Toxicity of protein hydrolysate solutions: Correlation of glutamate dose and neuronal necrosis to plasma amino acid levels in young mice

Stegink, Lewis D.; Shepherd, James A.; Brummel, Marvin C.; Murray, Louise M.

doi:10.1016/0300-483x(74)90020-1

Cited by 42 publications

(9 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This dose resulted in a 15-min plasma Glu concentration of 2.10 m M , more than 17-fold higher than baseline (122 µ M ). Our findings are consistent with reports that ARC neuronal damage in the mouse does not occur with a plasma Glu concentration below 500 µ M [24]. A plasma Glu increase of even 12-fold produces surprisingly little change in the Glu content of the ARC nucleus (∼0.12 µmol/mg protein) [25], even though the ARC Glu content may not peak until 3 h after MSG administration [7].…”

Section: Discussionsupporting

confidence: 82%

“…Although plasma Glu concentrations peak at 30 min following oral ingestion, they return to normal by 90 min after all three routes of administration [7, 8, 22, 23]. Identical oral loads of MSG may result in plasma Glu values ranging from 3 to 15 times baseline [7, 21, 23, 24], however, and attain peak levels less than one half those after intraperitoneal, and one third of those after subcutaneous injection [8]. Our treatment of nursing, sated mouse pups by subcutaneous injection of specific MSG doses avoids potential inconsistencies in the total dosage/BW received [7, 25], and achieves a more consistent level and period of Glu exposure than after other routes of administration [8, 17, 18].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Exogenous Glutamate Enhances Glutamate Receptor Subunit Expression during Selective Neuronal Injury in the Ventral Arcuate Nucleus of Postnatal Mice

Hu¹,

Fernstrom²,

Goldsmith³

1998

Neuroendocrinology

View full text Add to dashboard Cite

Administration of high doses of glutamate (Glu) leads to selective neurodegeneration in discrete brain regions near circumventriclular organs of the early postnatal mouse. The arcuate nucleus-median eminence complex (ARC-ME) appears to be the most Glu-sensitive of these brain regions, perhaps because of the intimate relationships between its neurons and specialized astroglial tanycytes. To investigate the mechanism of Glu-induced neuronal loss, we administered graded doses of the sodium salt of glutamate (MSG) to postnatal mice, measured their plasma Glu concentrations, and performed microscopic analyses of the ARC-ME region 5 h after treatment. Nursing, 7-day-old mouse pups (CD1, Charles River, Hollister, Calif.) were injected subcutaneously with single doses of 0.1–0.5 or 1.0–4.0 mg of MSG per g BW, or with water vehicle alone. Mice were decapitated 5 h later and the brains immediately fixed by immersion in buffered aldehydes. Frontal vibratome tissue sections at comparable levels of the ARC-ME were examined by light microscopy. A dose of 4.0 mg MSG/g BW caused neurodegeneration throughout the ARC region, while 1.0 mg/g MSG resulted in less extensive damage. Injection of 0.2 mg MSG/g BW, which raised plasma Glu concentrations 17-fold after 15 min, was the minimum dose tested at which nuclear and cytoplasmic changes were observed in a small group of subependymal neurons near the lateral recesses of the third ventricle. Higher doses of 0.3–0.5 mg MSG caused injury to additional neurons situated farther laterally, but damage remained confined to the ventral region of the ARC nucleus. Ultrastructural examination showed some subependymal neurons with pyknotic nuclei, reduced cytoplasmic volume, and swollen subcellular organelles, while others had fragmented and condensed nuclear material. Immunostaining for tyrosine hydroxylase indicated that dopamine neurons were spared at the threshold dose, but suffered damage after higher doses of MSG. Immunostaining for Glu receptor subtypes revealed that 0.2 mg MSG/g BW enhanced neuronal expression of NMDAR1 and of GluR2/4, and that higher doses of MSG preferentially increased NMDAR1 expression in injured neurons. These results extend previous reports of Glu sensitivity in the ARC-ME region of 7-day postnatal mice. A dose of 0.2 mg MSG/g BW s.c. causes clear but discrete injury to specific subependymal neurons of undetermined phenotype near the base of the third ventricle. Slightly higher doses of MSG evoke damage of additional neurons confined to the ventral region of the ARC traversed by tanycytes. These same greater amounts of MSG promote dose-related increase in the expression of NMDAR1 more than of GluR2/4 in injured ARC neurons, suggesting that elevated Glu receptor levels may contribute to or be related to neuronal cell death. Taken together with previous findings, the data suggest that Glu responsitivity in the ARC-ME of the postnatal mouse may result from transient developmental conditions involving the numerical ratios and juxtaposition between tanycytes and neurons...

show abstract

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Exogenous Glutamate Enhances Glutamate Receptor Subunit Expression during Selective Neuronal Injury in the Ventral Arcuate Nucleus of Postnatal Mice

Hu¹,

Fernstrom²,

Goldsmith³

1998

Neuroendocrinology

View full text Add to dashboard Cite

show abstract

“…Doses of aspartate or glutamate that produce plasma glutamate plus aspartate concentrations lower than 60 pmol/dl (6 to 10 times normal) do not produce lesions in the infant rodent (44)(45)(46)(47)(48)(49). Lesions are noted only when very large doses of glutamate or aspartate are administered and plasma glutamate plus aspartate concentrations exceed 60 to 100 pmol/dl.…”

Section: Discussionmentioning

confidence: 99%

Plasma Glutamate Concentrations in 1-Year-Old Infants and Adults Ingesting Monosodium L-Glutamate in Consommé

et al. 1986

View full text Add to dashboard Cite

ABSTRACT. This study tested the hypothesis that infants metabolize glutamate more slowly than adults. Eight l-yrold infants ingested 160 ml of a beef consommi: providing monosodium L-glutamate at 0, 25, and 50 mg/kg body weight. Plasma glutamate and aspartate concentrations were measured sequentially for the next 2 h. The results were compared to values noted in nine adult subjects ingesting equivalent doses of monosodium L-glutamate in consomme. In adults, mean (+ SD) peak plasma glutamate concentrations were 5.59 f 1.56, 10.2 + 2.08, and 17.0 f The ability of human infants to metabolize MSG has been one area of concern in considering glutamate's safety as a food additive. Olney (1-3) postulated that human infants metabolized dicarboxylic amino acids more slowly than adults, and projected theoretical plasma glutamate concentrations for infants at much higher values than those for adults following glutamate ingestion.The present study directly tested this hypothesis by measuring the plasma glutamate and aspartate response in 1-yr-old infants fed a beef consommi containing graded doses of MSG. The results of these studies were compared with previously reported (4) plasma glutamate and aspartate values in normal adults administered equivalent doses of MSG in the same consomm6. MATERIALS AND METHODSEight infants (four male, four female) were studied. The proposed study was explained to at least one of the parents and informed, written consent was obtained. The protocol of the study was reviewed and approved by the Committee on Research Involving Human Subjects of the University of Iowa.Each child ingested 160 ml of beef consommC providing 0,25, and 50 mg/kg body weight of added MSG in a balanced crossover design. Each infant was randomly assigned to receive consommi providing either 0 or 25 mg MSG/kg body weight, followed by the other dose at least 1 wk later. After these two tests had been completed and the results evaluated, each infant ingested consommi providing MSG at 50 mg/kg body weight. All tests were begun at 0800 h following an overnight fast.The monohydrate of monosodium L-glutamate was purchased from a local grocery store (Accent International, Pet Incorporated, St. Louis MO). The soup was prepared from a special beef consommk base supplied by the Ajinomoto Company (Tokyo, Japan). The composition of the soup base is shown in Table 1. As noted in Table 1, 160 ml of reconstituted soup contained 37 mg of free glutamate, for a mean dose of 4.1 mg/kg body weight. Thus, the true final doses of MSG studied in these infants were 4.1, 29.1 and 54.1 mg/kg body weight.Each infant was assigned by random allocation into one of two equal groups that differed with respect to time of blood sampling. Since only four blood samples were obtained from each infant after dosing, two different sampling schedules were utilized so as to obtain samples during the entire absorptive period. Blood samples at each dose level were obtained from four infants at 0, 30, 60, and 120 min After ingestion of the consommG Blood samples from ...

show abstract

“…Evidence from animal models suggests that a spike in plasma glutamate is the mechanism by which glutamate causes symptoms. 47,48 Research has shown that when MSG is consumed on its own (i.e., in a calorie-free beverage), the plasma concentration of glutamate peaks 30 minutes to 1 hour after ingestion. 39,58 However, when MSG is ingested with carbohydrates, measurable plasma concentrations of glutamate are not achieved.…”

Section: Discussionmentioning

confidence: 99%

Association between salt substitutes/enhancers and changes in sodium levels in fast-food restaurants: a cross-sectional analysis

2018

View full text Add to dashboard Cite

Toxicity of protein hydrolysate solutions: Correlation of glutamate dose and neuronal necrosis to plasma amino acid levels in young mice

Cited by 42 publications

References 22 publications

Exogenous Glutamate Enhances Glutamate Receptor Subunit Expression during Selective Neuronal Injury in the Ventral Arcuate Nucleus of Postnatal Mice

Exogenous Glutamate Enhances Glutamate Receptor Subunit Expression during Selective Neuronal Injury in the Ventral Arcuate Nucleus of Postnatal Mice

Plasma Glutamate Concentrations in 1-Year-Old Infants and Adults Ingesting Monosodium L-Glutamate in Consommé

Association between salt substitutes/enhancers and changes in sodium levels in fast-food restaurants: a cross-sectional analysis

Contact Info

Product

Resources

About