In vitro discrimination of fluoroquinolones toxicity on tendon cells: involvement of oxidative stress.
Tendinopathy are classic side effects observed with fluoroquinolones antibiotics. 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), and ciprofloxacin (CIP), in various concentrations. Cell viability, redox status changes, reduced glutathione content, and reactive oxygen species production were assessed using neutral red, Alamar blue, monobromobimane and 2,7-dichlorofluorescindiacetate fluorescent probes, respectively. Living adherent tenocytes were analyzed using a cold light cytofluorometer adapted to 96-well microplates. 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 and 62% (*p < 0.05) for PEF and 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 72 h, respectively]. 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.
Laboratoire de Toxicologie, Faculté des Sciences Pharmaceutiques et Biologiques, Université Paris, Paris, France.
F
F
Pouzaud
K
K
Bernard-Beaubois
M
M
Thevenin
J-M
JM
Warnet
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G
Hayem
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P
Rat
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024841:Fluoroquinolones / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism; D013710:Tendons / Q000166:cytology / Q000187:drug effects*
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D017382:Reactive Oxygen Species; D005978:Glutathione