Aspartame Ingestion Research Articles

Aspartame Consumption Increases Glutathione Peroxidase Level and Depression- Like Behavior in Rats

Aspartame is a worldwide used artificial sweetener and is consumed by millions of adults and children as part of their diet. The connection between aspartame ingestion and depression has been studied with contradictory results. We hypothesized that this correlation might be explained by high levels of oxidative stress. We wanted to examine the biochemical effects of consuming higher or lower doses of aspartame on the antioxidant enzyme- glutathione peroxidase (GPX) and on the depression-like behaviors of rats in the forced swim test model. 40 lab rats were divided into 4 groups; two groups were treated by gavage with either 75 mg/kg/day of aspartame or 125 mg/kg/day of aspartame. The control group received a gavage with vehicle (water). The naive group received no experimental intervention. Our statistical analysis revealed that the rats from the control group and the naive group presented a significantly lower level of GPX compared to the groups that received 75mg/kg/day or the group that received the maximum dosage of 125mg/kg/day aspartame. Furthermore, a shorter duration of the immobility was reported in the control and the naive groups when compared to the groups which received any of the two dosages of aspartame. Therefore, the results presented by our study suggest that aspartame consumption (in both high and low dosages) increases both the oxidative stress and the depression-like symptoms in the forced swim model. In addition, an aspartame dose-response was not found for either of our two variables: oxidative stress or depression. In conclusion, the daily consumption of aspartame for 4 weeks, in both high dosage and low dosage, had a negative impact on both oxidative stress level and the frequency of depression- like behaviors of the animals in the forced swim test. These results suggest that the correlation between aspartame ingestion and depression might be explained by oxidative stress levels.

Intake of Non-Nutritive Sweeteners in Chilean Children after Enforcement of a New Food Labeling Law that Regulates Added Sugar Content in Processed Foods.

After enforcement of a new food labeling law in 2016, Chile exhibits a greater offer to reduced sugar products with addition of non-nutritive sweeteners (NNS). Many of these products are consumed by children, who are at greater risk of reaching the acceptable daily intake (ADI) of these food additives. The objective of this study was to evaluate the intake levels of NNS in Chilean schoolchildren after the enactment of the aforementioned law. A total of 250 Chilean children 6–12 years old were surveyed. NNS intake was assessed through a food frequency questionnaire. All children evaluated consumed at least one NNS during the previous month. Sucralose had the highest consumption frequency reaching 99.2%, followed by acesulfame-K (92.8%), stevia (86.0%), and aspartame (85.2%). Aspartame showed the highest median intake, which came mainly from beverages (96%). No children exceeded the ADI of any NNS. Smaller children exhibited a higher body weight-adjusted intake of sucralose, acesulfame-K, stevia, and aspartame (p < 0.05). In Chile, a wide range of processed foods with NNSs is available and all schoolchildren evaluated consumed at least one product containing NNS. However, this consumption does not exceed defined ADIs for any of the six sweeteners authorized for food use in Chile.

Effect of Short-Term Normal-Dose and High-Dose Aspartame Consumption on Sweet-Taste Preference Among College-Aged Students

Abstract Objectives The consumption of non-nutritive sweeteners (NNS) through foods and beverages have increased worldwide. The effects of NNS consumption on body weight, glycemic control, or type 2 diabetes incidence are not well understood. While studies in animal models suggest potentially harmful effects of NNS on metabolic health, randomized controlled trials in humans suggest moderate benefits of NNS use on body weight. The relationship between artificial sweeteners and metabolic disease may be linked to their purported effects on sweet taste preference. The Evidence Analysis Library of the Academy of Nutrition and Dietetics has given a grade of V, concluding that adequately powered studies have not been conducted to evaluate effect of aspartame on preference for sweet taste. Thus, the goal of this study was to test the effect of aspartame, an artificial non-saccharide sweetener, on sweet taste preference in college-aged students. We hypothesized that a short-term increased intake of aspartame will increase sweet-taste preference. Methods Sixteen college-aged students, between the ages of 18 and 24 were recruited from Samford University, and randomized into 2 experimental groups and a control group. The experimental groups received either a nomal-dose of 543 mg aspartame (EQUAL) or a high-dose of 2172 mg aspartame, which was the equivalent to drinking 3 or 12, 12-oz cans of aspartame-containing beverage, respectively. The control group received 200 mg blue food-coloring, which was also added to experimental groups. The intervention period was for 7 days. Body weight, height, 24-hour food recall (ASA-24), and the Monell two-series forced-choice test for sweet preference testing were completed, both before and after the intervention period. Results Our studies showed a significant increase in sweet taste preference for the higher dose aspartame group. This was not associated with an increase in total or added sugars, total fat intake, or change in body weight. Conclusions These findings raise the possibility that a short-term increased intake of aspartame may influence sweet taste preference in college-aged students. Funding Sources None.

Neurometabolic effects of sweetened solution intake during adolescence related to depressive-like phenotype in rats.

Exposure to artificial sweeteners, such as aspartame, during childhood and adolescence has been increasing in recent years. However, the safe use of aspartame has been questioned owing to its potentially harmful effects on the developing brain. The aim of this study was to test whether the chronic consumption of aspartame during adolescence leads to a depressive-like phenotype and to investigate the possible mechanisms underlying these behavioral changes. Adolescent male and female rats were given unlimited access to either water, solutions of aspartame, or sucrose in their home cages from postnatal day 21 to 55. Forced swim test revealed that both chronic aspartame and sucrose intake induced depressive-like behaviord, which was more pronounced in males. Additionally, repeated aspartame intake was associated with increased cerebrospinal fluid (CSF) aspartate levels, decreased hippocampal neurogenesis, and reduced activation of the hippocampal leptin signaling pathways in males. In females, we observed a main effect of aspartame: reducing PI3K/AKT one of the brain-derived neurotrophic factor pathways; aspartame also increased CSF aspartate levels and decreased the immunocontent of the GluN2A subunit of the N-methyl-d-aspartic acid receptor. The findings revealed that repeated aspartame intake during adolescence is associated with a depressive-like phenotype and changes in brain plasticity. Interestingly, males appear to be more vulnerable to the adverse neurometabolic effects of aspartame than females, demonstrating a sexually dimorphic response. The present results highlighted the importance of understanding the effects caused by the constant use of this artificial sweetener in sensitive periods of development and contribute to regulation of its safe use.

Does curcumin protect against hazards of aspartame intake on the cerebellar cortex of male adult albino rats? Histological and immunohistochemical study

Background: Aspartame is an artificial sweetener and unfortunately its intake might cause a dangerous effect on the cerebellar cortex. Curcumin has a neuroprotective role in many diseases.Objective: The study aimed to assess the possible ameliorating role of curcumin against the structural changes of cerebellar cortex that had been associated with aspartame administration in adult wistar rats.Materials and Methods: 48 male adult wistar rats were divided equally into 4 groups. Group I or control, group II or curcumin group each rat received curcumin 100mg/kg/day, group III, each rat received aspartame 250 mg/kg/day and in group IV, each rat received curcumin and aspartame as group II and group III concomitantly. The doses were given orally once daily for 8 weeks. By the end of the experiment, all animals were sacrificed, specimens of cerebellum were processed and stained with hematoxylin and eosin, Glial Fibrillary Acidic Protein (GFAP) and caspase-3 for histological and immunohistochemical studies. Morphometric and statistical studies were performed.Results: Cerebellar cortex of aspartametreated group showed features of neurodegeneration of purkinje cells with areas of neuropil loss in the molecular and granular layers. Also, area percentage of GFAP immunoexpression was increased. The number of purkinje cells that showed positive immunoreaction of caspase 3 was also increased. On concomitant administration of curcuminwith aspartame, the structural changes of cerebellar cortex were decreased.Conclusion: Curcumin intake partially protects the cerebellar cortex from hazards of aspartame intake ,so supplementation of curcuminin diet is recommended with regular intake of aspartame.

Effect of l-carnitine on aspartame-induced oxidative stress, histopathological changes, and genotoxicity in liver of male rats.

Background Aspartame (ASP) is used for treatment of obesity and diabetes mellitus. This study was designed to illustrate the biochemical responses and histopathological alterations besides the genotoxicity of ASP alone or with l-carnitine (LC) in the liver of rats. Methods Animals were separated into six groups: control, lower dose of ASP (ASP-LD; 75 mg/kg), higher dose of ASP (ASP-HD; 150 mg/kg), l-carnitine (LC; 10 mg/kg), ASP-LD plus LC, and ASP-HD plus LC. Treatment was carried out orally for 30 consecutive days. Results ASP raised the activity of some enzymes of liver markers and disturbed the lipid profile levels. The hepatic reduced glutathione (GSH) levels, the marker enzymes of antioxidant activities, were obviously diminished, and, possibly, the lipid peroxidation, C-reactive protein, and interleukins levels were increased. ASP significantly increased the DNA deterioration in comparison with the control in a dose-dependent manner. LC prevented ASP-induced liver damage as demonstrated by the enhancement of all the above parameters. Results of histopathological and electron microscopic examination proved the biochemical feedback and the improved LC effect on liver toxicity. Conclusions The co-treatment of LC showed different improvement mechanisms against ASP-induced liver impairment. So, the intake of ASP should be regulated and taken with LC when it is consumed in different foods or drinks to decrease its oxidative stress, histopathology, and genotoxicity of liver.

Acute Impact of the Artificial Sweetener Aspartame on the Ultrastructures of Hepatocyte in Mice

A non-saccharide artificial sweetener, aspartame (L-aspartyl-L-phenylalanine methyl ester) is used worldwide as a sugar substitute in many foods and beverages. The objective of this work was to clarify the acute impact of various doses of daily ingestion of Aspartame at the cellular level of the liver tissues in mice. Sixty adult male mice were divided into five groups including control fed normal diet and tap water, while other 4 groups (12 each) were daily fed orally with 1 mL of either 40, 500, 1000 and 1500 mg/Kg b.wt. APM dissolved in distilled water using gavages for consecutive 5 weeks. Liver samples fixed in 10% formalin were cut as 5 μm using Leica microtome and the sections were stained with both routine Heamatoxylene and Eosin (H & E) as well as Transmission electron Microscope (TEM). Histological results showed cellular changes in the hepatic tissues which were proportional with the increased doses. The hepatocytes had developed fatty droplets in the cytoplasm of almost all cells, loss of nuclei, necrosis detectable at LM level. Lymphatic nodules were also generated around the triads and the central hepatic veins as well as intracellular gaps with higher doses. The TEM results demonstrated degradation of mitochondria indicating the direct acute effects of the aspartame on hepatic tissues which all were proportional with the increased doses. It is concluded that the daily ingestion of aspartame, even at lower doses, has acute effects and is dose dependant on hepatic cells which could exert further risks onto other tissues of consumers on the long run.

Moderate intake of aspartame and sucralose with meals, but not fructose, does not exacerbate energy and glucose metabolism in estrogen-deficient rats.

Both nutritive and non-nutritive sweeteners may influence energy and glucose metabolism differently. The hypothesis that sucrose, fructose, aspartame, and sucralose intake differently modulate energy and glucose metabolism was tested in an estrogen-deficient animal model. At 30 min after giving aspartame and sucralose (10 mg/kg body weight), an oral glucose tolerance test (OGTT) was conducted with glucose, sucrose, and fructose in ovariectomized (OVX) rats. After OGTT, they were continuously fed high fat diets including either 10% corn starch (Control), 10% sucrose (Sucrose), 10% fructose (Fructose), 0.05% aspartame + 9.95% starch (Aspartame) or 0.05% sucralose + 9.95% starch (Sucralose) for 8 week. During 30 min after acute administration of aspartame and sucralose, serum glucose concentrations increased despite slightly increased serum insulin levels before glucose infusion. However, glucose tolerance was not significantly different among the groups. In chronic study, serum glucose concentrations were lowest and insulin highest at the overnight-fasted state in Aspartame and Sucralose. Postprandial serum glucagon-like peptide-1 (GLP-1) and insulin levels were higher in Aspartame and Sucralose than Control. Hepatic insulin signaling (pAkt → pGSK-3β) and phosphoenolpyruvate carboxykinase (PEPCK) expression were lower in Sucralose and Aspartame than the Fructose. Serum acetate levels produced by gut microbiota were higher were lower in the fructose group than Aspartame and Sucralose groups. In conclusion, aspartame and sucralose with a meal might be preferable sweeteners to fructose and sucrose in estrogen deficient rats, and possibly post-menopausal women; however, this needs to be confirmed in human studies.

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

The non-caloric sweetener aspartame can be potentially harmful to the developing brain, as some studies suggest an association between aspartame intake and adverse neural effects. This study aimed to evaluate the possible effects of aspartame, with or without associated early nutritional deficiency, on behavioral parameters suggestive of anxiety and electrophysiological features of the excitability-related phenomenon known as cortical spreading depression (CSD). Newborn Wistar rats (n = 80) were suckled under favorable (L9; n = 40) or unfavorable lactation conditions (L15; n = 40), consisting of litters with 9 or 15 pups, respectively. In each lactation condition, animals were divided into 4 groups that received per gavage, from postnatal day 8 to 28, 75mg/kg/d or 125mg/kg/d aspartame (groups ASP75 and ASP125), or water (vehicle group), or no treatment (naive group). Behavioral tests (elevated plus-maze [EPM]) were performed at postnatal days 86-95 and CSD was recorded between postnatal days 96-115. Compared to the control groups, aspartame dose-dependently reduced body weight, suggesting a negative impact on animal development; aspartame also caused behavioral changes suggestive of anxiety (shorter stay in the open arms in the EPM) and decelerated CSD (lower propagation speed). Some of these parameters were more affected in L15 animals, suggesting an interaction among aspartame and lactation condition. We concluded that early consumption of aspartame adversely affects development of the organism (weight loss), with actions on behavioral (anxiety-like) and cerebral electrophysiological (CSD) parameters. The data suggest caution in aspartame consumption by lactating mothers and their infants.

P-11 - N-acetylcysteine protects against changes in the glutathione related-system in mice brain caused by the administration of aspartame

Objectives Aspartame is one of the most popular sweeteners in the world. Several studies have linked its use to a dysregulation of glutathione homeostasis in the brain, making it more susceptible to oxidative stress. The aim of the present study was to evaluate the effects of N-acetylcysteine (NAC) on thioredoxin and glutathione-related antioxidant systems in brain regions of aspartame-treated mice. Methods Adult Swiss mice were treated with aspartame (80 mg/kg, v.o.) for 90 days, and from day 60 to day 90, immediately after aspartame treatment, the mice received NAC (163 mg/kg, i.p.). After the last doses, the animals were anesthetized and euthanized for brain removal. The analyzes were performed in cortex, cerebellum and hippocampus. Aspartame administration caused a severe depletion of non-protein thiols levels, as well as glutathione peroxidase activity. Both changes were restored by NAC treatment. Aspartame also triggered a decrease in the mRNA levels of catalytic subunit of glutamate cysteine ligase (Gclc) and cystathionine gamma-lyase (Cth). Conclusion NAC treatment restored Gclc mRNA levels. NAC treatment restored most of changes in glutathione-related system in brain regions of mice after chronic intake of aspartame.

P-358 - Chronic aspartame intake causes deficient glutathione synthesis and induces cxcl1 up-regulation in mice liver

Reduced glutathione (GSH) depletion and inflammation have been linked to chronic aspartame consumption. However, the cause of aspartame-induced GSH depletion and the role of pro- and anti-inflammatory cytokines in aspartame-triggered inflammation are still unknown. The aims of this research were to investigate if aspartame causes GSH depletion due to deficient synthesis and also which pro- and anti-inflammatory genes are involved in aspartame-related inflammation in mice liver. Mice were divided into three groups: control, aspartame (80 mg kg-1, v.o., 3 months), aspartame treated with N-acetylcysteine (NAC) (1 mmol kg-1, i.p., last month). Aspartame markedly reduced GSH, γ-glutamylcysteine and cysteine levels. It also triggered down-regulation of the catalytic unit of glutamate cysteine ligase (gclc). Moreover, aspartame produced liver inflammation as confirmed through histologic analysis. It also caused the up-regulation of cxcl1 (the equivalent in mouse to human il-8) and down-regulation of il-10. In conclusion, chronic aspartame intake generates GSH depletion due to decreased cysteine levels and gclc downregulation. Moreover, pro- (cxcl1) and anti-inflammatory (il-10) cytokines are involved in aspartame-related inflammation. NAC abrogated all aspartame-induced changes.

Aspartame Consumption for 12 Weeks Does Not Affect Glycemia, Appetite, or Body Weight of Healthy, Lean Adults in a Randomized Controlled Trial

BackgroundLow-calorie sweeteners are often used to moderate energy intake and postprandial glycemia, but some evidence indicates that they may exacerbate these aims. ObjectiveThe trial's primary aim was to assess the effect of daily aspartame ingestion for 12 wk on glycemia. Effects on appetite and body weight were secondary aims. MethodsOne hundred lean [body mass index (kg/m2): 18–25] adults aged 18–60 y were randomly assigned to consume 0, 350, or 1050 mg aspartame/d (ASP groups) in a beverage for 12 wk in a parallel-arm design. At baseline, body weight and composition were determined, a 240-min oral-glucose-tolerance test (OGTT) was administered, and measurements were made of appetite and selected hormones. Participants also collected a 24-h urine sample. During the intervention, the 0-mg/d ASP group consumed capsules containing 680 mg dextrose and 80 mg para-amino benzoic acid. For the 350-mg/d ASP group, the beverage contained 350 mg aspartame and the 1050-mg/d ASP group consumed the same beverage plus capsules containing 680 mg dextrose and 700 mg aspartame. Body weight, blood pressure, heart rate, and waist circumference were measured weekly. At weeks 4, 8, and 12, participants collected 24-h urine samples and kept appetite logs. Baseline measurements were repeated at week 12. ResultsWith the exception of the baseline OGTT glucose concentration at 60 min (and resulting area under the curve value), there were no group differences for glucose, insulin, resting leptin, glucagon-like peptide 1, or gastric inhibitory peptide at baseline or week 12. There also were no effects of aspartame ingestion on appetite, body weight, or body composition. Compliance with the beverage intervention was ∼95%. ConclusionAspartame ingested at 2 doses for 12 wk had no effect on glycemia, appetite, or body weight among healthy, lean adults. These data do not support the view that aspartame is problematic for the management of glycemia, appetite, or body weight. This trial was registered at www.clinicaltrials.gov as NCT02999321.

Histological changes of tongue papillae induced by the artificial sweetener Aspartame and the protective effect of Platelet-rich plasma

Aspartame (ASP) is one of the most controversial food additives found in various food products all over the world. Once ingested, ASP is metabolized to phenylalanine, aspartic acid, and methanol. The aims of the study are to evaluate the effects of ASP administration on the dorsal surface of rats’ tongues and to investigate the possible protective effect of Platelet-rich plasma (PRP). Thirty adult male albino rats were used and divided into three equal groups. The control group received the vehicle only. ASP group received a dose of 250 mg/kg b wt for four weeks while the PRP group were treated as ASP group, in addition they received a single local injection with PRP in the right lateral border of the tongue. The most obvious changes were loss of normal conical appearance with hyperkeratosis of filiform papillae. The epithelial cells showed hyperplasia (acanthosis), cellular pleomorphism and nuclear hyperchromatism. Distorted and atrophied fungiform papilla with degeneration of epithelial cells and pyknotic nuclei were visible. In the lamina propria numerous dilated and congested blood vessels were obvious. SEM examination revealed disfigurement of tongue papillae. The fungiform papillae showed irregular wrinkled surface and ill-defined taste pore. PRP treatment almost restored the normal architecture of tongue papillae. Chronic aspartame ingestion could result in marked morphological alteration of dorsal surface of the tongue and PRP exerted a protective role against this effect.

Health Implications Associated with Aspartame Consumption: A Substantial Review.

Aspartame, an artificial sweetening agent belongs to dipeptide chemical category with a very strong sweetening potential. Although research findings in humans and non-human primates have demonstrated numerous negative effects of aspartame (biochemical, histological, neurological, behavioral, genetic etc)., the status of aspartame is still debatable. Present manuscript is a critical review of the substantial research findings related to aspartame intake on different research models. Purpose of this review was to spread the awareness about adverse effect of aspartame intake to outline the occurrence of health issues among the population. The process of uptake, storage, compartmentalization and distribution of aspartame within the body is associated with metabolic disorders and various clinical conditions. Available research literature indicates that higher amount of aspartame ingestion should be monitored carefully to avoid health implication within society.

Acute Impact of Artificial Sweetener, Aspartame on Blood Parameter in Mice

Aspartame (APM) or L-aspartyl-L-phenylalanine methyl ester, a common artificial non-saccharide sweetener used as a sugar substitute in many foods and beverages, has shown some side effects on consumers. The objective of the present study is to study the acute impact of various doses of daily ingestion of APM on blood parameters of mice. Sixty healthy 3 months old male mice raised in the departmental animal house were divided into five groups i.e. the control were fed normal diet and tap water, while other 4 groups (12 each) were daily orally fed with 1 mL of either 40, 500, 1000 or 1500 mg/Kg b wt, dissolved in distilled water using gavages for consecutive 5 weeks. Fresh blood samples collected directly from the heart at dissection were subjected to complete blood counting (CBC) using automated blood analyzer (Cell DYN-1700) in addition to manual differential Leucocytes (WBC) counting. There has been a significant increase (p ≤ 0.01) in WBC counts starting from the lowest dose (40 mg/Kg·b·wt); significant decrease (p ≤ 0.01) in both Hemoglobin percentages (Hb%) and in Lymphocyte percentages (p ≤ 0.004) in comparison with control. It is concluded that the ingestion of aspartame using the above doses has acute impact and is not dose-dependent on blood parameters which could exert further, on the long run, health risks on to other tissues of consumers.

The effect of aspartame ingestion in pregnant female albino rats on placental and fetal weights, umbilical cord length, and histology of fetal pancreas

Background and aim Sugar is one of the commonest causes of weight gain and diabetes. Aspartame is one of the most commonly used artificial sweeteners worldwide to replace sugar. This study aimed to study the effects of aspartame in pregnant female albino rats on fetal and placental weights, length of umbilical cord, and possible histological changes in fetal pancreas. Materials and methods Thirty-six adult female albino rats and nine adult male albino rats weighing between 220 and 250 g were used. Each four female rats were housed with one male rat to allow mating. Pregnant rats were divided into three groups (n=12 each): control group (group І), low-dose-treated group (group ІІ), and high-dose-treated group (group ІІІ). The low-dose-treated group received 14 mg/kg aspartame and the high-dose-treated group received 40 mg/kg aspartame daily from the first day of pregnancy to the 20th day of pregnancy. Results This study showed a highly significant reduction of maternal weight gain, placental weight, fetal weight, and umbilical cord length in both aspartame-treated groups. Fetal pancreas showed histopathological changes in both aspartame-treated groups as evidenced by light and electron microscopy. All the results in this study were dose related. Conclusion The use of aspartame during pregnancy might reduce fetal and placental weights and umbilical cord length and alter the histology of fetal pancreas.

Effects of chronic aspartame consumption on MPTP-induced Parkinsonism in male and female mice

Background: Parkinson’s disease is a progressive neurodegenerative disorder. Aspartame (l-aspartyl-l-phenylalanine methyl ester), a low calorie sweetener used in foods and beverages.Objectives: This study investigated the effect of chronic aspartame intake on Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).Method: Forty-eight mice (24 males and 24 females): control, aspartame, MPTP, and aspartame + MPTP groups tested by Y-maze, stepping, forced swimming and olfactory preference tests. Brain tissues examined for dopamine content, tyrosine hydroxylase, inducible nitric oxide synthase (iNOS), glutathione peroxidase, phosphorylated tau and α-synuclein protein. Histopathological evaluation of brain sections at the level of basal ganglia was done.Results: Decreased dopamine content, tyrosine hydroxylase expression, glutathione peroxidase expression and increased iNOS, tau and α-synuclein expression in groups received aspartame, MPTP or both agents simultaneously in both males and females group.Conclusions: Increased dopaminergic degeneration and complications with chronic aspartame consumption and more injury in male groups.

Protective Effect of Lycopene on Aspartame Induced Oxidative Stress and Histopathological Changes in Liver of Male Rats

Aspartame (ASP) is used with the people that suffering from obesity and diabetes mellitus. The study aimed to evaluate the biochemical responses as well as histopathological changes of ASP alone or with Lycopene (LY) in liver of rats. Rats were divided into six groups according to the treatment into control low dose of ASP (LD; 75 mg/Kg), high dose of ASP (HD; 150 mg/Kg), Lycopene (LY; 20 mg/Kg), ASP-LD plus LY and ASP-HD plus LY. All the Animals were treated orally for 30 successive days. ASP increased alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and I³-glutamyl transpeptidase (I³-GT) activities and changed the levels of lipid profile as well as creatinine and uric acid levels. It marked decreased antioxidant enzyme activity of SOD and increased the levels of lipid peroxidation (MDA), C-reactive protein and interleukins. LY prevented the ASP-induced liver injury as indicated by improving all the parameters previously illustrated. LY prevented the ASP-induced liver and kidney injury as indicated by improving all the parameters previously illustrated. Histopathological results confirm the biochemical finding and the ameliorating effect of LY on liver toxicities. In conclusion, co-treatment of LY possessed different protective mechanisms against ASP-induced liver toxicity. So, the intake of ASP should be restricted and taken with LY when it is used in food or beverages to decrease its toxicity.

Aspartame and Soft Drink-Mediated Neurotoxicity in Rats: Implication of Oxidative Stress, Apoptotic Signaling Pathways, Electrolytes and Hormonal Levels.

A significant association between fructose corn syrup in sweetened beverages consumption and increased risk of detrimental central nervous system effects has been recently reported. We hypothesized that the aspartame and soft drink induced disturbances in energy production and endocrine function, which play a role in the induction of brain damage. Therefore, we aimed to assess the effect of aspartame and soft drink on brain function and the link between energy status in the brain, oxidative stress and molecular pathways of apoptosis. Thirty rats were randomly assigned to drink water, aspartame (240mg/kg orally) and cola soft drinks (free access) daily for two months. Subchronic intake of aspartame and soft drink significantly disrupted the brain energy production, as indicated by inhibited serum and brain creatine kinase, specifically in soft drink-received rats. Moreover, they substantially altered serum electrolytes (increased Ca and Na, and depleted Cu, Fe, Zn and K levels), and accordingly the related hormonal status (increased T4 and PTH, and lowered T3 and aldosterone levels), particularly in soft drink-received rats reflecting brain damage. Additionally, significant increment of acetylcholine esterase activity concomitant with the reduction of antioxidant molecules (SOD, CAT, GSH-Px and GSH), and induction of malondialdehyde level are precisely indicative of oxidative brain damage. Brain mRNA transcripts of target genes showed that aspartame and soft drink induced upregulation of BAX, Casp3, P27 and Mdm2 (1.5-fold) and down-regulation of Bcl2, suggesting an activation of cellular apoptosis. Collectively, subchronic aspartame and soft drink-induced brain damage in rats may be driven via a mechanism that involves energy production disruption, electrolytes and hormonal imbalance, increased oxidative stress and activation of molecular pathway of neuronal apoptosis.

Disruption of redox homeostasis in liver function and activation of apoptosis on consumption of aspartame in folate deficient rat model

This study assesses the effect of long-term intake of aspartame on liver function and apoptosis signaling pathway in the Wistar albino rats. Several reports have suggested that methanol is one of the major metabolites of Aspartame. Non-primate animals are usually resistant to methanol-induced metabolic acidosis due to high levels of hepatic folate content; hence a folate deficiency model was induced by treating animals with methotrexate (MTX) prior to aspartame exposure. The aspartame treated MTX animals exhibited a marked significant increase in hepatic alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactic acid dehydrogenase (LDH) activity compared to controls. Aspartame treated MTX animals additionally exhibited down-regulation of genes namely B-cell lymphoma 2 (Bcl2) expression and up-regulation of Bcl-2-associated X protein (Bax), Fas-associated protein with death domain (FADD) and Caspase 3, 9 genes and apoptotic protein expression, indicating the augmentation of hepatic apoptosis. Nuclear condensation, micro vacuole formation in the cytoplasm and necrosis were observed in the liver of the aspartame treated animals on histopathology evaluation. Additionally, Immunohistochemical analysis revealed a significant increase in positive cells expressing Fas, FADD, Bax and Caspase 9 protein, indicating an increase in apoptotic protein expression in the liver. Thus, Aspartame may act as a chemical stressor which alters the functional status of liver, leading to hepatotoxicity.