Proteoglycan and collagen biochemical variations during fluoroquinolone-induced chondrotoxicity in mice

Although fluoroquinolone antibacterials have a broad therapeutic use, with a relatively low incidence of severe side effects, they have been reported to induce Lesions in the cartilage of growing animals by a mechanism that r emains unclear. This study was undertaken to determine the potentially dele terious effect of a high dose of pefloxacin (400 mg/kg of body weight) on t wo main constituents of cartilage in mice, i.e,, proteoglycans and collagen . Variations in levels of proteoglycan anabolism measured by in vivo [S-35] sulfate incorporation into cartilage and oxidative modifications of collage n assessed by detection of carbonyl derivatives were monitored after admini stration of pefloxacin. Treatment of mice with 1 day of pefloxacin treatmen t significantly decreased the rate of biosynthesis of proteoglycan for the first 24 h, However, no difference was observed after 48 h, The decrease in proteoglycan synthesis was accompanied by a marked drop in serum sulfate c oncentration and a concomitant increase in urinary sulfate excretion. The d ecrease in proteoglycan synthesis, also observed ex vivo, may suggest a dir ect effect of pefloxacin on this process, rather than it being a consequenc e of a low concentration of sulfate. On the other hand, treatment with pefl oxacin for 10 days induced oxidative damage to collagen. In conclusion, thi s study demonstrates, for the first time, that pefloxacin administration to mice leads to modifications in the metabolism and integrity of extracellul ar proteins, such as collagen and proteoglycans, which may account for the side effects observed. These results offer new insights to explain quinolon e-induced disorders in growing articular cartilage.