Effects of sulphur-containing compounds on paracetamol activation and covalent binding in a mouse hepatic microsomal...

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.