Carnitine metabolism and morphometric change of liver mitochondria in valproate-treated rats

The effect of the administration for 7 or 28 days of 50 mg/kg/day valproate (VPA) on carnitine metabolism and morphological changes of liver mitochondria in immature rats was evaluated. The dose of VPA was almost the same as that we clinically used. Carnitine concentrations in serum, red blood cells (RBC), muscle, liver and urine were measured. The rats treated with VPA for 7 days showed no significant change in carnitine concentration in each tissue examined or by morphology. In the serum, RBC and muscle of rats treated with VPA for 28 days, free carnitine levels decreased, while acylcarnitine levels and the ratio of acylcarnitine to free carnitine (acyl/free ratio) increased. Mitochondrial enlargement was also induced and urinary acyl/free ratio of VPA treated rats was higher than that of control rats after the 14th day of the treatment. These results suggest that carnitine deficiency and morphometric changes in mitochondria occur time dependent even if the dose of VPA is clinically appropriate.