吡哆素L-2-吡咯烷酮-5-羧酸酯对大鼠的生殖毒性

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 12 4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 4 0 0、80 0和 16 0 0mg/kg。雄鼠交配前连续给药 6 0d ,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　 4 0 0mg/kg组无明显毒副反应 ,80 0mg/kg组有个别鼠出现后肢麻痹 ,16 0 0mg/kg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 16 0 0mg/kg使雄鼠的交配率下降 5 0 % ,有统计学显著性。 80 0mg/kg组生育鼠 7只 ,16 0 0mg/kg组未生育 ,对雄鼠的生育率有统计学显著影响。 80 0mg/kg组雄鼠的精子数为 (5 9 4 0± 2 1 71)× 10 5,16 0 0mg/kg组雄鼠的精子数为 (0 4 0± 0 14 )× 10 5。 80 0mg/kg组活胎数为 (8± 3)只 ,16 0 0mg/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4 0 0mg/kg ,发育毒性的无作用剂量小于 4 0 0mg/kg。

Reproductive toxicity of metadoxine in rats

Objective To study the reproductive toxicity of metadoxine. Methods Male and female rats were goven 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 dosage of 1 600 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 significantly affected ( P <0.01). In the 800 and 1 600 mg/kg group, fertility of male rats was markedly reduced ( P <0.01).In the 800 mg/kg group, the effect on sperm counts of epididymis of male rats was markedly reduced ( P <0.05). In the 1 600 mg/kg group, testicle weight and body weight ratio and sperm counts of epididymis rate were significantly ( P <0.001) reduced. In the 1 600 mg/kg group, the fertility rate of female rats was remarkably ( P <0.001) reduced. In the 800 mg/kg group, the weight gain of pregnant rats was significantly reduced ( P <0.001). In both the 800 and 1 600 mg/kg groups, the gestation rate was greatly reduced ( P <0.001). In the 800 mg/kg group, mortality rate before nidation ( 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 reduced ( P <0.001). In the 800 mg/kg group, body length, tail length, body weight and sternum development of fetal rats were significantly affected ( P <0.001). Conclusion Under the presented experimental conditions, metadoxine has no teratogenic 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 400 mg/kg.