Histopathological evaluation of docetaxel effects in treatment of rheumatoid arthritis induced in rat model

Abstract

Rheumatoid arthritis is an immune-mediated condition that affects synovial joints. Synovial tissue, cartilage, bone, and less frequently extra-articular structures which in turn experience inflammatory changes. Paclitaxel's semi-synthetic equivalent, docetaxel, is an anti-neoplastic drug. Methotrexate is a treatment for early RA and may have a mildly negative impact on peptidyl arginine deiminase type 4 fluorescence test. However, 30% of patients fail to complete treatment within the first year due to resistance or side effects. The synovial membrane of Rheumatoid arthritis patient infiltrated with macrophages and neutrophils that express peptidyl arginine deiminase type 4 which their effect in rheumatoid arthritis pathogenesis lies in the generation of citrullinated neoepitopes that are Anti cyclic citrullinated peptide antibodies-targeted. The purpose of this study: was to assess the anti-inflammatory effects of docetaxel and methotrexate on the joint structure. Methods: Five groups of eight rats were formed from the 40 male Wister rats. Complete Freund’s adjuvant was injected subcutaneously into rats to induce the disease. The first group is control group which was the only group consists of (healthy untreated) rats. Second group was received complete Freund’s adjuvant. 0.5ml of ordinary saline was intraperitoneally administered to both the control and induction groups. Based on a preliminary experiment, the third group was given intraperitoneally 1 mg/kg/on alternative day docetaxel. The fourth group was given intraperitoneally 1 mg/kg/week of Methotrexate. Fifth group was given a half dose of both Methotrexate and docetaxel concurrently. Arthritis index was measured and Knee joint was histopathological examined. Results: significant Arthritis Index decrease in docetaxel group (p≤0.05). Significant lowering Histometric scoring (p≤0.05) in docetaxel, and Methotrexate group (cellular hyperplasia, formation of granulation tissue, infiltration of leukocytes, destroying of cartilage and intensity of erosion & Articular cartilage thickness) level in rats induced arthritis. Conclusion:  This study showed that docetaxel may have anti-arthritic effects through their significant lowering Histometric scoring(p≤0.05).