[Profile of hepatic and muscular acylcarnitines in chronically hyperammonemic mice after an acute treatment with sodium benzoate: dose-response study].
Sodium benzoate is conjugated with glycine in the liver and the kidney, which may cause the elimination of one mole of alpha-amino N for each mole of benzoate administered. However, muscle does not possess the enzyme activity to form benzoylglycine. The object of this study was to identify the secondary effects of acute sodium benzoate treatment on the concentrations of carnitine in liver and muscle when the glycine availability in these tissues is still assured. Our studies are based on chronically hyperammonemic spf/Y mice with a deficiency of ornithine transcarbamylase. The animals were given 2.5, 5.0 and 10.0 mmol/kg sodium benzoate intraperitoneally. Control groups of normal mice received identical treatments. Our results demonstrate that sodium benzoate influences the homeostasis of liver and muscle carnitine after only 15 minutes of treatment. We observed a reduction of short- and medium-chain acylcarnitines in the liver of normal mice, and an increase of free carnitine and long-chain acylcarnitines in the spf mice. In muscle, we found a reduction of free carnitine and short- and medium-chain acylcarnitines at doses of 5.0-10.0 mmol benzoate/kg in the normal mice. However, we observed a significant reduction of long-chain acylcarnitines in muscle tissue from spf mice. The carnitine concentrations in each tissue differ depending on the dose of sodium benzoate administered, which may suggest a biphasic effect. Our results indicate that sodium benzoate has a secondary effect on the liver and muscle concentration of carnitine from the beginning of its intramitochondrial metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)
Michalak
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A
Hôpital Sainte-Justine, Département de pédiatrie, université de Montréal, Chemin Côte-Ste-Catherine, Québec, Canada.
Qureshi
I A
IA
D000108:Acetylcarnitine / Q000032:analysis; D000641:Ammonia / Q000097:blood*; D000818:Animals; D001565:Benzoates / Q000494:pharmacology* / Q000627:therapeutic use; D019817:Benzoic Acid; D002331:Carnitine / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D008099:Liver / Q000737:chemistry* / Q000187:drug effects; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009132:Muscles / Q000737:chemistry* / Q000187:drug effects
D001565:Benzoates; D000108:Acetylcarnitine; D000641:Ammonia; D019817:Benzoic Acid; D002331:Carnitine
Profil des acylcarnitines hépatiques et musculaires chez les souris chroniquement hyperammoniémiques après un traitement aigu avec le benzoate de sodium: études dose-réponse.