Anti-Inflammatory Effects of Ketotifen in Acetic Acid-Induced Ulcerative Colitis in Rats

Ketotifen is a bronchodilator and anti-allergic drug with antagonistic effects on histamine H1 receptors. The present study evaluated the effects of ketotifen on ulcerative colitis induced by acetic acid in rats. Colitis was induced by 2 mL of 4% acetic acid in rats. It was treated with 2 mg/kg/day ketotifen or 1 mg/kg/day dexamethasone from two hours before the induction of colitis until four days after. The rats were sacrificed 24 hours after the last dose and the colon tissue was studied for macroscopic changes (ulcer area and severity and the weight/length ratio of colon), microscopic changes (inflammation severity, inflammation extent, crypt damage, and percent of involvement), and biochemical tests (myeloperoxidase activity, tumor necrosis factor-α, and interleukin-6). Ketotifen caused significant improvement of macroscopic and microscopic signs compared to negative control group. Myeloperoxidase activity in ketotifen and dexamethasone groups was significantly different from that in the negative control group. However, the two mentioned groups had no significant differences with the sham group in terms of myeloperoxidase activity and interleukin-6. Tumor necrosis factor-α decreased similarly in dexamethasone and sham groups. However, the level of this mediator was higher in the ketotifen group than in the dexamethasone group (P < 0.05). Ketotifen caused significant reductions in mucosal damage and the release of inflammatory mediators. No significant differences were seen between ketotifen (2 mg/kg) and dexamethasone (1 mg/kg) in reduction of macroscopic changes, histological test results, myeloperoxidase activity, and interleukin-6. Considering that ketotifen could alleviate the induced ulcerative colitis in rats, it may be a suitable drug for further evaluations in clinical trials on patients with irritable bowel disease.