Dapansutrile (Dapan) is a newly developed anti-inflammatory molecule that supresses the production of NLRP3 inflammasome-dependent IL-1β. Its hepatoprotective effects against autoimmune hepatitis (AIH) have not yet been explored. Hence, this study was conducted to examine the possible protective effects of Dapan against concanavalin A (Con A)-induced hepatitis in mice.

Mice were randomly divided into five groups (n = 6): control, Con A (15 mg/kg), Dapan (60 mg/kg), Dapan (6 mg/kg) + Con A, and Dapan (60 mg/kg) + Con A. Mice were euthanised at the end of the study, and blood and hepatic tissues were collected.

Hepatic function testing using lactate dehydrogenase, alanine aminotransferase, and aspartate aminotransferase levels, in addition to hepatic tissue histological examination, revealed that intraperitoneal administration of Dapan noticeably ameliorated Con A-induced hepatic enzyme impairment and histopathological disruption. Moreover, Dapan-treated mice had significantly lower malondialdehyde hepatic content and elevated reduced glutathione, superoxide dismutase, and total antioxidant capacity levels than non-treated mice in a dose-dependent manner. The Dapan-treated groups showed significantly lower levels of the inflammatory mediators, NLRP3, TNF-α, IL-6, and IL-1β, in addition to the immunomodulators CD8, CD4, INF-γ, and NFκB and inhibition of JNK and p38 MAPK levels compared to the Con A-treated group.

Our results showed that intraperitoneal administration of Dapan could be a therapeutic opportunity to inhibit the development of AIH via inhibition of inflammatory pathways.