Yamamoto Y, Yamamoto K, Abiru H, Fukui Y, Shiota K
Department of Legal Medicine, Kyoto University Faculty of Medicine, Japan.
Biol Neonate. 1995;68(1):33-8. doi: 10.1159/000244215.
Wistar rat embryos were explanted on day 10.5 of gestation and exposed in vitro to methamphetamine (MAMP) at a concentration of 0.1, 0.2, 0.4, 0.6, or 0.8 mM for 24 h, and the direct teratogenic effects of the drug on rat embryos were examined. The viability of cultured embryos was not affected by the MAMP treatment. The yolk sac diameter was reduced at MAMP concentrations of 0.6 and 0.8 mM. The crown-rump length and the somite number of the embryos decreased significantly and dependently on the MAMP concentrations at 0.4-0.8 mM. The protein content was also significantly reduced at 0.4-0.8 mM. The developmental score was decreased in a concentration-dependent manner. The frequency of malformed embryos significantly increased at 0.6 and 0.8 mM. The malformations induced in treated embryos included microcephaly, neural tube defects, incomplete rotation of the body axis, and tortuous spinal cord. Abnormal histological changes such as derangement and necrosis in the neuroepithelial tissue were observed in embryos exposed to high concentration of the drug. Our results revealed the direct embryotoxic and teratogenic effects of MAMP in the rat.
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、0.2、0.4、0.6或0.8 mM的甲基苯丙胺（MAMP）中24小时，检测该药物对大鼠胚胎的直接致畸作用。MAMP处理对培养胚胎的活力没有影响。在MAMP浓度为0.6和0.8 mM时，卵黄囊直径减小。在MAMP浓度为0.4 - 0.8 mM时，胚胎的顶臀长度和体节数显著减少，且呈浓度依赖性。在0.4 - 0.8 mM时，蛋白质含量也显著降低。发育评分呈浓度依赖性降低。在0.6和0.8 mM时，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、身体轴旋转不完全和脊髓扭曲。在暴露于高浓度药物的胚胎中观察到神经上皮组织紊乱和坏死等异常组织学变化。我们的结果揭示了MAMP对大鼠的直接胚胎毒性和致畸作用。
