Lipocalin-2 silencing alleviates sepsis-induced liver injury through inhibition of ferroptosis.

IF 3.7 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY
Yuping Li, Lu Li, Yuming Zhang, Qi Yun, Ruoli Du, Hongwei Ye, Zhenghong Li, Qin Gao
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引用次数: 0

Abstract

Introduction and objectives: Liver plays a key role in sepsis, a systemic inflammatory response syndrome caused by infection. Ferroptosis is involved in sepsis-induced liver injury. We aimed to assess the changes in ferroptosis in cecal ligation and puncture (CLP)-induced septic mice, and determine the role of lipocalin-2 (LCN2) in liver ferroptosis.

Materials and methods: CLP was used to induce sepsis in mice. The morphological changes in liver tissues and mitochondrial structure were observed using hematoxylin and eosin staining and transmission electron microscopy. The levels of serum alanine transaminase, aspartate aminotransferase, superoxide dismutase, and malondialdehyde were detected using the corresponding kits. The changes of reactive oxygen species level in liver tissues were detected using dihydroethidium as a fluorescence probe. LCN2, cysteine-glutamate reverse transport system, and dihydroorotate dehydrogenase protein levels in the liver were detected by western blotting. The ferroptosis inhibitor ferrostatin-1 (Fer-1), iron chelator dexrazoxane (DXZ), iron-dextran, and LCN2 knockdown studies were performed to determine role of ferroptosis and LCN2 in liver injury during sepsis.

Results: Ferroptosis levels increased in the liver tissues of CLP-induced septic mice. Both Fer-1 and DXZ suppressed ferroptosis and attenuated liver injury following sepsis challenge, whereas iron-dextran increased ferroptosis and liver injury in mice with sepsis. LCN2 knockdown suppressed ferroptosis and reduced oxidative stress in the liver.

Conclusions: Ferroptosis inhibition attenuates septic liver injury. LCN2 knockdown alleviates sepsis-induced liver injury by inhibiting ferroptosis and reducing oxidative stress.

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来源期刊
Annals of hepatology
Annals of hepatology 医学-胃肠肝病学
CiteScore
7.90
自引率
2.60%
发文量
183
审稿时长
4-8 weeks
期刊介绍: Annals of Hepatology publishes original research on the biology and diseases of the liver in both humans and experimental models. Contributions may be submitted as regular articles. The journal also publishes concise reviews of both basic and clinical topics.
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