Acetaminophen hepatotoxicity in vivo is not accompanied by oxidant stress.
Hepatotoxic doses of acetaminophen in Fischer 344 rats did not increase biliary efflux of oxidized glutathione. Pretreatment of the animals with bis(2-chloroethyl)-N-nitrosourea inhibited hepatic glutathione reductase by 73 percent but did not potentiate the hepatotoxicity of acetaminophen and did not produce an increase in biliary efflux of oxidized glutathione in response to acetaminophen. Hepatic protein thiol content was not depleted by acetaminophen. A proposed role for oxidant stress mechanisms mediated either by reactive oxygen species or by the direct oxidant action of a reactive metabolite in acetaminophen-induced hepatotoxicity is unsubstantiated and unlikely.
D000082:Acetaminophen / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001646:Bile / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009336:Necrosis; D010084:Oxidation-Reduction; D051381:Rats; D011916:Rats, Inbred F344
D000082:Acetaminophen; D005978:Glutathione