ferrostatin-1 and Acute-Lung-Injury

Ferroptosis is a new type of regulated cell death that is characterized by the overwhelming iron-dependent accumulation of lethal lipid reactive oxygen species and is involved in various diseases. However, the relationship between ferroptosis and lipopolysaccharide (LPS)-induced acute lung injury (ALI) remains largely unknown.. In this study, iron metabolism and ferroptosis-related gene mRNA levels in the lung tissues of LPS-induced ALI mice at different time points were detected. Then, the histological, cytokines production, and iron levels of LPS-induced ALI mice with or without the pretreatment of the ferroptosis inhibitor ferrostatin-1 (Fer-1) were measured after mice received the ferroptosis inhibitor ferrostatin-1 (Fer-1) intraperitoneally before LPS administration. Ferroptosis-related protein (GPX4, NRF2, and DPP4) expression was measured in the in vivo and in vitro ALI model. Finally, ROS accumulation and lipid peroxidation was measured in in vivo and in vitro study.. Our results showed that iron metabolism and ferroptosis-related gene mRNA demonstrated significant variation in LPS-treated pulmonary tissues. The ferroptosis inhibitor Fer-1 markedly attenuated the histologic injuries of the lung tissue and suppressed the production of cytokines in bronchoalveolar lavage fluid (BALF). Fer-1 administration reduced the levels of NRF2 and DPP4 protein induced by the LPS challenge. Furthermore, Fer-1 reversed the tendency of iron metabolism, MDA, SOD, and GSH levels induced by LPS administration in in vivo and in vitro.. Taken together, ferroptosis inhibition by ferrostatin-1 alleviated acute lung injury through modulating oxidative lipid damages induced by the LPS challenge.

Topics: Acute Lung Injury; Animals; Cytokines; Dipeptidyl Peptidase 4; Iron; Lipopolysaccharides; Mice; NF-E2-Related Factor 2; Oxidative Stress; RNA, Messenger

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.

Topics: Acute Lung Injury; Aldehydes; Amino Acid Transport System y+; Animals; Cell Line; Cell Survival; Cyclohexylamines; Ferroptosis; Humans; Iron; Lipopolysaccharides; Male; Malondialdehyde; Mice; Mice, Inbred C57BL; Phenylenediamines; Phospholipid Hydroperoxide Glutathione Peroxidase