Anti-Inflammatory Effect of Amitriptyline in a Rat Model of Acetic Acid-Induced Colitis: The Involvement of the Tlr4/Nf-Kb Signaling Pathway Publisher Pubmed



Dejban P^{1, 2, 3} ; Sahraei M² ; Chamanara M⁴ ; Dehpour A^{1, 2} ; Rashidian A^{1, 2} Show Affiliations
Source: Fundamental and Clinical Pharmacology Published:2021

Abstract

Inflammatory bowel disease (IBD) consists of ulcerative colitis and Crohn's disease, which affects gastrointestinal tract. The immune-mediated inflammation is mostly considered as the pathogenesis of IBD. It has been demonstrated that amitriptyline exerts anti-inflammatory influence; therefore, the aim of the current experiment is to evaluate the anti-inflammatory impact of amitriptyline on intestinal disorders following acetic acid-induced colitis in rats. Thirty male Wistar rats were randomly divided into five groups, including sham, control, dexamethasone (2 mg/kg), and amitriptyline (10 and 20 mg/kg). Intrarectal administration of acetic acid was applied to colitis induction in all study groups except for sham group. Animals were treated by oral administration of dexamethasone or amitriptyline. While macroscopic and microscopic lesions appeared after colitis induction treatment with dexamethasone and amitriptyline 10 and 20 mg/kg significantly improved lesions. Moreover, Toll-like receptor 4 (TLR4) and nuclear factor binding kappa light-chain (NF-ĸB expression), tumor necrosis factor-alpha (TNF-α) level, and myeloperoxidase (MPO) activity were increased after colitis induction, whereas treatment with dexamethasone (2 mg/kg) or amitriptyline (10 and 20 mg/kg) caused a noticeable decrease in the TLR4 and pNF-ĸB expression, TNF-α level, and MPO activity. In conclusion, amitriptyline plays an anti-inflammatory role through the suppression of TLR4/pNF-ĸB signaling pathway in the rat model of acute colitis. © 2020 Societe Francaise de Pharmacologie et de Therapeutique