Comparative study of effect of ranitidine and sitagliptin on healing of acetic acid induced gastric ulcer in rats

Abstract

Gastric ulcer healing is a complex process that is regulated by several promoting factors including Cyclooxygenase-2 (COX-2) and Inducible Nitric Oxide Synthase (iNOS). Diabetes mellitus is usually associated with delayed gastric ulcer healing. Hence, the current study was designed to compare the effect of sitagliptin (dipeptidyl peptidase-4 inhibitor) with ranitidine on gastric ulcer healing. The present study was conducted on 40 male albino rats that were divided into four equal groups: Group 1: normal control group, group 2: gastric ulcer model, Group 3: sitagliptin treated group, Group 4: ranitidine treated group. Rats were sacrificed ten days after ulcer induction and stomach was removed for histopathological examination and Immuno histochemical evaluation of COX-2 and iNOS. This study revealed that gastric ulcer healing was significantly impaired in the sitagliptin-treated group when compared with ranitidine treated group, evidenced by histopathological examination of stomach showing significantly larger ulcerated area and ulcer base maturation impairment.COX-2 and iNOS expression as well as mean vascular density (MVD) were significantly diminished in the sitagliptin-treated group as compared to ulcer model group as well as ranitidine treated group. A significant positive correlation was found between COX-2 and iNOS implying their synergistic action. A significant positive correlation was found between MVD on one hand and COX-2 and iNOS on the other hand pointing to their proangiogenic effect. This 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.