Pharmacol Exp Ther. 2003 Oct 20

In vitro discrimination of fluoroquinolones toxicity on tendon cells: Involvement of Oxidative Stress.

Pouzaud F, Bernard-Beaubois K, Thevenin M, Warnet JM, Hayem G, Rat P.

Faculte des Sciences Pharmaceutiques et Biologiques, Paris, France.

To investigate the mechanism of fluoroquinolone- associated tendinopathy and discriminate the intrinsic tenotoxic potential of each molecules. GENERAL METHODS: A previously validated model based on a spontaneously immortalized rabbit tendon cell line (Teno cell line) was used to evaluate cellular responses to the fluoroquinolones pefloxacin (PEF), ofloxacin (OFX), levofloxacin (LVX), ciprofloxacin (CIP), in various concentrations. Cell viability, redox status changes, reduced glutathione (GSH) content, and reactive oxygen species (ROS) production were assessed using neutral red, Alamar blue(R), monobromobimane and 2,7- dichlorofluorescin-diacetate (DCFH-DA) fluorescent probes, respectively. Living adherent tenocytes were analysed using a cold light cytofluorometer adapted to 96- well microplates. RESULTS: All fluoroquinolones showed moderate cytotoxicity after 24 h and more severe, significant toxicity after 72 h on tendon cells. Moreover two groups of fluoroquinolones may be differentiated: intrinsic toxicity for tendon cells was high with ciprofloxacin and pefloxacin (redox status decrease was 80%, 62% (*p<0.05) for PEF, CIP at 1 mM for 72 h, respectively), but moderate with ofloxacin and levofloxacin LVX (redox status decrease was 30% and 22% (*p<0.05) for OFX and LVX at 1 mM during 72h, respectively). CONCLUSIONS: Our model supports a role for early oxidative stress in the development of fluoroquinolone-induced tendinopathy. Moreover, our study indicates that intrinsic toxicity to tendon cells varies across fluoroquinolones. The Teno cell line may be a useful model for detecting and evaluating tendon toxicity of new fluoroquinolones and other drugs associated with tendinopathy.