Work

Dapansutrile mitigates concanavalin A- induced autoimmune hepatitis: Involvement of NLRP3/IL-1β and JNK/ p38 MAPK pathways

Year: 2025

Type: article

Abstract: AIM: 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. MAIN METHODS: 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. KEY FINDINGS: 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. SIGNIFICANCE: Our results showed that intraperitoneal administration of Dapan could be a therapeutic opportunity to inhibit the development of AIH via inhibition of inflammatory pathways.

Source: Biomedicine & Pharmacotherapy

DOI: 10.1016/j.biopha.2025.118026

Authors: Fahad O. Alenezi, Manar A. Nader, Dalia H. El-Kashef, Marwa E. Abdelmageed

Institution: Mansoura University

Language: English

Topic: Liver Diseases and Immunity

Subfield: Hepatology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,610