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

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
• magnesium hydride
• oxidative stress
• inflammation
• apoptosis

Author contributions

Hongtao Lu, Jin Cheng and Xuejun Sun designed this study; Yachen Si, Lulu Liu, Yinyin Zhang, Hongxia Li, Tingting Zhao and Su Liu performed the experiments and data analyses; Yachen Si, Lulu Liu and Hongtao Lu wrote the manuscript. All authors have reviewed the results and approved the final version of the manuscript.

Ethical approval

The animal study protocol was approved by Committee on Ethic of Medical Research, Naval Medical University (registration number: NMUMREC-2021–006).

Disclosure statement

No potential conflict of interest was reported by the author(s). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Data availability statement

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

Additional information

Funding

This work was supported by Medical Science and Technology Youth Cultivation Program (21QNPY035), Foundation of Naval Medical University (2022MS003; 2022QN019), Shanghai Rising-Star Program (20YF1458200), Health Service Key Project of Naval Medical Center of PLA (22M3201) and Clinical Research Special General Project of Shanghai Municipal Health Commission (202340097).