American Journal of Pharmacology and Toxicology

Sitagliptin Impairs Healing of Experimentally Induced Gastric Ulcers Via inhibition of iNOS and COX-2 Expression

Amina Unis and Eman Abdelzaher

DOI : 10.3844/ajptsp.2013.107.119

American Journal of Pharmacology and Toxicology

Volume 8, Issue 3

Pages 107-119


Gastric ulcer healing is a complex process that is regulated by several promoting factors including COX-2 and iNOS. Diabetes mellitus is usually associated with delayed gastric ulcer healing. Hence, the current study was designed to investigate the effect of sitagliptin (dipeptidyl peptidase-4 inhibitor) on gastric ulcer healing and expression of iNOS and COX-2 in rat stomach.The study was conducted on 30 rats divided into three equal groups. Group 1 served as normal control group. Gastric ulcer was induced, by serosal application of acetic acid, in group 2 (ulcer model group) and group 3 (sitagliptin-treated group). Sitagliptin was administrated from day 3 to day 10 in group 3. All rats were sacrificed on day 10 and stomachs were removed for pathological examination and immunohistochemical assessment of COX-2 and iNOS expression. Pathological examination revealed that gastric ulcer healing was significantly impaired in the sitagliptin-treated group as evidenced by the significantly larger ulcerated area and ulcer base maturation impairment.COX-2 and iNOS expression as well as mean MVD were significantly diminished in the sitagliptin-treated group as compared to the ulcer model group. A significant positive correlation was found between COX-2 and iNOS implying their synergistic action. We conclude that sitagliptin significantly impairs gastric ulcer healing in rats possibly through inhibition of iNOS and COX-2 expression. Our results raise the question of whether sitagliptin is advisable in diabetic patients with pre-existing gastric ulcer. Our preliminary experimental findings need to be substantiated by future human studies.


© 2013 Amina Unis and Eman Abdelzaher. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.