Protective effects of citicoline on TNBS-induced experimental colitis in rats

Abstract

The aim of this study was to investigate the effects of citicoline on the development of colitis and antioxidant parameters in rats subjected to tribenzene sulfonic acid (TNBS)-induced colitis. Twenty four Wistar Albino female rats were divided into four subgroups (n=6) (control, colitis control, colitis + 50 mg/kg citicoline, colitis + 250 mg/kg citicoline). Colitis was induced using an enema of TNBS and ethanol; following which citicoline was administrated for 3 days and effects of citicoline was subsequently evaluated. Based on microscopic damage scores, there was no difference between rats of the TNBS-colitis and 50 mg/kg citicoline treated groups, whereas treatment with 250 mg/kg citicoline, caused significant reduction in colon injury compared to that observed in rats of TNBS-colitis group. In terms of the biochemical analyses, myeloperoxidase (MPO), malondialdehyde (MDA), reduced glutathione (GSH), and IL-6 levels in rats from 250 mg/kg citicoline group were significantly different from that TNBS-colitis group. The levels of MPO, MDA, GSH and IL-6 in control rats were also significantly different those of rats in the TNBS-colitis group. Citicoline may have a positive protective effect on the inflammatory bowel disease treatment process and could, therefore, be used as an adjunct therapy in colitis. These effects of citicoline may exist through anti-inflammatory and antioxidant mechanism.

Keywords: TNBS; antioxidant system; citicoline; inflammatory bowel disease.

Figure 1

Histopathological features of the colon associated with colitis and the effects of citicoline on colon injury. Histological appearance in rat colonic mucosa of (A) normal (noncolitis), (B) Trinitrobenzene sulfonic acid (TNBS)-induced colitis, (C) TNBS-colitis + citicoline (50 mg/kg), (D) TNBS-colitis + citicoline (250 mg/kg). Colitis was produced after TNBS administration and was characterized by necrosis of the mucosa, diffuse infiltration of inflammatory cells in the mucosa and submucosa, and sub-mucosal edema (B). Treatment with citicoline 50 mg/kg did not change the morphological signs of cell damage associated with TNBS administration (C); treatment with cticoline 250 mg/kg greatly reduced the morphological alterations associated with TNBS administration, protecting the mucosal structure (D). Original magnification was 10x (A-D) on hematoxylin and eosin stained preparations.

Figure 2

Effects of citicoline (50 and 250 mg/kg) administered intraperitoneally for three consecutive days after induction of colitis on microscopic damage scores, myeloperoxidase (MPO) and malondialdehyde (MDA) activity in rat colonic mucosa. Data are presented as means ± SEM. ^ap<0.05 versus control, ^bp<0.05 colitis control, ^cp<0.001 versus control, ^dp<0.01 versus colitis control.

Figure 3

Effects of citicoline (50 and 250 mg/kg) administered intraperitoneally for three consecutive days after induction of colitis on glutathione (GSH) and IL-6 levels in rat. Data are presented as means ± SEM. ^ap<0.001 versus control, ^bp<0.05 versus colitis control, ^cp<0.01 versus control.