PMID: 2096383Nov 1, 1990Paper

Antidotal effect of lipopolysaccharide against acetaminophen-induced mortality in mice

Pharmacology & Toxicology
M IshikawaK Sasaki

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.

References

Jan 1, 1977·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·R Kato
Feb 1, 1979·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·K SasakiG Takayanagi
Feb 1, 1976·Biochemical Pharmacology·F GorodischerS J Yaffe
Sep 1, 1976·Archives of Biochemistry and Biophysics·D M Bissell, L E Hammaker
Jan 1, 1986·Annual Review of Pharmacology and Toxicology·G J Mannering, L B Deloria
Jun 30, 1982·Biochemical and Biophysical Research Communications·G SinghN Stebbing
Oct 1, 1981·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·K SasakiG Takayanagi
May 1, 1959·Archives of Biochemistry and Biophysics·G L ELLMAN

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Citations

Dec 25, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Grace L SuStewart C Wang
Dec 3, 2009·Journal of Toxicology and Environmental Health. Part a·Jane F MaddoxPatricia E Ganey
Jul 13, 2011·Liver International : Official Journal of the International Association for the Study of the Liver·Hartmut JaeschkeMary L Bajt

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