Studies on the metabolism of amino acids and related compounds in vivo. VIII. Influence of the route of administration of l-arginine.HCl on protecting rats against ammonia toxicity

Abstract

Purified l-arginine, alone as the hydrochloride, or in combination with other compounds so as to yield a nearly neutral reaction, has been administered to rats by various routes, at various times ranging from that simultaneous with the intraperitoneal injection of an LD 99.9 dose of ammonium salt, to that 2 hr. prior to the ammonia injection. The criterion employed for the effectiveness of the protecting agent under these circumstances was the quite severe one of whether the animal did or did not survive the lethal dose of ammonium salt. The most effective routes of administration of arginine, as measured by the proportion of survivors from the ammonia injection, were the intraperitoneal and the intrasplenic, the latter permitting almost complete protection at the lowest dosage levels of arginine in the shortest space of time between arginine and ammonia injections. Subcutaneous and oral routes for the administration of arginine and other agents were the poorest i.e., the lowest proportion of survivors from ammonia injection, whilst the intravenous route was only moderately effective at all levels of arginine dosages studied. It would appear that for maximum protection by arginine in the event of ammonia toxicity, a direct route to the liver should be sought. Of all the agents studied, l-arginine.HCl, the neutral salts l-arginine- l-glutamate and l-arginine- l-aspartate, the neutral peptide l-arginyl- l-glutamate, l-ornithine.HCl, and mixtures of l-arginine.HCl with sodium l-glutamate, sodium α-ketoglutarate, glucose or sodium chloride, none was more effective, and most were less effective, than l-arginine. HCl itself at the tested levels.