Effects of sulphur-containing compounds on paracetamol activation and covalent binding in a mouse hepatic microsomal system.
The interactions of cysteamine, N-acetylcysteine, 2-mercaptopropionylglycine and methionine with N-acetyl 4-aminophenol (paracetamol) have been examined during its metabolism to a covalently bound product in an in vitro mouse hepatic microsomal system. Of the compounds used only methionine failed to reduce the amount of covalently bound [3H]paracetamol-derived radioactivity. These results indicate that the effecitveness of methionine in reducing paracetamol hepatotoxicity in vivo is achieved by mechanisms other than those involving direct interactions with the hepatic mixed-function oxidase system or its oxidation products. In contrast, cysteamine, N-acetylcysteine and 2-mercaptopropionylglycine can directly inhibit the binding of [3H]paracetamol-derived radioactivity in vitro, and may do so by processes which affect both the formation and the subsequent binding of a reactive paracetamol metabolite.
D000082:Acetaminophen / Q000378:metabolism*; D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D003543:Cysteamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008715:Methionine / Q000494:pharmacology; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000378:metabolism; D013455:Sulfur / Q000494:pharmacology*; D008625:Tiopronin / Q000494:pharmacology
D000082:Acetaminophen; D003543:Cysteamine; D013455:Sulfur; D008715:Methionine; D008625:Tiopronin; D006899:Mixed Function Oxygenases; D000111:Acetylcysteine