Carnitine musculaire chez les souris hyperammoniémiques: effet du traitement au benzoate de sodium

Abstract

The object of this study was to measure carnitine levels in skeletal muscles of experimental mice with acute, subacute, and chronic hyperammonemia, with or without sodium benzoate treatment. Normal Swiss–ICR mice in which acute hyperammonemia was created through intraperitoneal injection of ammonium acetate showed a significant decrease in free carnitine in the skeletal muscles. The same phenomenon was observed in spf mice with chronic congenital hyperammonemia caused by an X-linked deficiency of liver ornithine transcarbamylase. In spf mice with subacute hyperammonemia created through treatment with an arginine-deficient diet, free carnitine of muscles increased compared with basal levels seen in chronic hyperammonemia. The changes in carnitine metabolism during chronic and subacute hyperammonemia were accompanied by a significant increase of creatine kinase levels in the plasma, which are an index of damage to the sarcolemma. A decrease in free and esterified levels of carnitine in the muscles was observed among normal mice treated with sodium benzoate. A decrease in esterified carnitine was also noticed among spf mice given an acute treatment with sodium benzoate as well as among normal and spf mice given a prolonged treatment with sodium benzoate. Plasma creatine kinase levels were high in normal mice, after both acute and prolonged treatments. However, the levels in spf mice treated with sodium benzoate were not significantly different from those in untreated spf controls in which a significant increase in plasma creatine kinase was already caused by chronic hyperammonemia. This study indicates that the metabolism and (or) distribution of carnitine go through significant changes during various levels of hyperammonemia, and that a treatment with sodium benzoate causes a secondary deficiency in carnitine of muscles. The increase in plasma levels of creatine kinase could signify a secondary effect of these factors on the function or the integrity of the sarcolemma.Key words: hyperammonemia, carnitine, sodium benzoate, mice, muscle.