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

• Published in: Basic & clinical pharmacology & toxicology 2023-08, Vol.133 (2), p.156-167
• Main Authors: Ostovaneh, Aysa, Eslami, Faezeh, Rahimi, Nastaran, Dejban, Pegah, Shafaroodi, Hamed, Abbasi, Ata, Shahsavarhaghighi, Shirin, Dehpour, Ahmad Reza
• Format: Article
• Language: English
• Subjects: Animals; Cytokines; Damage; Ethanol; Ethanol - toxicity; gastric damages; Indomethacin; Indomethacin - pharmacology; Inflammation; Injury prevention; Interleukins; Male; rat; Rats; Rats, Wistar; Receptors; Serotonin; Stomach Ulcer - chemically induced; Stomach Ulcer - drug therapy; Stomach Ulcer - prevention & control; Sumatriptan; Sumatriptan - pharmacology; Tumor necrosis factor; Tumor Necrosis Factor-alpha; Tumor necrosis factor-TNF; Ulcers; Water immersion
• ISSN: 1742-7835; 1742-7843
• DOI: 10.1111/bcpt.13905

The current study was aimed to investigate the beneficial effect of sumatriptan, a 5‐hydroxytryptamine 1B/1D (5HT1B/1D) receptor agonist, on gastric ulcer in rats via stimulating 5HT1B/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 5HT1B/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‐α) and interleukin‐1beta (IL‐1β) and histopathological changes were performed on the 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 the 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 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 5HT1B/1D receptors. Gastric ulcers induced by NSAID, stress and ethanol can lead to an elevation in the levels of pro‐inflammatory cytokines, specifically TNF‐α and IL‐1β, thereby causing injury to the gastric mucosa in rats. In contrast, sumatriptan, a 5HT1B/1D receptor agonist, has been found to possess gastroprotective properties against gastric ulceration induced by NSAIDs (indomethacin), stress and ethanol in rat models. The gastroprotective effect of sumatriptan occurs through the possible involvement of the 5HT1B/1D receptors and the reduction of TNF‐α and IL‐1β.