Intra-articular injection of an antioxidant formulation did not improve structural degeneration in a rat model of post-traumatic osteoarthritis

Summary Background/objective Oxidative stress plays an important role in osteoarthritis (OA), causing inflammation and matrix degradation in joints. Previous studies have shown that antioxidants such as quercetin and vitamin C are potential candidates for treating OA. We aimed to determine whether a formulation of quercetin and vitamin C, together with an iron chelator, could retard OA progression in a post-traumatic OA rat model. Methods Twelve rats received anterior cruciate ligament transection for OA induction. At 20 weeks postoperation, weekly intra-articular injection of 50 μL of either saline or a formulation of quercetin dehydrate, sodium-L-ascorbate, and deferoxamine mesylate was given consecutively for 4 weeks ( n  = 5). Gait analysis was performed at pretreatment, and at 1 week and 5 weeks post-treatment. Microcomputed tomography scanning and histological scoring were performed at 5 weeks post-treatment. Results Gait analysis showed that intra-articular injections of antioxidant formulation did not improve pain-associated Limb Idleness Index over time ( p  = 0.449, Friedman test). However, at 5 weeks post-treatment, the treatment group exhibited a significantly lower Limb Idleness Index than the control group ( p  = 0.047, Mann–Whitney U test). At 5 weeks post-treatment, microcomputed tomography analysis revealed that there was no difference in any parameter between the treatment and control groups ( p  > 0.05, Student t test). Severe OA histopathological changes were found in both groups. The Osteoarthritis Research Society International scores of the treatment and control groups were 20 (range, 20–26) and 20 (range, 9–26), respectively ( p  = 0.382, Mann–Whitney U test). Conclusion Intra-articular injection of an antioxidant formulation containing quercetin, vitamin C, and deferoxamine did not retard OA progression in advanced-stage OA. Future studies should aim to determine whether giving antioxidants in early OA, with prolonged drug retention, would be effective in retarding OA progression.