The early effects of valproic acid in low doses in liver metabolism

The effect of low doses of valproic acid (VPA), 0.6 mM in arterial blood, in liver metabolism was studied. Twenty four hour fasted rats were infused into the jugular vein with VPA at a dose of 4 mg/kg/min during 50 min. The right carotid artery was also catheterized in order to draw arterial blood samples for determining VPA concentrations and acid-base parameters. After VPA infusion, a tissue sample of liver was obtained and freeze-clamped. VPA did not change the arterial blood acid-base parameters. The liver tissue concentration of pyruvate and alanine increased in VPA group while lactate concentrations did not change. Concentration of glutamine, glutamate, malate, citrate and aspartate in the liver fell significantly. These results suggest that VPA in low doses may modify the hepatic metabolism of the rat in vivo.