Disulfiram attenuates lipopolysaccharide-induced acute kidney injury by suppressing oxidative stress and NLRP3 inflammasome activation in mice.

Abstract

OBJECTIVES:

Disulfiram (DSF), an old drug for treating chronic alcohol addiction, has been reported to exhibit widely pharmacological actions. This study aimed to explore the protective effect of DSF on lipopolysaccharide (LPS)-induced acute kidney injury (AKI).

METHODS:

C57BL/6J mice were treated with 15 mg/kg LPS (i.p.) with or without DSF pre-treatment (i.p.). The histopathological analysis was conducted by H&E staining and TUNEL kit assay. An automatic biochemical analyser was used to determine the serum creatinine and blood urea nitrogen (BUN). Expressions of 8-OHdG, NLRP3 and IL-1β in the kidney tissues were observed by IHC staining. The protein expressions of β-actin, Bax, Bcl-2, NLRP3, caspase-1 (p20), pro-IL-1β and IL-1β were analysed by western blot.

KEY FINDINGS:

DSF attenuated the histopathologic deterioration of the kidney and inhibited the elevation of creatinine and BUN levels in mice. DSF inhibited LPS-induced cell apoptosis. Moreover, DSF treatment reversed the LPS-induced excessive oxidative stress. The NLRP3 inflammasome activation induced by the LPS, as indicated by up-regulation of NLRP3 expression, cleaved caspase-1 (p20) and IL-1β, was also suppressed by DSF.

CONCLUSIONS:

The study here shows that DSF protects against the AKI induced by LPS at least partially via inhibiting oxidative stress and NLRP3 inflammasome activation.

• Authors: Jie Huang, Shanshan Wei, Zhenyu Peng, Zijun Xiao, Yuanying Yang, Jiaqin Liu, Bikui Zhang, Wenqun Li
• Journal: The Journal of pharmacy and pharmacology (J Pharm Pharmacol) Vol. 74 Issue 2 Pg. 259-267 (Feb 01 2022) ISSN: 2042-7158 [Electronic] England
• PMID: 34923585 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Inflammasomes
• Lipopolysaccharides
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Creatinine
• Disulfiram

Topics

• Acute Kidney Injury (drug therapy)
• Animals
• Apoptosis (drug effects)
• Blood Urea Nitrogen
• Creatinine (blood)
• Disease Models, Animal
• Disulfiram (pharmacology)
• In Situ Nick-End Labeling
• Inflammasomes (metabolism)
• Lipopolysaccharides
• Male
• Mice
• Mice, Inbred C57BL
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)
• Oxidative Stress (drug effects)