Clinical and in vitro studies have demonstrated
that fluoroquinolones are toxic to chondrocytes; however, the exact
mechanism of fluoroquinolone arthropathy is unknown. We investigated
the toxicity of ciprofloxacin on normal cartilage and on cartilaginous tumors.
Normal human cartilage, enchondroma, and chondrosarcoma explants
were cultured either alone or with the addition of ciprofloxacin
at 1, 10, or 20 mg/L of medium. Samples were collected
up to twenty-one days after treatment and were processed for electron
microscopy and conventional light microscopy. The specimens were
characterized morphologically with use of conventional light microscopy,
electron microscopy, and immunohistochemistry to identify extracellular
matrix, cell proliferation, and apoptosis.
Cultures of normal chondrocytes expressed type-II collagen. Electron
microscopy revealed a large amount of glycogen in the cells; the
presence of fat droplets, rough endoplasmic reticulum, and prominent
Golgi apparatus; and a proteoglycan layer surrounding the cells.
With prolonged ciprofloxacin treatment and with increased doses,
there was an increase in dilated rough endoplasmic reticulum, the
appearance of phagosomes, and disintegrated bundles of vimentin
filaments. The treated chondrocytes showed a decrease in cell proliferation,
but there was no induction of apoptosis or effect on the expression
of extracellular matrix proteins. Ciprofloxacin-treated chondrosarcoma
cultures and tissue samples showed changes in cartilage matrix composition.
Ultrastructural analysis demonstrated clumped glycogen, dilation
of endoplasmic reticulum, numerous abnormal lysosomes containing
degeneration products, and a decreased proteoglycan deposit surrounding
the tumor cells. Treated chondrosarcoma cells and tissue specimens
did not proliferate, and apoptosis was induced. In contrast, the
in vitro growth of other noncartilaginous malignant tumors like
osteosarcoma and liposarcoma was unaffected by ciprofloxacin.
Our results indicate that ciprofloxacin is toxic to chondrocytes. In
vitro and in vivo treated chondrosarcomas
are the most affected.