Xiao Kai, Wang Li, Liu Yuqing, Peng Cheng, Yan Guangyan, Zhang Jianjun, Zhuo Yanqiang, Li Hongxia
National Chengdu Center for Safety Evaluation of Drugs, West China Hospital, Sichuan University, Chengdu, Peoples Republic of China.
Birth Defects Res B Dev Reprod Toxicol. 2007 Jun;80(3):208-12. doi: 10.1002/bdrb.20116.
Aconitum is widely used in traditional medicine for its anti-inflammatory, analgesic, and cardiotonic properties. Knowledge is limited, however, on its effects on embryonic development.
Whole embryo culture was applied to explore the effects of aconitine on rat embryos during their critical period of organogenesis. All embryos isolated on gestational day 9.5 were exposed to 0, 1, 2.5, 5, and 10 microg/ml of aconitine with and without S9 mix, and scored for their growth and differentiation at the end of the 48-hr culture period.
The embryonic growth and development were adversely affected at the concentration of 2.5 microg/ml aconitine without S9 mix, represented as reduced crown-rump length and head length, decreased number of somites, and lower morphologic score. When the concentration of aconitine was increased to 5 microg/ml, it induced severe dysmorphogenesis effects, including cardiac defect (undivided cardiac tube and inflated pericardial cavity), irregular somites, and brain malformation (e.g., narrow brain vesicles). In the presence of S9 mix, Aconitine toxicity to rat embryos was reduced to a certain extent.
Our study showed that Aconitine had direct embryotoxic effects during the rat organogenetic period. NOAEL was about 1 microg/ml and metabolism in S9 mix could induce the attenuation of Aconitine toxicity. Until more is known about the effects of Aconitine in pregnant women, we suggest its use should be treated with caution.
乌头因其抗炎、镇痛和强心特性而在传统医学中被广泛使用。然而,关于其对胚胎发育的影响,相关知识有限。
采用全胚胎培养法,在大鼠器官发生关键期探究乌头碱对胚胎的影响。将妊娠第9.5天分离的所有胚胎暴露于0、1、2.5、5和10微克/毫升的乌头碱中,有无S9混合物,在48小时培养期结束时对其生长和分化进行评分。
在无S9混合物的情况下,2.5微克/毫升乌头碱浓度对胚胎生长和发育产生不利影响,表现为顶臀长度和头长度缩短、体节数量减少以及形态学评分降低。当乌头碱浓度增加到5微克/毫升时,会诱导严重的畸形发生效应,包括心脏缺陷(心脏管未分隔和心包腔膨胀)、不规则体节以及脑畸形(如脑泡狭窄)。在有S9混合物存在的情况下,乌头碱对大鼠胚胎的毒性在一定程度上降低。
我们的研究表明,乌头碱在大鼠器官发生期具有直接胚胎毒性作用。无可见有害作用水平约为1微克/毫升,S9混合物中的代谢可诱导乌头碱毒性减弱。在更多了解乌头碱对孕妇的影响之前,我们建议应谨慎使用。