skf - 525a、n -甲基- 2 -硫代咪唑、苯巴比妥钠或3 -甲基胆蒽预处理对乙硫脲致仓鼠致畸性的影响

K. S. Khera, C. Whalen, F. Iverson
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引用次数: 13

摘要

研究了乙烯硫脲致畸作用在仓鼠体内的致畸性,以确定其致畸作用最脆弱的器官。妊娠第11天,以1.5%的明胶水溶液分别给药600、1200、1800或2400 mg ETU/kg。这些剂量水平均未产生任何明显的母体毒性。然而,在2400mg /kg剂量下,胎儿毒性表现为明显的死亡、体重下降,以及与剂量相关的脑积水、小脑发育不良、腭裂、迟发性颅骨骨化和趾外畸形发生率。脑室系统和小脑是最易发生畸形的部位。在单独的实验中研究了代谢调节剂对ETU致畸性的影响。在妊娠第11天通过胃插管给药,在N -甲基- 2 -硫代咪唑灌胃剂量为200或400 mg/kg后立即给药,或在SKF - 525A灌胃剂量为40 mg/kg后1小时给药。SKF‐525A预处理显著提高…
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Effects of pretreatment with skf‐525a, n‐methyl‐2‐thioimidazole, sodium phenobarbital, or 3‐methylcholanthrene on ethylenethiourea‐induced teratogenicity in hamsters
Teratogenicity of ethylenethiourea (ETU) was studied in the hamster to define the organ most vulnerable to its teratogenic action. A single intragastric dose of 600, 1200, 1800 or 2400 mg ETU/kg was given in 1.5% aqueous gelatin on d 11 of pregnancy. None of these dose levels produced any apparent maternal toxicity. However, fetal toxicity was apparent in the form of deaths, reduced body weight at the 2400 mg/kg dose, and dose‐related incidences of hydrocephalus, hypoplastic cerebellum, cleft palate, delayed calvarial ossification, and ectrodactyly. The ventricular system of the brain and the cerebellum were among the most sensitive sites for malformations. Effects of metabolic modifiers on the teratogenicity of ETU were studied in separate experiments. Doses of ETU were administered by gastric intubation on d 11 of pregnancy either immediately after an intragastric dose of 200 or 400 mg N‐methyl‐2‐thioimidazole/kg, or 1 h after an ip 40‐mg/kg dose of SKF‐525A. The SKF‐525A pretreatment significantly incr...
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