IN VIVO EXPERIMENT OF HIGH-DOSE GENTAMICIN INFLUENCES ON ARTICULAR CARTILAGE

Introduction & Aim Continuous Local Antibiotic Perfusion (CLAP) therapy has emerged as a promising treatment option for joint infections by delivering high local concentrations of antibiotics directly into the joint space. Gentamicin (GM), commonly used in this context, can reach concentrations exceeding the minimum biofilm eradication concentration (MBEC), potentially enhancing antibacterial efficacy. However, the safety of such high concentrations for articular cartilage remains insufficiently understood, particularly under in vivo conditions. The aim of this study was to evaluate the dose-dependent chondrotoxicity of gentamicin in a rat knee model and to assess its potential implications for CLAP therapy. Methods All procedures were approved by the institutional animal care committee. A total of 30 µL of gentamicin solution at concentrations ranging from 0 to 10,000 µg/mL was administered via intra-articular injection into the knee joints of Sprague–Dawley rats once daily for 7 consecutive days. Following the treatment period, animals were euthanized, and cartilage tissues were harvested for analysis. Chondrocyte viability was quantified to assess cellular toxicity. Gene expression analysis of cartilage-related anabolic and catabolic markers was performed using reverse transcription polymerase chain reaction (RT-PCR). Histological evaluation was conducted using Safranin-O staining, and cartilage degeneration was semi-quantitatively assessed using the OARSI scoring system. Results Chondrocyte viability demonstrated a significant dose-dependent reduction, with marked decreases observed at concentrations of 3,000 µg/mL and 10,000 µg/mL compared to controls. Histological analysis revealed relatively preserved cartilage surface architecture across most groups, although subtle degenerative changes were identified at higher concentrations. Consistent with these findings, OARSI scores were significantly elevated in the higher-dose groups, indicating early cartilage degeneration despite limited macroscopic structural disruption. In contrast, gene expression analysis showed no statistically significant differences in key anabolic or catabolic cartilage-related markers among the groups. Conclusion High concentrations of gentamicin induce dose-dependent cytotoxic effects on chondrocytes in vivo, even in the absence of pronounced structural cartilage damage over short-term exposure. While concentrations comparable to those used in CLAP therapy may be relatively tolerated at the tissue level, the observed cellular toxicity raises concerns regarding potential long-term cartilage health. These findings highlight the importance of optimizing antibiotic dosing strategies in CLAP therapy and underscore the need for further investigations into safe concentration thresholds and exposure durations in clinical settings.