Gastroprotective Effects of Betahistine Against an Indomethacin-Induced Gastric Mucosal Ulcer in Rats: The Role of Cinc-2Α Gene Publisher



S Tarani SHAGHAYEGH ; G Vahabzadeh GELAREH ; Hf Huseini Hasan FALLAH ; A Khavandegar ARMIN ; B Tavakolifar BAHAREH ; R Jazayeri ROSHANAK
Source: Medical Journal of the Islamic Republic of Iran Published:2024

Abstract

Background: The role of histamine H3 receptors (H3Rs) in gastric protection and anti-inflammatory function is controversial. In this study, we investigated the gastroprotective effect of a histamine H3 receptor antagonist drug, betahistine, on cytokine-induced neutrophil chemoattractant (CINC) gene expression in a rat model of indomethacin-induced gastric mucosal injury. Methods: In this experiment, rats were divided into four groups; the control group received no treatment, group 2 was treated with indomethacin at a dose of 25 mg/kg, group 3 pre-treated with famotidine at a dose of 50 mg/kg, and group 4 pre-treated with betahistine (as a reference drug) at a dose of 50 mg/kg. The last two groups were followed by indomethacin administration (25 mg/kg), three days later. The obtained values were expressed as the mean and standard error of the mean (mean ± SEM). The level of statistical significance was set at α = 0.05 Results: Indomethacin treatment resulted in large ulcerative lesions with a mean ulcer index of 29± 13.63 mm. However, ulcerative indices were significantly improved in groups pre-treated with famotidine (15.5 ± 8.68 mm; P < 0.05) and betahistine (11±5.66 mm, P < 0.01), compared to the indomethacin-treated group. The expression levels of gastric CINC-2ɑ were significantly elevated in indomethacin-induced groups by 0.028±0.05 in the indomethacin group, 0.005±0.01 in indomethacin + famotidine, and 0.012±0.03 in indomethacin + betahistine groups, compared to the control group (P < 0.05). Besides, pre-treatment with betahistine significantly reduced the expression of CINC-2ɑ induced by indomethacin administration (P < 0.05). Conclusion: Betahistine for five days before administrating indomethacin reduced the ulcer index and downregulated the expression of CINC-2α significantly. Overall, pre-treatment with betahistine protects against the gastric damage induced by indomethacin by lowering the expression of CINC-2ɑ. © 2024 Elsevier B.V., All rights reserved.