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

Yachen Si; Lulu Liu; Yinyin Zhang; Hongxia Li; Tingting Zhao; Su Liu; Xuejun Sun; Jin Cheng; Hongtao Lu

doi:10.1080/0886022X.2024.2330629

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. Epub 2024 Mar 17.

Authors

Yachen Si^{1

2}, Lulu Liu³, Yinyin Zhang², Hongxia Li², Tingting Zhao³, Su Liu², Xuejun Sun^{2

4}, Jin Cheng⁵, Hongtao Lu²

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.

MeSH terms

Acetaminophen / toxicity
Acute Kidney Injury* / chemically induced
Acute Kidney Injury* / prevention & control
Animals
Chemical and Drug Induced Liver Injury*
Magnesium
Mice
NF-kappa B / metabolism
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Oxidative Stress

Substances

NF-kappa B
NLR Family, Pyrin Domain-Containing 3 Protein
Acetaminophen
Magnesium

Grants and 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).