title: Antidotal effect of lipopolysaccharide against acetaminophen-induced mortality in mice.
abstract: The possibility that pretreatment with LPS (lipopolysaccharide obtained from Escherichia coli), an immune system stimulant and interferon inducer, could prevent the hepatotoxic effects of acetaminophen (NAPAP) was investigated in mice. When mice were pretreated with LPS (4 mg/kg), intraperitoneally for 24 hr the mortality caused by NAPAP was considerably reduced. Histological examination of the livers and leakage of the enzymes into the blood demonstrated that NAPAP-induced necrosis was decreased in LPS-treated mice compared to that induced by NAPAP alone. Pretreatment with 400 mg/kg or 800 mg/kg of NAPAP decreased the amount of covalently-bound acetaminophen metabolites. Since the level of hepatic glutathione and microsomal cytochrome P-450 were depressed in these experiments, it is concluded that LPS depresses the cytochrome P-450 species responsible for the formation of the toxic metabolites and that less reactive species are available for binding to cell macromolecules.
authors.affiliation: Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku College of Pharmacy, Sendai, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ishikawa
authors.forename: K
authors.initials: K
authors.lastname: Tanno
authors.forename: M
authors.initials: M
authors.lastname: Sasaki
authors.forename: Y
authors.initials: Y
authors.lastname: Takayanagi
authors.forename: K
authors.initials: K
authors.lastname: Sasaki
mesh_terms: D000082:Acetaminophen / Q000378:metabolism / Q000633:toxicity*; D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051379:Mice; D013997:Time Factors
chemical_list: D008070:Lipopolysaccharides; D000082:Acetaminophen; D003577:Cytochrome P-450 Enzyme System; D000633:Aminopyrine N-Demethylase; D005978:Glutathione