Ciprofol Prevents Ferroptosis in LPS Induced Acute Lung Injury by Activating the Nrf2 Signaling Pathway

Overview

Journal BMC Pulm Med

Publisher Biomed Central

Specialty Pulmonary Medicine

Date 2024 Nov 28

PMID 39609781

Authors

Qin Zhao

Chang Kong

Xiuyun Wu

Yong Ling

Jia Shi

Shaona Li

Youzhuang Zhu

Jianbo Yu

Affiliations

Soon will be listed here.

Abstract

Background: Patients who suffered from sepsis-induced acute lung injury (ALI) always need sedation for mechanical ventilation in intensive care unit (ICU). Ciprofol(Cip), a novel intravenous anesthetic, was revealed to have anti-inflammatory and antioxidative properties. Ferroptosis, categorized as a type of newly non-apoptotic cell death, participates in the development of lung injury. This study aimed to identify the effect of ciprofol on sepsis-induced ALI and to determine whether ferroptosis is involved.

Methods And Results: To create ALI models, MLE12 alveolar epithelial. Cells and lipopolysaccharide (LPS)-stimulated C57BL/6J mice were used. Our results displyed that Cip reduced lung injury and ferroptosis. In the LPS-induced sepsis mice model, Cip pretreatment partially reduced respiratory system damage, as evaluated by HE, TUNEL and inflammatory factors. By raising GSH levels, ciprofol activated the Nrf2 antioxidative pathway, blocked ferroptosis, increased ferroptosis-related protein (GPX4 and SLC7A11) expressions, and reduced Fe content, as well as MDA and 4-HNE levels. However, the protective effects of Cip on lung injury and ferroptosis diminished in Nrf2-KO mice. Additionally, Cip activated the Nrf2 pathway and reduced cell death by preventing detrimental lipid peroxidation and ferroptosis in vitro. However, these effects were not observed in siNrf2-treated cells.

Conclusion: Our study demonstrated that Cip may prevent septic lung injury by suppressing ferroptosis through the Nrf2 pathway.

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