Gastroprotective Effect of Sumatriptan Against Indomethacin-, Stress- and Ethanol-Induced Gastric Damage in Male Rats: Possible Modulatory Role of 5-Hydroxytryptamine 1B/1D Receptors and Pro-Inflammatory Cytokines.

The current study was aimed to investigate the beneficial effect of sumatriptan, a 5-hydroxytryptamine 1B/1D (5HT(1B/1D)) receptor agonist, on gastric ulcer in rats via stimulating 5HT(1B/1D) receptors and suppressing pro-inflammatory cytokines. Rats were allocated into three models of gastric ulcer: indomethacin (30 mg/kg, PO), water immersion restraint stress (WRS) and ethanol (5 ml/kg PO). Animals were administered with sumatriptan (0.01, 0.1, 0.3 and 1 mg/kg, i.p) 30 min before gastric ulcer induction. GR-127935 (0.01 mg/kg, i.p, a selective 5HT(1B/1D) antagonist) was administered 30 min before sumatriptan (0.1 mg/kg) injection. Macroscopic assessments (J-score), ELISA analysis of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1 beta) and histopathological changes were performed on the rat's stomach tissues. Gastric ulcer induction in three models caused an increase in J-score, TNF-alpha, IL-1 beta and microscopic features. Sumatriptan (0.1 mg/kg) significantly improved gastric injury induced by indomethacin, WRS and ethanol through the reduction in the J-score, TNF-alpha, IL-1 beta and microscopic lesions. Concurrent administration of GR-127935 (0.01 mg/kg) with sumatriptan (0.1 mg/kg) reversed the gastroprotective effect of sumatriptan in three models. Sumatriptan possessed gastroprotective effects on indomethacin-, WRS- and ethanol-induced gastric damage in rats via the possible involvement of the 5HT(1B/1D) receptors.