Alterations of urinary acetylcarnitine in valproate-treated rats: the effect of L-carnitine supplementation.

Urinary excretion of acetylcarnitine was measured by high-performance liquid chromatography in two experimental groups of valproate-treated rats. In the urine of mature rats weighing 180 to 200 g treated with valproate (500 mg/kg/day), acetylcarnitine levels were higher than those in controls on days 4 and 7, while L-carnitine-supplemented rats showed lower levels than the valproate group. The valproate-treated rats showed an increased acetylcarnitine/acylcarnitine ratio on and after day 4, while the L-carnitine-supplemented rats showed no significant change compared to the controls on any days. In the urine of immature rats weighing 80 to 90 g treated with valproate (50 mg/kg/day), acetylcarnitine levels were increased after the 14th day of treatment. These results suggest that an increase in urinary acetylcarnitine occurs when small doses of valproate are administered for a longer time. We speculate that increased acetylcarnitine is not a product of beta-oxidation in mitochondria, because L-carnitine supplementation decreases the acetylcarnitine levels. Although the mechanism of acetylcarnitine excretion during valproate administration is not clear, L-carnitine supplementation is effective in decreasing the level of urinary acetylcarnitine and keeping the acetylcarnitine/acylcarnitine ratio normal.