Disulfiram inhibits oxidative stress and NLRP3 inflammasome activation to prevent LPS-induced cardiac injury
Abstract
Sepsis-induced cardiac injury leads to the high rate of mortality, the therapeutics for this disorder are limited. Disulfiram (DSF) is an FDA-approved treatment for chronic alcohol addiction, and its cardio-protection is gradually discovered in recent years. In present study, mice were injected with lipopolysaccharide (LPS, 15 mg/kg) to induce a septic cardiac injury model, and aimed to investigate the protective effect of DSF on sepsis-induced cardiac injury and the underlying mechanisms. Results showed that DSF treatment alleviated the lowered left heart function and myocardial cell apoptosis induced by LPS. Moreover, we found that LPS increased myocardium lipid peroxidation, DNA damage and the activation of NLRP3 inflammasome, which were significantly reduced by DSF. These results suggested the protective role of DSF in LPS-induced cardiac injury, and the mechanism involved the inhibition on the oxidative stress and NLRP3 inflammasome activation. Given the potent cardiac protection effect of DSF, repurposing DSF in the clinic would represent a new strategy to protect and treat sepsis-induced cardiac injury.
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DIS inhibits oxidative stress and Nod-like receptor protein 3 inflammasome activation, thus preventing lipopolysaccharide-induced cardiac injury.
“DIS inhibits oxidative stress and Nod-like receptor protein 3 (NLRP3) inflammasome activation, thus preventing LPS-induced cardiac injury.118”
From Off-label and repurposed use of disulfiram beyond alcohol dependence: A systematic review of clinical and preclinical evidence (2026) · cites this paper as [118]
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- Authors
- Wei, S., Xiao, Z., Huang, J., Peng, Z., Zhang, B., & Li, W.
- Affiliations
- Central South University (CN)
- Corresponding author
- Zhang, Bikui
- Li, Wenqun
- Venue
- International Immunopharmacology
- Publisher
- Elsevier BV
- Published
- 2022-04
- Volume
- 105
- Pages
- 108545
- ISSN
- 1567-5769 (ISSN-L)
- OpenAlex
- W4210277118
- Cited by
- 35
- References
- 28
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 6 · 2023: 11 · 2022: 5
- FWCI
- 5.26
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- International Immunopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Keywords
- disulfiram, lipopolysaccharide, NLRP3 inflammasome, oxidative stress, cardiomyocyte apoptosis, lipid peroxidation, DNA damage, drug repurposing, cardioprotection
- MeSH terms
- NLR Family, Pyrin Domain-Containing 3 Protein, Animals, Disulfiram, Lipopolysaccharides, Oxidative Stress, Mice, Inflammasomes
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