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 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.