Correlation of glutamate plus aspartate dose, plasma amino acid concentration and neuronal necrosis in infant mice.
Eight-day-old mice were given by gavage glutamate and aspartate mixtures providing each amino acid at 125, 250 or 500 mg/kg body weight (250, 500 and 1000 mg total dicarboxylic amino acids/kg) and the degree and extent of neuronal necrosis were determined. Similar studies were carried out in mice given monosodium L-glutamate at 250 or 500 mg/kg body weight. Plasma aspartate and glutamate concentrations were determined at each dose level. No animal given either glutamate or the glutamate plus aspartate mixture at 250 mg/kg developed neuronal necrosis. However, neuronal necrosis developed in 30% of animals given glutamate at 500 mg/kg (12+/-2 necrotic neurons/section in the region of maximal damage) and in 17% of animals given 250 mg glutamate/kg plus 250 mg aspartate/kg (11-13 necrotic neurons/section in the region of maximal damage). The threshold mean peak plasma glutamate plus aspartate concentration associated with neuronal necrosis was 128+/-24 mumol/dl. Using these data, and previously published data for aspartate-induced neurotoxicity (Finkelstein et al. Toxicology 1983, 29, 109), the individual threshold plasma glutamate and aspartate concentrations associated with neuronal necrosis were calculated to be 110 mumol/dl for aspartate and 75 mumol/dl for glutamate.
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000473:pathology; D001224:Aspartic Acid / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000008:administration & dosage / Q000097:blood / Q000633:toxicity*; D051379:Mice; D009336:Necrosis / Q000139:chemically induced; D009474:Neurons / Q000187:drug effects* / Q000473:pathology
D005971:Glutamates; D001224:Aspartic Acid