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Immunochemical Detection of Drug-Protein Adducts in Acetaminophen Hepatotoxicity

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Biological Reactive Intermediates V

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 387))

Abstract

In overdose the over-the-counter analgesic acetaminophen may produce a centrilobular hepatic necrosis (1,2). In addition this toxicity may be accompanied by nephrotoxicity (1,3). The mechanism of hepatotoxicity has been studied extensively in experimental animals. It was shown that inhibition of the drug metabolizing enzymes resulted in a diminution of the toxicity, whereas induction of the drug metabolizing enzymes resulted in an increase in the toxicity (4). These data indicated that metabolism of acetaminophen was critical in the development of the toxicity. Moreover, administration of radiolabeled acetaminophen resulted in covalent binding of radiolabel to protein in the necrotic hepatocytes (5). In vitro experiments revealed that the metabolism was by a cytochrome P-450 dependent mechanism (6). It was postulated that covalent binding of this metabolite to critical proteins was the mechanism of the hepatotoxicity.

Supported by NIH Grant 1R01 GM48749

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Author information

Authors and Affiliations

  1. Division of Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, 72205, USA

    Jack A. Hinson, Dean W. Roberts, N. Christine Halmes, Jennifer D. Gibson & Neil R. Pumford

  2. Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, Arkansas, 72079, USA

    Dean W. Roberts

Authors
  1. Jack A. Hinson
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  2. Dean W. Roberts
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  3. N. Christine Halmes
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  4. Jennifer D. Gibson
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  5. Neil R. Pumford
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Editor information

Editors and Affiliations

  1. Environmental and Occupational Health Sciences Institute, Rutgers University, Piscataway, New Jersey, USA

    Robert Snyder  & Charlotte M. Witmer  & 

  2. University of Arizona, Tuscon, Arizona, USA

    I. Glenn Sipes

  3. Medical University of South Carolina, Charleston, South Carolina, USA

    David J. Jollow

  4. University of Texas, Austin, Texas, USA

    Terrence J. Monks

  5. Thomas Jefferson University, Philadelphia, Pennsylvania, USA

    James J. Kocsis  & George F. Kalf  & 

  6. GSF Institute of Toxicology, Technical University, Munich, Germany

    Helmut Greim

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© 1996 Springer Science+Business Media New York

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Hinson, J.A., Roberts, D.W., Halmes, N.C., Gibson, J.D., Pumford, N.R. (1996). Immunochemical Detection of Drug-Protein Adducts in Acetaminophen Hepatotoxicity. In: Snyder, R., et al. Biological Reactive Intermediates V. Advances in Experimental Medicine and Biology, vol 387. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9480-9_7

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  • DOI: https://doi.org/10.1007/978-1-4757-9480-9_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-9482-3

  • Online ISBN: 978-1-4757-9480-9

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