Acetaminophen-induced hepatotoxicity

Jack A. Hinson, Lance R. Pohl, Terrence Monks, James R. Gillette

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

In large doses the commonly used analgesic acetaminophen produces a centrilobular hepatic necrosis in man and experimental animals. The toxicity is mediated by a reactive metabolite formed by a cytochrome P-450 mixed-function oxidase system in hepatic microsomes. Following therapeutic doses the reactive metabolite is efficiently detoxified by glutathione. Following large doses, however, the total hepatic glutathione concentration is decreased to approximately 20% of normal and the reactive metabolite covalently binds to protein. Changes in protein covalent binding caused by various treatments correlates with changes in the incidence and severity of the hepatic necrosis. The reactive metabolite is believed to be N-acetylimidoquinone and is apparently formed by a previously uncharacterized mechanism for cytochrome P-450.

Original languageEnglish (US)
Pages (from-to)107-116
Number of pages10
JournalLife Sciences
Volume29
Issue number2
DOIs
StatePublished - Jul 13 1981
Externally publishedYes

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Acetaminophen
Metabolites
Liver
Cytochrome P-450 Enzyme System
Glutathione
Necrosis
Microsomes
Mixed Function Oxygenases
Protein Binding
Toxicity
Analgesics
Animals
Proteins
Incidence
Therapeutics

ASJC Scopus subject areas

  • Pharmacology

Cite this

Hinson, J. A., Pohl, L. R., Monks, T., & Gillette, J. R. (1981). Acetaminophen-induced hepatotoxicity. Life Sciences, 29(2), 107-116. https://doi.org/10.1016/0024-3205(81)90278-2

Acetaminophen-induced hepatotoxicity. / Hinson, Jack A.; Pohl, Lance R.; Monks, Terrence; Gillette, James R.

In: Life Sciences, Vol. 29, No. 2, 13.07.1981, p. 107-116.

Research output: Contribution to journalArticle

Hinson, JA, Pohl, LR, Monks, T & Gillette, JR 1981, 'Acetaminophen-induced hepatotoxicity', Life Sciences, vol. 29, no. 2, pp. 107-116. https://doi.org/10.1016/0024-3205(81)90278-2
Hinson, Jack A. ; Pohl, Lance R. ; Monks, Terrence ; Gillette, James R. / Acetaminophen-induced hepatotoxicity. In: Life Sciences. 1981 ; Vol. 29, No. 2. pp. 107-116.
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