Kato M, Onodera T
Drug Safety Research Center, Daiichi Seiyaku Co., Ltd., Tokyo, Japan.
Fundam Appl Toxicol. 1988 Jul;11(1):120-31. doi: 10.1016/0272-0590(88)90276-x.
Oral doses of 300 or 900 mg/kg/day of ofloxacin, a quinolone antibacterial agent, for 8 weeks induced a high incidence osteochondrotic 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 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 deep zone.
口服剂量为300或900毫克/千克/天的喹诺酮类抗菌剂氧氟沙星,连续8周给药可在大鼠中诱发高发病率的骨软骨病变。病变的好发部位是股骨内侧髁的尾部区域。早期变化包括关节软骨中间带增厚,深部带明显变薄。随着给药过程的进展,增厚的中间带软骨细胞柱越来越多,可见许多退变细胞,软骨基质与番红O的染色强度略有降低。给药结束后,关节软骨明显增厚,主要由中间带软骨组成。在晚期病例中,沿潮线形成裂隙,偶尔延伸至关节面。这导致关节软骨糜烂。在裂隙下方,有软骨下骨的局灶性坏死和骨髓腔的纤维化病变。萘啶酸在大鼠中也产生类似病变。当在4周龄开始治疗时,这两种药物可诱发大鼠骨软骨病,但在8周龄时则不会。这种病变在发育过程中与大鼠自发性骨软骨病不同,后者的特征是固有增厚的深部带保留。