Lack of correlation between hydrogen peroxide production and nitric oxide production by cultured rabbit articular chondrocytes treated with fluoroquinolone antimicrobial agents.

The arthrotoxicity of fluoroquinolone antibacterial agents so far remains unexplained. Recent experimental data have indicated an early stimulation of the oxidative metabolism within articular chondrocytes. An in vitro model was designed to analyse the production of oxygen-derived reactive species and glutathione by immature rabbit articular chondrocytes, and the influence of different fluoroquinolones on this model was examined. Primary cultures of chondrocytes were exposed to pefloxacin, ofloxacin or ciprofloxacin at 10 mug/ml, for 24 or 48 hr. Flow cytometric analysis used the vital tracer 2',7'-dichlorofluorescein diacetate (DCFH-DA) and evaluated the production of H(2)O(2) and NO by chondrocytes. Separately, NO production and intracellular glutathione levels were evaluated, with the Greiss colorimetric technique and the Tietze method, respectively. With each fluoroquinolone tested, intracellular levels of the fluorescent compound dichlorofluorescein (oxidized form of DCFH-DA) were significantly higher in treated chondrocytes than in control cells. No significant modification of NO or of glutathione cellular levels was noted. Fluoroquinolones stimulate H(2)O(2) production in immature articular chondrocytes, but have no apparent effect on either NO or glutathione production, at least in the early stages of the chondrotoxicity.