Behavioral and electrophysiological brain effects of aspartame on well-nourished and malnourished rats

Magalhães, Paula Catirina Germano; Abadie-Guedes, Ricardo; Mendonça, Manoel Augusto Barbosa da Costa; Souza, Aline Duarte de; Guedes, Rubem Carlos Araújo

doi:10.1007/s11011-018-0361-9

Cited by 7 publications

(8 citation statements)

References 41 publications

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“…There was a significant reduction of weight in aspartame administrated group compared with control group. Similar finding was observed by Magalhães et al 2018 [48] because aspartame showed interference with metabolism, liver function and appetite of animals, increasing satiety and thus reducing food intake .However, in the current study, the body weight of the animals that were treated with MSG and ASP were lower than those within the control group. These results came in accordance with other reported studies [49] .…”

Section: Discussionsupporting

confidence: 90%

The possible neuroprotective effect of astaxanthin on monosodium glutamate and aspartame induced hippocampal changes in albino rats: (Histological and immuno-histochemical study)

Fotouh

Sayed

Altayeb

et al. 2020

Egyptian Journal of Histology

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Background: Food additives are substances added to food to improve its safety, freshness, taste, texture, or appearance. They include aroma enhancer eg : monosodium glutamate(MSG) or sweetener eg.: aspartame (ASP). Aim of the Study: This current study was performed to study the microscopic alterations induced by MSG, ASP individually and in combination and the possible protective effect of astaxanthin (AST) on those induced changes. Materials and Methods: Forty nine adult male albino rats were used in this study divided into; control group (fourteen rats) two rats for each experimental group and experimental group (thirty five rats) subdivided into seven subgroups:ASP group, MSG group, ASP andMSG group,AST group,ASP andAST group, MSG andAST group, ASPandMSG andAST group. Oral administration was done in the morning daily for 6 weeks for all groups. When the duration of the study ended, blood samples were collected from rat tail and paraffin sections were prepared from the cerebral hemisphere of each animal. They were subjected to hematoxylin and eosin stain and immunohistochemical stain for Caspase3 and Glial Fibrillary Acidic Protein (GFAP). Statistical analysis were done for assessment of body weight, reduced glutathione (GSH) and tumor necrosis factor α (TNF-α) level. Results: The groups that received ASP (I), MSG (II) individually or in combination (III) exhibited shrunken cells with darkly stained nuclei and surrounded with pericellular haloes and some areas even revealed loss of the cells with increase in immunoreactivity for GFAP and Caspase 3. These groups also showed elevation in the level of TNFα and decrease in the level of GSH. On treatment with AST groups V, VI and VII showed reduced pycknosis, decreased immunoreactivity for GFAP and Caspase 3. It also showed reduction in the level of TNFα and increased level of GSH. Conclusion: ASP and MSG individually or in combination induce alternation in hippocampus and AST administration ameliorate those changes

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Section: Discussionsupporting

confidence: 90%

The possible neuroprotective effect of astaxanthin on monosodium glutamate and aspartame induced hippocampal changes in albino rats: (Histological and immuno-histochemical study)

Fotouh

Sayed

Altayeb

et al. 2020

Egyptian Journal of Histology

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“…One common finding was the alteration of spatial orientation resulting in longer escape latencies in maze tests, such as the Morris water maze or Y-maze, upon intake of aspartame [19,39,63] or impaired flexibility of spatial memory for aspartate [122]. Another important effect is increased anxiety, explaining immobility, diminished ambulation and grooming [38], poorer performance in open field tests [63] and elevated maze-plus tests [40], reduced aggression, lengthened intervals between attacks, reduced number of bites per session [41], increased latency to reward [36], and decreased latency in passive avoidance tests for aspartatefed mice [118]. Similar phenomena consisting of signs of depression and poor spatial orientation, without effects on working memory, were evidenced in an outstanding clinical trial on healthy young student volunteers fed for 8 days on a high-aspartame diet containing 25 mg/kg/day [42].…”

Section: Neurological and Cytotoxic Effects By Activation Of Nmda And...mentioning

confidence: 99%

Aspartame Safety as a Food Sweetener and Related Health Hazards

Shaher,

Mihailescu,

Amuzescu

2023

Preprint

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Aspartame is the methyl-ester of the aspartate-phenylalanine dipeptide. Over time it became a very popular artificial sweetener. However, since its approval by the main food safety agencies, several concerns have been raised related to neuropsychiatric effects and neurotoxicity, due to its ability to activate glutamate receptors, as well as carcinogenic risks by increased production of reactive oxygen species. Within this review we critically evaluated reports concerning the safety of aspartame. Some studies evidenced subtle mood and behavioral changes upon daily high-dose intake below the admitted limit. Epidemiology studies also evidenced associations between daily aspartame intake and higher predisposition for malignant diseases like non-Hodgkin lymphomas and multiple myelomas, particularly in males, but association by chance still could not be excluded. While the debate over the carcinogenic risk of aspartame is ongoing, it is clear that its use may pose some dangers in peculiar cases, such as patients with seizures or other neurological diseases; it should be totally forbidden for patients with phenylketonuria, and reduced doses or complete avoidance are advisable during pregnancy. It would be also highly desirable for every product containing aspartame to clearly indicate on the label the exact amount of the substance and some risk warnings.

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“…In the central nervous system, it binds to and activates N-methyl D-aspartate (NMDA) ionotropic glutamate receptors, allowing Ca 2+ to enter and then activate neuronal nitric oxide synthase (nNOS), resulting in the production of nitric oxide (NO) and free oxygen/nitrogen radicals peroxynitrite (ONOO -) and NO • [1]. In vitro investigations of aspartame or aspartate binding to NMDA receptors have been carried out to determine whether pharmacological modulation of ligand-gated ion channels can improve nervous system function or reduce aberrant activity that may be the cause of nervous system illnesses [24,28,35,37,38]. Aspartate, resulted from aspartame intestinal breakdown, can efficiently activate NMDARs [9], in addition to other neurotransmitter imbalances caused by aspartate and phenylalanine [10,22].…”

Section: Introductionmentioning

confidence: 99%

An in Vitro Model of Aspartame Cytotoxicity via Heterologous Expression of Nmda Receptors

SHAHER

2023

FARMACIA

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Within the last 40 years, aspartame (L-aspartyl-L-phenylalanyl-methylester) became a very popular artificial sweetener, being introduced in over 6000 food products worldwide, including solid foods, beverages, and drugs for oral administration. However, its safety and toxicity have been subject of concern since its discovery, due to potentially harmful effects of its intestinal decomposition products: aspartate, phenylalanine, and methanol. Neuropsychological effects have been reported occasionally, such as headache, blurred vision, insomnia, torpor, memory loss, nausea, speech impairment, personality changes, loss of energy, hyperactivity, hearing problems. Our aim in the present study was to determine the effects of aspartame at various concentrations on the viability of cells transiently transfected with the combination of N-methyl-Daspartate (NMDAR) ionotropic glutamate receptor subunits NR1+NR2b, as well as to prove direct activation of NMDAR currents by aspartame via whole-cell patch-clamp experiments. CHO-K1 cells transfected with NR1+NR2b via plasmid constructs containing the two genes fused with enhanced green fluorescent protein (eGFP) gene were exposed for 2 -4 h to aspartame in progressive decimal dilutions (0.1 µM to 10 mM) and assessed by flow cytometry after propidium iodide (PI) staining, showing increased percentages of dead cells (PI+) at aspartame concentrations of 1 µM or higher, while nontransfected cells featured increased PI+ percentages at aspartame concentrations above 1 mM. We also showed in HEK293T cells transfected by electroporation with the same plasmid combination (NR1+NR2b) transient outward NMDAR currents at +40 mV elicited by brief pulses of glutamate 100 µM or aspartame 100 µM. RezumatÎn ultimii 40 ani, aspartamul a devenit un îndulcitor artificial popular, fiind introdus la nivel mondial în peste 6000 alimente, băuturi și medicamente pentru administrare orală. Totuși, siguranța și toxicitatea sa au fost subiecte de interes încă de la descoperire, datorită potențialelor efecte nocive ale produșilor săi de descompunere intestinală: aspartat, fenilalanină, metanol. Efecte neuropsihice au fost raportate uneori, precum cefalee, vedere neclară, insomnie, torpoare, pierderi de memorie, greață, tulburări de vorbire, schimbarea personalității, pierderea energiei, hiperactivitate, tulburări auditive. Scopul nostru a fost de a determina efectele aspartamului la diverse concentrații asupra viabilității celulelor transfectate tranzient cu combinația de subunități de receptor de N-metil-D-aspartat (NMDAR) NR1+NR2b, şi de a demonstra direct activarea de către aspartam a NMDAR în experimente de whole-cell patch-clamp. Celule CHO-K1 transfectate cu NR1+NR2b prin plasmide conținând cele 2 gene cuplate cu eGFP au fost expuse 2 -4 h la diluții decimale progresive de aspartam (0,1 µM-10 mM) și măsurate prin citometrie în flux după marcare cu iodură de propidiu (PI), arătând procentaje crescute de celule moarte (PI+) la concentrații de aspartam peste 1 µM, în timp ce celulele netransfectate au avut p...

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Behavioral and electrophysiological brain effects of aspartame on well-nourished and malnourished rats

Cited by 7 publications

References 41 publications

The possible neuroprotective effect of astaxanthin on monosodium glutamate and aspartame induced hippocampal changes in albino rats: (Histological and immuno-histochemical study)

The possible neuroprotective effect of astaxanthin on monosodium glutamate and aspartame induced hippocampal changes in albino rats: (Histological and immuno-histochemical study)

Aspartame Safety as a Food Sweetener and Related Health Hazards

An in Vitro Model of Aspartame Cytotoxicity via Heterologous Expression of Nmda Receptors

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