Ferrostatin-1 Ameliorated Oxidative Lipid Damage in LPS-induced Acute Lung Injury

Copyright © 2023 Elsevier Inc. All rights reserved..

INTRODUCTION: 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.

METHODS: 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.

RESULTS: 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.

CONCLUSIONS: Taken together, ferroptosis inhibition by ferrostatin-1 alleviated acute lung injury through modulating oxidative lipid damages induced by the LPS challenge.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:290

Enthalten in:

The Journal of surgical research - 290(2023) vom: 15. Okt., Seite 266-275

Sprache:

Englisch

Beteiligte Personen:

Liu, Yuqi [VerfasserIn]
Zhang, Xinyi [VerfasserIn]
Cao, Yumeng [VerfasserIn]
Chen, Xia [VerfasserIn]
Zhu, Jiali [VerfasserIn]
Zou, Yun [VerfasserIn]

Links:

Volltext

Themen:

Acute lung injury
Alveolar epithelium
Cytokines
Dipeptidyl Peptidase 4
E1UOL152H7
EC 3.4.14.5
Ferroptosis
Ferrostatin-1
Inflammatory cytokines
Iron
Journal Article
Lipopolysaccharides
NF-E2-Related Factor 2
RNA, Messenger
Reactive oxygen species

Anmerkungen:

Date Completed 10.07.2023

Date Revised 24.11.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.jss.2023.05.006

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM358227399