RESUMO
Aspartame is an artificial sweetener used in drinks and many foods. International Agency for Research on Cancer classified aspartame as possibly carcinogenic to humans (IARC Group 2B). In this study, a sensitive and selective spectrofluorimetric method was developed to detect aspartame. The method is based on switching on the fluorescence activity of aspartame upon its condensation with O-phthalaldehyde (Roth's reaction) in the presence of 2-mercaptoethanol. The reaction product was detected fluorometrically at λem of 438 nm after λex of 340 nm. All reaction conditions required to yield the optimal fluorescence intensity were observed and investigated. Furthermore, the approach was validated according to ICH guidelines. Upon plotting the concentrations of aspartame against their associated fluorescence intensity values, the relationship between the two variables was linear within the range of 0.5-3.0 µg/mL. Furthermore, the method was employed to analyze the quantity of aspartame in commercial packages and soft drinks with an acceptable level of recovery. In addition, the Green Solvents Selecting Tool, Complementary Green Analytical Procedure Index, and the Analytical Greenness Metric tool were used to evaluate the sustainability and the greenness of the developed methodology.
Assuntos
Aspartame , Bebidas Gaseificadas , Espectrometria de Fluorescência , Edulcorantes , Comprimidos , Aspartame/análise , Edulcorantes/análise , Espectrometria de Fluorescência/métodos , Comprimidos/análise , Bebidas Gaseificadas/análise , o-Ftalaldeído/química , Química Verde , Mercaptoetanol/químicaRESUMO
INTRODUCTION: Aspartame, invented in 1965 by GD-Searle, is an intense artificial sweetener taste approximately 200 times as sweet as sucrose and used as an additive in more than 6,000 products. Aspartame (APM) was submitted for pre-marketing safety evaluation in early 1980. The studies, performed by GD-Searle, produced controversial results. AREAS COVERED: Because of the great commercial diffusion of aspartame, in 1997 the Ramazzini Institute (RI) started a large experimental project on rodents to test the carcinogenic effects of aspartame following an experimental model with more sensitive characteristics, namely a large number of rat and mice, starting treatment from prenatal life, observation until spontaneous death. Overall, the project included studying 2270 rats and 852 mice. These studies have shown that aspartame is a carcinogenic agent in experimental animals, inducing a significant dose-related increased incidence of several types of malignant tumors and, among them, hematological neoplasia, and liver cancer. EXPERT OPINION: The results of these studies on aspartame by the Ramazzini Institute opened a real front on the evaluation of artificial sweeteners and their possible health risks. Adequate long-term carcinogenicity bioassays on other diffuse artificial sweeteners such as acesulfame-k, sucralose, saccharin, including their blends, are likewise important for public health.
Assuntos
Aspartame , Carcinógenos , Relação Dose-Resposta a Droga , Neoplasias , Edulcorantes , Aspartame/efeitos adversos , Aspartame/administração & dosagem , Animais , Edulcorantes/efeitos adversos , Edulcorantes/administração & dosagem , Edulcorantes/farmacologia , Camundongos , Neoplasias/induzido quimicamente , Neoplasias/patologia , Ratos , Humanos , Carcinógenos/toxicidade , Carcinógenos/administração & dosagem , Testes de CarcinogenicidadeRESUMO
A microfluidic tongue-on-a-chip platform has been evaluated relative to the known sensory properties of various sweeteners. Analogous metrics of typical sensory features reported by human panels such as sweet taste thresholds, onset, and lingering, as well as bitter off-flavor and blocking interactions were deduced from the taste receptor activation curves and then compared. To this end, a flow cell containing a receptor cell array bearing the sweet and six bitter taste receptors was transiently exposed to pure and mixed sweetener samples. The sample concentration gradient across time was separately characterized by the injection of fluorescein dye. Subsequently, cellular calcium responses to different doses of advantame, aspartame, saccharine, and sucrose were overlaid with the concentration gradient. Parameters describing the response kinetics compared to the gradient were quantified. Advantame at 15 µM recorded a significantly faster sweetness onset of 5 ± 2 s and a longer lingering time of 39 s relative to sucrose at 100 mM with an onset of 13 ± 2 s and a lingering time of 6 s. Saccharine was shown to activate the bitter receptors TAS2R8, TAS2R31, and TAS2R43, confirming its known off-flavor, whereas addition of cyclamate reduced or blocked this saccharine bitter response. The potential of using this tongue-on-a-chip to bridge the gap with in vitro assays and taste panels is discussed.
Assuntos
Receptores Acoplados a Proteínas G , Edulcorantes , Paladar , Humanos , Edulcorantes/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Língua/metabolismo , Língua/efeitos dos fármacos , Sacarose/metabolismo , Sacarina/metabolismo , Papilas Gustativas/metabolismo , Papilas Gustativas/efeitos dos fármacos , Dispositivos Lab-On-A-Chip , Aspartame/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Aspartame (L-aspartyl L-phenylalanine methyl ester) is an artificial sweetener widely used as a sugar substitute. There are concerns regarding the effects of high aspartame doses on the kidney owing to oxidative stress; however, whether the maximum allowed dose of aspartame in humans affects the kidneys remains unknown. Therefore, in this study, we investigated whether the maximum allowed dose of aspartame in humans affects the kidneys. METHODS: In this study, animals were fed a folate-deficient diet to mimic human aspartame metabolism. Eight-week-old ICR mice were divided into control (CTL), 40 mg/kg/day of aspartame-administered (ASP), folate-deficient diet (FD), and 40 mg/kg/day of aspartame-administered with a folate-deficient diet (FD + ASP) groups. Aspartame was administered orally for eight weeks. Thereafter, we evaluated aspartame's effect on kidneys via histological analysis. RESULTS: There were no differences in serum creatinine and blood urea nitrogen levels between the CTL and ASP groups or between the FD and FD + ASP groups. There was no histological change in the kidneys in any group. The expression of superoxide dismutase and 4-hydroxy-2-nonenal in the kidney did not differ between the CTL and ASP groups or the FD and FD + ASP groups. CONCLUSION: Our findings indicate that the allowed doses of aspartame in humans may not affect kidney function or oxidative states.
Assuntos
Aspartame , Rim , Camundongos Endogâmicos ICR , Estresse Oxidativo , Edulcorantes , Animais , Aspartame/farmacologia , Rim/efeitos dos fármacos , Rim/metabolismo , Edulcorantes/farmacologia , Edulcorantes/administração & dosagem , Camundongos , Masculino , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Superóxido Dismutase/metabolismo , Nitrogênio da Ureia SanguíneaRESUMO
The research employed network toxicology and molecular docking techniques to systematically examine the potential carcinogenic effects and mechanisms of aspartame (L-α-aspartyl-L-phenylalanine methyl ester). Aspartame, a commonly used synthetic sweetener, is widely applied in foods and beverages globally. In recent years, its safety issues, particularly the potential carcinogenic risk, have garnered widespread attention. The study first constructed an interaction network map of aspartame with gastric cancer targets using network toxicology methods and identified key targets and pathways. Preliminary validation was conducted through microarray data analysis and survival analysis, and molecular docking techniques were employed to further examine the binding affinity and modes of action of aspartame with key proteins. The findings suggest that aspartame has the potential to impact various cancer-related proteins, potentially raising the likelihood of cellular carcinogenesis by interfering with biomolecular function. Furthermore, the study found that the action patterns and pathways of aspartame-related targets are like the mechanisms of known carcinogenic pathways, further supporting the scientific hypothesis of its potential carcinogenicity. However, given the complexity of the in vivo environment, we also emphasize the necessity of validating these molecular-level findings in actual biological systems. The study introduces a fresh scientific method for evaluating the safety of food enhancers and provides a theoretical foundation for shaping public health regulations.
Assuntos
Aspartame , Carcinógenos , Simulação de Acoplamento Molecular , Aspartame/química , Aspartame/efeitos adversos , Aspartame/metabolismo , Aspartame/toxicidade , Humanos , Carcinógenos/toxicidade , Carcinógenos/química , Edulcorantes/química , Edulcorantes/efeitos adversos , Edulcorantes/toxicidade , Neoplasias Gástricas/induzido quimicamenteRESUMO
Aspartame, an artificial sweetener, is consumed by millions of people globally. There are multiple reports of aspartame and its metabolites affecting cognitive functions in animal models and humans, which include learning problems, headaches, seizures, migraines, irritable moods, anxiety, depression, and insomnia. These cognitive deficits and associated symptoms are partly attributed to dysregulated excitatory and inhibitory neurotransmitter balance due to aspartate released from aspartame, resulting in an excitotoxic effect in neurons, leading to neuronal damage. However, microglia, a central immunocompetent cell type in brain tissue and a significant player in inflammation can contribute to the impact. Microglia rapidly respond to changes in CNS homeostasis. Aspartame consumption might affect the microglia phenotype directly via methanol-induced toxic effects and indirectly via aspartic acid-mediated excitotoxicity, exacerbating symptoms of cognitive decline. Long-term oral consumption of aspartame thus might change microglia's phenotype from ramified to activated, resulting in chronic or sustained activation, releasing excess pro-inflammatory molecules. This pro-inflammatory surge might lead to the degeneration of healthy neurons and other glial cells, impairing cognition. This review will deliberate on possible links and research gaps that need to be explored concerning aspartame consumption, ecotoxicity and microglia-mediated inflammatory cognitive impairment. The study covers a comprehensive analysis of the impact of aspartame consumption on cognitive function, considering both direct and indirect effects, including the involvement of microglia-mediated neuroinflammation. We also propose a novel intervention strategy involving tryptophan supplementation to mitigate cognitive decline symptoms in individuals with prolonged aspartame consumption, providing a potential solution to address the adverse effects of aspartame on cognitive function.
Assuntos
Aspartame , Disfunção Cognitiva , Microglia , Microglia/efeitos dos fármacos , Microglia/imunologia , Humanos , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Animais , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/induzido quimicamente , Edulcorantes , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/metabolismo , Encéfalo/imunologiaRESUMO
AIM: To evaluate whether caffeine combined with a moderate amount of glucose reduces the risk for exercise-related hypoglycaemia compared with glucose alone or control in adult people with type 1 diabetes using ultra-long-acting insulin degludec. MATERIALS AND METHODS: Sixteen participants conducted three aerobic exercise sessions (maximum 75 min) in a randomized, double-blind, cross-over design. Thirty minutes before exercise, participants ingested a drink containing either 250 mg of caffeine + 10 g of glucose + aspartame (CAF), 10 g of glucose + aspartame (GLU), or aspartame alone (ASP). The primary outcome was time to hypoglycaemia. RESULTS: There was a significant effect of the condition on time to hypoglycaemia (χ2 = 7.674, p = .0216). Pairwise comparisons revealed an 85.7% risk reduction of hypoglycaemia for CAF compared with ASP (p = .044). No difference was observed between GLU and ASP (p = .104) or between CAF and GLU (p = .77). While CAF increased glucose levels during exercise compared with GLU and ASP (8.3 ± 1.9 mmol/L vs. 7.7 ± 2.2 mmol/L vs. 5.8 ± 1.4 mmol/L; p < .001), peak plasma glucose levels during exercise did not differ between CAF and GLU (9.3 ± 1.4 mmol/L and 9.1 ± 1.6 mmol/L, p = .80), but were higher than in ASP (6.6 ± 1.1 mmol/L; p < .001). The difference in glucose levels between CAF and GLU was largest during the last 15 min of exercise (p = .002). Compared with GLU, CAF lowered perceived exertion (p = .023). CONCLUSIONS: Pre-exercise caffeine ingestion combined with a low dose of glucose reduced exercise-related hypoglycaemia compared with control while avoiding hyperglycaemia.
Assuntos
Glicemia , Cafeína , Estudos Cross-Over , Diabetes Mellitus Tipo 1 , Exercício Físico , Hipoglicemia , Insulina de Ação Prolongada , Humanos , Insulina de Ação Prolongada/administração & dosagem , Insulina de Ação Prolongada/uso terapêutico , Método Duplo-Cego , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Masculino , Feminino , Cafeína/administração & dosagem , Adulto , Hipoglicemia/prevenção & controle , Hipoglicemia/induzido quimicamente , Glicemia/metabolismo , Glicemia/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/administração & dosagem , Glucose/metabolismo , Pessoa de Meia-Idade , Aspartame/administração & dosagem , Aspartame/efeitos adversosRESUMO
Thank you for the opportunity to respond to the concerns raised by Ayoub-Charette et al [...].
Assuntos
Aspartame , Transtorno Autístico , Masculino , Humanos , Estudos de Casos e Controles , Dieta , NutrientesRESUMO
The case-control study by Fowler et al [...].
Assuntos
Aspartame , Transtorno Autístico , Masculino , Humanos , Edulcorantes , Estudos de Casos e Controles , DietaRESUMO
Aspartame (APM) is one of the most widely used artificial sweeteners worldwide. Studies have revealed that consuming APM may negatively affect the body, causing oxidative stress damage to multiple organs and leading to various neurophysiological symptoms. However, it's still unclear if consuming APM and one's daily biological rhythm have an interactive effect on health. In this study, healthy adult C57BL/6 mice were randomly divided into four groups: Control group (CON), oral gavage sham group (OGS), daytime APM intragastric group (DAI) and nighttime APM intragastric group (NAI). DAI and NAI groups were given 80â¯mg/kg body weight daily for 4 weeks. We found that DAI and NAI groups had significantly increased mean body weight, higher serum corticosterone levels, up-regulated pro-inflammatory responses in serum and brain, and exacerbated depressive-like behaviors than the CON and the two APM intake groups. Moreover, all these changes induced by APM intake were more significant in the DAI group than in the NAI group. The present study, for the first time, revealed that the intake of APM and daily biological rhythm have an interactive effect on health. This suggests that more attention should be paid to the timing of APM intake in human beings, and this study also provides an intriguing clue to the circadian rhythms of experimental animals that researchers should consider more when conducting animal experiments.
Assuntos
Aspartame , Peso Corporal , Corticosterona , Citocinas , Depressão , Camundongos Endogâmicos C57BL , Edulcorantes , Animais , Corticosterona/sangue , Aspartame/toxicidade , Depressão/induzido quimicamente , Depressão/sangue , Masculino , Camundongos , Peso Corporal/efeitos dos fármacos , Citocinas/sangue , Citocinas/metabolismo , Edulcorantes/administração & dosagem , Edulcorantes/toxicidade , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/fisiologia , Comportamento Animal/efeitos dos fármacosRESUMO
The use of aspartame (ASP) and potassium acesulfame (ACK) to reduce weight gain is growing; however, contradictory effects in body mass index control and neurobiological alterations resulting from artificial sweeteners consumption have been reported. This study aimed to evaluate the impact of the chronic consumption of ASP and ACK on mood-related behavior and the brain expression of serotonin genes in male Wistar rats. Mood-related behaviors were evaluated using the swim-forced test and defensive burying at two time points: 45 days (juvenile) and 95 days (adult) postweaning. Additionally, the mRNA expression of three serotoninergic genes (Slc6a4, Htr1a, and Htr2c) was measured in the brain areas (prefrontal cortex, hippocampus, and hypothalamus) involved in controlling mood-related behaviors. In terms of mood-related behaviors, rats consuming ACK exhibited anxiety-like behavior only during the juvenile stage. In contrast, rats consuming ASP showed a reduction in depressive-like behavior during the juvenile stage but an increase in the adult stage. The expression of Slc6a4 mRNA increased in the hippocampus of rats consuming artificial sweeteners during the juvenile stage. In the adult stage, there was an upregulation in the relative expression of Slc6a4 and Htr1a in the hypothalamus, while Htr2c expression decreased in the hippocampus of rats consuming ASP. Chronic consumption of ASP and ACK appears to have differential effects during neurodevelopmental stages in mood-related behavior, potentially mediated by alterations in serotoninergic gene expression.
Assuntos
Aspartame , Edulcorantes , Ratos , Masculino , Animais , Aspartame/efeitos adversos , Ratos Wistar , Edulcorantes/efeitos adversos , RNA Mensageiro/genética , PotássioRESUMO
SCOPE: The disturbance of the hypothalamic-pituitary-gonadal (HPG) axis, gut microbiota (GM) community, and short-chain fatty acids (SCFAs) is a triggering factor for pubertal onset. The study investigates the effects of the long-term intake of aspartame on puberty and GM in animals and humans. METHODS AND RESULTS: Aspartame-fed female offspring rats result in vaginal opening time prolongation, serum estrogen reduction, and serum luteinizing hormone elevation. , 60 mg kg-1 aspartame treatment decreases the mRNA levels of gonadotropin-releasing hormone (GnRH), Kiss1, and G protein-coupled receptor 54 (GPR54), increases the mRNA level of RFamide-related peptide-3 (RFRP-3), and decreases the expression of GnRH neurons in the hypothalamus. Significant differences in relative bacterial abundance at the genus levels and decreased fecal SCFA levels are noted by 60 mg kg-1 aspartame treatment. Among which, Escherichia-Shigella is negatively correlated with several SCFAs. In girls, high-dose aspartame consumption decreases the risk of precocious puberty. CONCLUSIONS: Aspartame reduces the chance of puberty occurring earlier than usual in female offspring and girls. Particularly, 60 mg kg-1 aspartame-fed female offspring delays pubertal onset through the dysregulation of HPG axis and GM composition by inhibiting the Kiss1/GPR54 system and inducing the RFRP-3. An acceptable dose of aspartame should be recommended during childhood.
Assuntos
Kisspeptinas , Puberdade Tardia , Humanos , Ratos , Feminino , Animais , Kisspeptinas/metabolismo , Kisspeptinas/farmacologia , Aspartame/efeitos adversos , Aspartame/metabolismo , Puberdade Tardia/metabolismo , Ratos Sprague-Dawley , Maturidade Sexual/fisiologia , Hormônio Liberador de Gonadotropina/genética , Hipotálamo/metabolismo , Puberdade , RNA Mensageiro/metabolismoRESUMO
This study aims to evaluate the prevalence of artificial sweeteners in multivitamin supplements registered in Italy. The National Registry of Dietary Supplements was examined in December 2023 to extract data relating to supplements identified as "multivitamins". Then, for each supplement the specific composition was searched online. 179 multivitamin products were identified, and for 96 of them it was possible to access the complete list of their ingredients online. Among these, 47 supplements (49%) do not contain added sugars, while the remaining 49 (51%) have one or more sweeteners in their composition (29 of which have at least two among the ingredients). Among the 49 supplements in the second group, the greatest prevalence of artificial sweeteners is found in effervescent tablets (100%), soluble powders (100%) and gummies or chewing tablets (63%), while the lowest prevalence was detected in capsules/tablets to be swallowed (19%). In relative terms, aspartame and sucralose are mostly found in effervescent tablets and diluted powders, but other formulations are not always free of these substances. In conclusion, the significant presence of artificial sweeteners in multivitamin supplements requires attention, especially considering the long-term health impact. Consumer awareness and medical evaluation are crucial for an informed choice and the protection of health.
Assuntos
Suplementos Nutricionais , Edulcorantes , Humanos , Prevalência , Vitaminas , AspartameRESUMO
(1) Background: Clinical results on the effects of excess sugar consumption on insulin sensitivity are conflicting, possibly due to differences in sugar type and the insulin sensitivity index (ISI) assessed. Therefore, we compared the effects of consuming four different sugars on insulin sensitivity indices derived from oral glucose tolerance tests (OGTT). (2) Methods: Young adults consumed fructose-, glucose-, high-fructose corn syrup (HFCS)-, sucrose-, or aspartame-sweetened beverages (SB) for 2 weeks. Participants underwent OGTT before and at the end of the intervention. Fasting glucose and insulin, Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), glucose and insulin area under the curve, Surrogate Hepatic Insulin Resistance Index, Matsuda ISI, Predicted M ISI, and Stumvoll Index were assessed. Outcomes were analyzed to determine: (1) effects of the five SB; (2) effects of the proportions of fructose and glucose in all SB. (3) Results: Fructose-SB and the fructose component in mixed sugars negatively affected outcomes that assess hepatic insulin sensitivity, while glucose did not. The effects of glucose-SB and the glucose component in mixed sugar on muscle insulin sensitivity were more negative than those of fructose. (4) Conclusion: the effects of consuming sugar-SB on insulin sensitivity varied depending on type of sugar and ISI index because outcomes assessing hepatic insulin sensitivity were negatively affected by fructose, and outcomes assessing muscle insulin sensitivity were more negatively affected by glucose.
Assuntos
Xarope de Milho Rico em Frutose , Resistência à Insulina , Adulto Jovem , Humanos , Glucose , Teste de Tolerância a Glucose , Aspartame/farmacologia , Zea mays , Sacarose/farmacologia , Frutose/efeitos adversos , Xarope de Milho Rico em Frutose/efeitos adversos , Bebidas , InsulinaRESUMO
The purpose of this study is to further investigate the relationship between sweetener exposure and the risk of endometrial cancer (EC). Up until December 2022, a literature search in an electronic database was carried out utilizing PubMed, Web of Science, Ovid, and Scopus. The odds ratio (OR) and 95 % confidence interval (CI) were used to evaluate the results. Sweeteners were divided into nutritional sweeteners (generally refers to sugar, such as sucrose and glucose) and non-nutritional sweeteners (generally refers to artificial sweeteners, such saccharin and aspartame). Ten cohort studies and two case-control studies were eventually included. The study found that in 12 studies, compared with the non-exposed group, the incidence rate of EC in the sweetener exposed group was higher (OR = 1·15, 95 % CI = [1·07, 1·24]). Subgroup analysis showed that in 11 studies, the incidence rate of EC in the nutritional sweetener exposed group was higher than that in the non-exposed group (OR = 1·25, 95 % CI = [1·14, 1·38]). In 4 studies, there was no difference in the incidence rate of EC between individuals exposed to non-nutritional sweeteners and those who were not exposed to non-nutritional sweeteners (OR = 0·90, 95 % CI = [0·81, 1·01]). This study reported that the consumption of nutritional sweeteners may increase the risk of EC, whereas there was no significant relationship between the exposure of non-nutritional sweeteners and the incidence of EC. Based on the results of this study, it is recommended to reduce the intake of nutritional sweeteners, but it is uncertain whether use of on-nutritional sweeteners instead of nutritional sweetener.
Assuntos
Neoplasias do Endométrio , Adoçantes não Calóricos , Feminino , Humanos , Aspartame/efeitos adversos , Neoplasias do Endométrio/epidemiologia , Neoplasias do Endométrio/etiologia , Adoçantes não Calóricos/efeitos adversos , Sacarina/efeitos adversos , Sacarose/efeitos adversos , Edulcorantes/efeitos adversos , Estudos Observacionais como AssuntoRESUMO
Aspartame (ASP) as an important sugar substitute is widely used in pharmaceutical and food processing. Here, we compared the effects of ASP and sucrose on mice pancreatic islet cells in vivo and observed that ASP with the condition of high concentration and long-term exposure (HASP) could cause insulin secretion (500 mg/kg for 1 month). Next, we conducted iTRAQ mass spectrometry to profile the global phosphoproteome and found that phosphorylation of zipper-interacting protein kinase (ZIPK) in murine pancreatic islet tissues were induced at Thr197, Thr242, Thr282, and Ser328 by high-sucrose (HS) treatment, but only induced at Thr197 and Ser328 by HASP treatment. Simultaneously, phosphorylation of STAT3 could be induced at Tyr705 and Ser727 by HS but not by HASP. Furthermore, presence of activated STAT3 accompanied with autophagy was observed in HS treatment. In turn, the inactivation of STAT3 as well as enhanced expression of caspase 3 was observed in HASP treatment. We generated Thr242APro and Thr282Pro on ZIPK using CRISPR-Cas9 in ß-TC3 cells and found the weakened interaction with STAT3 as well as the reduced phosphorylation of STAT3 even under HS stimulation. Finally, we observed that ankyrin repeat domain containing 11 (ANKRD11) could interact with ZIPK and play an inhibitory role in the phosphorylation of Thr242APro and Thr282Pro of ZIPK. However, HASP can induce the retention of ANKRD11 in the cytoplasm by phenylpyruvic acid (the metabolite of ASP). Taken together, this study determined that ASP with high concentration and long-term exposure could lead to caspase-dependent apoptosis of pancreatic islet cells through ANKRD11/ZIPK/STAT3 inhibition. Our results give evidence of adverse effects of aspartame on islet cells in some extreme conditions, which might help people to reconsider the biosafety of non-nutritive sweeteners.
Assuntos
Apoptose , Aspartame , Ilhotas Pancreáticas , Animais , Camundongos , Apoptose/efeitos dos fármacos , Aspartame/efeitos adversos , Aspartame/metabolismo , Caspase 3/metabolismo , Proteínas Quinases Associadas com Morte Celular/efeitos dos fármacos , Proteínas Quinases Associadas com Morte Celular/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/metabolismo , Fosforilação , Transdução de Sinais , Fator de Transcrição STAT3/metabolismo , Sacarose/metabolismo , Sacarose/farmacologia , Fatores de Transcrição/metabolismoRESUMO
Objective: The purpose of this review was to assess the current evidence regarding the associated physiological and cognitive effects of aspartame (APM) consumption and Parkinson's Disease (PD). METHODS: A total of 32 studies demonstrating effects of APM on monoamine deficiencies, oxidative stress, and cognitive changes were reviewed. RESULTS: Multiple studies demonstrated decreased brain dopamine, decreased brain norepinephrine, increased oxidative stress, increased lipid peroxidation, and decreased memory function in rodents after APM use. In addition, PD animal models have been found to be more sensitive to the effects of APM. DISCUSSION: Overall, studies of APM use over time yielded more consistent results; however, no study has examined long-term effects on APM in human PD patients. Based on the current evidence, long-term human based observational research is needed to further investigate the potential effect of APM on PD.
Assuntos
Aspartame , Doença de Parkinson , Animais , Humanos , Cognição , Estresse Oxidativo , NeurotransmissoresRESUMO
BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) present substantial challenges to clinical intervention, necessitating the formulation of novel antimicrobial strategies to counteract them. Nanomaterials offer a distinctive avenue for eradicating bacteria by employing mechanisms divergent from traditional antibiotic resistance pathways and exhibiting reduced susceptibility to drug resistance development. Non-caloric artificial sweeteners, commonly utilized in the food sector, such as saccharin, sucralose, acesulfame, and aspartame, possess structures amenable to nanomaterial formation. In this investigation, we synthesized gold nanoparticles decorated with non-caloric artificial sweeteners and evaluated their antimicrobial efficacy against clinical CRE strains. RESULTS: Among these, gold nanoparticles decorated with aspartame (ASP_Au NPs) exhibited the most potent antimicrobial effect, displaying minimum inhibitory concentrations ranging from 4 to 16 µg/mL. As a result, ASP_Au NPs were chosen for further experimentation. Elucidation of the antimicrobial mechanism unveiled that ASP_Au NPs substantially elevated bacterial reactive oxygen species (ROS) levels, which dissipated upon ROS scavenger treatment, indicating ROS accumulation within bacteria as the fundamental antimicrobial modality. Furthermore, findings from membrane permeability assessments suggested that ASP_Au NPs may represent a secondary antimicrobial modality via enhancing inner membrane permeability. In addition, experiments involving crystal violet and confocal live/dead staining demonstrated effective suppression of bacterial biofilm formation by ASP_Au NPs. Moreover, ASP_Au NPs demonstrated notable efficacy in the treatment of Galleria mellonella bacterial infection and acute abdominal infection in mice, concurrently mitigating the organism's inflammatory response. Crucially, evaluation of in vivo safety and biocompatibility established that ASP_Au NPs exhibited negligible toxicity at bactericidal concentrations. CONCLUSIONS: Our results demonstrated that ASP_Au NPs exhibit promise as innovative antimicrobial agents against clinical CRE.
Assuntos
Anti-Infecciosos , Enterobacteriáceas Resistentes a Carbapenêmicos , Nanopartículas Metálicas , Animais , Camundongos , Ouro/química , Nanopartículas Metálicas/química , Edulcorantes , Aspartame , Espécies Reativas de Oxigênio , Antibacterianos/farmacologia , Bactérias , Testes de Sensibilidade MicrobianaRESUMO
Photolytic transformation of aspartame - a widely used artificial sweetener - under the simulated sunlight was studied for the first time. The experiments were conducted in pH range of 2.5 - 7.0 and in eight soft drinks available in the market. The highest degradation rate in the tested buffered solutions was observed under the neutral pH conditions. Irradiation of the soft drinks resulted in significantly (up to tenfold) faster degradation of aspartame, regardless of its initial concentration in the beverage. Such considerable acceleration of decomposition, not reported for aspartame so far, was ascribed to influence of the co-occurring ingredients, which can act as the photosensitizers. These findings indicate that some formulations may be particularly unfavorable in the context of aspartame photostability. Qualitative analysis of the studied processes revealed formation of six phototransformation products including three previously not described. In silico estimation of toxicity showed that some of the identified photoproducts, including the novel phenolic derivatives, may be more harmful than the parent compound. Taking into account relatively extensive formation of those products in the soft drinks, such finding may be particularly important from the food safety point of view.
Assuntos
Aspartame , Edulcorantes , Aspartame/análise , Edulcorantes/toxicidade , Edulcorantes/análise , Bebidas Gaseificadas/análise , Bebidas/análiseRESUMO
The objective was to assess aspartame excretion in saliva and the salivary insulin, total protein (TP), and alpha-amylase (AMI) levels in response to the ingestion of sweetened beverages (sodium cyclamate, aspartame, acesulfame, and sucrose). Fifteen healthy participants were included in a single-blinded trial with the intake of Diet soft drink, Regular soft drink, Water + sweeteners, Low sucrose content (3.5 g), and Water (blank) in 5 different days. In each day, saliva was collected at T0 (fasting), T1 (15 min after test-drink intake), T2 (30 min), T3 (60 min), and T4 (120 min) for the measurement of salivary aspartame (HPLC), TP, AMI (ELISA assays) and insulin levels (chemiluminescence). Chi-square, Friedman, ANOVA and Spearman correlation tests were applied. The late-perceived sweet/sour residual flavor was reported at a frequency of 80%, 60% and 20% after ingestion of artificially sweetened drinks, beverages with sucrose, and plain water, respectively (p < 0.05). Aspartame was detected in saliva after artificially sweetened drinks intake, with highest area under the peak for the Diet soft drink (p = 0.014). No change was observed for TP and AMI levels during the 120 min. Insulin levels increased 1 h after soft-drinks ingestion (regular and diet), while the levels did not change for Low sucrose content and Water + sweeteners test-drinks. Salivary aspartame correlated with insulin levels only after Diet soft drink intake (rho ≥ 0.7; p < 0.05). As aspartame can be detected in saliva and swallowed again until completely excreted, these results contribute to the knowledge of the biological fate of artificial sweeteners and the study of health outcomes.