Efficacy of a novel 3-hydroxypyridine derivative in the stabilization of free radical oxidation in post-traumatic osteoarthritis: A randomized preclinical study
Year: 2026
Type: article
Abstract: Background. While diverse conservative options exist, the prevalence of post-traumatic osteoarthritis remains high. This fact necessitates the search for novel multitarget pathogenetic agents to prevent disease progression and irreversible joint tissue degeneration resulting from delayed treatment. Objective. To evaluate the effect of a novel 3-hydroxypyridine derivative (2-ethyl-6-methyl-3-hydroxypyridinium 4-isobutylphenylpropanoate) on free radical oxidation and antioxidant status in an experimental model of post-traumatic osteoarthritis. Methods. A randomized preclinical study was conducted on 55 outbred white male rats weighing 190–220 g. The rats were divided into five groups: intact animals (Group 1; n = 15) and four groups with induced knee joint injury (Groups 2–5; n = 10 each). Group 2 remained untreated, while Groups 3, 4, and 5 received pharmacotherapy with ibuprofen (6.35 mg/kg), ethylmethylhydroxypyridine succinate (45.58 mg/kg), and 2-ethyl-6-methyl-3-hydroxypyridinium 4-isobutylphenylpropanoate (11.65 mg/kg), respectively. Free radical oxidation and antioxidant status were evaluated in plasma and erythrocytes based on biochemiluminescence data, concentrations of primary and secondary lipid peroxidation products, and antioxidant enzyme activity. Statistical analysis of the obtained data was conducted via one-way analysis of variance followed by Tukey’s post hoc test. Calculations were performed using the SPSS Statistics 20.0 software (IBM, USA). Differences were considered statistically significant at p < 0.05. Results. The compound 2-ethyl-6-methyl-3-hydroxypyridinium 4-isobutylphenylpropanoate demonstrated the highest efficacy compared to both ethylmethylhydroxypyridine succinate and ibuprofen. The pronounced antioxidant effect of this novel 3-hydroxypyridine derivative was characterized by the stabilization of free radical oxidation by the end of the experiment, with the evaluated parameters approaching reference values. Specifically, compared to the ibuprofen-treated group, the conjugated diene level was 45% lower ( p 2 < 0.001). Similarly, in plasma and erythrocyte samples undergoing spontaneous oxidation, malondialdehyde levels were lower by 35% and 24%, respectively ( p 2 < 0.001). The conjugated diene level in the ethylmethylhydroxypyridine succinate group exceeded that of the novel compound group by 20% ( p 3 < 0.001), while plasma and erythrocyte malondialdehyde levels were higher by 7% ( p 3 = 0.048) and 9% ( p 3 = 0.041), respectively. Furthermore, an increased antioxidant activity was observed in Group 5. The plasma superoxide dismutase activity was 86% greater than in the ibuprofen-treated group ( p 2 < 0.001) and surpassed the group treated with ethylmethylhydroxypyridine succinate by 37% ( p 3 < 0.001). The total chemiluminescence produced was 32% higher than in the ibuprofen-treated group ( p 2 < 0.001) and 12% greater than in the ethylmethylhydroxypyridine succinate group ( p 3 = 0.028), indicating an enhanced antioxidant potential. Conclusion. The novel compound 2-ethyl-6-methyl-3-hydroxypyridinium 4-isobutylphenylpropanoate effectively inhibits lipid peroxidation and restores antioxidant enzyme activity. Its administration mitigates free-radical damage to joint tissues and accelerates the restoration of antioxidant potential, both by enhancing the activity of key enzymes and directly lowering free-radical levels. These findings indicate its high predicted efficacy as a pathogenetic agent in the comprehensive management of post-traumatic osteoarthritis.
Language: Russian
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7204766518