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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.
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P. David Josephy (2005) studied this question.
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