Febuxostat attenuates ulcerative colitis by the inhibition of NF-κB, proinflammatory cytokines, and oxidative stress in mice

Abstract

Ulcerative colitis is a chronic inflammatory disorder characterized by oxidative stress and upregulation of proinflammatory mediators in colonic tissue. Febuxostat, a xanthine oxidase inhibitor has been shown to exert anti-inflammatory and antioxidant effects. The aim of this study was to investigate the protective effect of febuxostat against ulcerative colitis, and to elucidate the potential mechanisms involved. Experimental colitis was induced in mice by intrarectal administration of 5% acetic acid. Mice were treated with febuxostat (10 and 20 mg/kg/day, orally) for three days. Results showed that body weight loss, colon shortening, macroscopic damage and histopathological changes of colonic mucosa were reduced in mice treated with febuxostat. Treatment of mice with febuxostat significantly increased the levels of glutathione (GSH) and superoxide dismutase (SOD), and decreased the levels of malondialdehyde (MDA), carbonyl protein, xanthine oxidase, nitric oxide (NO) and myeloperoxidase (MPO) activity of colon tissue compared with those in the acetic acid-induced colitis group. The expression of nuclear factor kappa B (NF-κB) as a key regulator of inflammation in the colonic tissue was decreased by febuxostat. Furthermore treatment with febuxostat significantly reduced the levels of proinflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and interferon (IFN)-γ, while increased the levels of IL-10 compared with the colitis group. These results suggest that febuxostat is able to decrease the severity of acetic acid-induced colitis by inhibition of oxidative stress and inflammatory responses through NF-κB pathway.

Keywords: Colitis; Febuxostat; Inflammation; NF-κB; Oxidative stress.