Valproic acid-induced increase in carnitine acetyltransferase in rat hepatocytes is not due to an induction of peroxisomes.

Valproic acid induced a dose-dependent increase in carnitine acetyltransferase (CAT) activity in rat hepatic mitochondrial fractions isolated by differential centrifugation. An increase in CAT and carnitine palmitoyltransferase (CPT) also occurred in cultured rat hepatocytes in a concentration-and time-dependent fashion. A maximal increase of 8-fold in the activity of CAT and 2-fold in the activity of CPT was induced by 3 mM valproic acid in 72 h. Valproic acid had no effect on cytochrome P-450 levels in cultured rat hepatocytes. Electron-microscopic examination of rat hepatocytes showed that there was no increase in the number of peroxisomes but there was a marked proliferation of mitochondria in parallel with an increase in glutathione level and succinic dehydrogenase in the liver cells after incubation with valproic acid in vitro.