Valproic acid increased markedly both carnitine acetyltransferase (CAT) and carnitine palmyitoyltransferase (CPT) in a dose dependent fashion in rat hepatocytes. A maximal increase of 800% of CAT and 200% of CPT was induced by 3 mM valproic acid in 72 h. Even though valproic acid increased the peroxisomal marker enzyme there was no increase in the number of peroxisomes in cells as examined by electron microscopy. However, there was a marked increase in the number of mitochondria which could account for the increase in CAT and CPT. Another peroxisomal marker, namely a 80 kD protein, was not increased by valproic acid indicating that valproic acid is not an inducer of peroxisomes. Valproic acid did not change cytochrome P-450 but increased markedly liver cell GSH.
