PMID: 3214175Dec 1, 1988Paper

Potentiation in the intact rat of the hepatotoxicity of acetaminophen by 1,3-bis(2-chloroethyl)-1-nitrosourea

Archives of Biochemistry and Biophysics
D NakaeJ L Farber

Abstract

Studies of the killing of cultured hepatocytes by acetaminophen indicate that the cells are injured by an oxidative stress that accompanies the metabolism of the toxin (J. L. Farber et al. (1988) Arch. Biochem. Biophys. 267, 640-650). The present report documents that the essential features of the killing of cultured hepatocytes by acetaminophen are reproduced in the intact animal. Male rats had no evidence of liver necrosis 24 h after administration of up to 1000 mg/kg of acetaminophen. Induction of mixed function oxidase activity by 3-methylcholanthrene increased the hepatotoxicity of acetaminophen. Inhibition of glutathione reductase by 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) potentiated the hepatotoxicity of acetaminophen in male rats induced with 3-methylcholanthrene. Whereas the pretreatment with BCNU reduced the GSH content by 40%, a comparable depletion of GSH by diethylmaleate did not potentiate the toxicity of acetaminophen. The antioxidant diphenylphenylenediamine (25 mg/kg) and the ferric iron chelator deferoxamine (1000 mg/kg) prevented the liver necrosis produced by 500 mg/kg acetaminophen in rats pretreated with BCNU. Neither protective agent prevented the fall in GSH produced by acetaminophen. It is conclude...Continue Reading

References

Dec 31, 1987·Biochemical and Biophysical Research Communications·M E KyleJ L Farber
Feb 15, 1985·Biochemical and Biophysical Research Communications·R J GersonJ L Farber
Nov 27, 1985·Biochemical and Biophysical Research Communications·C V Smith, J R Mitchell
Oct 1, 1974·European Journal of Biochemistry·D J Worthington, M A Rosemeyer
Nov 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·G BellomoS Orrenius

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Citations

Jun 9, 1993·Biochemical Pharmacology·G M Adamson, A W Harman
Apr 1, 1993·European Journal of Pharmacology·J LindenthalT Taylor
Nov 4, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Carol R GardnerDebra L Laskin
Jun 1, 1996·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·E KobayashiY Konishi

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