Acetaminophen toxicity to cultured rat embryos.
We tested the effects of acetaminophen on cultured rat embryo development. When added directly to culture media at 300 microM, a concentration approximately twice the human therapeutic blood level, acetaminophen caused abnormalities in the cultured embryos. Sera from both rats and monkeys following gavage with acetaminophen were also toxic to cultured embryos. The sera toxicities were related to acetaminophen concentrations, and the toxicity could be removed by serum dialysis. With regard to the metabolism of acetaminophen, glutathione levels in the yolk sac decreased in a concentration related fashion with addition of the drug. Also, buthionine sulfoximine, an inhibitor of glutathione synthesis, appeared to enhance acetaminophen embryo toxicity, and N-acetylcysteine, a glutathione precursor, appeared to protect embryos from acetaminophen toxicity. These results suggested that acetaminophen embryo toxicity resulted from direct exposure of embryos to acetaminophen and not a maternal metabolite.
Weeks
B S
BS
Center for Environmental Health, Department of Animal Science, University of Connecticut, Storrs.
Gamache
P
P
Klein
N W
NW
Hinson
J A
JA
Bruno
M
M
Khairallah
E
E
D000082:Acetaminophen / Q000097:blood / Q000633:toxicity*; D000818:Animals; D019328:Buthionine Sulfoximine; D046508:Culture Techniques; D005260:Female; D005978:Glutathione / Q000378:metabolism; D008253:Macaca mulatta; D008431:Maternal-Fetal Exchange / Q000187:drug effects; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013723:Teratogens
D013723:Teratogens; D008717:Methionine Sulfoximine; D000082:Acetaminophen; D019328:Buthionine Sulfoximine; D005978:Glutathione