Fujimoto T, Fuyuta M, Kiyofuji E, Hirata S
Teratology. 1979 Oct;20(2):297-301. doi: 10.1002/tera.1420200213.
Previous investigations (Fuyuta et al., '76, '79) have shown that a single oral administration of 25 mg/kg methylmercuric chloride (MMC) to pregnant ICR mice on day 10 of pregnancy induced cleft palate in a remarkably high incidence in fetuses. Based on these findings, the present study dealing with the prevention of cleft palate by Tiopronin, (2-mercaptopropionyl glycine, Tp), was initiated. Twenty females in the positive control group were given 25 mg/kg MMC orally on day 10 of pregnancy and then given physiological saline intraperitoneally. Twenty females in the negative control group were given distilled water orally and then given saline intraperitoneally. Cleft palate was found in 98.1% of fetuses in the positive control group and none of them in the negative control group. Twenty females were pretreated with a single oral dose of 25 mg/kg MMC on day 10 of pregnancy and were posttreated with Tp intraperitoneally, immediately and at every 24, 48 and 72 hours after the MMC treatment. The doses of Tp were 320, 160 and 80 mg/kg/day. The incidences of cleft palate in fetuses were reduced to 1.49, 31.3 and 47.8% in the Tp-treated groups with the doses of 320, 160 and 80 mg/kg/day, respectively. Tiopronin could effectively prevent the expected incidence of cleft palate. Other types of abnormalities as well as fetotoxicity represented by reduced fetal body weight were also effectively prevented with the Tp-treatment.
先前的研究(Fuyuta等人,1976年,1979年)表明,在妊娠第10天给怀孕的ICR小鼠单次口服25毫克/千克甲基氯化汞(MMC),可使胎儿腭裂的发生率显著升高。基于这些发现,本研究开始探讨硫普罗宁(2-巯基丙酰甘氨酸,Tp)对腭裂的预防作用。阳性对照组的20只雌性小鼠在妊娠第10天口服25毫克/千克MMC,然后腹腔注射生理盐水。阴性对照组的20只雌性小鼠口服蒸馏水,然后腹腔注射生理盐水。阳性对照组98.1%的胎儿出现腭裂,阴性对照组无一例出现腭裂。20只雌性小鼠在妊娠第10天单次口服25毫克/千克MMC进行预处理,并在MMC处理后立即以及每隔24、48和72小时腹腔注射Tp进行后处理。Tp的剂量分别为320、160和80毫克/千克/天。在分别给予320、160和80毫克/千克/天剂量Tp治疗的组中,胎儿腭裂的发生率分别降至1.49%、31.3%和47.8%。硫普罗宁可有效预防预期的腭裂发生率。Tp治疗还有效预防了其他类型的异常以及以胎儿体重减轻为代表的胚胎毒性。