Lipocalin-2 silencing alleviates sepsis-induced liver injury through inhibition of ferroptosis
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...
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| Language: | English |
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Elsevier
2025-01-01
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| Series: | Annals of Hepatology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268124005398 |
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| author | Yuping Li Lu Li Yuming Zhang Qi Yun Ruoli Du Hongwei Ye Zhenghong Li Qin Gao |
| author_facet | Yuping Li Lu Li Yuming Zhang Qi Yun Ruoli Du Hongwei Ye Zhenghong Li Qin Gao |
| author_sort | Yuping Li |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e4690fb6f2ad4cf4a4145c3e4e274410 |
| institution | DOAJ |
| issn | 1665-2681 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj-art-e4690fb6f2ad4cf4a4145c3e4e2744102025-08-20T03:18:27ZengElsevierAnnals of Hepatology1665-26812025-01-0130110175610.1016/j.aohep.2024.101756Lipocalin-2 silencing alleviates sepsis-induced liver injury through inhibition of ferroptosisYuping Li0Lu Li1Yuming Zhang2Qi Yun3Ruoli Du4Hongwei Ye5Zhenghong Li6Qin Gao7School of Life Sciences, Bengbu Medical University, Bengbu, Anhui 233000, PR China; Anhui Nerve Regeneration Technology and Medical new Materials Engineering Research Center, Bengbu, Anhui 233000, PR ChinaDepartment of Physiology, Bengbu Medical University, Bengbu, Anhui 233000, PR China; Key Laboratory of Cardiovascular and cerebrovascular Diseases, Bengbu Medical University, Bengbu, Anhui 233000, PR ChinaDepartment of Physiology, Bengbu Medical University, Bengbu, Anhui 233000, PR China; Key Laboratory of Cardiovascular and cerebrovascular Diseases, Bengbu Medical University, Bengbu, Anhui 233000, PR ChinaSchool of Life Sciences, Bengbu Medical University, Bengbu, Anhui 233000, PR China; Key Laboratory of Cardiovascular and cerebrovascular Diseases, Bengbu Medical University, Bengbu, Anhui 233000, PR ChinaDepartment of Physiology, Bengbu Medical University, Bengbu, Anhui 233000, PR China; Key Laboratory of Cardiovascular and cerebrovascular Diseases, Bengbu Medical University, Bengbu, Anhui 233000, PR ChinaDepartment of Physiology, Bengbu Medical University, Bengbu, Anhui 233000, PR China; Key Laboratory of Cardiovascular and cerebrovascular Diseases, Bengbu Medical University, Bengbu, Anhui 233000, PR ChinaSchool of Life Sciences, Bengbu Medical University, Bengbu, Anhui 233000, PR China; Department of Physiology, Bengbu Medical University, Bengbu, Anhui 233000, PR China; Anhui Nerve Regeneration Technology and Medical new Materials Engineering Research Center, Bengbu, Anhui 233000, PR China; Corresponding authors.Department of Physiology, Bengbu Medical University, Bengbu, Anhui 233000, PR China; Key Laboratory of Cardiovascular and cerebrovascular Diseases, Bengbu Medical University, Bengbu, Anhui 233000, PR China; Corresponding authors.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.http://www.sciencedirect.com/science/article/pii/S1665268124005398Sepsis-induced liver injuryLipocalin 2FerroptosisxCTDHODH |
| spellingShingle | Yuping Li Lu Li Yuming Zhang Qi Yun Ruoli Du Hongwei Ye Zhenghong Li Qin Gao Lipocalin-2 silencing alleviates sepsis-induced liver injury through inhibition of ferroptosis Annals of Hepatology Sepsis-induced liver injury Lipocalin 2 Ferroptosis xCT DHODH |
| title | Lipocalin-2 silencing alleviates sepsis-induced liver injury through inhibition of ferroptosis |
| title_full | Lipocalin-2 silencing alleviates sepsis-induced liver injury through inhibition of ferroptosis |
| title_fullStr | Lipocalin-2 silencing alleviates sepsis-induced liver injury through inhibition of ferroptosis |
| title_full_unstemmed | Lipocalin-2 silencing alleviates sepsis-induced liver injury through inhibition of ferroptosis |
| title_short | Lipocalin-2 silencing alleviates sepsis-induced liver injury through inhibition of ferroptosis |
| title_sort | lipocalin 2 silencing alleviates sepsis induced liver injury through inhibition of ferroptosis |
| topic | Sepsis-induced liver injury Lipocalin 2 Ferroptosis xCT DHODH |
| url | http://www.sciencedirect.com/science/article/pii/S1665268124005398 |
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