Selective Alterations in the Profiles of Newly Synthesized Proteins by Acetaminophen (APAP) and its Dimethylated Analogues: Relationship to Oxidative Stress
Acetaminophen (N-acetyl-p-aminophenol, APAP), one of the most widely used analgesic, antipyretic drugs currently available, when taken in excess of therapeutic doses can be activated by cytochrome P-450 to a highly reactive metabolite, Nacetylbenzoquinoneimine (NAPQI) (Dahlin, et al., 1984). NAPQI has been characterized as a strong electrophile and a potent oxidizing agent (Blair, et al., 1980) and both properties can lead to adverse effects on cellular metabolism (Albano, et al., 1985; Porubek, et al., 1987; Birge, et al., 1988). In order to more effectively evaluate the mechanisms of action of APAP and their physiological consequences, it becomes crucial not only to identify the early metabolic events that are altered, but also whether the functional impairments can be restored or have become irreversible.
KeywordsAntipyretic Drug Selective Alteration Acetaminophen Hepatotoxicity APAP Toxicity Strong Electrophile
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