Gastroprotective mechanisms of imipramine on indomethacin-induced gastric ulcer in male Wistar rats

Abstract

Tricyclic antidepressant drugs were used in the past for the treatment and management of endogenous depression and mood disorders. They have also been used in the treatment of gastric ulcer as far back as five decades ago. However, there is scanty information on the effect of imipramine on gastric acid secretion, gastric mucus secretion and antioxidative activity as a basis for its anti-ulcer effect. In this study, the antisecretory and gastroprotective effects of imipramine pretreatment in male Wistar rats were investigated. One hundred rats (180-250g) were used in this study. The animals were divided into four study groups. Each group was further divided into five subgroups of five rats each. Groups 1 (Control), Groups II, III, and IV had 10, 25,40mg/kg Imipramine respectively, while group V served as positive control; 20mg/kg Omeprazole, a proton pump inhibitor. All drugs were administered orally for 14 days. Gastric antisecretory, mucogenic and antioxidative effects of imipramine were determined using standard methods in the text. Level of statistical significance were determined using the one-way analysis of variance (ANOVA), followed by students’t-test. P< 0.05 was considered significant. Imipramine significantly decreased basal acid secretion when compared with the control. There was significant increase in gastric acid secretion in all the pretreated groups after intravenous administration of carbachol. Gastric mucus secretion and gastric mucus cell count increased significantly in all imipramine pretreated groups when compared with the control. It also significantly decreased parietal cell count per field and MDA activity when compared with the control. The SOD and CAT activity was significantly increased at all doses when compared with the control. Imipramine significantly reduced indomethacin induced ulcers when compared with the control. This study suggests that imipramine possesses gastroprotective activity via multiple mechanisms, among which are antisecretory, mucogenic and antioxidant activities.

Keywords: Imipramine, Gastric acid, Indomethacin, Gastric Mucus