CHARACTERIZATION OF FLUOROQUINOLONE-INDUCED ACHILLES-TENDON TOXICITY IN RATS - COMPARISON OF TOXICITIES OF 10 FLUOROQUINOLONES AND EFFECTS OF ANTIINFLAMMATORY COMPOUNDS

Fluoroquinolone antibacterial agents have been reported to induce tend on lesions in juvenile rats. In the present study, we characterized fl uoroquinolone-induced Achilles tendon lesions by comparing the effects of 10 fluoroquinolones and examining the potential of one of these an timicrobial agents, pefloxacin, to induce tendon lesions when coadmini stered with one of nine anti-inflammatory compounds. Among the 10 fluo roquinolones tested, fleroxacin and pefloxacin were the most toxic, in ducing legions at a dose of 100 mg/kg of body weight or more, while lo mefloxacin, levofloxacin, and ofloxacin or sparfloxacin and enoxacin i nduced lesions at 300 mg/kg or more and 900 mg/kg, respectively. In co ntrast, norfloxacin, ciprofloxacin, and tosufloxacin had no effect eve n at the high dose of 900 mg/kg. The severity of the Achilles tendon l esions appeared to correlate with the structure of the substituent at the seventh position. Furthermore, pefloxacin-induced tendon lesions w ere inhibited by coadministration with dexamethasone and N-nitro-L-arg inine methyl ester. Phenidone (1-phenyl-3-pyrazolidinone) and odeca-5, 10-diynyl)3,5,6-trimethyl-1,4-benzoquinone (AA861) also decreased the incidence of tendon lesions. In contrast, catalase, dimethyl sulfoxide , indomethacin, pyrilamine, and cimetidine did not modify these tendon lesions. These results suggest that nitric oxide and 5-lipoxigenase p roducts partly mediate fluoroquinolone-induced tendon lesions.