title: Acetaminophen: potentially toxic metabolite formed by human fetal and adult liver microsomes and isolated fetal liver cells.
abstract: 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.
mesh_terms: D000082:Acetaminophen / Q000378:metabolism* / Q000633:toxicity; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000196:embryology; D008431:Maternal-Fetal Exchange; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D011247:Pregnancy
chemical_list: D000082:Acetaminophen; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D005978:Glutathione