Mackler B, Grace R, Tippit D F, Lemire R J, Shepard T H, Kelley V C
Teratology. 1975 Dec;12(3):291-6. doi: 10.1002/tera.1420120311.
Pregnant rats were treated with various inhibitors of mitochondrial oxidative energy metabolism and with lowered oxygen tension, and the embryo fetuses examined for the occurrence of congenital malformations and for changes in enzymatic activities. Treatment with all agents tested resulted in the production of skeletal anomalies. Sodium phenobarbital was the most teratogenic of the drugs tested and produced a high incidence of malformations which included cleft palate, tail anomalies, spinal retroflexion, domed head, and facial hypoplasia. Diphenylhydantoin produced a low incidence of syndactyly and oligodactyly. In addition to its effects on fetal growth and development chloramphenicol appeared to interfere with implantation. Tissue preparations from embryos exposed to sodium phenobarbital and chloramphenicol showed markedly lowered levels of DPNH oxidase activity. Cytochrome oxidase activity was also markedly lowered in the preparations from chloramphenicol-exposed embryos. Enzyme activities in preparations from embryos exposed to malonate and diphenylhydantoin appeared unaffected, although the drugs are strong inhibitors of electron transport in vitro; the lack of apparent effect may be due to the fact that both drugs do not bind to the enzyme preparations and were diluted 100- to 200-fold during preparation and assay of the tissue homogenates.
给怀孕大鼠使用各种线粒体氧化能量代谢抑制剂并降低氧张力，然后检查胚胎胎儿是否出现先天性畸形以及酶活性的变化。所有测试药物的处理均导致骨骼异常。苯巴比妥钠是所测试药物中致畸性最强的，产生了高畸形发生率，包括腭裂、尾巴异常、脊柱后弯、圆头和面部发育不全。苯妥英钠导致并指和少指的发生率较低。除了对胎儿生长发育有影响外，氯霉素似乎还会干扰着床。暴露于苯巴比妥钠和氯霉素的胚胎组织制剂显示DPNH氧化酶活性水平明显降低。暴露于氯霉素的胚胎制剂中的细胞色素氧化酶活性也明显降低。暴露于丙二酸和苯妥英钠的胚胎制剂中的酶活性似乎未受影响，尽管这两种药物在体外是电子传递的强抑制剂；缺乏明显影响可能是由于这两种药物都不与酶制剂结合，并且在组织匀浆的制备和测定过程中被稀释了100至200倍。
