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Background Drowning-induced acute lung injury (ALI) has been a major cause of accidental death worldwide. Severe oxidative stress injury is the key factor in drowning-induced ALI. 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 attenuates drowning-induced ALI via inhibiting ferroptosis. Methods In this study, we employed Nrf2-specific agonist (dimethyl fumarate), Nrf2 inhibitor (ML385), Nrf2-knockout mice and ferroptosis inhibitor (Ferrostatin-1) to investigate the beneficial roles of Nrf2 on drowning-induced ALI and the underlying mechanisms. Results In this study, we firstly showed 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. However, ML385 promoted cell death and lipid ROS production. Furthermore, Nrf2 knockout aggravated seawater drowning-induced ALI in mice. Conclusions In summary, these results suggest that Nrf2 alleviate drowning-induced ALI in MLE-12 cells and mice through inhibiting ferroptosis. |
