Protective effect of mirtazapine against acetic acid-induced ulcerative colitis in rats: Role of NLRP3 inflammasome pathway.

AIMS: Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) that causes long-lasting inflammation on the innermost lining of the colon and rectum. Mirtazapine (MRT) is a well-known antidepressant that was proven to have anti-inflammatory activity; however, to date, its role has not been investigated in UC. The current study aimed to investigate the role and mechanism of MRT in UC. MAIN METHOD: Acetic acid (AA) was used for UC induction, and sulfasalazine (SLZ) was used as a positive control. Rats were divided into five equal groups; as follows; normal control, AA, SLZ (received SLZ in a dose of 250 mg/kg for 14 days), MRT10 (received MRT in a dose of 10 mg/kg/day for 14 days), and MRT30 (received MRT in a dose of 30 mg/kg/day for 14 days) groups. Macroscopic and microscopic examinations together with oxidative stress parameters evaluation were done. NOD-like receptors-3 (NLRP3), caspase-1, TNF-α, and nuclear factor kappa B (NF-κB) expression together with interleukin (IL)-1ß and IL-18 levels were examined. KEY FINDING: MRT, in a dose-dependent manner, prevented the macroscopic and microscopic colonic damage and corrected the oxidative stress induced by AA. Moreover, MRT decreased the colonic tissue NLRP3 inflammasome, caspase-1, NF-κB, TNF-α expressions, IL-1ß, and IL-18 levels that were elevated in colonic tissue by the AA. SIGNIFICANCE: MRT has a dose-dependent protective effect against UC that was mediated mainly by its anti-inflammatory activity with modulation of NLRP3/caspase-1 inflammatory pathway.