The effect of
hyperammonemia on plasma and urinary levels of
carnitine was studied in different groups of +/Y (normal) and spf/Y (chronically hyperammonemic) mice. Experimental models of acute and subacute
hyperammonemia were prepared in +/Y and spf/Y mice by the use of
ammonium acetate ip
injections and
arginine-free diets, respectively. In acute
hyperammonemia, the plasma levels of both free and acylcarnitines increased significantly whereas acyl/free
carnitine ratio was decreased, indicating a mobilization of
carnitine from the storage sites. The subacute
hyperammonemia model showed the same tendency in respect of plasma and urinary carnitines; however, the values in plasma were more significantly different. The effect of
sodium benzoate on plasma
carnitine levels, during both an acute and a prolonged treatment, consisted in a significant lowering of free
carnitine and a significant increase in the acyl/free
carnitine ratio, in both +/Y normal and spf/Y mouse models. The changes in the urinary profile, on
benzoate treatments, were not significant. These results demonstrate the individual effects of
hyperammonemia and
benzoate therapy on
carnitine metabolism, which may be helpful in understanding and ameliorating the therapeutic approach to hereditary hyperammonemias.