Simvastatin abolishes nitric oxide- and reactive oxygen species-induced cyclooxygenase-2 expression by blocking the nuclear factor κB pathway in rabbit articular chondrocytes.

Nitric oxide (NO) and reactive oxygen species (ROS) have been shown to be linked with numerous diseases, including osteoarthritis (OA). Our study aimed to examine the effect of simvastatin on NO- or ROS-induced cyclooxygenase-2 (COX-2) expression in OA. Simvastatin has attracted considerable attention since the discovery of its pharmacological effects on different pathogenic processes, including inflammation. Here, we report that simvastatin treatment blocked sodium nitroprusside (SNP)- and interleukin 1 beta (IL-1β)-induced COX-2 production. In addition, simvastatin attenuated SNP-induced NO production and IL-1β-induced ROS generation. Treatment with simvastatin prevented SNP- and IL-1β-induced nuclear factor kappa B (NF-κB) activity. Inhibiting NO production and ROS generation using N-acetylcysteine (NAC) and NG-monomethyl- l-arginine ( l-NMMA), respectively, accelerated the influence of simvastatin on NF-κB activity. In addition, NAC blocked SNP and simvastatin-mediated COX-2 production and NF-κB activity but did not alter IL-1β and simvastatin-mediated COX-2 expression. l-NMMA treatment also abolished IL-1β-mediated COX-2 expression and NF-κB activation, whereas SNP and simvastatin-mediated COX-2 expression were not altered compared with the levels in the SNP and simvastatin-treated cells. Our findings suggested that simvastatin blocks COX-2 expression by inhibiting SNP-induced NO production and IL-1β-induced ROS generation by blocking the NF-κB pathway.