Dejban, Pegah

AbstractThe current study was aimed to investigate the beneficial effect of sumatriptan, a 5‐hydroxytryptamine 1B/1D (5HT1B/1D) receptor agonist, on gastric ulcer in rats via stimulating 5HT1B/1D receptors and suppressing pro‐inflammatory cytokines. Rats were allocated into three models of gastric ulcer: indomethacin (30 mg/kg, PO), water immersion restraint stress (WRS) and ethanol (5 ml/kg PO). Animals were administered with sumatriptan (0.01, 0.1, 0.3 and 1 mg/kg, i.p) 30 min before gastric ulcer induction. GR‐127935 (0.01 mg/kg, i.p, a selective 5HT1B/1D antagonist) was administered 30 min before sumatriptan (0.1 mg/kg) injection. Macroscopic assessments (J‐score), ELISA analysis of tumour necrosis factor‐alpha (TNF‐α) and interleukin‐1beta (IL‐1β) and histopathological changes were performed on the rat's stomach tissues. Gastric ulcer induction in three models caused an increase in J‐score, TNF‐α, IL‐1β and microscopic features. Sumatriptan (0.1 mg/kg) significantly improved gastric injury induced by indomethacin, WRS and ethanol through the reduction in the J‐score, TNF‐α, IL‐1β and microscopic lesions. Concurrent administration of GR‐127935 (0.01 mg/kg) with sumatriptan (0.1 mg/kg) reversed the gastroprotective effect of sumatriptan in three models. Sumatriptan possessed gastroprotective effects on indomethacin‐, WRS‐ and ethanol‐induced gastric damage in rats via the possible involvement of the 5HT1B/1D receptors.

Background and objectives Urinary stone disease has been associated with inflammation, but the specific cell interactions that mediate events remain poorly defined. This study compared calcification and inflammatory cell patterns in kidney tissue from radical nephrectomy specimens of patients without and with a history of urinary stone disease. Design, setting, participants, & measurements Nontumor parenchyma of biobanked radical nephrectomy specimens from age- and sex-matched stone formers ( n =44) and nonstone formers ( n =82) were compared. Calcification was detected by Yasue staining and inflammatory cell populations by immunohistochemistry for CD68 (proinflammatory M1 macrophages), CD163 and CD206 (anti-inflammatory M2 macrophages), CD3 (T lymphocytes), and tryptase (mast cells). Calcifications and inflammatory cells were quantified in cortex and medulla using Image-Pro analysis software. Results Calcification in the medulla of stone formers was higher than in nonstone formers ( P <0.001). M1 macrophages in the cortex and medulla of stone formers were greater than in nonstone formers ( P <0.001), and greater in stone former medulla than stone former cortex ( P =0.02). There were no differences in age, sex, body mass index, tumor characteristics (size, stage, or thrombus), vascular disease status, or eGFR between the groups. M2 macrophages, T lymphocytes, and mast cells did not differ by stone former status. There was a correlation between M1 macrophages and calcification in the medulla of stone formers (rho=0.48; P =0.001) and between M2 macrophages and calcification in the medulla of nonstone formers (rho=0.35; P =0.001). T lymphocytes were correlated with calcification in the cortex of both nonstone formers (rho=0.27; P =0.01) and stone formers (rho=0.42; P =0.004), whereas mast cells and calcification were correlated only in the cortex of stone formers (rho=0.35; P =0.02). Conclusions Higher medullary calcification stimulated accumulation of proinflammatory rather than anti-inflammatory macrophages in stone formers.

ABSTRACTInflammatory 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.

Inflammatory bowel disease (IBD) is a lifelong and recurrent disease of the gastrointestinal tract that afflicts many people in the world. Growing evidence has currently indicated that dysfunction of immune system, particularly toll‐like receptors 4 (TLR4) signaling pathway dysfunction plays a pivotal part in the pathogenesis of IBD. TLR4 signaling is involved both in the pathogenesis and in the efficacy of treatment of IBD. There are some medicinal products and herbal medicines, which their role in the treatment of IBD through modulation of TLR4 signaling has been implicated. The purpose of this review article is to summarize those medicinal products and herbal medicines.