Ultrastructural changes induced by the des-F(6)-quinolone garenoxacin (BMS-284756) and two fluoroquinolones in Achilles tendon from immature rats.

Garenoxacin is a des-(6)-fluoroquinolone exhibiting a comparatively low chondrotoxic potential in juvenile animals. We studied the effects of the drug on Achilles tendons in immature Wistar rats treated by oral intubation once daily (1) for 5 consecutive days from postnatal week 4 onward at doses of 0 (vehicle), 200 and 600 mg/kg body weight (b wt), and (2) for 21 consecutive days from postnatal day 4 onward at doses of 0 (vehicle), 80, 240 or 300 mg/kg b wt; ofloxacin or ciprofloxacin were used as comparators. Achilles tendon specimens were studied by electron microscopy. In comparison with vehicle-treated controls, ultrastructural changes were detectable in all samples from the garenoxacin-, ofloxacin-, or ciprofloxacin-treated rats (one animal per group). We found degenerative changes such as multiple vacuoles and large vesicles in the cytoplasm of tenocytes that resulted from swelling and dilatation of cell organelles (mitochondria, endoplasmic reticulum), densified nuclei and clumped chromatin; furthermore, cells that detached from the extracellular matrix, a general decrease of the fibril diameter and an increase in the distance between the collagenous fibrils were recognizable. The degree of changes increased with increasing doses. It remains unclear what these findings mean with respect to a possible risk in juvenile patients treated with garenoxacin or the other quinolones, but our results underline the fact that, in principle, this des-(6)-fluoroquinolone also has the potential to cause changes in connective tissue structures.