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.