The molecular toxicology of acetaminophen.
The history of the development of the analgestic drug acetaminophen is reviewed with an emphasis on the characteristics of its overdose toxicity. The P450-catalyzed oxidation of acetaminophen generates a reactive electrophile that binds covalently to proteins. Involvement of specific P450 enzymes in acetaminophen toxicity can be probed by experiments with knock-out mice. The identification of specific target proteins may help to clarify the mechanism of acetaminophen hepatoxocity.
David Josephy
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Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada. djosephy@uoguelph.ca
D000082:Acetaminophen / Q000009:adverse effects / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004347:Drug Interactions; D000431:Ethanol / Q000009:adverse effects; D006801:Humans; D010084:Oxidation-Reduction; D011485:Protein Binding
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System