Abstract
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.
Key words
Hepatotoxicity - Clinical dose of valproate - Carnitine - Immature rat
