Studies on the metabolism of amino acids and related compounds in vivo. V. Effects of combined administration of nonprotective compounds and subprotective levels of l-arginine.HCL on ammonia toxicity in rats

Abstract

A level of l-arginine. HCl on the one hand, and of monosodium l-glutamate, l-glutamine, disodium α-ketoglutarate, monosodium l-aspartate, l-asparagine, disodium oxalacetate, l-alanine, sodium pyruvate, glucose, or sodium chloride on the other, neither of which on intraperitoneal injection will protect rats against an intraperitoneal injection of an LD 99.9 dose of ammonium acetate, will however do so when employed together. Survival of all animals was observed when 1 mmole l-arginine. HCl/kg. body weight was mixed with 4 mmoles/kg. of one of the following: glutamate, ketoglutarate, and glucose. Aspartate and its derivatives were less effective in this connection, and replacement of the 1 mmole/kg. dose of l-arginine. HCl by an equivalent amount of l-ornithine. HCl led to no protection whatever against ammonia toxicity. Each of the effective components of the mixtures, such as 1 mmole/kg. of l-arginine. HCl and 4 mmoles/kg. of l-glutamate, reduces the blood NH 3 N level of animals given a lethal dose of ammonium acetate to a significant extent, but only when employed together is the blood NH 3 N reduced to the normal level with survival of the animals. It is suggested that the effective partners in such mixtures accomplish the ammonia detoxification by involving separate mechanisms.