The toxicity of metabolites of sodium valproate in cultured hepatocytes.
Sodium valproate is hepatotoxic in both humans and rat hepatocytes. The toxicity is dose related and frequently associated with simultaneous ingestion of drugs which induce the drug metabolizing system. For these reasons, metabolites of sodium valproate were tested for toxicity using rat hepatocyte cultures. The sodium salts of three metabolites, 2-propylpent-4-enoate, 4-hydroxyvalproate, and perhaps 5-hydroxyvalproate, were toxic in this system. In addition, 2-propylpent-4-enoate was toxic in a dose-related fashion. All are omega and omega-1 oxidation products in the microsome-mediated pathway of valproate metabolism.
D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008099:Liver / Q000187:drug effects*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014635:Valproic Acid / Q000378:metabolism / Q000633:toxicity*
D014635:Valproic Acid; D007770:L-Lactate Dehydrogenase