Abstract
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.
Highlights
Gastric ulcer is considered one of the most prevalent et al, 2013)
The current study was designed to investigate the effect of sitagliptin on gastric ulcer healing and expression of Inducible Nitric Oxide Synthase (iNOS) and COX-2 in rat stomach.The study was conducted on 30 rats divided into three equal groups
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 Microvessel Density (MVD) were significantly diminished in the sitagliptin-treated group as compared to the ulcer model group
Summary
Gastric ulcer is considered one of the most prevalent et al, 2013). COX-2 induces the synthesis of gastrointestinal disorders. Amina Unis and Eman Abdelzaher / American Journal of Pharmacology and Toxicology 8 (3): 107-119, 2013 inflammatory pathway cross-link with the more wellknown COX-2 pathway This synergistic molecular interaction between the two inflammatory systems may cast more light on their healing promoting effects on gastric ulcer (Kim et al, 2005). It was reported that hyperglycemia together with the increased production of proinflammatory cytokines result in sustained inflammatory reaction and may be responsible for the delay of healing at the ulcer area (Cosentino et al, 2003). Such previously stated reports necessitate studying the effect of antidiabetic drugs on gastric ulcer healing. Recent studies demonstrated that DPP-4 inhibitors or related compounds may possess marked inflammatory modifying effects through modulation of cytokine production (Alonso et al, 2012)
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