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Correlation of glutamate plus aspartate dose, plasma amino acid concentration and neuronal necrosis in infant mice

Food and Chemical Toxicology
Publication Date
DOI: 10.1016/0278-6915(85)90103-6


Abstract 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 μmol/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 μmol/dl for aspartate and 75 μmol/dl for glutamate.

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