Ogata A, Fujitani T, Yoneyama M, Sasaki M, Suzuki K
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Food Chem Toxicol. 1989 Feb;27(2):117-23. doi: 10.1016/0278-6915(89)90006-9.
The effects of cysteine (CYS), glutathione (GSH) and diethylmaleate (DM) on the teratogenicity of thiabendazole (TBZ) were investigated. On day 9 of gestation mice were given ip a dose of 0, 50 or 100 mg CYS/kg body weight, or 0, 400 or 800 mg GSH/kg, or 0, 0.05, 0.10, 0.15 or 0.60 DM/kg. One hr later they were dosed orally with 0, 250, 500 or 1000 mg TBZ/kg. All foetuses were removed from the uterus on day 18 of gestation, and were examined for external and skeletal anomalies. The number of malformed foetuses was increased in mice pretreated with CYS or GSH and was decreased in those pretreated with DM, in comparison with numbers in the corresponding group treated with TBZ alone GSH pretreatment enlarged the area under the curve (AUC) of TBZ and 5-hydroxyTBZ, a representative metabolite, in foetal tissue. DM pretreatment reduced the AUC of TBZ and 5-hydroxyTBZ.
研究了半胱氨酸(CYS)、谷胱甘肽(GSH)和马来酸二乙酯(DM)对噻苯达唑(TBZ)致畸性的影响。在妊娠第9天,给小鼠腹腔注射剂量为0、50或100mg CYS/kg体重,或0、400或800mg GSH/kg,或0、0.05、0.10、0.15或0.60mg DM/kg。1小时后,给它们口服0、250、500或1000mg TBZ/kg。在妊娠第18天从子宫中取出所有胎儿,并检查其外部和骨骼异常情况。与仅用TBZ处理的相应组相比,用CYS或GSH预处理的小鼠中畸形胎儿的数量增加,而用DM预处理的小鼠中畸形胎儿的数量减少。GSH预处理增大了胎儿组织中TBZ及其代表性代谢物5-羟基TBZ的曲线下面积(AUC)。DM预处理降低了TBZ和5-羟基TBZ的AUC。