Comparative Study between Effect of Simvastatin (5 mg/Kg) and Simvastatin (50 mg/Kg) in an Early Treatment of Experimentally Induced Colitis in Mice

Abstract

Inflammatory bowel disease (IBD) (ulcerative colitis and Crohn's disease) is a chronic intestinal inflammatory disease characterized by tissue edema, increased gut epithelial permeability, and extensive infiltration of the gut by leukocytes. Statins, in addition to their cholesterol-lowering activity, have pleiotropic effects, including immune-modulatory and anti-inflammatory effects. Simvastatin is a commonly prescribed statins with antioxidant and anti-inflammatory properties Thus; the aim of this study is to compare effect of simvastatin (5 mg/kg) and simvastatin (50 mg/kg) as an early treatment of experimentally induced ulcerative colitis in mice. For the first time in the current study, Simvastatin was administered after the appearance of signs and symptoms of the disease as an early treatment model. Twenty four mice were divided into four groups; control group, non treated DSS-induced colitis group, simvastatin (5 mg/kg/d) -treated DSS-induced colitis group, simvastatin (50 mg/kg/d) -treated DSS-induced colitis group. simvastatin at dose of (5 mg/kg/d) reduced MDA and TNF-α .While simvastatin at dose of (50 mg/kg/d ) showed a significant increase in colon length of mice,a significant decrease in NO and MDA levels and a significant increase in r GSH level. Simvastatin (5 mg/kg/d) and (50 mg/kg/d) reduced the percentage of DAI by 25% and 41% respectively. The sums of histopathological scores were improved after simvastatin treatment. It can be concluded that effects of simvastatin treatment was mostly dose dependant. Unfortunately the high dose has no clinical application in human due to toxicity. So it is advised to use simvastatin with a dose of 5mg/kg as an early treatment of dss induced colitis model.