Sucheston M E, Hayes T G, Eluma F O
Teratog Carcinog Mutagen. 1986;6(6):537-46. doi: 10.1002/tcm.1770060607.
The anticonvulsant drugs carbamazepine, Na valproate, and phenytoin have been suspected as a cause of human congenital defects. The malformations produced may include cleft lip and/or palate, heart defects, skeletal defects, and low body weights. Since the toxic effects of these anticonvulsant drugs manifest themselves in terms of fetal growth retardation, evaluation of the state of ossification attained in the fetus is important. In the present study, pregnant CD-1 mice received on gestational days 8-16 an oral dose of 375, 563, 938 mg/kg of carbamazepine; or 225, 338, 563 mg/kg of Na valproate; or 50, 75, 125 mg/kg of phenytoin. These groups were compared to two control groups. On day 17, the dams were killed by cervical dislocation and one-third of the live fetuses were weighed and fixed for skeletal examination. Photographs were taken of the fore- and hindlimb skeletons. From these photographs, the length and width measurement of ossified regions of the humerus and femur were determined using a Zeiss Video-Plan Morphometrics Computer. Of the three anticonvulsant drugs studied, the greatest correlation between reduced fetal weights and retarded ossification of the long bones was phenytoin at the 125 mg/kg dosage. Our results also showed that long bone ossification, when compared to the fetal weight, indicated that 59-66% of variability in weight is predictable by bone measurements.
抗惊厥药物卡马西平、丙戊酸钠和苯妥英钠被怀疑是导致人类先天性缺陷的原因。所产生的畸形可能包括唇裂和/或腭裂、心脏缺陷、骨骼缺陷以及低体重。由于这些抗惊厥药物的毒性作用表现为胎儿生长迟缓，因此评估胎儿的骨化状态很重要。在本研究中，怀孕的CD-1小鼠在妊娠第8至16天口服剂量为375、563、938毫克/千克的卡马西平；或225、338、563毫克/千克的丙戊酸钠；或50、75、125毫克/千克的苯妥英钠。将这些组与两个对照组进行比较。在第17天，通过颈椎脱臼处死母鼠，三分之一的活胎称重并固定用于骨骼检查。拍摄前肢和后肢骨骼的照片。从这些照片中，使用蔡司视频平面形态计量学计算机测定肱骨和股骨骨化区域的长度和宽度。在所研究的三种抗惊厥药物中，在125毫克/千克剂量下，苯妥英钠导致胎儿体重减轻与长骨骨化迟缓之间的相关性最大。我们的结果还表明，与胎儿体重相比，长骨骨化表明59-66%的体重变异性可通过骨骼测量预测。
