Glutathione and cysteine enhance and diethylmaleate reduces thiabendazole teratogenicity in mice.
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.
Ogata
A
A
Department of Toxicology, Tokyo Metropolitan Research Laboratory of Public Health, Japan.
Fujitani
T
T
Yoneyama
M
M
Sasaki
M
M
Suzuki
K
K
D000014:Abnormalities, Drug-Induced; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000494:pharmacology*; D004347:Drug Interactions; D005260:Female; D005333:Fetus / Q000032:analysis / Q000378:metabolism; D005978:Glutathione / Q000494:pharmacology*; D008298:Maleates / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D013827:Thiabendazole / Q000032:analysis / Q000378:metabolism / Q000633:toxicity*
D008298:Maleates; C014476:diethyl maleate; D005978:Glutathione; D003545:Cysteine; D013827:Thiabendazole