Licofelone Attenuates Acetic Acid-Induced Colitis in Rats Through Suppression of the Inflammatory Mediators.

Abstract

Licofelone is a dual Cyclooxygenase 1,2 (COX1,2)/5-lipoxygenase) 5-LOX (inhibitor with analgesic and anti-inflammatory effects with possible functions on inflammatory bowel disease (IBD), which is a chronic recurrent condition with no particular treatment. This study evaluated the anti-inflammatory effects of licofelone on acetic acid-induced colitis in rats. Ten groups of male Wistar rats (n = 6) were used. Sham, control group, licofelone at doses of 2.5, 5, and 10 mg/kg, L-NG-nitro arginine methyl ester (L-NAME) (10 mg/kg, i.p.), aminoguanidine (AG) (100 mg/kg, i.p.), 30 min before using licofelone (10 mg/kg). Also, three groups received L-NAME, aminoguanidine, or dexamethasone. Macroscopic, microscopic, and biochemical analysis of myeloperoxidase (MPO), and nuclear factor-kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β), superoxide dismutase (SOD), reactive oxygen species (ROS), and Toll-like receptor 4 (TLR-4) were assessed in colon tissue. Licofelone at a dose of 10 mg/kg attenuated colitis, increased SOD activity, and significantly reduced colonic levels of the abovementioned inflammatory factors. In addition, licofelone improved macroscopic and microscopic symptoms in the acetic acid-induced colitis model. Moreover, the concurrent use of nitric oxide synthase (NOS) inhibitors with 10 mg/kg of licofelone reversed the observed positive effects, demonstrating the function of nitric oxide in IBD pathogenesis and the probable mechanism for licofelone in the healing process of induced colitis. A reduced level of inflammatory factors confirmed the anti-inflammatory activity of licofelone as a dual COX1,2/5-LOX inhibitor. Furthermore, outcomes revealed the protective role of licofelone in treating experimental colitis. The findings are suggestive of the potential use of licofelone in IBD.