The therapeutic effects of edaravone on collagen‐induced arthritis in rats

Abstract

Current research suggests that synovial phagocytic cells remove excessive amounts of free oxygen radicals (reactive oxygen species [ROS]), thereby preventing damage to synovial tissues. Moreover, ROS may affect the expression of growth arrest and DNA damage inducible α (GADD45A), thus further promoting the activation of synovial fibroblasts. Male adult rats were assessed for progression of collagen‐induced arthritis (CIA) using a macroscopic arthritis scoring system of the hind paws and by measuring the changes in the rat s body weight, and activity level before and after diagnosis of CIA. Rats were intraperitoneally injected twice daily with edaravone at doses of 3, 6, and 9\u2009mL/kg. Samples were taken at 2, 4, and 6 weeks, respectively. Edaravone was found to significantly reduce macroscopic arthritis and microscopic pathology scores in CIA rats. The concentration of endothelial nitric oxide synthase‐6, glutathione, and heme oxygenase‐1 in the serum of rats decreased, as was the production of ROS around the synovium and inflammatory factors. Moreover, ROS‐1 increased the expression of the nuclear factor‐κB (NF‐κB) p65 protein by altering the expression level of GADD45A, causing aggravation of tissue damage. Edaravone also significantly improved the physiological condition of CIA rats, including appetite, weight changes, and loss of fur, as well as limb mobility. We believe that edaravone acts to reduce the expression of NF‐ĸB p65 by clearing ROS, which causes reduced expression of GADD45A, and subsequently reduces the level of apoptosis and inflammatory response proteins, thereby reducing the symptoms of CIA. We, therefore, propose that edaravone is an effective option for clinical treatment of rheumatic arthritis.