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Montelukast suppresses the development of irritable bowel syndrome phenotype possibly through modulating NF-κB signaling in an experimental model

Montelukast suppresses the development of irritable bowel syndrome phenotype possibly through... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Inflammopharmacology Springer Journals

Montelukast suppresses the development of irritable bowel syndrome phenotype possibly through modulating NF-κB signaling in an experimental model

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References (61)

Publisher
Springer Journals
Copyright
Copyright © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022
ISSN
0925-4692
eISSN
1568-5608
DOI
10.1007/s10787-021-00907-7
Publisher site
See Article on Publisher Site

Abstract

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.

Journal

InflammopharmacologySpringer Journals

Published: Feb 1, 2022

Keywords: Irritable bowel syndrome; Montelukast; Acetic acid; Visceral hypersensitivity; Inflammation; Rats

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