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

被引:0
作者
Reza Hosseini
Nahid Fakhraei
Hedyeh Malekisarvar
Delaram Mansourpour
Fatemeh Nili
Morteza Farahani
Ahmad Reza Dehpour
机构
[1] Neuroscience Institute,Electrophysiology Research Center
[2] Tehran University of Medical Sciences,Brain and Spinal Cord Injury Research Center
[3] Neuroscience Institute,School of Population and Public Health, Faculty of Medicine
[4] Tehran University of Medical Sciences,Department of Pathology
[5] University of British Columbia,Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine
[6] Imam Khomeini Hospital Complex,Experimental Medicine Research Center
[7] Tehran University of Medical Sciences,Department of Pharmacology, School of Medicine
[8] Tehran University of Medical Sciences,undefined
[9] Tehran University of Medical Sciences,undefined
[10] Tehran University of Medical Sciences,undefined
来源
Naunyn-Schmiedeberg's Archives of Pharmacology | 2022年 / 395卷
关键词
Experimental colitis; Sumatriptan; 5-HT; receptors; Inflammation; Rat;
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摘要
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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页码:563 / 577
页数:14
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