PhD Scientific Days 2025

Poster Session III. - H: Pharmaceutical Sciences and Health Technologies

Flagellin Pretreatment Ameliorates Indomethacin-induced Enteropathy in Mice

Name of the presenter

Haghighi Arezoo

Institute/workplace of the presenter

Department of Pharmacology and Pharmacotherapy

Authors

Arezoo Haghighi¹, Zsuzsanna O. Demeter¹, Anna Zsidai¹, Samaneh Haghighi², Gerda Wachtl¹, Klára Gyires¹, Zoltán S. Zádori¹

1: Department of Pharmacology and Pharmacotherapy
2: Institute of Translational Medicine, Semmelweis University, Budapest, Hungary

Text of the abstract

Introduction: Previous studies have shown that treatment with flagellin, the toll-like receptor 5 (TLR5) ligand, reduces gastrointestinal injury induced by various stimuli. In addition, we found that indomethacin (IND)-induced small intestinal injury (enteropathy) in rats is associated with downregulation of TLR5, and TLR5 expression negatively correlates with intestinal inflammation. Therefore, we hypothesised that pretreatment with flagellin can reduce IND-induced enteropathy.
Aim: To assess the protective effect of flagellin in two different doses against indomethacin-induced small intestinal damage.
Methods: Enteropathy was induced in mice by IND at a dose of 40 mg/kg. Flagellin was injected intraperitonelly 2 h before and 4 h after IND administration at 2 different doses (10 and 30 mg/mouse). Tissue levels of inflammatory proteins and TLRs were assessed by Western blot and qPCR.
Results: IND induced enteropathy after 24 h, characterised by intestinal ulceration and inflammation. Tissue levels of several inflammatory mediators and cytokines were elevated, including MPO, PTX3, COX2 and IL-1β. The ratio of Bax to Bcl-2 increased, indicating increased apoptosis. In addition, IND increased the gene expression of TLR2 and TLR4 and decreased that of TLR1, TLR5 and TLR9. Most of these changes were prevented by flagellin treatment, except for the downregulation of TLR5 expression.
Conclusion: Our study suggests that flagellin treatment may be a potential strategy to protect the small intestine against IND-induced enteropathy.
Grant: NKFI FK 138842, SE250+