氧氟沙星对小鼠生殖毒性和致畸性的研究

Exploration on the Reproductive Toxicity and Teratogenicity of Ofloxacin

目的研究氧氟沙星对昆明系小鼠胚胎和胎鼠发育的影响,确定其是否存在生殖毒性和致畸性。方法①雄鼠分别灌服各剂量氧氟沙星,连续10d,末次给药24h后与母鼠合笼,在妊娠第三天取胚胎,记录各剂量组胚胎发育率。②孕鼠妊娠零天给药,分别经口灌服高、中、低剂量[36、72和360mg(kg.bw)]氧氟沙星溶液,连续给药3d,在妊娠第三天收集胚胎,记录胚胎发育率。③孕鼠妊娠零天给药,分别经口灌服各剂量氧氟沙星溶液,连续给药10d,在妊娠第16天取出胎鼠,记录胎鼠体重、胎盘重、活胎数、胎鼠外观畸形和内脏畸形等指标。结果给药组与对照组相比,雄鼠服用高剂量组360mg(kg.bw)氧氟沙星对着床前胚胎发育影响显著(P<0.05),而中等剂量和低剂量组对着床前胚胎发育的影响不显著(P>0.05)。雌鼠服用不同剂量氧氟沙星对着床前胚胎发育影响不显著(P>0.05)。氧氟沙星对受孕鼠的活胎数和吸收胎数均无明显影响,给药组的活鼠体重、胎盘重均未见明显差异(P>0.05);药物组和对照组均未出现外观畸形和内脏畸形,也不存在剂量和效应关系。结论孕鼠服用不同剂氧氟沙星对昆明系小鼠胚胎和胎鼠发育无明显的影响,表明氧氟沙星对雌性鼠不具有明显的生殖毒性和致畸性;但雄鼠服用高剂量氧氟沙星对着床前胚胎发育影响显著。

Objective To investigate the effects of ofloxacin on mouse embryonic development and to determine wether ofloxacin is of reproductive and teratogenic toxicity. Methods\ Ofloxacin was administered orally by gavage to groups of inseminated mice for 3 days (day 0 to day 2 post insemination) and for 10 days (day 0 to day 9 post insemination), and to male mice for 10 days at a daily dose of 0, 36, 72 and 360 mg/kg b.w. respectively. The mouse fetuses were taken for examination at 16d of pregnancy. Results\ The results indicated that ofloxacin did not show effects on the number of living fetuses, dead fetuses and absorbed fetuses. The body weight, placenta weight of fetuses in all treatment groups had no significant difference (p>0 05) as compared with those of the control. Ofloxacin did not produce significant difference on the development of pre implantation embryos in female mice, but significant difference was observed in male mice. Conclusion\ The results of this study showed no evidence for reproductive and teratogenic toxicity of ofloxacin.