Fraxetin with Low Dose Methotrexate Ameliorates Pristane-Induced Arthritis in Rats: Histological and Immunohistochemical Study
Background and Objective: Pristane-Induced Arthritis (PIA) is a model of rheumatoid arthritis with a chronic relapsing course. Fraxetin (FXT) is a natural coumarin with antioxidant, anti-inflammatory and antifibrotic properties. This research evaluated the ameliorating effect of fraxetin with low dose Methotrexate (MTX) of PIA in rats. Materials and Methods: The 80 (100-200 g) Lewis female rats (8-10 weeks) divided into eight groups (10 rats each), group 1 (control), group 2 (vehicle): Rats received 0.5% CMC (carboxymethyl cellulose), group 3 (Pristane-induced arthritis (PIA)): Rats received an intradermal injection of 150 μL pristane oil, group 4 (PIA+MTX LD): PIA rats received low dose MTX (1 mg/kg/day) orally, group 5 (PIA+FXT LD): PIA rats received low dose fraxetin (25 mg/kg/day) orally, group 6 (PIA+FXT HD): PIA rats received high dose of fraxetin (50 mg/kg/day) orally, group 7 (PIA+FXT LD+MTX LD): PIA rats received low dose fraxetin plus low dose MTX and group 8 (PIA+FXT HD+MTX LD): PIA rats received high dose fraxetin plus low dose MTX orally. Treatments started from day 4 after PIA injection till the end of week 8. Knee joint specimens were processed for histopathology and immunohistochemistry. Results: Group 3 showed significantly increased total and differential leukocyte count, articular erosions, synovial inflammatory infiltrations, significantly reduced articular cartilage width, significantly decreased periodic acid-Schiff, significantly increased mean collagen area percent, significantly increased TGF-β1(anti-transforming growth factor-β1) stained synovial fibroblasts. The PIA groups treated with MTX and FXT exhibited a dose-dependent reduction of the previous findings. Conclusion: FXT dose-dependent with low dose MTX ameliorates PIA in rats.
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