Assessment of Protection Offered by The Nrf2 Pathway Against Hyperoxia-Induced Acute Lung Injury In Nrf2 Knockout Rats

Shock ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Said H. Audi ◽  
Elizabeth R. Jacobs ◽  
Pardis Taheri ◽  
Swetha Ganesh ◽  
Anne V. Clough
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nrf2 Pathway ◽  
Nrf2 Knockout

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

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu-bao Qiu ◽  
Bin-bin Wan ◽  
Gang Liu ◽  
Ya-xian Wu ◽  
Dan Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Knockout Mice ◽  
Lipid Peroxide ◽  
Dimethyl Fumarate ◽  
Redox Balance ◽  
Glutathione Depletion ◽  
Stress Injury ◽  
Nrf2 Knockout

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.

scholarly journals Propofol Activation of the Nrf2 Pathway Is Associated with Amelioration of Acute Lung Injury in a Rat Liver Transplantation Model

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Weifeng Yao ◽  
Gangjian Luo ◽  
Guosong Zhu ◽  
Xinjin Chi ◽  
Ailan Zhang ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Water Content ◽  
High Dose ◽  
Lung Pathology ◽  
Lung Water ◽  
Sod Activity ◽  
Nrf2 Pathway ◽  
Lung Water Content

Objective. This study aimed to investigate whether propofol pretreatment can protect against liver transplantation-induced acute lung injury (ALI) and to explore whether Nrf2 pathway is involved in the protections provided by propofol pretreatment.Method. Adult male Sprague-Dawley rats were divided into five groups based on the random number table. Lung pathology was observed by optical microscopy. Lung water content was assessed by wet/dry ratio, and PaO2was detected by blood gas analysis. The contents of H2O2, MDA, and SOD activity were determined by ELISA method, and the expression of HO-1, NQO1, Keap1, and nuclear Nrf2 was assayed by western blotting.Results. Compared with saline-treated model group, both propofol and N-acetylcysteine pretreatment can reduce the acute lung injury caused by orthotopic autologous liver transplantation (OALT), decrease the lung injury scores, lung water content, and H2O2and MDA levels, and improve the arterial PaO2and SOD activity. Furthermore, propofol (but not N-acetylcysteine) pretreatment especially in high dose inhibited the expression of Keap1 and induced translocation of Nrf2 into the nucleus to further upregulate the expression of HO-1 and NQO1 downstream.Conclusion. Pretreatment with propofol is associated with attenuation of OALT-induced ALI, and the Nrf2 pathway is involved in the antioxidative processes.

scholarly journals Lycium barbarum polysaccharide reduces hyperoxic acute lung injury in mice through Nrf2 pathway

2019 ◽  
Vol 111 ◽  
pp. 733-739 ◽  
Author(s):  
Guizhen Zheng ◽  
Huijuan Ren ◽  
Hongqiang Li ◽  
Xiuhua Li ◽  
Tiancao Dong ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lycium Barbarum ◽  
Nrf2 Pathway ◽  
Lycium Barbarum Polysaccharide

scholarly journals Penehyclidine hydrochloride inhibits renal ischemia/reperfusion-induced acute lung injury by activating the Nrf2 pathway

Aging ◽  
2020 ◽  
Vol 12 (13) ◽  
pp. 13400-13421 ◽  
Author(s):  
Zhaohui Liu ◽  
Yan Li ◽  
Lili Yu ◽  
Yulin Chang ◽  
Jingui Yu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Nrf2 Pathway ◽  
Penehyclidine Hydrochloride

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

2020 ◽  
Author(s):  
Yu-bao Qiu ◽  
Bin-bin Wan ◽  
Gang Liu ◽  
Ya-xian Wu ◽  
Dan Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Knockout Mice ◽  
Lipid Peroxide ◽  
Dimethyl Fumarate ◽  
Redox Balance ◽  
Glutathione Depletion ◽  
Stress Injury ◽  
Nrf2 Knockout

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.

scholarly journals Vitexin attenuates lipopolysaccharide-induced acute lung injury by controlling the Nrf2 pathway

PLoS ONE ◽  
2018 ◽  
Vol 13 (4) ◽  
pp. e0196405 ◽  
Author(s):  
Ying Lu ◽  
Ting Yu ◽  
Jingyao Liu ◽  
Lina Gu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Nrf2 Pathway

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

2020 ◽  
Author(s):  
Yu-bao Qiu ◽  
Bin-bin Wan ◽  
Gang Liu ◽  
Ya-xian Wu ◽  
Dan Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Knockout Mice ◽  
Lipid Peroxide ◽  
Dimethyl Fumarate ◽  
Redox Balance ◽  
Glutathione Depletion ◽  
Stress Injury ◽  
Nrf2 Knockout

Abstract Background: Ferroptosis is a new type of nonapoptotic cell death model that was closely related to 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. These findings may guide the development of a new therapeutic approach for seawater drowning-induced ALI 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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