The covalent binding to protein of valproic acid and its hepatotoxic metabolite, 2-n-propyl-4-pentenoic acid, in rats and in isolated rat hepatocytes.


The covalent binding of radioactivity to protein following administration of 14C-labeled analogs of valproic acid (VPA) and a hepatotoxic metabolite thereof, 2-n-propyl-4-pentenoic acid (delta 4-VPA), was investigated in male rats. Covalent binding occurred in a number of tissues, the level of binding being greatest to proteins in liver for each compound… (More)