acetaminophen
Acetaminophen (Tylenol) is a commonly used analgesic drug.
Acetaminophen is detoxified in the liver through sulfation and glucuronidation, and small amounts are converted by cytochrome P-450-catalyzed oxidation to an electrophilic, highly toxic metabolite.
This metabolite itself is detoxified by interaction with GSH. When large doses of the drug are ingested, GSH is depleted, and thus the toxic metabolites accumulate in the cell, destroy nucleophilic macromolecules, and covalently bind proteins and nucleic acids.
The decrease in GSH concentration, coupled with covalent binding of toxic metabolites, increases drug toxicity, resulting in massive liver cell necrosis, usually 3 to 5 days after the ingestion of toxic doses.
This hepatotoxicity correlates with lipid peroxidation and can be reduced by administration of antioxidants, suggesting that the oxidative damage may be more important than covalent binding in the ultimate toxicity of the drug.
References
Robbins
Cohen SD, Khairallah EA: Selective protein arylation and acetaminophen-induced hepatotoxicity. Drug Metab Rev 29:59, 1997.