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Effect of sumatriptan on acetic acid-induced experimental colitis in rats: a possible role for the 5‐HT1B/1D receptors

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Abstract

Mucosal inflammation in colitis is associated with changes in the intestinal serotonin (5-HT) level. Sumatriptan, a 5‐HT1B/1D receptor agonist, has demonstrated anti-inflammatory characteristics. The purpose of this study was to determine the effects of sumatriptan in a rat model of acute experimental colitis and to elucidate the probable participation of presynaptic 5-HT1B/1D receptors. To induce colitis, acetic acid (4%) was injected intrarectally. Treatments were given intraperitoneally (IP) once daily over 3 consecutive days starting 1-h post-induction. Sumatriptan was given at 0.5, 1, 2, and 5 mg/kg. GR-127935, a 5-HT1B/1D receptor antagonist, was injected (0.1 and 0.3 mg/kg) 30 min prior to the most effective dose of sumatriptan (1 mg/kg). On day 4, the colon samples were isolated. Significant enhancements of the tissue tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), microscopic and macroscopic damages, body weight losses, and also reductions in tissue superoxide dismutase (SOD) and 5-HT were observed in colitis rats. On the other hand, sumatriptan at doses 0.5, 1, and 2 mg/kg could diminish pathologic changes in the measured biomarkers, histopathologic damages, and body weight losses. Although GR-127935 at dose 0.3 mg/kg could markedly improve the pathologic indexes, its sub-effective dose (0.1 mg/kg) reversed the protective effect of sumatriptan (1 mg/kg). Moreover, sumatriptan (1 and 5 mg/kg) and GR-127935 (0.3 mg/kg) increased the serotonin level. Post-treatment with low-dose sumatriptan demonstrated a protective impact on this peripheral inflammatory condition. Notably, this protective effect may be mediated, at least in part, through 5-HT1B/1D receptors, as well as anti-inflammatory and anti-oxidative characteristics.

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Funding

The study was supported by two grants, one from the Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran (No. 29643–139-02–94), and the other one from the Iran National Science Foundation (INSF) under the grant no. 96002757.

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Prof. ARD and NF conceived and designed the study; RH, NF, HM, DM, and FN conducted experiments; RH, NF, FN, and MF performed analysis and interpretation of data; RH, NF, and HM wrote the manuscript; Prof. ARD supervised the study. All authors read and approved the manuscript and all data were generated in-house.

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Correspondence to Ahmad Reza Dehpour.

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All the experimental procedures were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 8023, revised 1978). Moreover, the Research and Medical Ethics Committees of Tehran University of Medical Science approved the study under the ethical code IR.TUMS.REC.1394.1872.

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Hosseini, R., Fakhraei, N., Malekisarvar, H. et al. Effect of sumatriptan on acetic acid-induced experimental colitis in rats: a possible role for the 5‐HT1B/1D receptors. Naunyn-Schmiedeberg's Arch Pharmacol 395, 563–577 (2022). https://doi.org/10.1007/s00210-022-02215-5

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