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.
Murakami
K
K
Department of Pediatrics, Kansai Medical University, Osaka, Japan.
Sugimoto
T
T
Nishida
N
N
Woo
M
M
Araki
A
A
Kobayashi
Y
Y
D000108:Acetylcarnitine / Q000378:metabolism / Q000652:urine*; D000818:Animals; D002331:Carnitine / Q000008:administration & dosage / Q000494:pharmacology*; D002853:Chromatography, Liquid; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000494:pharmacology*
D014635:Valproic Acid; D000108:Acetylcarnitine; D002331:Carnitine