TOXIC EFFECTS OF QUINOLONE ANTIBACTERIAL AGENTS ON THE MUSCULOSKELETAL SYSTEM IN JUVENILE RATS

Quinolone antibacterial agents have adverse effects on the musculoskel etal system in humans, consisting mainly of myalgia and arthralgia, an d additionally of tendon disorders and rhabdomyolysis. The present stu dy was conducted to examine the toxic effects of quinolones on the mus culoskeletal system in juvenile rats using light microscopy, 5-bromo-2 '-deoxyuridine (BrdU) immunohistochemistry and electron microscopy. Si ngle oral administration of 900 mg/kg pefloxacin (PFLX) or levofloxaci n (LVFX) was found to induce lesions in the muscle + fascia, tendon sheath, and synovial membrane, in addition to articular cartilage in t he fore- and hindlimbs. Articular cartilage lesions were not necessari ly associated with changes in the muscle, tendon, and synovial membran e, or the reverse. Among all lesions, the ankle and elbow showed the h ighest incidence and severity. Changes were more severe in the PFLX th an in the LVFX group. Lesions in the muscle + fascia, tendon + sheath, and synovial membrane were similar and characterized by edema and inc reased number of mononuclear cells, many of which were positively stai ned with BrdU, as well as vascular endothelial cells in the Achilles t endon sheath and synovial membrane in the ankle. Electron microscopic examination revealed an increased number of fibroblasts and macrophage s and collagen deposition in the matrix of the synovial membrane and t endon sheath. Capillary endothelial cells were hypertrophied, increase d in number, and stratified. These results suggest that quinolones hav e toxic potentials in the muscle, tendon, and synovial membrane in add ition to articular cartilage, and that local vascular hyperpermeabilit y may contribute to the development of these lesions.