Liang Aihua, Li Chunying, Liu Ting, Zhao Yong, Cao Chunyu, Xun Baoyun, Wang Jinhua
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China.
Zhongguo Zhong Yao Za Zhi. 2009 Nov;34(21):2794-8.
To observe the effect of Cinnabaris on mouse embryos after pregnant mice were treated by Cinnabaris in different periods of pregnancy.
Two separate experiments were performed: First, Cinnabaris was orally given into pregnant mice at the doses of 0.08, 0.4, 4.0 g x kg(-1) from D6 to D19 after pregnancy; Second, Cinnabaris was orally given into mice at the same doses mentioned above from D14 prior to pregnancy until D19 after pregnancy. All animals were sacrificed on D 20 of pregnancy by caesarean section. The numbers of survival, dead and absorbed fetuses were calculated and the survival fetus weight was measured. The survival fetuses were treated by two methods: One third survival fetuses were fixed and stained by Bouin solution for organ examination and the remaining two thirds fetuses were stained for skeleton examination.
No obvious embryo toxicity was observed in the first experiment at Cinnabaris dose levels of 0.08, 0.4, or 4 g x kg(-1) x d(-1). There was no significant effect on embryonic development and the numbers of the survival, dead and absorbed fetus. No obvious malformations on appearance, organ, and skeleton examination of fetuses were found. The second experiment showed that the rates of abortion and absorbed fetus in 0.4, 4 g x kg(-1) x d(-1) Cinnabaris group were higher but without statistical significance compared with control group. Appearance and organ examination of Cinnabaris groups fetus showed no obvious malformation, but skeleton malformation was found in 0.4, 4 g x kg(-1) x d(-1) groups (the rates of skeleton malformation were 46.7% and 77.8%, respectively).
No obvious embryonic development toxicity was observed when Cinnabaris was orally given in intermediate and late pregnant period, but the embryos in the early stage of pregnancy was more sensitive to Cinnabaris. When Cinnabaris was given prior to pregnancy until the whole period of pregnancy, it may be harmful for the fetuses at above the dose level 0.08 g x kg(-1) x d(-1) (equivalent to 5 times clinical intake dose), both in a dose-dependent manner.
观察妊娠小鼠在孕期不同阶段经朱砂处理后对小鼠胚胎的影响。
进行了两个独立实验:其一,在妊娠第6天至第19天,以0.08、0.4、4.0 g·kg⁻¹的剂量给妊娠小鼠灌胃朱砂;其二,在妊娠前第14天至妊娠后第19天,以上述相同剂量给小鼠灌胃朱砂。所有动物在妊娠第20天通过剖腹产处死。计算存活、死亡和吸收胎儿的数量,并测量存活胎儿的体重。对存活胎儿采用两种方法处理:三分之一的存活胎儿用Bouin液固定染色用于器官检查,其余三分之二的胎儿染色用于骨骼检查。
在第一个实验中,当朱砂剂量为0.08、0.4或4 g·kg⁻¹·d⁻¹时,未观察到明显的胚胎毒性。对胚胎发育以及存活、死亡和吸收胎儿的数量均无显著影响。在胎儿的外观、器官和骨骼检查中未发现明显畸形。第二个实验表明,0.4、4 g·kg⁻¹·d⁻¹朱砂组的流产率和吸收胎儿率高于对照组,但无统计学意义。朱砂组胎儿的外观和器官检查未发现明显畸形,但在0.4、4 g·kg⁻¹·d⁻¹组发现骨骼畸形(骨骼畸形率分别为46.7%和77.8%)。
在妊娠中期和晚期灌胃朱砂未观察到明显的胚胎发育毒性,但妊娠早期的胚胎对朱砂更敏感。在妊娠前至整个孕期给予朱砂时,在高于0.08 g·kg⁻¹·d⁻¹(相当于临床摄入量的5倍)的剂量水平下,可能对胎儿有害,且呈剂量依赖性。