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

Document Type : Original Article (s)

Authors

1 Professor, Department of Pharmaceutics, School of Pharmacy AND Novel Drug Delivery Systems Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

2 Professor, Department of Pharmacology, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran

3 Student of Pharmacy, School of Pharmacy AND Novel Drug Delivery Systems Research Center AND Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: 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.Methods: 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).Findings: 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).Conclusion: 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.

Keywords

References

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Journal of Isfahan Medical School
Volume 31, Issue 226 - Serial Number 226
January and February 2013
Pages 138-149

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History

  • Receive Date: 05 December 2012
  • Revise Date: 01 November 2024
  • Accept Date: 06 April 2022

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