Ogata A, Yoneyama M, Sasaki M, Suzuki K, Imamichi T
Food Chem Toxicol. 1987 Feb;25(2):119-24. doi: 10.1016/0278-6915(87)90144-x.
To study the effects of SKF-525A, an inhibitor of cytochrome P-450, and of sodium phenobarbital (PB), a drug-metabolizing enzyme inducer, on the teratogenicity of thiabendazole (TBZ), pregnant mice were given ip either a single dose of 40 mg SKF-525A/kg 1 hr before oral dosing with 250 or 500 mg TBZ/kg or a dose of 75 mg PB/kg/day on three consecutive days before oral administration of a dose of 500 or 1000 mg TBZ/kg. In either case the TBZ dose was given on day 9 of gestation. All foetuses were removed from the uterus on day 18 of gestation, and were examined for external and skeletal anomalies. The spectrum of malformations in the groups of mice pretreated with SKF-525A or PB was similar to that in mice treated only with TBZ. In the group pretreated with SKF-525A, however, the incidence of resorbed foetuses was higher than in the group treated with TBZ alone and there was a tendency towards an increase in the number of foetuses with skeletal fusion and reduction deformity of the limbs, an anomaly characteristically induced by TBZ. On the other hand, in mice pretreated with PB, the incidence of resorbed foetuses tended to be lower, the numbers and body weights of live foetuses were higher and the incidence of external and skeletal malformations was lower than in the groups treated with TBZ only. No reduction deformity of the limbs was observed in the groups pretreated with PB. These results suggest that with TBZ the ultimate teratogen may be the parent compound rather than its metabolites.
为研究细胞色素P - 450抑制剂SKF - 525A以及药物代谢酶诱导剂苯巴比妥钠（PB）对噻苯达唑（TBZ）致畸性的影响，给怀孕小鼠腹腔注射以下药物：在口服250或500mg/kg TBZ前1小时，单次注射40mg/kg SKF - 525A；或者在口服500或1000mg/kg TBZ前连续三天每天注射75mg/kg PB。两种情况下，TBZ均在妊娠第9天给药。在妊娠第18天从子宫中取出所有胎儿，检查其外部和骨骼异常情况。用SKF - 525A或PB预处理的小鼠组中的畸形谱与仅用TBZ处理的小鼠相似。然而，在SKF - 525A预处理组中，吸收胎儿的发生率高于仅用TBZ处理的组，并且骨骼融合和肢体减少畸形（TBZ特有的一种异常）的胎儿数量有增加的趋势。另一方面，在PB预处理的小鼠中，吸收胎儿的发生率趋于降低，活胎儿的数量和体重更高，外部和骨骼畸形的发生率低于仅用TBZ处理的组。在PB预处理组中未观察到肢体减少畸形。这些结果表明，对于TBZ，最终致畸物可能是母体化合物而非其代谢产物。
