Biochemical and histopathological evidence for the beneficial effects of modafinil on the rat model of inflammatory bowel disease: involvement of nitric oxide pathway.

Abstract

Inflammatory bowel disease is an intestinal disorder presented by recurrent inflammation in the gastrointestinal tract. It has been reported that modafinil, also known as an awakening drug, has anti-inflammatory characteristics. The objective of this experiment is to investigate the protective effects of modafinil on colitis induced by acetic acid in rat and the involvement of nitric oxide pathway. Colitis was induced by intra-rectal instillation of 1ml acetic acid (4%). After one h of colitis induction (first day), intraperitoneal injection of dexamethasone (1mg/kg), modafinil (50, 100, and 150mg/kg), nitric oxide synthase inhibitors (NOS)-N (G)-nitro-L-arginine methyl ester (L-NAME) 10mg/kg, 7-nitroindazole 40mg/kg, and aminoguanidine 50mg/kg-was performed and continued for 2 consecutive days. Ultimately, macroscopic, microscopic, and biochemical assessments were performed. While induction of colitis caused severe macroscopic lesions, administration of dexamethasone and modafinil (100 and 150mg/kg) significantly improved macroscopic ulcers. Interestingly, the combination of modafinil with NOS inhibitors reversed the beneficial effects of modafinil on macroscopic destructions. In addition, the elevated level of interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) was decreased by modafinil. However, treatment with NOS inhibitors before modafinil neutralized the anti-inflammatory influence of modafinil. Additionally, histological disorders emerged by acetic acid in colon tissue remarkably were disappeared after treatment with modafinil. In conclusion, modafinil has a protective effect on injuries induced by acetic acid in the colon of rat, which is presumably via the inhibition of inflammatory cascade and mediation of NO pathway.