Interferon gamma/Interleukin-4 Modulation, Anti-inflammatory and Antioxidant Effects of Hesperidin in Complete Freund's Adjuvant (CFA)-Induced Arthritis Model of Rats

Background: This study sought to assess the effect of hesperidin on serum inflammatory cytokines and oxidative damage in liver of complete Freund's adjuvant (CFA)-induced arthritic rats.Method: Fifty-six adult female Wistar rats (220 - 250g) were acclimatized for two weeks. Intraplantar injection of CFA was done for the induction of arthritis and confirmed on the 14^th day prior to oral administration of 40 and 80 mg/kg of hesperidin or dexamethasone for 45 days.Result: The result showed that treatment with both doses of hesperidin and dexamethasone in the joint of arthritic rats significantly (p < 0.05) diminished paw swelling/edema and arthritis score as well as enhanced latency in thermal hyperalgesia test. In addition, hesperidin treatment in arthritis rats showed significant (p < 0.01) improvement in red blood cells and platelets counts as well as hemoglobin and hematocrit compared to the arthritis control rat group. Furthermore, hesperidin treatment significantly (p < 0.05) reduced serum interferon gamma (IFN-γ) and interleukin-4 (IL-4) levels in arthritic rat. In addition, treatment with hesperidin significantly (p < 0.05) decreased the liver of thiobarbituric acid reactive species and reactive oxygen species levels but raised the levels of total and non-protein thiols of rat induced with CFA. The reduced activities of liver δ-aminolevulinate dehydratase, catalase, glutathione-S transferase in arthritic rats were significantly (p < 0.05) increased with hesperidin treatment in arthritic rats. This study suggests that hesperidin demonstrated an anti-arthritic effect via modulation of serum IFN-γ and IL-4 levels as well as protection against oxidative damage.Conclusion: Hence, hesperidin could be a potential immune-modulatory, anti-inflammatory and anti-oxidant agent.

Keywords: Rheumatoid arthritis; arthritic score; cytokines; hesperidin; paw swelling.