Effect of simvastatin on evolution of experimental autoimmune encephalomyelitis in C57BL/6 mice

ABSTRACT

Simvastatin is an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme a reductase and widely used as cholesterol-lowering agent. It is a promising candidate for future treatment in multiple sclerosis [MS], as it has been shown to exhibit immunomodulatory and anti-inflammatory effects. This study examined the effect of simvastatin on the evolution of experimental autoimmune encephalomyelitis [EAE], as an animal model for MS. EAE was induced by immunization of 8 week old C57BL/6 mice with MOG35-55 peptide with complete Freunds adjuvant. Therapy with simvastatin [1mg/kg/every day given as oral] was started on day 3 before the immunization until 25 day after immunization Total antioxidant capacity [TAC] was assessed by ferric reducing-antioxidant power [FRAP] method. Nitric oxide [NO] production was also estimated by Griess reaction. The results show that simvastatin-treated mice had significantly less incidence and clinical score of EAE than non-treated [control] EAE induced mice [p=0.001 and p=0.0001, respectively]. Moreover, treated mice displayed a significantly delayed disease onset compared with control mice. Simvastatin significantly increased TAC and level serum uric acid [p=0.001], but had no effect on serum nitrite production. Our results suggest that simvastatin therapy may be effective in the prevention of symptomatic EAE. This resistance to encephalomyelitis may be associated with the inhibition of oxidative stress and the increase of antioxidant capacity