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吡哆素L-2-吡咯烷酮-5-羧酸酯对大鼠的生殖毒性

Reproductive Toxicity of Metadoxine in Rats

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【作者】 王茵; 祝慧娟; 来伟旗; 陈建国; 梅松; 张炜煜; 张幸;

【Author】 Wang Yin,Zhu Hui-juan,Lal Wei-qi,et al (Institute of Health Food,Zhejiang Academy of Medical Sciences,Hangzhou,310013)

【机构】 浙江省医学科学院保健食品研究所; 浙江大学医学院毒理研究室;

【摘要】 目的研究吡哆素L-2-吡咯烷酮-5-羧酸酯对大鼠的生殖毒性。方法雄鼠80只,雌鼠124只随机分4 组,溶剂对照组,3个剂量组吡哆素L-2-吡咯烷酮-5-羧酸酯分别为400、800和1600mg/kg。雄鼠交配前连续给药 60d,交配期间继续给药;雌鼠交配前连续给药14d,交配后给药至妊娠第14天;分别观察生殖毒性试验指标。结果 400mg/kg组无明显毒副反应,800mg/kg组有个别鼠出现后肢麻痹,1600mg/kg组引起雌雄大鼠后肢麻痹,消瘦。吡哆素L-2-吡咯烷酮-5-羧酸酯1600mg/kg使雄鼠的交配率下降50%,有统计学显著性。800mg/kg组生育鼠 7只,1600mg/kg组未生育,对雄鼠的生育率有统计学显著影响。800mg/kg组雄鼠的精子数为(59.10±21.7)×105, 1600mg/kg组雄鼠的精子数为(0.40±0.14)×105。800mg/kg组活胎数为(8±3)只,1600mg/kg组无受孕鼠。结论吡哆素 L-2-吡咯烷酮-5-羧酸酯在本实验条件对SD大鼠无致畸性,无作用剂量为400mg/kg,发育毒性的无作用剂量小于400mg/kg。

【Abstract】 Objective To study the reproductive toxicity of metadoxine.Methods Male and female rats were given metadoxine before pregnancy and early gestation,i.e.to feed metadoxine to male rats for 60 days before copulation and continue feeding during copulation,and feed metadoxine to female rats for 14 days before copulation.Results No significant toxic effect was observed in the 400 mg/kg group.A few rats showed paralysis of hind leg in the 800 mg/kg group.The dossge of 1600 mg/kg caused significant paralysis of hind legs,emaciation,and reduced weight gain.In the 1600 mg/kg group,the mating rate of male rats was was significantly affcted (P<0.01).In the 800 and 1600mg/kg group,fertility of male rats was markedly reduced(P<0.01).In the 1600mg/kg group, the fertility rate of female rats was femarkably (P<0.001)reduced.In the 800 mg/kg group,the effect on sperm counts of epididymis of male rats was markedly reduced (P<0.05).In the 1600 mg/kg group,testicle weight and body weight ratio and sperm counts of epididymis rate were significantly (P<0.001)reduced.In the 800mg/kg group,the weight gain of pregnant rats was significantly reduced (P<0.001).In both the 800 and 1600 mg/kg groups,the gestation rate was greatly reduced(P<0.001). In the 800 mg/kg group,mortality rate before midation (P<0.001) and average live fetus number were signficantly redeuced (P<0.05).In the 400 mg/kg group,the fetal weight was significantly re-duced(P<0.001).In the 800 mg/kg group,body length,tail length,body weight and stermum development of fetal rats were significantly affected(P<0.001).Conclusion Under the presented experimental conditions,metadoxine has no teratogentic effects on SD rats and the no effect dose is 400 mg/ kg.And the no effect dose for the developmental toxicity is less than 400mg/kg.

  • 【会议录名称】 浙江省医学科学院建院55周年院庆论文专辑
  • 【会议时间】2005-05
  • 【分类号】R114
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