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Inflammatory bowel disease (IBD) consists of ulcerative colitis and Crohn's disease, which affects gastrointestinal tract. The immune-mediated inflammation is mostly considered as the pathogenesis of IBD. It has been demonstrated that amitriptyline exerts anti-inflammatory influence; therefore, the aim of the current experiment is to evaluate the anti-inflammatory impact of amitriptyline on intestinal disorders following acetic acid-induced colitis in rats. Thirty male Wistar rats were randomly divided into five groups, including sham, control, dexamethasone (2 mg/kg), and amitriptyline (10 and 20 mg/kg). Intrarectal administration of acetic acid was applied to colitis induction in all study groups except for sham group. Animals were treated by oral administration of dexamethasone or amitriptyline. While macroscopic and microscopic lesions appeared after colitis induction treatment with dexamethasone and amitriptyline 10 and 20 mg/kg significantly improved lesions. Moreover, Toll-like receptor 4 (TLR4) and nuclear factor binding kappa light-chain (NF-ĸB expression), tumor necrosis factor-alpha (TNF-α) level, and myeloperoxidase (MPO) activity were increased after colitis induction, whereas treatment with dexamethasone (2 mg/kg) or amitriptyline (10 and 20 mg/kg) caused a noticeable decrease in the TLR4 and pNF-ĸB expression, TNF-α level, and MPO activity. In conclusion, amitriptyline plays an anti-inflammatory role through the suppression of TLR4/pNF-ĸB signaling pathway in the rat model of acute colitis., (© 2020 Société Française de Pharmacologie et de Thérapeutique.)

Status epilepticus (SE) is a life-threatening neurologic disorder that can be as both cause and consequence of neuroinflammation. In addition to previous reports on anti-inflammatory property of the anti-migraine medication sumatriptan, we have recently shown its anticonvulsive effects on pentylenetetrazole-induced seizure in mice. In the present study, we investigated further (i) the effects of sumatriptan in the lithium-pilocarpine SE model in rats, and (ii) the possible involvement of nitric oxide (NO), 5-hydroxytryptamin 1B/1D (5-HT 1B/1D ) receptor, and inflammatory pathways in such effects of sumatriptan. Status epilepticus was induced by lithium chloride (127 mg/kg, i.p) and pilocarpine (60 mg/kg, i.p.) in Wistar rats. While SE induction increased SE scores and mortality rate, sumatriptan (0.001-1 mg/kg, i.p.) improved it (P < 0.001). Administration of the selective 5-HT 1B/1D antagonist GR-127935 (0.01 mg/kg, i.p.) reversed the anticonvulsive effects of sumatriptan (0.01 mg/kg, i.p.). Although both tumor necrosis factor-α (TNF-α) and NO levels were markedly elevated in the rats' brain tissues post-SE induction, pre-treatment with sumatriptan significantly reduced both TNF-α (P < 0.05) and NO (P < 0.001) levels. Combined GR-127935 and sumatriptan treatment inhibited these anti-inflammatory effects of sumatriptan, whereas combined non-specific NOS (L-NAME) or selective neuronal NOS (7-nitroindazole) inhibitors and sumatriptan further reduced NO levels. In conclusion, sumatriptan exerted a protective effect against the clinical manifestations and mortality rate of SE in rats which is possibly through targeting 5-HT 1B/1D receptors, neuroinflammation, and nitrergic transmission., (© 2020 Société Française de Pharmacologie et de Thérapeutique.)