THE EFFECT OF VALPROIC ACID ON ZN-65 DISTRIBUTION IN THE PREGNANT RAT
THE EFFECT OF VALPROIC ACID ON ZN-65 DISTRIBUTION IN THE PREGNANT RAT
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DOI：
10.1093/jn/119.4.607
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发表时间：
1989-04-01
影响因子：
4.2
通讯作者：
HURLEY, LS
中科院分区：
文献类型：
--
作者：
KEEN, CL;PETERS, JM;HURLEY, LS
在妊娠第13 d灌胃后24 h，观察丙戊酸对Sprague-Dawley大鼠母体和胚胎组织中65Zn分布的影响。与对照组相比，丙戊酸处理显著提高了母体肝脏中65Zn的保留率，而降低了子宫、胎盘和胚胎中65Zn的保留率。与对照组相比，经丙戊酸处理的母鼠肝脏的凝胶层析显示出更高的65Zn计数，并与分子量为6500的蛋白峰相关，这是锌结合蛋白金属硫蛋白的近似分子量。这些结果支持了丙戊酸致畸性的观点，部分原因是由于药物诱导的锌在母体肝脏中的隔离导致母体血浆锌减少，随后胚胎锌摄取减少，从而诱导胚胎锌缺乏。
The effect of valproic acid on the distribution of gavaged 65Zn in maternal and embryonic tissue of Sprague-Dawley rats was examined 24 h after gavaging of the drug on d 13 of pregnancy. Valproic acid treatment resulted in a significantly higher retention of 65Zn in maternal liver and lower amounts in uterus, placenta and embryos than in controls. Compared to controls, gel chromatography of maternal liver from valproic acid-treated dams showed higher 65Zn counts associated with a protein peak of molecular weight of 6,500, the approximate molecular weight of the Zn-binding protein metallothionein. These results support the idea that the teratogenicity of valproic acid is in part due to an induction of embryonic Zn deficiency secondary to a drug-induced sequestering of Zn into maternal liver that results in a decrease in maternal plasma Zn and subsequent reduction in embryonic Zn uptake.