TISSUE ACYLCARNITINE AND ACYL-COENZYME-A PROFILES IN CHRONICALLY HYPERAMMONEMIC MICE TREATED WITH SODIUM BENZOATE AND SUPPLEMENTARY L-CARNITINE

The aim of the present study, was to establish the hepatic profile of acyl-coenzyme A (acyl-CoA) in relation to the hepatic profile of acylc arnitines in chronically hyperammonemic spf mice (hereditary deficienc y in ornithine transcarbamylase) treated with sodium benzoate alone or in combination with L-carnitine. The muscular profile of the acylcarn itines and the stability of sarcolemma were also assessed in the same mice. Following administration of sodium benzoate, we observed decreas es in hepatic total and free coenzyme A and in acetyl-CoA, which was a ccompanied by an increase in hepatic acyl-CoA. This treatment also res ulted in increased free carnitine, decreased total carnitine, and decr eased short and medium chain acylcarnitines in the liver. Increases in plasma creatine kinase levels, muscular free, total, and in short and medium chain acylcarnitines were also observed in this treatment grou p. In mice receiving a combination of sodium benzoate and L-carnitine, increases in free and total coenzyme A, acetyl-CoA and in free, total and esterified hepatic carnitines were observed. In this treatment gr oup, the plasma level of creatine kinase was found to be reduced, whil e the free muscular carnitine was increased. Our results indicate that sodium benzoate is implicated in the decrease of total hepatic coenzy me A, through either an inhibition of CoA synthesis or activation of i ts degradation. The inhibition distribution of hepatic coenzyme-A and of hepatic and muscular carnitine (free or esterified) is altered foll owing administration of sodium benzoate which results in a further des tabilization of the sarcolemma induced by hyperammonemia. Supplemental treatment with L-carnitine was shown to have a positive effect by inc reasing hepatic coenzyme A and carnitine levels and restoring the stab ility of the sarcolemma caused by the treatment of sodium benzoate alo ne.