Aoki M, Ono Y, Kunii O, Goldstein E
Second Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
J Antimicrob Chemother. 1994 Sep;34(3):383-90. doi: 10.1093/jac/34.3.383.
The direct effect of four quinolones on the intracellular production and extracellular release of reactive oxygen species was investigated in vitro using a chemiluminescence (CL) assay. Polymorphonuclear leucocytes (PMNs) were obtained from healthy volunteers and exposed for 10 min at 37 degrees C to 1.6, 6.25 and 25 mg/L ofloxacin, ciprofloxacin, sparfloxacin and temafloxacin. The luminol-dependent CL response of the PMNs was then measured for 30 min following stimulation with nonopsonized zymosan or phorbol myristate acetate (PMA). The intracellular CL response was also measured for 30 min during phagocytosis of lumispheres. The integrated CL was calculated and compared for cells which were incubated with the antibiotic and unincubated controls. Preincubation with ofloxacin resulted in increased zymosan and PMA-induced, luminol-dependent CL. Similar increases were observed for ciprofloxacin except that 25 mg/L decreased the PMA-induced, luminol dependent CL. Preexposure to ofloxacin and ciprofloxacin did not affect lumisphere-induced CL significantly, although there was a tendency for this to decrease after exposure to ciprofloxacin. In contrast sparfloxacin and temafloxacin caused progressive decreases in zymosan and PMA-induced, luminol-dependent PMN CL which reached statistical significance at the higher concentrations. The same pattern was observed in the experiments using lumispheres. These findings indicate that these quinolones modulate the oxygen metabolism of PMNs and that this effect varies with the individual drug.
采用化学发光(CL)分析法在体外研究了4种喹诺酮类药物对活性氧细胞内产生和细胞外释放的直接影响。从健康志愿者获取多形核白细胞(PMN),并于37℃将其暴露于1.6、6.25和25mg/L的氧氟沙星、环丙沙星、司帕沙星和替马沙星中10分钟。然后在用未调理酵母聚糖或佛波酯肉豆蔻酸酯(PMA)刺激后,测量PMN的鲁米诺依赖性CL反应30分钟。在吞噬发光微球期间也测量细胞内CL反应30分钟。计算并比较与抗生素孵育的细胞和未孵育对照的积分CL。预先用氧氟沙星孵育导致酵母聚糖和PMA诱导的、鲁米诺依赖性CL增加。环丙沙星也观察到类似的增加,只是25mg/L降低了PMA诱导的、鲁米诺依赖性CL。预先暴露于氧氟沙星和环丙沙星对发光微球诱导的CL没有显著影响,尽管暴露于环丙沙星后有降低的趋势。相比之下,司帕沙星和替马沙星导致酵母聚糖和PMA诱导的、鲁米诺依赖性PMN CL逐渐降低,在较高浓度时达到统计学显著性。在使用发光微球的实验中也观察到相同的模式。这些发现表明这些喹诺酮类药物调节PMN的氧代谢,并且这种作用因药物而异。