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Toxic effects of quinolone antibacterial agents on the musculoskeletal system in juvenile rats
1Drug Safety Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan. JDN07402@niftyserve.or.jp
Abstract:
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.
Insights
Quinolone antibiotics like pefloxacin and levofloxacin can harm juvenile rat musculoskeletal systems, causing lesions in muscles, tendons, and cartilage. These findings highlight potential risks of these drugs on growing joints and connective tissues.
Area of Science:
- Pharmacology
- Toxicology
- Musculoskeletal System Research
Background:
- Quinolone antibacterials are known to cause musculoskeletal adverse effects in humans, including myalgia, arthralgia, tendon disorders, and rhabdomyolysis.
- The specific toxic mechanisms and targets within the musculoskeletal system, especially in juvenile populations, require further investigation.
Purpose of the Study:
- To investigate the toxic effects of quinolone administration on the musculoskeletal system of juvenile rats.
- To elucidate the cellular and tissue-level changes induced by pefloxacin and levofloxacin in muscles, tendons, cartilage, and synovial membranes.
Main Methods:
- Light microscopy, 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry, and electron microscopy were employed.
- Juvenile rats were administered single oral doses of pefloxacin (PFLX) or levofloxacin (LVFX) at 900 mg/kg.
- Histopathological examination of fore- and hindlimb tissues, including muscle + fascia, tendon + sheath, synovial membrane, and articular cartilage, was performed.
Main Results:
- Single oral administration of PFLX or LVFX induced lesions in muscle + fascia, tendon + sheath, synovial membrane, and articular cartilage.
- The ankle and elbow joints exhibited the highest incidence and severity of lesions.
- Histological findings included edema, increased mononuclear cells (BrdU-positive), and vascular changes, particularly in the Achilles tendon sheath and synovial membrane.
Conclusions:
- Quinolones possess toxic potential affecting muscle, tendon, synovial membrane, and articular cartilage in juvenile rats.
- The observed lesions were more severe with pefloxacin compared to levofloxacin.
- Local vascular hyperpermeability is suggested as a contributing factor to the development of quinolone-induced musculoskeletal toxicity.