To study the effect and mechanism of dimethyl fumarate [DMF] in adjuvant induced arthritis model in rats

Currently available disease modifying anti-rheumatoid drugs have limitations like dose-dependent toxicity and tolerance.Dimethyl fumarate has demonstrated anti-inflammatory and immunomodulatory properties in various animal models. Thus, the present study aimed to evaluate the effects and mechanism of DMF in a murine model of adjuvant-induced arthritis. A total of 84 rats were divided into early treatment groups (n=48) and late treatment groups (n=36). There were 8 subgroups and 6 subgroups (n=6 in each group) in the early and late treatment groups, respectively. Experimental rheumatoid arthritis (RA) was induced in Wistar rats by injecting complete Freund's adjuvant (CFA) intradermally at the base of the tail. Anti-rheumatic effects were evaluated by arthritis and histopathological scoring of ankle joints. To evaluate anti-oxidant properties,GSH, catalase, SOD, and lipid peroxidation were measured. ESR, WBC count, TNF-α and IL-6 levels were measured to evaluate the immunomodulatory properties of DMF. DMF demonstrated anti-inflammatory effects by decreasing arthritis and histopathological scores compared to the CFA control group, though the difference was not statistically significant. DMF exhibited immunomodulatory properties as decreases in TLC count, serum TNF-α, and plasma IL-6 levels were observed. In all the above-mentioned parameters, the best response was achieved with the early combination therapy of DMF 30 mg/kg and methotrexate [Mtx] 0.1 mg/kg. In the present study, DMF demonstrated antirheumatoid effects in a rat model of CFA-induced arthritis. The best antirheumatoid effect was achieved with the early combination of DMF and Mtx.