IN-VITRO STUDY OF CYTOTOXICITY OF QUINOLONES ON RABBIT TENOCYTES

Tendinitis and tendon rupture complicating fluoroquinolone therapy hav e been reported recently, especially affecting men over 60 years. Thes e new quinolones are more potent antimicrobial agents than older nonfl uorinated compounds like nalidixic acid. We compared the effects of on e quinolone (nalidixic acid) and two fluoroquinolones (norfloxacin and pefloxacin) on cultured rabbit Achilles tendon cells. First, we exami ned their effects on cell viability, mitochondrial succinate dehydroge nase 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 mitochondri a represent a biological target of fluoroquinolones. Moreover, the ext racellular 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 deco rin was decreased with 10(-4) mol/L pefloxacin only. The decrease of t ranscripts encoding decorin suggests that this matrix component is ano ther target of pefloxacin and modification of decorin seems to be an e arly event (before mitochondrion alteration) which may contribute to t he explanation of tendon rupture.