Nitazoxanide alleviates CFA-induced rheumatoid arthritis in Wistar rats by modulating the STAT-3 and NF-κB pathways.

Background and objective: Rheumatoid arthritis (RA) is a chronic autoimmune condition characterized by joint pain and inflammation. RA involves elevated expression of nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), which drive synovial inflammation and joint destruction primarily through the STAT-3 signalling pathway. Nitazoxanide (NTZ) has been shown in previous studies to inhibit the signalling of STAT-3.

Methods: This study evaluated the anti-arthritic effects of NTZ in a rat model of complete Freund's adjuvant (CFA) induced arthritis. NTZ was administered orally at doses of 400, 200, and 100 mg/kg over 28 days. Various parameters, including changes in paw swelling, body weight, arthritic index, haematological measurements, levels of inflammatory cytokines, and histopathological analysis, were monitored.

Results: NTZ treatment significantly improved body weight and reduced paw swelling, edema, and the arthritic index in CFA-induced arthritic rats. The treatment also decreased white blood cell counts while increasing red blood cell and haemoglobin levels. NTZ effectively modulated inflammatory cytokine levels and showed improvement in the histopathology of the ankle joints.

Conclusion: NTZ exhibited significant anti-arthritic activity through the inhibition of the STAT-3 and NF-κB pathways, emphasizing its potential as a therapeutic option for rheumatoid arthritis.