Interferon gamma/interleukin-4 modulation, anti-inflammatory and antioxidant effects of hesperidin in complete Freund’s adjuvant (CFA)-induced arthritis model of rats

Abstract

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 (220–250 g) were acclimatized for two weeks. Intraplantar injection of CFA was done for the induction of arthritis and confirmed on the 14th 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 < .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 < .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 < .05) reduced serum interferon gamma (IFN-γ) and interleukin-4 (IL-4) levels in arthritic rat. In addition, treatment with hesperidin significantly (p < .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 < .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
• hesperidin
• paw swelling
• arthritic score
• cytokines

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors are highly grateful to the World Academy of Science (TWAS), Italy, Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil [Grant number: 190134/2014-3] and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil [Process Number: 88887.357232/2019-00].