Possible involvement of nitric oxide in the quinolone-induced tendon lesions in rats.
Quinolone antibacterial agents have been reported to induce adverse effects on the tendon and the musculoskeletal system in humans. We have previously demonstrated that Achilles tendon lesions could be induced in juvenile rats by a single oral administration of quinolones at high doses with simultaneous induction of lesions in the muscle, synovial membrane and articular cartilage. In the present investigation, we examined the involvement of nitric oxide (NO) in pefloxacin (PFLX)-induced lesions of the Achilles tendon in juvenile rats. The incidence of lesions was diminished markedly by co-administration of a potent NO synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME). Further, the urinary nitrate/nitrite excretion was decreased significantly by 4 h after administration, unchanged between 4 and 8 h, and significantly increased in the 8- to 24-h samples in the PFLX group, as compared to the control group. In contrast, the serum concentration of nitrate/nitrite was significantly higher in the PFLX group 4 h after administration, but there was no difference from controls was observed at 8 and 24 h. These results suggest that NO is involved in the induction of Achilles tendon lesions in juvenile rats by pefloxacin (PFLX) and may be similar to the tendon disorder of humans receiving quinolones.
Kashida
Y
Y
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co. Ltd., Tokyo, Japan.
Kato
M
M
D042462:4-Quinolones; D000125:Achilles Tendon / Q000187:drug effects* / Q000473:pathology; D000818:Animals; D000890:Anti-Infective Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D024841:Fluoroquinolones; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D015363:Quinolones / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015366:Pefloxacin
D042462:4-Quinolones; D000890:Anti-Infective Agents; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D015363:Quinolones; D015366:Pefloxacin