Immunosuppressive, Anti-Inflammatory, and Antioxidant Effects of Simvastatin on Pristane Induced Arthritis

The current therapeutic approaches to the autoimmune disease rheumatoid arthritis depend mainly on synthetic anti-arthritis compounds that usually cause many adverse effects. The anti-arthritic effect of the hypocholesterolemic drug simvastatin (Sim) has been confirmed, however, its actual mechanism of action has not been investigated yet. Therefore, this study aimed to unveil the biochemical and molecular changes that accompany the application of Sim as anti-arthritic in a mouse model of pristane-induced arthritis. Female Swiss albino mice (20-30g) were randomly divided into 5 groups (n= 10/group): control, Sim control, pristane-induced arthritis, Sim co-treated, and Sim post-treated group. Sim treatment significantly 1) downregulated the expression of immunomodulatory genes [interferon gamma (IFN gamma) and lactoferrin (LF)], 2) decreased the expression of inflammation-related genes [tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL1 beta)], 3) declined the expression of matrix metalloproteinase-3 (MMP3), transforming growth factor beta (TGF beta), and oxidized-LDL receptor (OLR1), 4) upregulated the expression of the anti-inflammatory gene IL10, 5) reduced the levels of the oxidative markers [lipid peroxide marker malondialdehyde (MDA) and nitric oxide (NO)], 6) increased the levels of antioxidant markers [reduced glutathione (GSH) and superoxide dismutase (SOD)]. These findings conclude that administration of Sim relieved pristane-induced arthritis, with best improvement in the Sim co-treated (prevention) group. Thus, Sim could be used as a protective drug against rheumatoid arthritis based on its immunomodulatory, anti-inflammatory, and antioxidant effects.