ABSTRACT
Leflunomide and methotrexate have proven to be efficacious in reducing joint inflammation and joint destruction in clinical models of arthritis and in rheumatoid arthritis. The objective of this study was to evaluate the effects of both drugs as well as their combination therapy on the synovium and cartilage of adjuvant arthritis as a model of rheumatoid arthritis [RA] in humans. This study was carried out on forty animals stratified into 5 groups: normal, adjuvant arthritis [AA] control, AA who received leflunomide in a dose of 20 mg/kg orally, AA who received intraperitoneal methotrexate in a dose of 0.3 mg/kg twice weekly and AA who received both leflunomide and methotrexate of the same dose given in groups 3 and 4. All animals were sacrificed after 3 weeks; the right knee was dissected and examined with light microscopy. Oxidants markers [nitric oxide [NO] and malondialdhyde [MAD]] and antioxidants markers [glutathione [GSH], erythrocyte superoxide dismutase [SOD] and ceruloplasmin [CP]] were all measured. All the treatment modalities showed variable degrees of improvement of synovial and cartilage scoring in comparison to AA [the non-treated group]. The leflunomide treated group [group 3] showed the best improvement of synovial pathology, while the combined therapy group [group 5] showed the best improvement of cartilage pathology. The oxidative stress markers showed some changes with different modalities of treatment where, nitric oxide did not change significantly between all groups. Malondialdhyde [MAD] was significantly lower in the methotrexate [MTX] treated group as compared to AA controls. Also, superoxide dismutase [SOD] was significantly lower in the leflunomide treated group, MTX treated group as well as in the group who received combined therapy as compared to AA the controls. Glutathione [GSH] level was significantly decreased with combination therapy as compared to the leflunomide treated group. Serum ceruloplasmin [CP] showed a significant decrease in its level in the MTX treated group as compared to the AA controls. MTX treatment [group 4] was the best in controlling oxidative stress markers. Further study is needed to evaluate the duration and dose effect of each drug on synovium, cartilage and oxidative markers