Rollins D E, von Bahr C, Glaumann H, Moldéus P, Rane A
Science. 1979 Sep 28;205(4413):1414-6. doi: 10.1126/science.38505.
A reactive metabolite of acetaminophen is hepatotoxic in humans when the drug is ingested in large overdoses. The ability of the human fetal and adult liver to oxidize acetaminophen by trapping the potentially toxic metabolite as a glutathione conjugate has been measured. Oxidation by fetal liver was approximately ten times slower than by adult liver. However, there was a definite increase in acetaminophen oxidation with fetal age. Isolated human fetal liver cells conjugated acetaminophen with sulfate but not with glucuronic acid. The results indicate that the human fetal liver is able to detoxify acetaminophen by conjugation. However, it also catalyzes the formation of an active metabolite of acetaminophen through oxidation. Hence the fetus remains at risk should a large dose of the drug cross into the fetal circulation.
当对乙酰氨基酚大量过量摄入时，其一种反应性代谢产物对人类具有肝毒性。已对人类胎儿肝脏和成人肝脏通过将潜在有毒代谢产物捕获为谷胱甘肽共轭物来氧化对乙酰氨基酚的能力进行了测定。胎儿肝脏的氧化速度比成人肝脏慢约十倍。然而，随着胎龄增加，对乙酰氨基酚的氧化有明显增加。分离出的人类胎儿肝细胞将对乙酰氨基酚与硫酸盐而非葡萄糖醛酸结合。结果表明，人类胎儿肝脏能够通过结合作用使对乙酰氨基酚解毒。然而，它也通过氧化作用催化形成对乙酰氨基酚的活性代谢产物。因此，如果大剂量药物进入胎儿循环，胎儿仍有风险。
