Ferrostatin-1 alleviates lipopolysaccharide-induced acute lung injury via inhibiting ferroptosis

TLDR

Ferroptosis is a newly recognized form of cell death distinct from necrosis, apoptosis, or autophagy, yet its role in lipopolysaccharide‑induced acute lung injury (ALI) remains largely unexplored. The study aimed to investigate the relationship between ferroptosis and LPS‑induced ALI using BEAS‑2B cells treated with LPS and the ferroptosis inhibitor ferrostatin‑1. The authors assessed ferroptosis by measuring cell viability (CCK‑8), lipid peroxidation markers (MDA, 4‑HNE), iron levels, and the expression of SLC7A11 and GPX4 in BEAS‑2B cells and in a mouse LPS‑induced ALI model, and evaluated the effect of ferrostatin‑1. LPS induced ferroptosis in BEAS‑2B cells and mouse lungs, reducing viability and antioxidant proteins while increasing lipid peroxidation and iron, and ferrostatin‑1 reversed these changes and alleviated ALI, indicating ferroptosis as a potential therapeutic target.

Abstract

Ferroptosis is a newly recognized type of cell death, which is different from traditional necrosis, apoptosis or autophagic cell death. However, the position of ferroptosis in lipopolysaccharide (LPS)-induced acute lung injury (ALI) has not been explored intensively so far. In this study, we mainly analyzed the relationship between ferroptosis and LPS-induced ALI.In this study, a human bronchial epithelial cell line, BEAS-2B, was treated with LPS and ferrostatin-1 (Fer-1, ferroptosis inhibitor). The cell viability was measured using CCK-8. Additionally, the levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and iron, as well as the protein level of SLC7A11 and GPX4, were measured in different groups. To further confirm the in vitro results, an ALI model was induced by LPS in mice, and the therapeutic action of Fer-1 and ferroptosis level in lung tissues were evaluated.The cell viability of BEAS-2B was down-regulated by LPS treatment, together with the ferroptosis markers SLC7A11 and GPX4, while the levels of MDA, 4-HNE and total iron were increased by LPS treatment in a dose-dependent manner, which could be rescued by Fer-1. The results of the in vivo experiment also indicated that Fer-1 exerted therapeutic action against LPS-induced ALI, and down-regulated the ferroptosis level in lung tissues.Our study indicated that ferroptosis has an important role in the progression of LPS-induced ALI, and ferroptosis may become a novel target in the treatment of ALI patients.