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Friday, March 2, 2001

Studies find impact of ciprofloxacin

Clinical and in vitro studies have demonstrated that fluoroquinolones are toxic for chondrocytes, however, the exact mechanism of fluoroquinolone arthropathy is unknown. A study in scientific exhibit 12 investigated the toxicity of a fluoroquinolone, ciprofloxacin on normal cartilage and cartilagenous tumors.

The researchers also characterized morphological effects of ciprofloxacin in vivo using chondrosarcoma specimens from treated patients. Their results indicate that while ciprofloxacin is mildly toxic to chondrocytes, chondrosarcomas are most severely affected.

The researchers say normal human cartilage, enchondroma and chondrosarcoma explants were cultured in cartilage medium, either alone or with the addition of ciprofloxacin at 1, 10 and 20 mg/liter medium. Samples were collected after three, 10 and 21 days of antibiotic treatment and processed for electron microscopy and conventional light microscopy.

The in vitro specimens were characterized morphologically by conventional light microscopy, electron microscopy and by immunohistochemistry to identify extracellular matrix, cell proliferation and apoptosis. Cultures of normal chondrocytes and enchondromas expressed type II collagen.

Electron microscopy revealed 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 and increased doses of ciprofloxacin treatment, there was an increase in dilated rough endoplasmic reticulum, the appearance of phagosomes and disintegrated bundles of vimentin filaments.

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 non-cartilagenous malignant tumors like osteosarcoma and liposarcoma was unaffected by ciprofloxacin.

The researchers are Richard D. Lackman, MD; Hinke A.B. Multhaupt, PhD; Michael J. Warhol, MD; and Patricia Rafferty, MT (ASCP), all of Pennsylvania Hospital, Philadelphia, Pa.; and J. C. Alvarez, MD, department of orthopaedics, University of Pennsylvania, Philadelphia, Pa.

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Last modified 15/February/2001 by IS