[Studies on the pharmacological bases of fetal toxicity of drugs. (I). Relation of fetal toxicity and tissue concentration of acetylsalicylic acid with pyrogen in pregnant rats].

The mechanism for the enhancing effect of pyrogen (lipopolysaccharide, LPS) on the fetal toxicity of acetylsalicylic acid (ASA) was studied in pregnant rats. The lethality of ASA was significantly enhanced by LPS in male rats. The fetal toxicity of ASA including fetal death, resorption, growth retardation, and skeletal anomalies (wavy rib and asymmetry of sternebra) was slightly observed in the dams that received a single dose of ASA (125 to 500 mg/kg, p.o.) on the 15th day of gestation, but it was markedly increased by LPS (20 micrograms/kg, i.v.). The enhancement of the toxicity of ASA by LPS was also observed in the maternal body weight gain until term. The plasma concentrations of ASA and salicylic acid (SA), the major metabolite of ASA, were increased by LPS. The tissue concentrations of SA were also increased in the following order: placenta, brain, fetus, uterus, liver and kidney. The ATP levels of placenta and fetus were not influenced by ASA alone, but markedly decreased by both LPS and ASA.