Reduced glutathione ameliorates sepsis-induced acute kidney injury in mouse model: involvement of cuproptosis

Background Cuproptosis, a copper-induced form of programmed cell death, has been implicated in the pathogenesis of acute kidney injury (AKI) and sepsis. Reduced glutathione (GSH), a potent antioxidant, exhibits both anti-inflammatory and anti-oxidative properties. However, its potential role in modu...

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Main Authors: Lu Wang, Long Jiang, Jingjing Wang, Wen Tang, Zhigao Wang, Rennan Guo, Daquan Zhang
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2025.2518227
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author Lu Wang
Long Jiang
Jingjing Wang
Wen Tang
Zhigao Wang
Rennan Guo
Daquan Zhang
author_facet Lu Wang
Long Jiang
Jingjing Wang
Wen Tang
Zhigao Wang
Rennan Guo
Daquan Zhang
author_sort Lu Wang
collection DOAJ
description Background Cuproptosis, a copper-induced form of programmed cell death, has been implicated in the pathogenesis of acute kidney injury (AKI) and sepsis. Reduced glutathione (GSH), a potent antioxidant, exhibits both anti-inflammatory and anti-oxidative properties. However, its potential role in modulating cuproptosis in AKI remains unexplored. This study investigates the effects of reduced GSH on cuproptosis in a sepsis-induced AKI mouse model.Methods A sepsis mouse model was established via cecal ligation and puncture (CLP). Reduced GSH was administered to CLP-induced mice. Survival rates, bacterial load, inflammatory cytokine levels, oxidative stress markers, kidney function, copper (Cu) levels, and the expression of SLC31A1 were evaluated.Results Reduced GSH treatment significantly improved survival rates and reduced bacterial loads in CLP mice. Additionally, reduced GSH attenuated inflammation and oxidative stress in the septic mice. It restored kidney function, decreased Cu levels in both urine and kidney tissues, and downregulated the expression of SLC31A1.Conclusion Reduced GSH ameliorates sepsis-induced AKI by suppressing cuproptosis, offering potential therapeutic implications for the management of AKI in septic conditions.
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series Renal Failure
spelling doaj-art-7fa4815462af4f6888f76117bda3a4e52025-08-20T03:23:06ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492025-12-0147110.1080/0886022X.2025.2518227Reduced glutathione ameliorates sepsis-induced acute kidney injury in mouse model: involvement of cuproptosisLu Wang0Long Jiang1Jingjing Wang2Wen Tang3Zhigao Wang4Rennan Guo5Daquan Zhang6Department of Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, ChinaDepartment of Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, ChinaDepartment of Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, ChinaDepartment of Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, ChinaDepartment of Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, ChinaDepartment of Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, ChinaDepartment of Critical Care Medicine, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang Uygur Autonomous Region, ChinaBackground Cuproptosis, a copper-induced form of programmed cell death, has been implicated in the pathogenesis of acute kidney injury (AKI) and sepsis. Reduced glutathione (GSH), a potent antioxidant, exhibits both anti-inflammatory and anti-oxidative properties. However, its potential role in modulating cuproptosis in AKI remains unexplored. This study investigates the effects of reduced GSH on cuproptosis in a sepsis-induced AKI mouse model.Methods A sepsis mouse model was established via cecal ligation and puncture (CLP). Reduced GSH was administered to CLP-induced mice. Survival rates, bacterial load, inflammatory cytokine levels, oxidative stress markers, kidney function, copper (Cu) levels, and the expression of SLC31A1 were evaluated.Results Reduced GSH treatment significantly improved survival rates and reduced bacterial loads in CLP mice. Additionally, reduced GSH attenuated inflammation and oxidative stress in the septic mice. It restored kidney function, decreased Cu levels in both urine and kidney tissues, and downregulated the expression of SLC31A1.Conclusion Reduced GSH ameliorates sepsis-induced AKI by suppressing cuproptosis, offering potential therapeutic implications for the management of AKI in septic conditions.https://www.tandfonline.com/doi/10.1080/0886022X.2025.2518227Reduced GSHAKIsepsis cuproptosisCLP
spellingShingle Lu Wang
Long Jiang
Jingjing Wang
Wen Tang
Zhigao Wang
Rennan Guo
Daquan Zhang
Reduced glutathione ameliorates sepsis-induced acute kidney injury in mouse model: involvement of cuproptosis
Renal Failure
Reduced GSH
AKI
sepsis cuproptosis
CLP
title Reduced glutathione ameliorates sepsis-induced acute kidney injury in mouse model: involvement of cuproptosis
title_full Reduced glutathione ameliorates sepsis-induced acute kidney injury in mouse model: involvement of cuproptosis
title_fullStr Reduced glutathione ameliorates sepsis-induced acute kidney injury in mouse model: involvement of cuproptosis
title_full_unstemmed Reduced glutathione ameliorates sepsis-induced acute kidney injury in mouse model: involvement of cuproptosis
title_short Reduced glutathione ameliorates sepsis-induced acute kidney injury in mouse model: involvement of cuproptosis
title_sort reduced glutathione ameliorates sepsis induced acute kidney injury in mouse model involvement of cuproptosis
topic Reduced GSH
AKI
sepsis cuproptosis
CLP
url https://www.tandfonline.com/doi/10.1080/0886022X.2025.2518227
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