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 the 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 sumatriptan (0.01, 0.1, 0.3, and 1 mg/kg, i.p) 30 minutes before gastric ulcer induction. GR-127935 (0.01 mg/kg, i.p, a selective 5HT 1B/1D antagonist) was administered thirty minutes before sumatriptan (0.1 mg/kg) injection. Macroscopic assessments (J-score), ELISA analysis of tumor necrosis factor-alpha (TNF-α) and interleukin-1beta (IL-1β), and histopathological changes were performed on rat's stomach tissues. Gastric ulcer induction in three models caused an increase in J score, TNF-α, IL-1β, and microscopic features. Sumatriptan (0.1 mg/kg) significantly improved gastric injury induced by indomethacin, WRS, and ethanol through reduction in the J-score, TNF-α, IL-1β and microscopic lesions. Concurrent administration of GR-127935 (0.01 mg/kg) with sumatriptan (0.1 mg/kg) reversed gastroprotective effect of sumatriptan in three models. Sumatriptan possessed gastro-protective effects on indomethacin-, WRS- and ethanol- induced gastric damage in rats via possible involvement of the 5HT 1B/1D receptors.