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Respiratory Research
Published in: Respiratory Research 1/2020

Open Access 01-12-2020 | Acute Respiratory Distress-Syndrome | Research

Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis

Authors: Yu-bao Qiu, Bin-bin Wan, Gang Liu, Ya-xian Wu, Dan Chen, Mu-dan Lu, Jun-liang Chen, Ren-qiang Yu, Dao-zhen Chen, Qing-feng Pang

Published in: Respiratory Research | Issue 1/2020

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Abstract

Background

Ferroptosis is a new type of nonapoptotic cell death model that was closely related to reactive oxygen species (ROS) accumulation. Seawater drowning-induced acute lung injury (ALI) which is caused by severe oxidative stress injury, has been a major cause of accidental death worldwide. The latest evidences indicate nuclear factor (erythroid-derived 2)-like 2 (Nrf2) suppress ferroptosis and maintain cellular redox balance. Here, we test the hypothesis that activation of Nrf2 pathway attenuates seawater drowning-induced ALI via inhibiting ferroptosis.

Methods

we performed studies using Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the potential roles of Nrf2 on seawater drowning-induced ALI and the underlying mechanisms.

Results

Our data shows that Nrf2 activator dimethyl fumarate could increase cell viability, reduced the levels of intracellular ROS and lipid ROS, prevented glutathione depletion and lipid peroxide accumulation, increased FTH1 and GPX4 mRNA expression, and maintained mitochondrial membrane potential in MLE-12 cells. However, ML385 promoted cell death and lipid ROS production in MLE-12 cells. Furthermore, the lung injury became more aggravated in the Nrf2-knockout mice than that in WT mice after seawater drowning.

Conclusions

These results suggested that Nrf2 can inhibit ferroptosis and therefore alleviate ALI induced by seawater drowning. The effectiveness of ferroptosis inhibition by Nrf2 provides a novel therapeutic target for seawater drowning-induced ALI.
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Metadata
Title
Nrf2 protects against seawater drowning-induced acute lung injury via inhibiting ferroptosis
Authors
Yu-bao Qiu
Bin-bin Wan
Gang Liu
Ya-xian Wu
Dan Chen
Mu-dan Lu
Jun-liang Chen
Ren-qiang Yu
Dao-zhen Chen
Qing-feng Pang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Respiratory Research / Issue 1/2020
Electronic ISSN: 1465-993X
DOI
https://doi.org/10.1186/s12931-020-01500-2

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