Immunochemical Detection of Drug-Protein Adducts in Acetaminophen Hepatotoxicity
In overdose the over-the-counter analgesic acetaminophen may produce a centrilobular hepatic necrosis (1,2). In addition this toxicity may be accompanied by nephrotoxicity (1,3). The mechanism of hepatotoxicity has been studied extensively in experimental animals. It was shown that inhibition of the drug metabolizing enzymes resulted in a diminution of the toxicity, whereas induction of the drug metabolizing enzymes resulted in an increase in the toxicity (4). These data indicated that metabolism of acetaminophen was critical in the development of the toxicity. Moreover, administration of radiolabeled acetaminophen resulted in covalent binding of radiolabel to protein in the necrotic hepatocytes (5). In vitro experiments revealed that the metabolism was by a cytochrome P-450 dependent mechanism (6). It was postulated that covalent binding of this metabolite to critical proteins was the mechanism of the hepatotoxicity.
KeywordsSodium Selenite Covalent Binding Western Immunoblot Reactive Metabolite Protein Adduct
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