Student Research Committee, Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Inflammopharmacology. 2022 Feb;30(1):313-325. doi: 10.1007/s10787-021-00907-7. Epub 2022 Jan 10.
Irritable bowel syndrome (IBS) is a functional gut disorder with multi-factorial pathophysiology that causes recurring pain or discomfort in the abdomen, as well as altered bowel habits. Montelukast, a well-known cysteinyl leukotriene receptor 1 (CysLT1R) antagonist, is widely used for the anti-inflammatory management of asthma. The present study aimed to evaluate the effects of pharmacological inhibition of CysLT1R on acetic acid-induced diarrhea-predominant IBS (D-IBS) in rats. Behavioral pain responses to noxious mechanical stimulation were decreased in the montelukast-treated rats as compared to the model animals following colorectal distension (CRD)-induced visceral hypersensitivity. Stool frequency decreased dose-dependently by montelukast in IBS rats exposed to restraint stress. A significantly shorter immobility time was also observed in IBS rats who received montelukast vs IBS group in the forced swimming test (depression-like behavior). Furthermore, there were significant decreases in the NF-κB protein expression, inflammatory cytokine (TNF-α, and IL-1ß) levels, and histopathological inflammatory injuries concomitant with increased anti-inflammatory cytokine, IL-10, in montelukast-treated rats compared with the IBS group. Cysteinyl leukotriene production and CysLT1R mRNA expression showed no remarkable differences among the experimental groups. The present results suggest the possible beneficial effects of montelukast in the management of D-IBS symptoms. The molecular mechanism underlying such effects, at least to some extent, might be through modulating CysLT1R-mediated NF-κB signaling. Yet, more studies are required to demonstrate the clinical potential of this drug for IBS therapy.
肠易激综合征（IBS）是一种具有多因素病理生理学的功能性肠道疾病，可导致腹部反复疼痛或不适，以及肠道习惯改变。孟鲁司特是一种众所周知的半胱氨酰白三烯受体 1（CysLT1R）拮抗剂，广泛用于哮喘的抗炎管理。本研究旨在评估 CysLT1R 药理学抑制对乙酸诱导的腹泻为主的肠易激综合征（D-IBS）大鼠的影响。与模型动物相比，经孟鲁司特治疗的大鼠在结直肠扩张（CRD）引起内脏高敏性后，对有害机械刺激的行为疼痛反应降低。孟鲁司特在暴露于束缚应激的 IBS 大鼠中剂量依赖性地降低粪便频率。在强迫游泳试验（抑郁样行为）中，接受孟鲁司特的 IBS 大鼠的不动时间也明显缩短。此外，与 IBS 组相比，孟鲁司特治疗的大鼠 NF-κB 蛋白表达、炎症细胞因子（TNF-α和 IL-1β）水平和组织病理学炎症损伤显著降低，抗炎细胞因子 IL-10 增加。半胱氨酰白三烯产生和 CysLT1R mRNA 表达在实验组之间没有明显差异。这些结果表明孟鲁司特在 D-IBS 症状管理中的可能有益作用。这种作用的分子机制至少在一定程度上可能是通过调节 CysLT1R 介导的 NF-κB 信号。然而，需要更多的研究来证明这种药物治疗 IBS 的临床潜力。
