Protective effect of L-carnitine on hyperammonemia.

Inborn errors of the urea cycle, liver malfunction and drug-induced hepatotoxicity are causes of life-threatening encephalopathies arising from hyperammonemia. L-Carnitine prevented entirely ammonia toxicity in mice when injected intraperitoneally 30 min before a lethal dose of ammonium acetate. Survival depends on the dose of L-carnitine injected, e.g., 0, 60, 70, 80 and 100% with 0, 1, 2, 8 and 16 mmol L-carnitine/kg, respectively. At the highest doses L-carnitine abolishes the convulsions that accompany acute ammonia intoxication. At lower doses it delayed their onset. The protective effect was associated with a marked decrease of blood ammonia, while in unprotected mice ammonemia was lethal in less than 15 min. When sustained hyperammonemia was induced by urease injections, protection was also obtained. The mechanism of protection is under investigation, however, since L-carnitine facilitates fatty acid entry into mitochondria, possibly ATP or reducing equivalents are increased.