Prevention of ammonia toxicity by L-carnitine: metabolic changes in brain.
L-Carnitine when injected in mice 30 min before an LD100 of ammonium acetate (12 mmol/kg body weight, intraperitoneal) reduced mortality (100% survival with 16 mmol L-carnitine/kg) and prevented the appearance of symptoms of ammonia toxicity. Brain ammonia decreased in the animals given L-carnitine. Ammonia decreased the levels of glutamate in brain; they were partially restored by L-carnitine, which also reduced the increase in brain glutamine in animals given only ammonia. The redox state of the brain was altered following ammonia intoxication. The ratio of lactate to pyruvate in the cytosol increased while that of glutamate to alpha-ketoglutarate in the mitochondria decreased. These ratios were partially restored by L-carnitine. The implications of these findings are discussed relative to the mechanism of ammonia toxicity.
D000085:Acetates / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002331:Carnitine / Q000494:pharmacology*; D005973:Glutamine / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction
D000085:Acetates; D005973:Glutamine; D009243:NAD; C018824:ammonium acetate; D002331:Carnitine