Abstract
The metabolism of 2-n-propyl-4-pentenoic acid (delta 4-VPA), a putative toxic biotransformation product of valproic acid (VPA), was examined in the isolated perfused rat liver. Metabolites excreted into perfusion medium and bile were characterized by GLC and GC/MS techniques and their identities were verified by synthesis. A total of eight metabolites was detected, the structures of which could be best accounted for by initial oxidation reactions catalyzed by either cytochrome P-450 or the fatty acid beta-oxidation complex. Evidence was obtained which indicates that metabolism of delta 4-VPA by each of these enzyme systems can lead to the generation of chemically reactive intermediates which may contribute to the hepatotoxic properties of VPA.
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|
