Action of the antiepileptic drug, valproic acid, on fatty acid oxidation in isolated rat hepatocytes.
Valproate at 0.1 to 5 mM strongly inhibited oxidation of 1-(14C)-palmitate in isolated rat hepatocytes. Valproate at the same concentrations markedly decreased ketogenesis from 1 mM oleate. Valproate in a dose up to 5 mM did not significantly affect cellular concentration of ATP but lowered beta-hydroxybutyrate/acetoacetate and lactate/pyruvate ratios which paralleled its effect on ketogenesis. Moreover concomitant acetyl-CoA levels were drastically decreased by valproate. From this it may be concluded that inhibition of fatty acid oxidation by valproate results in reduced production of two carbons units and a drop of NADH/NAD+ ratio in rat hepatocyte. This suggests that valproate seriously interferes with beta-oxidation of physiological long-chain fatty acids.
D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D007657:Ketone Bodies / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014635:Valproic Acid / Q000494:pharmacology*
D005227:Fatty Acids; D007657:Ketone Bodies; D014635:Valproic Acid