Comparing the Efficacy of Carvedilol and Celecoxib to Prednisolone in Acetic Acid-Induced Ulcerative Colitis in Male Albino Rats

Ulcerative colitis refers to destruction of mucosal layer of distal colon and rectum. Exact mechanism for pathophysiology is still unclear but inflammation and oxidative stress may play a caustic role. Neutrophil and monocyte infiltration results in free radical generation which damages intestinal mucosa. Many treatments as steroids are used to reduce inflammation but cannot cause remission. Carvedilol is a third-generation nonselective β-blocker which possesses anti-oxidant, anti-inflammatory properties and can reduce gastric ulceration. Celecoxib is a selective cyclooxygenase -2 (COX-2) inhibitor which decrease risk of gastrointestinal bleeding. The current study was designed to compare the efficacy of carvedilol and celecoxib to prednisolone in acetic acid-induced ulcerative colitis model. A total of 40 adult male albino rats were randomly divided into five groups: Control group: Rats received 2 ml of saline transrectal. Acetic acid (AA) group: Rats were transrectal injected with 2ml acetic acid. Prednisolone +AA group: Rats were pre-treated with prednisolone in a dose 4mg/kg /day. Carvedilol +AA group: Rats were pre-treated with carvedilol in a dose 30 mg/kg/day. Celecoxib +AA group: Rats were pre-treated with celecoxib in a dose 5mg/kg/day. All drugs were given orally for 7 days. At end of experiment, distal colon was removed, one part of specimen was preserved in 10% formalin for histological examination and other part was homogenized for evaluation of tumor necrosis factor alpha (TNF-α), reduced glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO) and mitogen-activated protein kinase ( p38 MAPK). Data of present study revealed that treatment of rats with carvedilol or celecoxib before induction of colitis significantly reduced levels of TNF-α, MDA, NO and mRNA level of p38 MAPK while both drugs increased GSH level. Protective effects of Carvedilol and celecoxib are due to anti-inflammatory, anti-oxidant effects and ability to decrease synthesis of MAPK which reduce cytokines signaling in epithelial cells of gut mucosa.