Dapsone Ameliorates Colitis through TLR4/NF-kB Pathway in TNBS Induced Colitis Model in Rat

Background. Crohn's disease (CD), a type of inflammatory bowel disease (IBD), emerges with severe gastrointestinal (GI) tract inflammation, sometimes known as hostile abdomen. Conventional treatment of CD has several limitations such as insufficient response to treatment, and intolerable side effects of drugs. In addition, the high cost of biologic drugs prevents patients from continuing their treatment. Dapsone showed vigorous anti-inflammatory effects on the skin diseases, lung diseases and inflammatory diseases of the nervous system. Hence, we decided to investigate the effect of dapsone on animal model of CD. Methods. In this study, colitis was induced by instillation of 2,4,6-trinitrobenzenesulfonic acid (TNBS) 100 mg/kg. Rats were treated with daily gavage of dapsone (10, 12.5 and 20 mg/kg). Seven days after induction of colitis, specimens were collected for pathological and molecular assessments. Results. Dapsone (12.5 and 20 mg/kg) preserved the histologic architecture of the colon and prevented crypts irregularity. Additionally, it decreased tissue edema and hindered inflammatory cells infiltration. Besides, all doses of dapsone decreased tissue concentration of tumor necrosis factor alpha (TNF-alpha) and interferon gamma (INF gamma). Western blot revealed that dapsone could attenuate inflammation via downregulation of toll-like receptor 4 (TLR4) and dephosphorylation of nuclear factor kB (NF-kB). Conclusion. Based on these findings, dapsone attenuates inflammation and decreases TNF-alpha and INF-gamma in animal model of CD. It acts through TLR4/NF-kB pathway to exert these effects. (C) 2021 Instituto Mexicano del Seguro Social (IMSS). Published by Elsevier Inc. All rights reserved.

Automated summary

Dapsone has shown anti-inflammatory effects and reduced levels of TNF-alpha and INF-gamma in an animal model of CD. It works through the TLR4/NF-κB pathway to attenuate inflammation by reducing tissue edema, inhibiting inflammatory cell infiltration, and maintaining the histologic architecture of the colon.