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.

Abstract

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.

• Authors: Aysa Ostovaneh, Faezeh Eslami, Nastaran Rahimi, Pegah Dejban, Hamed Shafaroodi, Ata Abbasi, Shirin Shahsavarhaghighi, Ahmad Reza Dehpour
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 133 Issue 2 Pg. 156-167 (Aug 2023) ISSN: 1742-7843 [Electronic] England
• PMID: 37248787 (Publication Type: Journal Article)
• Copyright: © 2023 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.

Chemical References

• Sumatriptan
• Cytokines
• Indomethacin
• Serotonin
• Tumor Necrosis Factor-alpha
• Ethanol

Topics

• Rats
• Male
• Animals
• Sumatriptan (pharmacology)
• Cytokines
• Indomethacin (pharmacology)
• Serotonin
• Stomach Ulcer (chemically induced, drug therapy, prevention & control)
• Tumor Necrosis Factor-alpha
• Rats, Wistar
• Ethanol (toxicity)