Protective Effects of Glutathione on the Teratogenicity of 5-Fluorouracil in Mice and Rats

Abstract The influence of endogenous or exogenous glutathione (GSH) on the teratogenicity of 5-fluorouracil (5-FU) was studied after a single intraperitoneal injection of 5-FU at a teratogenic dose (20 or 30 mg/kg) to ICR mice on day 11 of gestation. Pretreatment with intravenous GSH at 300 mg/kg, 5 minutes before 5-FU administration, decreased the incidence of oligodactyly induced with 5-FU and lowered the fetal mortality, but it did not prevent the decrease in body weight of fetuses. Pretreatment with intraperitoneal diethylmaleate, which decreases the level of endogenous GSH, at 350 mg/kg 6 hours before 5-FU administration increased the incidence of oligodactyly. Pretreatment orally with GSH at a dose of 300 mg/kg 30 minutes before intraperitoneal injection of 5-FU at 30 mg/kg to Wistar rats on day 13 of gestation decreased the frequency of limb malformations, but it did not prevent the decrease in body weight of fetuses.