Thesis & Dissertations

Methotrexate -the first line of treatment - for rheumatoid arthritis (RA) exhibits deleterious adverse effects (hepatotoxicity) when used for prolonged time. Therefore, using treatments of natural origin as complementary therapy to treat and alleviate the symptoms of such incurable disease is considered a safer alternative. This study aimed to investigate the anti-inflammatory and anti-arthritic effects of indole-3-carbinol and silibinin in comparison with methotrexate in an experimental model of arthritis. The study also investigated the possible hepatoprotective effects of indole-3-carbinol and silibinin against hepatotoxicity induced by arthritis and methotrexate treatment. Arthritic rats were treated with silibinin (100 mg/kg), indole-3-carbinol (100 mg/kg) and/or methotrexate (2mg/kg). Indole-3-carbinol and silibinin alleviated the systemic consequences of arthritis by restoring the weight loss. Inflammatory mediators and markers including pro-inflammatory cytokines (TNF-α and IL-6), erythrocyte sedimentation rate and spleen index (I3C alone) were significantly decreased upon treatment with silibinin and indole-3-carbinol compared to arthritic non-treated rats. The treatments also ameliorated the damage exerted on the joint which was evident macroscopically (macroscopic scoring) and microscopically (synovial hyperplasia, cellular infiltration, pannus formation, cartilage erosion). In addition, indole-3-carbinol and silibinin showed promising results in alleviating the liver injury induced by arthritis by decreasing ALT and AST levels. In conclusion, our results suggest that both indole-3-carbinol and silibinin act as potent anti-inflammatory and anti-arthritic agents by decreasing the levels of the inflammatory mediators thereby alleviating the damage exerted on the joints and the systemic consequences triggered by arthritis.