© 1988 Oxford University Press
research-article |
Morphological Investigation of Osteochondrosis Induced by Ofloxacin in Rats
Drug Safety Research Center, Research Institute, Daiichi Setyaku Co, Ltd Tokyo, Japan
Received August 11, 1987; accepted January 25, 1988
Morphological Investigation of Osteochondrosis Induced by Ofloxacin in Rats. Kato, M., and Onodera, T. (1988). Fundam. Appl. Toxicol. 11, 120–131. Oral doses of 300 or 900 mg/ kg/day of ofloxacin, a quinolone antibacterial agent, for 8 weeks induced a high incidence osteo-chondrotic lesions in rats. The predilection site of the lesions was the caudal area of the medial femoral condyle. Early changes included thickening of the middle zone of the articular cartilage with a markedly thinned deep zone. As the course of administration progressed, the columns of chondrocytes in the thickened middle zone became more and more numerous, many degenerated cells were seen, and the staining intensity of the matrix of the cartilage with safranin-O decreased slightly. After the completion of dosing, the articular cartilage was markedly thickened and was made up mainly of middle zone cartilage. In advanced cases, a cleft was formed along the tidemark which occasionally extended to the articular surface. This resulted in erosion of the articular cartilage. Beneath the cleft there were focal necrosis of the subchondral bone and fibrotic lesions in the marrow space. Nalidixic acid also produced similar lesions in rats. The two drugs induced osteochondrosis in rats when treatment began at 4 weeks of age, but not at 8 weeks of age. This lesion was different in developmental process from the spontaneous osteochondrosis of rats, which is characterized by retention of the inherently thick deepzone.