Disulfiram attenuates lipopolysaccharide-induced acute kidney injury by suppressing oxidative stress and NLRP3 inflammasome activation in mice. (19th December 2021)

• Record Type: Journal Article
• Authors: Huang, Jie; Wei, Shanshan; Peng, Zhenyu; Xiao, Zijun; Yang, Yuanying; Liu, Jiaqin; Zhang, Bikui; Li, Wenqun
• Is Part Of: Journal of pharmacy and pharmacology. Volume 74:Number 2(2022)
• Page Start: 259
• Page End: 267
• Publication Date: 2021-12-19
• Subjects: disulfiram -- lipopolysaccharide -- acute kidney injury -- oxidative stress -- NLRP3 inflammasome; Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1093/jpp/rgab171
• Languages: English
• ISSNs: 0022-3573

Abstract

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.