Kato M, Onodera T
Drug Safety Research Center, Daiichi Seiyaku Co., Ltd., Tokyo, Japan.
Fundam Appl Toxicol. 1988 Jul;11(1):110-9. doi: 10.1016/0272-0590(88)90275-8.
Ofloxacin, a quinolone antibacterial agent, induced blisters and/or erosions in the articular cartilage of the humeral trochlea, femoral condyle, and femoral head of immature rats. Histologically, cavity formation was seen in the middle zone of the articular cartilage. Changes were detected as early as 5 hr after a single oral administration of 1000 or 3000 mg/kg. These changes were characterized by condensation, atrophy, and deformation of the nuclei of chondrocytes distributed in the middle zone. In such nuclei, aggregation of heterochromatin was observed. Degenerated cells with vacuolated and partially disintegrated cytoplasms were also seen in this zone. These lesions were followed by edema of the matrix accompanied with markedly decreased stainability with safranin-O, and a cavity was formed later by liquefaction of the cartilage. The changes were reversible, with rebounding occurring even with continued treatment with ofloxacin. The proliferation of chondrocytes around the lesion chiefly contributed to the repair. Ofloxacin had no adverse effects on the articular cartilage in rats when treatment was initiated at 8 weeks of age or later.
喹诺酮类抗菌剂氧氟沙星可在未成熟大鼠的肱骨滑车、股骨髁和股骨头的关节软骨中引起水疱和/或糜烂。组织学上,在关节软骨的中间区可见空洞形成。在单次口服1000或3000 mg/kg后5小时即可检测到变化。这些变化的特征是分布在中间区的软骨细胞核浓缩、萎缩和变形。在这些细胞核中,观察到异染色质聚集。在该区域还可见到细胞质有空泡化和部分崩解的退化细胞。这些病变随后伴有基质水肿,番红O染色性明显降低,随后软骨液化形成空洞。这些变化是可逆的,即使继续用氧氟沙星治疗也会出现反弹。病变周围软骨细胞的增殖对修复起主要作用。当在8周龄或更大年龄开始治疗时,氧氟沙星对大鼠关节软骨没有不良影响。