Effects of sildenafil on rat irritable bowel syndrome

Mohammad Jafar Zamani, Mohammad Sharifzadeh, Ali Rezaie, Fereshteh Mashayekhi and Mohammad Abdollahi

Background: Irritable bowel syndrome (IBS) is a disorder with unknown pathophysiology, although it would appear that stress of different types plays an important role in the onset and development of the disorder. It affects 10–15% of the general population. Currently, anticholinergics and prokinetics are the main therapies. Objective: The objective of this study was to examine the effects of sildenafil in an animal model of IBS. Methods: IBS was induced in rats using the wrap-restraint method and sildenafil was administered intragastrically by gavage at doses of 0.5, 1 and 5 mg/kg. Gastric emptying, small bowel transit and fecal excretion (index of large intestine motility) as well as concentrations of cyclic nucleotides (cGMP and cAMP) and total antioxidant capacity in the large intestine were determined. Results: Sildenafil at all doses used (0.5, 1 and 5 mg/kg) significantly reduced gastric emptying up to 120 min postdrug administration. All doses (0.5, 1 and 5 mg/kg) of sildenafil dose-dependently reduced small bowel transit up to 60 and 90 min after sildenafil administration. Treatment of rats using sildenafil (0.5, 1 and 5 mg/kg) increased the concentration of cAMP 40 min post administration. At 90 min postdrug administration, only sildenafil (5 mg/kg) increased cAMP concentration. At 40 min postdrug administration, sildenafil (1 and 5 mg/kg) and at 90 min, all doses of sildenafil increased the concentration of cGMP. Sildenafil (5 mg/kg) increased total antioxidant capacity and reduced fecal excrements in IBS rats. Conclusion: Sildenafil administration appears to have beneficial effects in the treatment of IBS in rats, which is in relation with the drugs potential to increase bowel total antioxidant capacity and cyclic nucleotides.