Yamamoto Y, Yamamoto K, Hayase T, Fukui Y, Shiota K
Department of Legal Medicine, Kyoto University Faculty of Medicine, Japan.
Reprod Toxicol. 1998 Mar-Apr;12(2):133-7. doi: 10.1016/s0890-6238(97)00154-8.
Wistar rat embryos were explanted on Day 10.5 of gestation and exposed in vitro to amphetamine (AMP) at concentrations of 0.1, 0.4, 0.8, 1.2, or 1.6 mM for 24 h, and the direct dysmorphogenic effects of the drug on the embryos were examined by comparisons with a control group. The viability of the cultured embryos was not affected by the AMP treatment. The yolk sac diameter was reduced at AMP concentrations of 1.2 and 1.6 mM. The crown-rump length, the somite number, and the protein content of the embryos were decreased significantly at these two doses, as was the developmental score. The frequency of malformed embryos was increased significantly at the two highest concentrations. The malformations induced in treated embryos included microcephaly, neural tube defects, incomplete rotation of the body axis, and tortuous spinal cord. Abnormal histologic changes, such as derangement and necrosis of the neuroepithelial tissue, were observed in the embryos exposed to the two highest concentrations of the drug. The observed embryotoxic effects appeared to depend on the AMP concentration. Our results demonstrated the direct embryotoxic effects of AMP on rats. The direct dysmorphogenic effect of AMP might be weaker than that of methamphetamine.
在妊娠第10.5天取出Wistar大鼠胚胎，于体外分别暴露于浓度为0.1、0.4、0.8、1.2或1.6 mM的苯丙胺（AMP）中24小时，并通过与对照组比较来检测该药物对胚胎的直接致畸作用。AMP处理未影响培养胚胎的活力。在AMP浓度为1.2和1.6 mM时，卵黄囊直径减小。在这两个剂量下，胚胎的顶臀长、体节数、蛋白质含量以及发育评分均显著降低。在两个最高浓度下，畸形胚胎的频率显著增加。处理后胚胎诱导的畸形包括小头畸形、神经管缺陷、体轴旋转不完全以及脊髓扭曲。在暴露于两个最高药物浓度的胚胎中观察到了异常的组织学变化，如神经上皮组织紊乱和坏死。观察到的胚胎毒性作用似乎取决于AMP浓度。我们的结果证明了AMP对大鼠有直接胚胎毒性作用。AMP的直接致畸作用可能比甲基苯丙胺弱。
