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In vivo and in vitro chondrotoxicity of ciprofloxacin in juvenile rats. | LitMetric
Aim : To study the relationship between chondrotoxicity and toxicokinetics of ciprofloxacin (CPFX).Methods : Rats, 4-week old, were treated with CPFX 0, 400, 800, and 1200 mg/kg ig once daily on seven consecutive days. The knee joint cartilage was examined histopathologically. The concentration of CPFX in venous blood and knee joint cartilage samples were determined by a microbioassay using Escherichia coli 44102. The effects of CPFX on proliferation of chondrocytes and secretion of soluble proteoglycans were determined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and 1,9-dimethylmethylene blue (DMB) assay, respectively.Results : Cartilage was severely lesioned after treatment with CPFX 800 or 1200 mg/kg for 7 d, such as matrix swelling and loss of chondrocytes. The thickness of cartilage was significantly decreased compared with the control group. The maximum serum concentration (Cmax), the area under the plasma concentration-time curve (AUC(0-infinity)), and concentration in cartilage was 16.3 +/- 2.1 mg/L, 97.2 +/- 12.3 mg x h x L(-1), and 13.4 +/- 2.8 microg x g(-1) and 21.8 +/- 2.5 mg/L, 143.1 +/- 22.3 mg x h x L(-1), and 20.3 +/- 3.5 microg x g(-1) after oral administration of CPFX 800 or 1200 mg/kg on d 1, respectively. The data on d 6 were similar with that on d 1. CPFX inhibited proliferation of chondrocytes and the secretion of soluble proteoglycans.Conclusion : CPFX concentrations in serum and cartilage could provide a better basis for risk assessment.
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