DETERMINATION OF THE SAFETY AND EFFECTIVENESS OF CARBOXYTHERAPY IN IN VIVO MODELS OF OSTEOARTHRITIS AND TENDON INFLAMMATION

Abstract

Local administration of carbon dioxide (carboxytherapy) is regarded as a promising approach for modulating inflammation, improving microcirculation, and stimulating reparative processes. However, traditional subcutaneous CO₂ delivery techniques are associated with variability of local effects, risk of mechanical tissue irritation, and insufficient standardization of administration parameters, which limits reproducibility of experimental findings. These limitations highlight the need to develop optimized CO₂ delivery techniques with controlled administration and improved safety. Objective. To evaluate the efficacy and safety of subcutaneous administration of a CO₂ + NaHCO₃ gas-buffer mixture in preclinical models of acute inflammation and monoiodoacetate (MIA)-induced osteoarthritis. Methods. The study was conducted in rats using formalin- and carrageenaninduced models of acute inflammation and a monoiodoacetic acid–induced osteoarthritis model. Animals received subcutaneous injections of a CO₂ + NaHCO₃ mixture (1:1) in small volumes; comparisons were performed against the classical subcutaneous CO₂ administration protocol described by Raymundo et al. Results. In acute inflammation models, administration of the CO₂ + NaHCO₃ mixture significantly reduced edema severity (p < 0.001). In the MIA-induced osteoarthritis model, treatment resulted in a statistically significant decrease in TNF-α and IL-6 levels and an increase in TGF-β1 concentration (all p < 0.001), indicating anti-inflammatory activity and modulatory effects on systemic inflammatory markers. Conclusions. The subcutaneous administration technique of the CO₂ + NaHCO₃ mixture investigated in this study demonstrated anti-inflammatory activity and a favorable safety profile in preclinical models, supporting the rationale for further research into its potential application for degenerative-inflammatory disorders of the musculoskeletal system.