Protective effect of D,L-carnitine on valproate-induced hyperammonemia and hypoketonemia in primary cultured rat hepatocytes.

The effect of D,L-carnitine on sodium valproate (VPA)-induced hyperammonemia and hypoketonemia was investigated in primary cultures of rat hepatocytes. Administration of VPA (0.1 to 1.0 mM) resulted in an increase of ammonia and a decrease of ketone bodies in culture medium. When D,L-carnitine was added with VPA to the medium, the level of ammonia decreased significantly and that of ketone bodies increased. A significant negative relationship was found between the concentrations of ammonia and the ketone bodies in the medium following administration of D,L-carnitine. Our results suggested that VPA suppressed the urea cycle metabolism and that a protective effect of D,L-carnitine on ketone metabolism was probably due to the reversal of the inhibition of beta-oxidation.