LACK OF CORRELATION BETWEEN HYDROGEN-PEROXIDE PRODUCTION AND NITRIC-OXIDE PRODUCTION BY CULTURED RABBIT ARTICULAR CHONDROCYTES TREATED WITHFLUOROQUINOLONE ANTIMICROBIAL AGENTS

The arthrotoxicity of fluoroquinolone antibacterial agents so far rema ins unexplained. Recent experimental data have indicated an early stim ulation of the oxidative metabolism within articular chondrocytes. An in vitro model was designed to analyse the production of oxygen-derive d reactive species and glutathione by immature rabbit articular chondr ocytes, and the influence of different fluoroquinolones on this model was examined. Primary cultures of chondrocytes were exposed to pefloxa cin, ofloxacin or ciprofloxacin at 10 mu g/ml, for 24 or 48 hr. Flow c ytometric analysis used the vital tracer 2',7'-dichlorofluorescein dia cetate (DCFH-DA) and evaluated the production of H2O2 and NO by chondr ocytes. 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 ce llular levels was noted. Fluoroquinolones stimulate H2O2 production in immature articular chondrocytes, but have no apparent effect on eithe r NO or glutathione production, at least in the early stages of the ch ondrotoxicity. Copyright (C) 1996 Elsevier Science Ltd.