Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 101, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2021.108174
Keywords
Ulcerative colitis; Mirtazapine; Inflammation; Oxidative stress; Nod-like receptor
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The study found that MRT has a protective effect against UC by reducing colonic damage and oxidative stress, as well as modulating the NLRP3/caspase-1 inflammatory 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-alpha, and nuclear factor kappa B (NF-Kappa B) expression together with interleukin (IL)-1 beta 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-Kappa B, TNF-alpha expressions, IL-1 beta, 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 antiinflammatory activity with modulation of NLRP3/caspase-1 inflammatory pathway.
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