Effect of sumatriptan on acetic acid-induced experimental colitis in rats: a possible role for the 5‐$ HT_{1B/1D} $ receptors
Abstract Mucosal inflammation in colitis is associated with changes in the intestinal serotonin (5-HT) level. Sumatriptan, a 5‐$ HT_{1B/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-$ HT_{1B/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-$ HT_{1B/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-$ HT_{1B/1D} $ receptors, as well as anti-inflammatory and anti-oxidative characteristics..
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Artikel |
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Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:395 |
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Enthalten in: |
Naunyn-Schmiedeberg's archives of pharmacology - 395(2022), 5 vom: 16. Feb., Seite 563-577 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Hosseini, Reza [VerfasserIn] |
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Links: |
Volltext [lizenzpflichtig] |
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Anmerkungen: |
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022 |
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doi: |
10.1007/s00210-022-02215-5 |
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PPN (Katalog-ID): |
OLC2078419311 |
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520 | |a Abstract Mucosal inflammation in colitis is associated with changes in the intestinal serotonin (5-HT) level. Sumatriptan, a 5‐$ HT_{1B/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-$ HT_{1B/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-$ HT_{1B/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-$ HT_{1B/1D} $ receptors, as well as anti-inflammatory and anti-oxidative characteristics. | ||
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