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Toxic Effects of Quinolone Antibacterial Agents on the Musculoskeletal System in Juvenile Rats

Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., 1-16-13 Kitakasai, Edogawa, Tokyo 134 Japan, JDN07402{at}niftyserve.or.jp

Michiyuki Kato

Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., 1-16-13 Kitakasai, Edogawa, Tokyo 134 Japan

Quinolone antibacterial agents have adverse effects on the musculoskeletal system in humans, consisting mainly of myalgia and arthralgia, and additionally of tendon disorders and rhabdomyolysis. The present study was conducted to examine the toxic effects of quinolones on the musculoskeletal system in juvenile rats using light microscopy, 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry and electron microscopy. Single oral administration of 900 mg/kg pefloxacin (PFLX) or levofloxacin (LVFX) was found to induce lesions in the muscle + fascia, tendon + sheath, and synovial membrane, in addition to articular cartilage in the fore- and hindlimbs. Articular cartilage lesions were not necessarily associated with changes in the muscle, tendon, and synovial membrane, or the reverse. Among all lesions, the ankle and elbow showed the highest incidence and severity. Changes were more severe in the PFLX than in the LVFX group. Lesions in the muscle + fascia, tendon + sheath, and synovial membrane were similar and characterized by edema and increased number of mononuclear cells, many of which were positively stained with BrdU, as well as vascular endothelial cells in the Achilles tendon sheath and synovial membrane in the ankle. Electron microscopic examination revealed an increased number of fibroblasts and macrophages and collagen deposition in the matrix of the synovial membrane and tendon sheath. Capillary endothelial cells were hypertrophied, increased in number, and stratified. These results suggest that quinolones have toxic potentials in the muscle, tendon, and synovial membrane in addition to articular cartilage, and that local vascular hyperpermeability may contribute to the development of these lesions.

Key Words: Muscle • tendon • tendon sheath • synovial membrane • pefloxacin • levofloxacin

Toxicologic Pathology, Vol. 25, No. 6, 635-643 (1997)
DOI: 10.1177/019262339702500615


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