Chronic Effect of Aspartame on Ionic Homeostasis and Monoamine Neurotransmitters in the Rat Brain

Abhilash, M. R.; Alex, Manju; Mathews, Varghese V.; Nair, R. Harikumaran

doi:10.1177/1091581814537087

Cited by 17 publications

(9 citation statements)

References 66 publications

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“…These results were contrary to those of Abhilash et al (33), who found that other artificial sweeteners as aspartame decreased dopamine in corpus striatum and cerebral cortex, and serotonin in corpus striatum. With respect to 5-HIAA levels, precursor of serotonin, it decreased in striatum and cerebellum/medulla oblongata of animals that received sweeteners and cytarabine alone or combined.…”

Section: Biochemical and Histological Changes Produced By Sweeteners contrasting

confidence: 57%

Biochemical and histological changes produced by sweeteners and cytarabine in the brain of young rats

García¹,

Brizuela²,

Peraza³

et al. 2018

Nutr Hosp

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Biochemical and histological changes produced by sweeteners and cytarabine in the brain of young rats Cambios bioquímicos e histológicos producidos por edulcorantes y citarabina en el cerebro de ratas jóvenes ResumenObjetivo: el objetivo fue evaluar el efecto de edulcorantes (splenda y stevia) sobre los niveles de dopamina, acido 5-hidroxiindolacetico (HIAA) y algunos biomarcadores de estrés oxidativo en presencia de citarabina. Métodos: cuarenta y ocho ratas Wistar machos con un peso aproximado de 80 g (cuatro semanas de edad), distribuidas en seis grupos de ocho animales cada uno, fueron tratados como sigue: grupo 1, control (NaCl 0,9% vehículo); grupo 2, citarabina (0,6 g/kg); grupo 3, stevia (0,6 g/kg); grupo 4, citarabina + stevia; grupo 5, splenda; y el grupo 6, citarabina + splenda. La citarabina fue administrada por vía intravenosa y la stevia y la splenda, por vía oral durante cinco días, utilizando una sonda orogástrica. Al final del tratamiento, los animales fueron sacrificados y se midieron los niveles de glucosa en sangre. Los cerebros fueron disecados para su análisis histológico y homogenizados para medir los niveles de dopamina, peroxidación lipídica (TBARS), metabolito de la serotonina (5-HIAA), actividad de la Na + , K + ATPasa y glutatión (GSH), usando métodos validados.Resultados: los edulcorantes aumentaron la glucosa en los animales que recibieron citarabina. La dopamina aumentó en la corteza y disminuyó en el estriado de los animales que recibieron stevia sola y combinada con citarabina. La 5-HIAA disminuyó en el estriado y el cerebelo/ médula oblongata de animales que recibieron edulcorantes y citarabina sola o combinada. El GSH se incrementó en los animales que recibieron edulcorantes. La lipoperoxidación disminuyó en los grupos que recibieron edulcorantes y citarabina. Estudios histopatológicos revelaron una degeneración neuronal importante en animales tratados con citarabina. Conclusión: los resultados muestran que los edulcorantes como stevia o splenda pueden conducir a la aparición de cambios desfavorables en los niveles de dopamina y 5-HIAA. Los cambios histológicos revelaron, además, lesiones marcadas de células neuronales en animales tratados con citarabina. AbstractObjective: The aim of this study was to evaluate the effect of splenda and stevia on dopamine and 5-HIAA levels, and some biomarkers of oxidative stress in the presence of cytarabine. Methods: Forty-eight young male Wistar rats each with a weight of 80 g (four weeks of age), distributed in six groups of eight animals each, were treated as follows: group 1, control (NaCl 0.9% vehicle); group 2, cytarabine (0.6 g/kg); group 3, stevia (0.6 g/kg); group 4, cytarabine + stevia; group 5, splenda; and group 6, cytarabine + splenda. Cytarabine was given intravenously (IV) while stevia and splenda were administered orally for five days, using orogastric tube. At the end of treatment, the animals were sacrificed and glucose levels in blood were measured. The brains were dissected for histological analysis and homogenated to mea...

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Section: Biochemical and Histological Changes Produced By Sweeteners contrasting

confidence: 57%

Biochemical and histological changes produced by sweeteners and cytarabine in the brain of young rats

García¹,

Brizuela²,

Peraza³

et al. 2018

Nutr Hosp

View full text Add to dashboard Cite

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“…Another source of neural effects may be excitotoxicity: Aspartame is metabolized into phenylalanine (50%) and aspartic acid (40%), as well as methanol (10%) . Brain levels of aspartic acid increase acutely after aspartame ingestion .…”

Section: Dietary Triggersmentioning

confidence: 99%

Migraine Triggers and Oxidative Stress: A Narrative Review and Synthesis

2015

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“…Phenylalanine also has the potential to directly interact with NMDARs by competing at the glycine binding site to modulate NMDAR activity [ 38 , 39 ]. Additionally phenylalanine may modulate glutamatergic signaling by altering CNS regional catecholamine levels, for example dopamine [ 40 , 41 ], which can in turn regulate NMDAR surface expression and activity [ 42 ]. Since phenylalanine has the potential to cross both the BBB and the placenta [ 43 ] and to preferentially accumulate in the fetus [ 44 ], this could affect glutamatergic signaling particularly in mice where the activity of phenylalanine hydroxylase, the enzyme necessary to convert phenylalanine to tyrosine, is not active until the last stages of gestation [ 45 , 46 ].…”

Section: Introductionmentioning

confidence: 99%

Effect of developmental NMDAR antagonism with CGP 39551 on aspartame-induced hypothalamic and adrenal gene expression

et al. 2018

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RationaleAspartame (L-aspartyl phenylalanine methyl ester) is a non-nutritive sweetener (NNS) approved for use in more than 6000 dietary products and pharmaceuticals consumed by the general public including adults and children, pregnant and nursing mothers. However a recent prospective study reported a doubling of the risk of being overweight amongst 1-year old children whose mothers consumed NNS-sweetened beverages daily during pregnancy. We have previously shown that chronic aspartame (ASP) exposure commencing in utero may detrimentally affect adulthood adiposity status, glucose metabolism and aspects of behavior and spatial cognition, and that this can be modulated by developmental N-methyl-D-aspartate receptor (NMDAR) blockade with the competitive antagonist CGP 39551 (CGP). Since glucose homeostasis and certain aspects of behavior and locomotion are regulated in part by the NMDAR-rich hypothalamus, which is part of the hypothalamic-pituitary-adrenal- (HPA) axis, we have elected to examine changes in hypothalamic and adrenal gene expression in response to ASP exposure in the presence or absence of developmental NMDAR antagonism with CGP, using Affymetrix microarray analysis.ResultsUsing 2-factor ANOVA we identified 189 ASP-responsive differentially expressed genes (DEGs) in the adult male hypothalamus and 2188 in the adrenals, and a further 23 hypothalamic and 232 adrenal genes significantly regulated by developmental treatment with CGP alone. ASP exposure robustly elevated the expression of a network of genes involved in hypothalamic neurosteroidogenesis, together with cell stress and inflammatory genes, consistent with previous reports of aspartame-induced CNS stress and oxidative damage. These genes were not differentially expressed in ASP mice with CGP antagonism. In the adrenal glands of ASP-exposed mice, GABA and Glutamate receptor subunit genes were amongst those most highly upregulated. Developmental NMDAR antagonism alone had less effect on adulthood gene expression and affected mainly hypothalamic neurogenesis and adrenal steroid metabolism. Combined ASP + CGP treatment mainly upregulated genes involved in adrenal drug and cholesterol metabolism.ConclusionASP exposure increased the expression of functional networks of genes involved in hypothalamic neurosteroidogenesis and adrenal catecholamine synthesis, patterns of expression which were not present in ASP-exposed mice with developmental NMDAR antagonism.

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Chronic Effect of Aspartame on Ionic Homeostasis and Monoamine Neurotransmitters in the Rat Brain

Cited by 17 publications

References 66 publications

Biochemical and histological changes produced by sweeteners and cytarabine in the brain of young rats

Biochemical and histological changes produced by sweeteners and cytarabine in the brain of young rats

Migraine Triggers and Oxidative Stress: A Narrative Review and Synthesis

Effect of developmental NMDAR antagonism with CGP 39551 on aspartame-induced hypothalamic and adrenal gene expression

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