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

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

  • Ren Fail. 2024 Dec;46(1):2330629. doi: 10.1080/0886022X.2024.2330629.
Yachen Si 1 2 Lulu Liu 3 Yinyin Zhang 2 Hongxia Li 2 Tingting Zhao 3 Su Liu 2 Xuejun Sun 2 4 Jin Cheng 5 Hongtao Lu 2
Affiliations

Affiliations

  • 1 Department of Internal Medicine, No. 944 Hospital of Joint Logistics Support Force, Jiuquan, China.
  • 2 Department of Naval Medicine, Naval Medical University, Shanghai, China.
  • 3 Department of Nephrology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, China.
  • 4 Center of Hydrogen Science, Shanghai Jiao Tong University, Shanghai, China.
  • 5 Internal Medicine III (Nephrology and Endocrinology), Naval Medical Center, Naval Medical University, Shanghai, China.
Abstract

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.

Keywords

Acetaminophen; acute kidney injury; apoptosis; inflammation; magnesium hydride; oxidative stress.

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