Magnesium hydride protects against acetaminophen-induced acute kidney injury by inhibiting TXNIP/NLRP3/nf-κb pathway

Acetaminophen (APAP)-induced acute kidney injury (APAP-AKI) has turned into one of reasons for clinic obtained renal insufficiency. Magnesium hydride (MgH2), as a solid-state hydrogen source, might be potentially applied in clinical practice. The current study aimed to investigate the protective eff...

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Main Authors: Yachen Si, Lulu Liu, Yinyin Zhang, Hongxia Li, Tingting Zhao, Su Liu, Xuejun Sun, Jin Cheng, Hongtao Lu
Format: Article
Language:English
Published: Taylor & Francis Group 2024-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2024.2330629
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author Yachen Si
Lulu Liu
Yinyin Zhang
Hongxia Li
Tingting Zhao
Su Liu
Xuejun Sun
Jin Cheng
Hongtao Lu
author_facet Yachen Si
Lulu Liu
Yinyin Zhang
Hongxia Li
Tingting Zhao
Su Liu
Xuejun Sun
Jin Cheng
Hongtao Lu
author_sort Yachen Si
collection DOAJ
description Acetaminophen (APAP)-induced acute kidney injury (APAP-AKI) has turned into one of reasons for clinic obtained renal insufficiency. Magnesium hydride (MgH2), as a solid-state hydrogen source, might be potentially applied in clinical practice. The current study aimed to investigate the protective effect of MgH2 against APAP-AKI. The results showed that MgH2 improved renal function and histological injury in mice of APAP-AKI. MgH2 also had protective effects on APAP-induced cytotoxicity in HK-2 cells. In addition, the increased level of reactive oxygen species (ROS) and expressions of inflammatory cytokines (TNF-α and IL-1β) and pro-apoptotic factors (Bad, Bax, Caspase3, and CytC) induced by APAP were downregulated with MgH2 treatment. Furthermore, the expressions of molecules related to TXNIP/NLRP3/NF-κB pathway (TXNIP, NLRP3, NF-κB p65 and p-NF-κB p65) in renal tissues and HK-2 cells were enhanced by APAP overdose, which were reduced by MgH2 administration. Collectively, this study indicated that MgH2 protects against APAP-AKI by alleviating oxidative stress, inflammation and apoptosis via inhibition of TXNIP/NLRP3/NF-κB signaling pathway.
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institution Kabale University
issn 0886-022X
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publishDate 2024-12-01
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series Renal Failure
spelling doaj-art-39570c01ceea416aa8ceccd5a5714e9d2025-01-23T04:17:48ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492024-12-0146110.1080/0886022X.2024.2330629Magnesium hydride protects against acetaminophen-induced acute kidney injury by inhibiting TXNIP/NLRP3/nf-κb pathwayYachen Si0Lulu Liu1Yinyin Zhang2Hongxia Li3Tingting Zhao4Su Liu5Xuejun Sun6Jin Cheng7Hongtao Lu8Department of Internal Medicine, No. 944 Hospital of Joint Logistics Support Force, Jiuquan, ChinaDepartment of Nephrology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, ChinaDepartment of Naval Medicine, Naval Medical University, Shanghai, ChinaDepartment of Naval Medicine, Naval Medical University, Shanghai, ChinaDepartment of Nephrology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, ChinaDepartment of Naval Medicine, Naval Medical University, Shanghai, ChinaDepartment of Naval Medicine, Naval Medical University, Shanghai, ChinaInternal Medicine III (Nephrology and Endocrinology), Naval Medical Center, Naval Medical University, Shanghai, ChinaDepartment of Naval Medicine, Naval Medical University, Shanghai, ChinaAcetaminophen (APAP)-induced acute kidney injury (APAP-AKI) has turned into one of reasons for clinic obtained renal insufficiency. Magnesium hydride (MgH2), as a solid-state hydrogen source, might be potentially applied in clinical practice. The current study aimed to investigate the protective effect of MgH2 against APAP-AKI. The results showed that MgH2 improved renal function and histological injury in mice of APAP-AKI. MgH2 also had protective effects on APAP-induced cytotoxicity in HK-2 cells. In addition, the increased level of reactive oxygen species (ROS) and expressions of inflammatory cytokines (TNF-α and IL-1β) and pro-apoptotic factors (Bad, Bax, Caspase3, and CytC) induced by APAP were downregulated with MgH2 treatment. Furthermore, the expressions of molecules related to TXNIP/NLRP3/NF-κB pathway (TXNIP, NLRP3, NF-κB p65 and p-NF-κB p65) in renal tissues and HK-2 cells were enhanced by APAP overdose, which were reduced by MgH2 administration. Collectively, this study indicated that MgH2 protects against APAP-AKI by alleviating oxidative stress, inflammation and apoptosis via inhibition of TXNIP/NLRP3/NF-κB signaling pathway.https://www.tandfonline.com/doi/10.1080/0886022X.2024.2330629Acetaminophenacute kidney injurymagnesium hydrideoxidative stressinflammationapoptosis
spellingShingle Yachen Si
Lulu Liu
Yinyin Zhang
Hongxia Li
Tingting Zhao
Su Liu
Xuejun Sun
Jin Cheng
Hongtao Lu
Magnesium hydride protects against acetaminophen-induced acute kidney injury by inhibiting TXNIP/NLRP3/nf-κb pathway
Renal Failure
Acetaminophen
acute kidney injury
magnesium hydride
oxidative stress
inflammation
apoptosis
title Magnesium hydride protects against acetaminophen-induced acute kidney injury by inhibiting TXNIP/NLRP3/nf-κb pathway
title_full Magnesium hydride protects against acetaminophen-induced acute kidney injury by inhibiting TXNIP/NLRP3/nf-κb pathway
title_fullStr Magnesium hydride protects against acetaminophen-induced acute kidney injury by inhibiting TXNIP/NLRP3/nf-κb pathway
title_full_unstemmed Magnesium hydride protects against acetaminophen-induced acute kidney injury by inhibiting TXNIP/NLRP3/nf-κb pathway
title_short Magnesium hydride protects against acetaminophen-induced acute kidney injury by inhibiting TXNIP/NLRP3/nf-κb pathway
title_sort magnesium hydride protects against acetaminophen induced acute kidney injury by inhibiting txnip nlrp3 nf κb pathway
topic Acetaminophen
acute kidney injury
magnesium hydride
oxidative stress
inflammation
apoptosis
url https://www.tandfonline.com/doi/10.1080/0886022X.2024.2330629
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