Ferrostatin-1 mitigates acute lung injury by reducing ferroptosis levels in gas explosions

Background: Gas explosion injuries are a severe form of trauma with high incidence and mortality rates, both in daily life and industrial settings. Acute lung injury (ALI) is one of the most serious complications of gas explosion injuries and is a leading cause of mortality in such cases. However, the mechanisms underlying gas explosioninduced ALI have not been fully elucidated, and the treatment process consumes a significant amount of medical resources. Therefore, it is crucial to conduct research on the injury mechanisms of gas explosion injuries, especially the mechanisms of gas explosion-induced ALI, which can effectively improve the treatment rate of this condition. In this study, we analyzed the relationship between a novel form of cell death, ferroptosis, and gas explosion-induced ALI, and explored its specific mechanisms. Methods: We established ALI rat model by Shock tube biological injury system, and detected lung injury-related indexes as well as ferroptosis related indexes, such as glutathione peroxidase 4(GPX4), 4-hydroxynonenal (4HNE), Malondialdehyde(MDA), Fe2 + . We also investigated the therapeutic effects of the ferroptosis inhibitor ferrostatin-1 (Fer-1) in ALI induced by gas explosion, as well as its specific mechanisms of action. Results: A rat ALI model by gas explosion was successfully established. After the gas explosion treatment, we observed that the systemic inflammatory reaction of rats was increased, and lung function, liver function, kidney function and cardiac function were damaged to different degrees. The inflammatory infiltration in the lung tissue was more severe, and the degree of lung injury and pulmonary edema increased. The ferroptosis markers GPX4 was decreased, while the levels of 4HNE, MDA and Fe2 + were increased. Treatment with Fer-1 significantly ameliorated gas explosion ALI damage and down-regulated the expression level of ferroptosis. Conclusions: Gas explosion-induced ALI in rats is characterized by enhanced inflammatory responses and reduced antioxidant capacity in lung tissues. The specific mechanism of injury involves ferroptosis. Fer-1 has been shown to mitigate the severity of ALI caused by gas explosion by suppressing ferroptosis expression levels in lung tissues via the Nrf2/GPX4 axis.