 230032, China.
FAU - Li, Zhao
AU  - Li Z
AD  - Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital 
      of Anhui Medical University, Hefei, Anhui 230601, China.
FAU - Wang, Wen-Jing
AU  - Wang WJ
AD  - Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital 
      of Anhui Medical University, Hefei, Anhui 230601, China.
FAU - Peng, Kun
AU  - Peng K
AD  - Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital 
      of Anhui Medical University, Hefei, Anhui 230601, China.
FAU - Liang, Nan-Nan
AU  - Liang NN
AD  - Department of Toxicology, Anhui Medical University, Hefei, Anhui 230032, China.
FAU - Wang, Yan
AU  - Wang Y
AD  - Department of Toxicology, Anhui Medical University, Hefei, Anhui 230032, China.
FAU - Li, Jian
AU  - Li J
AD  - Department of Toxicology, Anhui Medical University, Hefei, Anhui 230032, China.
FAU - Fu, Lin
AU  - Fu L
AD  - Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital 
      of Anhui Medical University, Hefei, Anhui 230601, China.
FAU - Zhao, Hui
AU  - Zhao H
AD  - Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital 
      of Anhui Medical University, Hefei, Anhui 230601, China.
FAU - Xu, De-Xiang
AU  - Xu DX
AD  - Department of Toxicology, Anhui Medical University, Hefei, Anhui 230032, China. 
      Electronic address: xudex@126.com.
FAU - Tan, Zhu-Xia
AU  - Tan ZX
AD  - Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital 
      of Anhui Medical University, Hefei, Anhui 230601, China. Electronic address: 
      tanzhuxia@126.com.
LA  - eng
PT  - Journal Article
DEP - 20221023
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 11056-06-7 (Bleomycin)
RN  - 0 (Reactive Oxygen Species)
RN  - 47BYS17IY0 (mitoquinone)
SB  - IM
MH  - Male
MH  - Mice
MH  - Humans
MH  - Animals
MH  - Bleomycin/toxicity
MH  - Reactive Oxygen Species/metabolism
MH  - *Ferroptosis
MH  - Mice, Inbred C57BL
MH  - Lung
MH  - *Acute Lung Injury/chemically induced/drug therapy/metabolism
MH  - Mitochondria
OTO - NOTNLM
OT  - Acute lung injury
OT  - Ferroptosis
OT  - Mitochondrial reactive oxygen species
OT  - Mitoquinone
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/10/27 06:00
MHDA- 2022/12/03 06:00
CRDT- 2022/10/26 18:15
PHST- 2022/07/12 00:00 [received]
PHST- 2022/09/20 00:00 [revised]
PHST- 2022/10/14 00:00 [accepted]
PHST- 2022/10/27 06:00 [pubmed]
PHST- 2022/12/03 06:00 [medline]
PHST- 2022/10/26 18:15 [entrez]
AID - S1567-5769(22)00843-8 [pii]
AID - 10.1016/j.intimp.2022.109359 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2022 Dec;113(Pt A):109359. doi: 
      10.1016/j.intimp.2022.109359. Epub 2022 Oct 23.