Department of Internal Medicine, No. 944 Hospital of Joint Logistics Support Force, Jiuquan, China.
Department of Naval Medicine, Naval Medical University, Shanghai, China.
Ren Fail. 2024 Dec;46(1):2330629. doi: 10.1080/0886022X.2024.2330629. Epub 2024 Mar 17.
Acetaminophen (APAP)-induced acute kidney injury (APAP-AKI) has turned into one of reasons for clinic obtained renal insufficiency. Magnesium hydride (MgH), as a solid-state hydrogen source, might be potentially applied in clinical practice. The current study aimed to investigate the protective effect of MgH against APAP-AKI. The results showed that MgH improved renal function and histological injury in mice of APAP-AKI. MgH 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 MgH 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 MgH administration. Collectively, this study indicated that MgH protects against APAP-AKI by alleviating oxidative stress, inflammation and apoptosis inhibition of TXNIP/NLRP3/NF-κB signaling pathway.
对乙酰氨基酚（APAP）诱导的急性肾损伤（APAP-AKI）已成为临床获得性肾功能不全的原因之一。氢化镁（MgH）作为一种固态氢源，可能在临床上具有应用潜力。本研究旨在探讨 MgH 对 APAP-AKI 的保护作用。结果表明，MgH 改善了 APAP-AKI 小鼠的肾功能和组织学损伤。MgH 对 APAP 诱导的 HK-2 细胞毒性也具有保护作用。此外，MgH 处理可下调 APAP 诱导的活性氧（ROS）水平和炎症细胞因子（TNF-α和 IL-1β）及促凋亡因子（Bad、Bax、Caspase3 和 CytC）表达。此外，APAP 过量会增强肾脏组织和 HK-2 细胞中与 TXNIP/NLRP3/NF-κB 通路相关的分子（TXNIP、NLRP3、NF-κB p65 和 p-NF-κB p65）的表达，而 MgH 给药则会降低其表达。综上所述，本研究表明，MgH 通过减轻氧化应激、炎症和抑制 TXNIP/NLRP3/NF-κB 信号通路的细胞凋亡来保护 APAP-AKI。
