The possible ameliorative effect of simvastatin versus sulfasalazine on acetic acid induced ulcerative colitis in adult rats

Objective: Inflammatory bowel diseases (IBD) are chronic and recurrent disorders of the gastrointestinal tract with unknown etiology and have two major forms, ulcerative colitis (UC) and Crohn diseases. In view of the adverse effects and incomplete efficacy of currently administered drugs, it is essential to investigate new and harmless drugs with more desirable beneficial effects. Statins have many additional pleiotropic effects other than their lipid-lowering effect. This study aims to investigate the role of simvastatin (SIM) at different doses against induced UC in rats. Methods: SIM (10, 20 mg/kg), and sulfasalazine as a standard therapy (100 mg/kg) were given from five days before and seven days after induction of UC by acetic acid (AA). Colonic mucosal inflammation was evaluated macroscopically and microscopically. Furthermore, the colonic tissue tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL 1B), nod-like receptor family pyrin domain-1 containing 3 (NLRP3), malondialdehyde (MDA), reduced glutathione (GSH) and super oxide dismutase (SOD) were assayed in addition to immunohistochemistry of caspase-1 and cyclooxygenase-2 (COX2). Results: SIM in a dose dependant manner significantly improved macroscopic and histological scores, diminished colonic levels of IL 1B, TNF-alpha, NLRP3, MDA, caspase-1 and COX2 and elevated GSH and SOD. Conclusion: SIM has anti-inflammatory, cytoprotective and antioxidants effects that are not directly related to its cholesterol lowering activity against AA induced colitis this makes it a new therapeutic target for UC.