Evidence mapPaperPMID 41310132Full record

ArticleScientific reports2025

Ferroptosis mediated by ferritinophagy is involved in liver injury caused by sepsis.

Haidan Zhang, Hongyao Li, Shixian Liu, Jiahui Zheng, Peiwu Li

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Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

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5 authors.

Haidan ZhangKey Laboratory of Emergency Medicine,Emergency Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu Province, 730000, China.
Hongyao LiKey Laboratory of Emergency Medicine,Emergency Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu Province, 730000, China.
Shixian LiuKey Laboratory of Emergency Medicine,Emergency Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu Province, 730000, China.
Jiahui ZhengKey Laboratory of Emergency Medicine,Emergency Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu Province, 730000, China.
Peiwu LiKey Laboratory of Emergency Medicine,Emergency Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, Gansu Province, 730000, China. lipeiw@lzu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background Ferritinophagy is a type of selective autophagy mediated by nuclear receptor coactivator 4 (NCOA4), and its overactivation can promote ferroptosis. However, the role of ferritinophagy in sepsis-induced liver injury needs to be further explored. The aim of this study was to investigate the role of ferritinophagy in liver injury caused by sepsis through the regulation of ferroptosis and its underlying mechanisms. Methods The sepsis rat model was established by cecal ligation and puncture (CLP). In the CLP + Fer-1 and CLP + 3-MA groups, Fer-1 (10 mg/kg) and 3-MA (20 mg/kg) were intraperitoneally injected at 1 h and 2 h before surgery, respectively. The levels of the serum inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were detected. The levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured. The pathological alterations in liver tissue and mitochondrial structure were examined. The levels of ferroptosis-related markers, including ferrous iron (Fe²⁺), malondialdehyde (MDA), glutathione peroxidase 4 (GPX4), glutathione (GSH), prostaglandin endoperoxide synthase 2 (PTGS2), and acyl-CoA synthetase long-chain family member 4 (ACSL4), were quantified. The expression levels of nuclear receptor coactivator 4 (NCOA4), ferritin heavy chain 1 (FTH1), autophagy-related protein p62/SQSTM1 (p62), and microtubule-associated protein 1 light chain 3B (LC3B) in liver tissue were detected. Result (1) Ferroptosis was activated in the hepatocytes of septic rats induced by CLP. (2) In sepsis, the expression of NCOA4 in hepatocytes increased, leading to the degradation of intracellular ferritin through ferritinophagy, an increase in intracellular Fe²⁺ concentration, and the induction of ferroptosis in hepatocytes. Conclusion Ferritinophagy is involved in sepsis-induced liver injury, and inhibiting ferritinophagy can alleviate hepatocyte ferroptosis and mitigate sepsis-induced liver injury.

Indexed as

AutophagyFerritinsFerroptosisLiverSepsisAnimalsDisease Models, AnimalIronMaleNuclear Receptor CoactivatorsRatsRats, Sprague-DawleyFerritinsIronNuclear Receptor CoactivatorsFerritinophagyFerroptosisLiver injuryNCOA4Sepsis

Identifiers

PMID41310132
PMCPMC12748720

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.