Itami T, Kanoh S
Nihon Yakurigaku Zasshi. 1982 May;79(5):357-67.
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.
在妊娠大鼠中研究了热原（脂多糖，LPS）增强乙酰水杨酸（ASA）对胎儿毒性的作用机制。LPS显著增强了雄性大鼠中ASA的致死性。在妊娠第15天接受单剂量ASA（125至500mg/kg，口服）的母鼠中，略微观察到ASA的胎儿毒性，包括胎儿死亡、吸收、生长迟缓以及骨骼异常（肋骨波浪状和胸骨节不对称），但LPS（20μg/kg，静脉注射）使其明显增加。在直至足月的母体体重增加方面也观察到LPS增强了ASA的毒性。LPS使ASA及其主要代谢产物水杨酸（SA）的血浆浓度升高。SA的组织浓度也按以下顺序升高：胎盘、脑、胎儿、子宫、肝脏和肾脏。胎盘和胎儿的ATP水平不受单独ASA的影响，但LPS和ASA共同作用使其显著降低。
