Ferrostatin-1 alleviates ventilator-induced lung injury by inhibiting ferroptosis.

Maoyao Ling, Liu Ye, Qi Zeng, Zhao Li, Sheng He, Jinyuan Lin, Jianlan Mo, Linghui Pan

International immunopharmacology 2023 Jul

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Ventilator-induced lung injury (VILI) has become an increasingly common complication in the clinic concerning mechanical ventilation. Previous research showed that VILI is the result of a response to cascade inflammation; however, the inflammatory mechanism involved remains unclear. As a newly recognized form of cell death, ferroptosis can release damage-related molecules (DAMPs) to trigger and amplify the inflammatory response and is involved in several inflammatory diseases. The present study aimed to investigate a previously unrecognized role of ferroptosis in VILI. A mouse model of VILI and a model of cyclic stretching (CS)-induced lung epithelial cell injury were established. Mice and cells were pretreated with ferrostain-1, an inhibitor of ferroptosis. Lung tissue and cells were then harvested to determine lung injury, inflammatory responses, indicators and protein expression associated with ferroptosis. Compared to the control group, mice subjected to high tidal volumes (HTV) for 4 h showed more severe pulmonary edema and inflammation and the activation of ferroptosis. Ferrostain-1 significantly ameliorated histological injury and inflammation in the VILI mouse and alleviated CS-induced lung epithelial cell injury. Mechanistically, ferrostain-1 markedly limited the activation of ferroptosis and recovered functionality of the SLC7A11/GPX4 axis both in vitro and in vivo, thus demonstrating its potential as a novel therapeutic target for VILI. Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

Citation

Maoyao Ling, Liu Ye, Qi Zeng, Zhao Li, Sheng He, Jinyuan Lin, Jianlan Mo, Linghui Pan. Ferrostatin-1 alleviates ventilator-induced lung injury by inhibiting ferroptosis. International immunopharmacology. 2023 Jul;120:110356