Naringenin mitigates titanium dioxide (TiO 2 )-induced chronic arthritis in mice: role of oxidative stress, cytokines, and NFκB

Objective To evaluate the effect and mechanisms of naringenin in TiO 2 -induced chronic arthritis in mice, a model resembling prosthesis and implant inflammation. Treatment Flavonoids are antioxidant and anti-inflammatory molecules with important anti-inflammatory effect. Mice were daily treated with the flavonoid naringenin (16.7–150 mg/kg, orally) for 30 days starting 24 h after intra-articular knee injection of 3 mg of TiO 2 . Methods TiO 2 -induced arthritis resembles cases of aseptic inflammation induced by prosthesis and/or implants. Mice were stimulated with 3 mg of TiO 2 and after 24 h mice started to be treated with naringenin. The disease phenotype, treatment toxicity, histopathological damage, oxidative stress, cytokine expression and NFκB were evaluated after 30 days of treatment. Results Naringenin inhibited TiO 2 -induced mechanical hyperalgesia (96%), edema (77%) and leukocyte recruitment (74%) without inducing toxicity. Naringenin inhibited histopathological index (HE, 49%), cartilage damage (Toluidine blue tibial staining 49%, and proteoglycan 98%), and bone resorption (TRAP-stained 73%). These effects were accompanied by inhibition of oxidative stress (gp91 phox 93%, NBT 83%, and TBARS 41%) cytokine mRNA expression (IL-33 82%, TNFα 76%, pro-IL-1β 100%, and IL-6 61%), and NFκB activation (100%). Conclusion Naringenin ameliorates TiO 2 -induced chronic arthritis inducing analgesic and anti-inflammatory responses with improvement in the histopathological index, cartilage damage, and bone resorption.