DHPO生殖毒性的毒理学评价

Primary study about reproductive toxicology of DHPO in mice

目的研究1,2-二甲基-3-羟基-4-吡啶酮(DHPO)的急性毒性及不同剂量、不同时间的生殖毒性。方法以昆明种近交小鼠为实验对象,首先进行半数致死量(LD50)实验,然后对DHPO低(1/8 LD50)、中(1/4 LD50)、高(1/2 LD50)剂量组染毒小鼠进行精子畸变率观察。结果DHPO染毒小鼠经口LD50为562.34 mg/kg。精子畸变实验显示,1/8 LD50组1、/4 LD50组与阴性对照组比较,在第14,28,35,42,70 d观察,差异均无统计学意义(P>0.05);1/2LD50组与阴性对照组比较,在第14,28,35 d观察,差异均有统计学意义(P<0.05),而在第42,70 d观察,差异无统计学意义(P>0.05)。结论DHPO的低(1/8 LD50)、中(1/4 LD50)剂量未显示有生殖毒性,高剂量(1/2 LD50)具有一定生殖毒性,但可在42 d后恢复。

Objective To evaluate the acute toxicity and reproductive toxicology of deferiprone（DHPO） under various doses and during different periods. Methods Median lethal dose（LD50 ） test was performed, then Kun Ming mice were administrated different doses of DHPO to cary out the sperm malformation test under low（1/8 LD50, mid（1/4 LD50）, high（1/ 2 LD50） doses. Results LD50 of DI-IPO was 562.34 mg/kg by gavage on mice. There were no significant differences in 1/8 LD50 group and 1/4 LD50 group in comparison with negative control group in observations conducted din the 14^th, 28^th, 35^th, 42^nd, and 70^th day （ P 〉 0.05） ; While significant differences appeared between 1/2 LD50 group and in negative control group in observations conducted in the 14^th, 28^th and 35^th day （P 〈 0.05） ;There were no significant differences between 1/2 LD50 group and negative control group in observations conducted in the 42^nd day and 70^th day（P 〉 0.05）. Conclusion There is no evidence to indicate that 1/8 LD50, 1/4 LD50 dose have reproductive toxicology（P 〉0.05）. High dose of DHPO（ 1/2 LD50） has some degrees of reproductive toxicology, but can recover within 42 days.