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.

Keywords: Apoptosis; Cardiac injury; Disulfiram; Lipopolysaccharide; NLRP3 inflammasome; Oxidative stress.