Acetaminophen Toxicity in Isolated Hepatocytes
Acetaminophen is an analgesic and antipyretic agent which is readily available and extensively used throughout the world. Therapeutic doses of up to 4g daily produce few side-effects but doses in excess of 10–15g can cause hepatic necrosis whilst larger doses are often fatal 1.
KeywordsCovalent Binding Reactive Metabolite Mercapturic Acid Butyl Hydroperoxide Acetaminophen Toxicity
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- 11.D. S. Davies, Drug hepatotoxicity: formation and importance of reactive metabolites, in: “Drug Reactions and the liver”, M. Davis, J. M. Tredger, and R. Williams, eds, Pitman Medical, London, (1981).Google Scholar
- 12.A. C. Huggett, The Mechanism of Paracetamol Toxicity, PhD Thesis, University of London.Google Scholar
- 15.L. B. G. Tee, A. R. Boobis, A. C. Huggett, and D. S. Davies, Reversal of paracetamol toxicity in isolated hepatocytes by dithiothreitol, (Submitted for publication 1985 ).Google Scholar
- 16.L. F. Prescott, Glutathione: a protective mechanism against hepatotoxicity, Biochem, Soc. Trans. 10: 84–85 (1982).Google Scholar
- 17.S. Kashiwamata, and D. M. Greenberg, Studies on cystathionine synthase of rat liver properties of the highly purified enzyme, Biochim. et Biophys. acta 212: 488–500 (1979).Google Scholar
- 18.D. Deme, 0. Durieu-Trautmann, and F. Chatagner, The thiol groups of rat liver cystathionas: Influence of pyridoxal phosphate,l-homoserine and l-alanine on the effect of p-chloromercuribenzoate and 5,5’-Dithiobis-(2-nitrobenzoate) on the enzyme, Eur. J. Biochem. 20: 269–274 (1971).Google Scholar
- 19.G. F. Seeling, and A. Meister, a-Glutamylcysteine synthetase. Interactions of an essential sulfhydryl group. J. Biol. Chem. 259: 3534–3538 (1984).Google Scholar
- 20.L. B. G. Tee, T. Seddon, A. R. Boobis, and D. S. Davies, Drug metabolising activity of freshly isolated human hepatocytes, Brit. J. Clin. Pharmac. 19: 279–294 (1985).Google Scholar