In vitro study of cytotoxicity of quinolones on rabbit tenocytes.
Tendinitis and tendon rupture complicating fluoroquinolone therapy have been reported recently, especially affecting men over 60 years. These new quinolones are more potent antimicrobial agents than older nonfluorinated compounds like nalidixic acid. We compared the effects of one quinolone (nalidixic acid) and two fluoroquinolones (norfloxacin and pefloxacin) on cultured rabbit Achilles tendon cells. First, we examined their effects on cell viability, mitochondrial succinate dehydrogenase and global activity, mitochondrial activity using microtitration methods. Pefloxacin and norfloxacin were more cytotoxic than nalidixic acid according to IC50 values. These results confirm that mitochondria represent a biological target of fluoroquinolones. Moreover, the extracellular matrix was studied by molecular hybridization. After a 72 h treatment, the level of type I collagen transcripts was not modified with any of the three antimicrobial agents, whereas mRNA encoding decorin was decreased with 10(-4) mol/L pefloxacin only. The decrease of transcripts encoding decorin suggests that this matrix component is another target of pefloxacin and modification of decorin seems to be an early event (before mitochondrion alteration) which may contribute to the explanation of tendon rupture.
Bernard-Beaubois
K
K
Laboratoire de Pharmacologie Cellulaire de l'Ecole Pratique des Hautes Etudes, Centre de Recherches Biomédicales des Cordeliers, Paris, France.
Hecquet
C
C
Hayem
G
G
Rat
P
P
Adolphe
M
M
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis / Q000235:genetics; D058575:Decorin; D016326:Extracellular Matrix Proteins; D008928:Mitochondria / Q000187:drug effects; D009268:Nalidixic Acid / Q000494:pharmacology*; D009643:Norfloxacin / Q000494:pharmacology*; D015366:Pefloxacin / Q000494:pharmacology*; D011509:Proteoglycans / Q000096:biosynthesis / Q000235:genetics; D011817:Rabbits; D013385:Succinate Dehydrogenase / Q000187:drug effects; D013710:Tendons / Q000166:cytology
D000890:Anti-Infective Agents; C546880:Dcn protein, rat; D058575:Decorin; D016326:Extracellular Matrix Proteins; D011509:Proteoglycans; D015366:Pefloxacin; D009268:Nalidixic Acid; D003094:Collagen; D013385:Succinate Dehydrogenase; D009643:Norfloxacin