Effects of sildenafil on rat irritable bowel syndrome

Abstract

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.

Black Tea Extract and its Thearubigins Relieve the Sildenafil‐Induced Delayed Gut Motility in Mice: A Possible Role of Nitric Oxide

“…In a rat model of irritable bowel syndrome, SLD (0.5, 1, and 5 mg/kg) given by gavage dose‐dependently reduced GE and SIT because of increasing concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) (Zamani et al ., ). In fasting rats, intravenous SLD (4 mg/kg) delayed GI transit of a radioactive liquid test meal injected directly into the duodenum 10 min earlier (Graça et al ., ).…”

Molecular evidences on the benefit of N-acetylcysteine in experimental colitis

“…Our lab studies have shown reliability of the experimental model of colitis in mouse and rat in terms of both biochemical and pathological changes [8][9][10]11,25].…”

Preliminary Biochemical Description of Brain Oxidative Stress Status in Irritable Bowel Syndrome Contention-Stress Rat Model

“…Several previous studies implicate oxidative stress and inflammatory features in the etiology of IBS [12][13][14][15]. However, the oxidative stress role in IBS was not fully understood due to the many implications that the other components of IBS could have on the yet nonspecific oxidative changes.…”