[Studies on the pharmacological bases of fetal toxicity of drugs (VII). Enhancement effect of bacterial pyrogen on the fetal toxicity of salicylic acid].

We reported previously that the acute and fetal toxicities of aspirin (ASA) were enhanced by bacterial endotoxin (LPS). In order to clarify the mechanism of the enhancement by LPS, the effects of LPS on the toxicities of salicylic acid (SA), the main metabolite of ASA, were investigated in rats. The following results were obtained: 1) The acute toxicity of SA was significantly potentiated by LPS in male rats. The LD50 of SA with LPS was about one third of that of SA alone. 2) The increase of maternal body weight was inhibited significantly after administration of SA (383 mg/kg, p.o.) with LPS (20 micrograms/kg, i.v.), but not after administration of SA alone. 3) The fetal toxicity of SA including fetal death, resorption, growth retardation and skeletal variations was slightly observed in the dam receiving a single dose of SA on the 15th day of pregnancy, but it was markedly increased by LPS (20 micrograms/kg, i.v.). 4) The half-life period of SA in plasma was increased significantly by the co-administration of LPS in male rats after administration of ASA or SA. All of these phenomena in the rats given SA closely resembled the phenomena previously reported in the rats given ASA. These results suggest that SA might play a main role in the acute and fetal toxicities of ASA, and one of the mechanism of the enhancement effect by LPS on ASA-induced fetal toxicity might be related to the increase of SA concentration in the fetus.