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1.
Food Chem ; 370: 130991, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34509947

RESUMO

Food producers have leaned towards alternative natural and synthetic sweeteners in food formulations to satisfy market demands. Even so, several synthetic sweeteners (e.g., aspartame, saccharin, sucralose) are becoming less popular due to health-related concerns, lower nutritional values, and controversies around their safety. Conversely, natural sweeteners confer favourable customer perceptions due to their association to a healthier lifestyle and higher nutritional values. This article discusses the evidence of natural sweeteners in the available commercial products. A comprehensive review of natural sweeteners is presented, which includes their resources, properties and extraction methods, as well as a discussion on several emerging technologies that offer improvements to the traditional extraction methods. Finally, the progress of natural sweeteners in the food industry is assessed, and the commercial food products containing these natural sweeteners are mentioned.


Assuntos
Aspartame , Edulcorantes , Indústria Alimentícia , Sacarina
2.
Int J Mol Sci ; 22(18)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34576027

RESUMO

Despite having been tagged as safe and beneficial, recent evidence remains inconclusive regarding the status of artificial sweeteners and their putative effects on gut microbiota. Gut microorganisms are essential for the normal metabolic functions of their host. These microorganisms communicate within their community and regulate group behaviors via a molecular system termed quorum sensing (QS). In the present study, we aimed to study the effects of artificial sweeteners on this bacterial communication system. Using biosensor assays, biophysical protein characterization methods, microscale thermophoresis, swarming motility assays, growth assays, as well as molecular docking, we show that aspartame, sucralose, and saccharin have significant inhibitory actions on the Gram-negative bacteria N-acyl homoserine lactone-based (AHL) communication system. Our studies indicate that these three artificial sweeteners are not bactericidal. Protein-ligand docking and interaction profiling, using LasR as a representative participating receptor for AHL, suggest that the artificial sweeteners bind to the ligand-binding pocket of the protein, possibly interfering with the proper housing of the native ligand and thus impeding protein folding. Our findings suggest that these artificial sweeteners may affect the balance of the gut microbial community via QS-inhibition. We, therefore, infer an effect of these artificial sweeteners on numerous molecular events that are at the core of intestinal microbial function, and by extension on the host metabolism.


Assuntos
Proteínas de Bactérias/genética , Microbioma Gastrointestinal/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Edulcorantes/efeitos adversos , Transativadores/genética , Aspartame/efeitos adversos , Técnicas Biossensoriais/métodos , Hidrolases de Éster Carboxílico/genética , Comunicação Celular/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Bactérias Gram-Negativas/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Sacarina/efeitos adversos , Sacarose/efeitos adversos , Sacarose/análogos & derivados , Edulcorantes/farmacologia
3.
Nutrients ; 13(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34444906

RESUMO

Diabetic kidney disease (DKD) has become a global health concern, with about 40% of people living with type 1 and type 2 diabetes mellitus developing DKD. Upregulation of vascular endothelial growth factor (VEGF) in the kidney is a significant pathology of DKD associated with increased glomerular vascular permeability. To date, however, current anti-VEGF therapies have demonstrated limited success in treating DKD. Recent studies have shown that artificial sweeteners exhibit anti-VEGF potential. The aim of this study was therefore to assess the effects of aspartame, saccharin, and sucralose on VEGF-induced leak using an in vitro model of the glomerular endothelium. Saccharin and sucralose but not aspartame protected against VEGF-induced permeability. Whilst the sweeteners had no effect on traditional VEGF signalling, GC-MS analysis demonstrated that the sweetener sucralose was not able to enter the glomerular endothelial cell to exert the protective effect. Chemical and molecular inhibition studies demonstrated that sweetener-mediated protection of the glomerular endothelium against VEGF is dependent on the sweet taste receptor, T1R3. These studies demonstrate the potential for sweeteners to exert a protective effect against VEGF-induced increased permeability to maintain a healthy endothelium and protect against vascular leak in the glomerulus in settings of DKD.


Assuntos
Permeabilidade Capilar/efeitos dos fármacos , Substâncias Protetoras/farmacocinética , Sacarina/farmacocinética , Sacarose/análogos & derivados , Edulcorantes/farmacologia , Aspartame/farmacocinética , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Células Endoteliais , Endotélio Vascular/metabolismo , Humanos , Técnicas In Vitro , Rim/irrigação sanguínea , Microvasos/metabolismo , Sacarose/farmacocinética , Fatores de Crescimento do Endotélio Vascular/metabolismo
4.
Nutrients ; 13(6)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200310

RESUMO

Aspartame is a sweetener introduced to replace the commonly used sucrose. It was discovered by James M. Schlatter in 1965. Being 180-200 times sweeter than sucrose, its intake was expected to reduce obesity rates in developing countries and help those struggling with diabetes. It is mainly used as a sweetener for soft drinks, confectionery, and medicines. Despite its widespread use, its safety remains controversial. This narrative review investigates the existing literature on the use of aspartame and its possible effects on the human body to refine current knowledge. Taking to account that aspartame is a widely used artificial sweetener, it seems appropriate to continue research on safety. Studies mentioned in this article have produced very interesting results overall, the current review highlights the social problem of providing visible and detailed information about the presence of aspartame in products. The studies involving the impact of aspartame on obesity, diabetes mellitus, children and fetus, autism, neurodegeneration, phenylketonuria, allergies and skin problems, its cancer properties and its genotoxicity were analyzed. Further research should be conducted to ensure clear information about the impact of aspartame on health.


Assuntos
Aspartame/efeitos adversos , Aspartame/metabolismo , Alimentos , Humanos , Transtornos Mentais/induzido quimicamente , Mutagênicos/toxicidade , Degeneração Neural/induzido quimicamente , Preparações Farmacêuticas/análise
5.
Biomed Res Int ; 2021: 9967035, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34258285

RESUMO

Nonnutritive sweeteners (NNSs) are sugar substitutes widely used to reduce the negative health effects of excessive sugar consumption. Dental caries, one of the most prevalent chronic diseases globally, results from a pathogenic biofilm with microecological imbalance and frequent exposure to sugars. Some research has shown that certain NNSs possess less cariogenic potential than sucrose, indicating their putative effect on oral microbiome. To uncover the alterations of acidogenic pathogens and alkali-generating commensals, as well as the biofilm cariogenic potential under the influence of NNSs, we selected four common NNSs (acesulfame-K, aspartame, saccharin, and sucralose) and established single-, dual-, and multispecies in vitro culture model to assess their effects on Streptococcus mutans (S. mutans) and/or Streptococcus sanguinis (S. sanguinis) compared to sucrose with the same sweetness. The results showed that NNSs significantly suppressed the planktonic growth, acid production, and biofilm formation of S. mutans or S. sanguinis compared with sucrose in single-species cultures. Additionally, decreased S. mutans/S. sanguinis ratio, less EPS generation, and higher pH value were observed in dual-species and saliva-derived multispecies biofilms with supplementary NNSs. Collectively, this study demonstrates that NNSs inhibit the cariogenic potential of biofilms by maintaining microbial equilibrium, thus having a promising prospect as anticaries agents.


Assuntos
Cárie Dentária/prevenção & controle , Diterpenos do Tipo Caurano/química , Microbiota , Boca/microbiologia , Adoçantes não Calóricos , Aspartame/análise , Biofilmes/efeitos dos fármacos , Cariogênicos/farmacologia , Cárie Dentária/etiologia , Glicosídeos/metabolismo , Humanos , Hibridização in Situ Fluorescente , Proteínas de Plantas/química , Sacarina/análise , Streptococcus mutans , Streptococcus sanguis , Sacarose/análogos & derivados , Sacarose/análise , Tiazinas/análise
6.
Int J Mol Sci ; 22(10)2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-34063332

RESUMO

Artificial sweeteners (AS) are synthetic sugar substitutes that are commonly consumed in the diet. Recent studies have indicated considerable health risks which links the consumption of AS with metabolic derangements and gut microbiota perturbations. Despite these studies, there is still limited data on how AS impacts the commensal microbiota to cause pathogenicity. The present study sought to investigate the role of commonly consumed AS on gut bacterial pathogenicity and gut epithelium-microbiota interactions, using models of microbiota (Escherichia coli NCTC10418 and Enterococcus faecalis ATCC19433) and the intestinal epithelium (Caco-2 cells). Model gut bacteria were exposed to different concentrations of the AS saccharin, sucralose, and aspartame, and their pathogenicity and changes in interactions with Caco-2 cells were measured using in vitro studies. Findings show that sweeteners differentially increase the ability of bacteria to form a biofilm. Co-culture with human intestinal epithelial cells shows an increase in the ability of model gut bacteria to adhere to, invade and kill the host epithelium. The pan-sweet taste inhibitor, zinc sulphate, effectively blocked these negative impacts. Since AS consumption in the diet continues to increase, understanding how this food additive affects gut microbiota and how these damaging effects can be ameliorated is vital.


Assuntos
Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Edulcorantes/farmacologia , Aspartame/administração & dosagem , Aspartame/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Células CACO-2 , Relação Dose-Resposta a Droga , Enterococcus faecalis/patogenicidade , Escherichia coli/patogenicidade , Microbioma Gastrointestinal/fisiologia , Hemólise/efeitos dos fármacos , Humanos , Sacarina/administração & dosagem , Sacarina/farmacologia , Sacarose/administração & dosagem , Sacarose/análogos & derivados , Sacarose/farmacologia , Edulcorantes/administração & dosagem
7.
Food Chem Toxicol ; 153: 112264, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33992720

RESUMO

This study aimed to investigate the molecular effects of the common natural sugar glucose and artificial sweetener aspartame on cancer stem cell (CSC) population and cancer aggressiveness of PANC-1 human pancreas adenocarcinoma cells. According to our findings while aspartame exposure significantly increased the CSC population, high glucose had no effect on it. The epithelial-mesenchymal transition marker N-cadherin increased only in the aspartame group. The findings indicate that a high level of glucose exposure does not effect the invasion and migration of PANC-1 cells, while aspartame increases both of these aggressiveness criteria. The findings also suggest that a high concentration of glucose maintains CSC population through induction of nuclear Oct3/4 and differentiation to parental cells via increasing cytoplasmic c-myc. Aspartame exposure to PANC-1 cells activated AKT and deactivated GSK3ß by increasing levels of ROS and cytoplasmic Ca+2, respectively, through T1R2/T1R3 stimulation. Then p-GSK3ß(Ser9) boosted the CSC population by increasing pluripotency factors Oct3/4 and c-myc via NICD, GLI1 and p21. In the aspartame group, T1R1 silencing further increased the CSC population but decreased cell viability and suppressed the p21, NICD and GLI activation. The presence and amount of T1R subunits in the membrane fraction of PANC-1 cells are demonstrated for the first time in this study, as is the regulatory effect of T1R1's on CSC population. In conclusion, the present study demonstrated that long-term aspartame exposure increases CSC population and tumor cell aggressiveness through p21, NICD, GLI1. Moreover, while aspartame had no tumorigenic effect, it could potentially advance an existing tumor.


Assuntos
Adenocarcinoma/metabolismo , Aspartame/farmacologia , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Pancreáticas/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glucose/farmacologia , Humanos , Células-Tronco Neoplásicas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo
8.
Environ Health ; 20(1): 42, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845854

RESUMO

BACKGROUND: Aspartame is one of the world's most widely used artificial sweeteners and is an ingredient in more than 5000 food products globally. A particularly important use is in low-calorie beverages consumed by children and pregnant women. The Ramazzini Institute (RI) reported in 2006 and 2007 that aspartame causes dose-related increases in malignant tumors in multiple organs in rats and mice. Increased cancer risk was seen even at low exposure levels approaching the Acceptable Daily Intake (ADI). Prenatal exposures caused increased malignancies in rodent offspring at lower doses than in adults. These findings generated intense controversy focused on the accuracy of RI's diagnoses of hematopoietic and lymphoid tissue tumors (HLTs). Critics made the claim that pulmonary lesions observed in aspartame-exposed animals were inflammatory lesions caused by Mycoplasma infection rather than malignant neoplasms. METHODS: To address this question, RI subjected all HLTs from aspartame-exposed animals to immunohistochemical analysis using a battery of markers and to morphological reassessment using the most recent Internationally Harmonized Nomenclature and Diagnostic (INHAND) criteria. FINDINGS: This immunohistochemical and morphological re-evaluation confirmed the original diagnoses of malignancy in 92.3% of cases. Six lesions originally diagnosed as lymphoma (8% of all HLTs) were reclassified: 3 to lymphoid hyperplasia, and 3 to chronic inflammation with fibrosis. There was no evidence of Mycoplasma infection. INTERPRETATION: These new findings confirm that aspartame is a chemical carcinogen in rodents. They confirm the very worrisome finding that prenatal exposure to aspartame increases cancer risk in rodent offspring. They validate the conclusions of the original RI studies. These findings are of great importance for public health. In light of them, we encourage all national and international public health agencies to urgently reexamine their assessments of aspartame's health risks - especially the risks of prenatal and early postnatal exposures. We call upon food agencies to reassess Acceptable Daily Intake (ADI) levels for aspartame. We note that an Advisory Group to the International Agency for Research on Cancer has recommended high-priority reevaluation of aspartame's carcinogenicity to humans.


Assuntos
Aspartame/toxicidade , Neoplasias/induzido quimicamente , Edulcorantes/toxicidade , Animais , Feminino , Masculino , Camundongos , Ratos Sprague-Dawley
9.
Nutrients ; 13(2)2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33672234

RESUMO

Aspartame is a phenylalanine containing sweetener, added to foods and drinks, which is avoided in phenylketonuria (PKU). However, the amount of phenylalanine provided by aspartame is unidentifiable from food and drinks labels. We performed a cross-sectional online survey aiming to examine the accidental aspartame consumption in PKU. 206 questionnaires (58% female) were completed. 55% of respondents (n = 114) were adults with PKU or their parent/carers and 45% (n = 92) were parents/carers of children with PKU. 74% (n = 152/206) had consumed food/drinks containing aspartame. Repeated accidental aspartame consumption was common and more frequent in children (p < 0.0001). The aspartame containing food/drinks accidentally consumed were fizzy drinks (68%, n = 103/152), fruit squash (40%, n = 61/152), chewing gum (30%, n = 46/152), flavoured water (25%, n = 38/152), ready to drink fruit squash cartons (23%, n = 35/152) and sports drinks (21%, n = 32/152). The main reasons described for accidental consumption, were manufacturers' changing recipes (81%, n = 123/152), inability to check the ingredients in pubs/restaurants/vending machines (59%, n = 89/152) or forgetting to check the label (32%, n = 49/152). 23% (n= 48/206) had been prescribed medicines containing aspartame and 75% (n = 36/48) said that medicines were not checked by medics when prescribed. 85% (n = 164/192) considered the sugar tax made accidental aspartame consumption more likely. Some of the difficulties for patients were aspartame identification in drinks consumed in restaurants, pubs, vending machines (77%, n = 158/206); similarities in appearance of aspartame and non-aspartame products (62%, n = 127/206); time consuming shopping/checking labels (56%, n = 115/206); and unclear labelling (55%, n = 114/206). These issues caused anxiety for the person with PKU (52%, n = 106/206), anxiety for parent/caregivers (46%, n = 95/206), guilt for parent/carers (42%, n = 87/206) and social isolation (42%, n = 87/206). It is important to understand the impact of aspartame and legislation such as the sugar tax on people with PKU. Policy makers and industry should ensure that the quality of life of people with rare conditions such as PKU is not compromised through their action.


Assuntos
Acidentes/estatística & dados numéricos , Aspartame/análise , Alimentos/estatística & dados numéricos , Fenilalanina/análise , Fenilcetonúrias/dietoterapia , Adulto , Aspartame/efeitos adversos , Criança , Estudos Transversais , Feminino , Alimentos/efeitos adversos , Análise de Alimentos , Rotulagem de Alimentos , Humanos , Legislação sobre Alimentos , Masculino , Fenilalanina/efeitos adversos , Restaurantes
10.
Biosci Biotechnol Biochem ; 85(2): 464-466, 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33604621

RESUMO

Here, we report a novel industrial aspartame production route, involving the enzymatic production of α-l-aspartyl-l-phenylalanine ß-methylester from l-aspartic acid dimethylester and l-phenylalanine by α-amino acid ester acyl transferase. The route also involves the chemical transformation of α-l-aspartyl-l-phenylalanine ß-methylester to α-l-aspartyl-l-phenylalanine methylester hydrochloride (aspartame hydrochloride) in an aqueous solution with methanol and HCl, followed by HCl removal to form aspartame.


Assuntos
Aciltransferases/metabolismo , Aspartame/química , Aspartame/síntese química , Indústrias , Técnicas de Química Sintética , Metanol/química , Água/química
11.
Compr Rev Food Sci Food Saf ; 20(2): 1554-1583, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33580569

RESUMO

The global rise in obesity, type II diabetes, and other metabolic disorders in recent years has been attributed in part to the overconsumption of added sugars. Sugar reduction strategies often rely on synthetic and naturally occurring sweetening compounds to achieve their goals, with popular synthetic sweeteners including saccharin, cyclamate, acesulfame potassium, aspartame, sucralose, neotame, alitame, and advantame. Natural sweeteners can be further partitioned into nutritive, including polyols, rare sugars, honey, maple syrup, and agave, and nonnutritive, which include steviol glycosides and rebaudiosides, luo han guo (monk fruit), and thaumatin. We choose the foods we consume largely on their sensory properties, an area in which these sugar substitutes often fall short. Here, we discuss the most popular synthetic and natural sweeteners, with the goal of providing an understanding of differences in the sensory profiles of these sweeteners versus sucrose, that they are designed to replace, essential for the effectiveness of sugar reduction strategies. In addition, we break down the influence of these sweeteners on metabolism, and present results from a large survey of consumers' opinions on these sweeteners. Consumer interest in clean label foods has driven a move toward natural sweeteners; however, neither natural nor synthetic sweeteners are metabolically inert. Identifying sugar replacements that not only closely imitate the sensory profile of sucrose but also exert advantageous effects on body weight and metabolism is critical in successfully the ultimate goals of reducing added sugar in the average consumer's diet. With so many options for sucrose replacement available, consumer opinion and cost, which vary widely with suagr replacements, will also play a vital role in which sweeteners are successful in widespread adoption.


Assuntos
Diabetes Mellitus Tipo 2 , Edulcorantes , Aspartame , Aditivos Alimentares , Humanos , Açúcares
12.
Artigo em Inglês | MEDLINE | ID: mdl-33455539

RESUMO

In this work the binding of artificial sweetener aspartame with human serum albumin (HSA) was studied at physiological pH. Binding studies of aspartame (APM) with HSA are useful to understand APM -HSA interaction, mechanism and providing guidance for the application and design of new and more efficient artificial sweeteners. The interaction was investigated by spectrophotometric, spectrofluorometric competition experiment and circular dichroism (CD) techniques. The results indicated that the binding of APM to HSA caused fluorescence quenching of HSA through static quenching mechanism with binding constant 1.42 × 10+4 M-1 at 298 K and the number of binding sites is approximately one. Thermodynamic parameters, enthalpy changes (ΔH) and entropy changes (ΔS) were calculated to be -41.20 kJ mol-1 and -58.19 J mol-1 K-1, respectively, according to van't Hoff equation, which indicated that reaction is enthalpically driven. Quenching of the fluorescence of HSA was found to be a static quenching process. The binding constants and number of binding sites were obtained at three different temperatures (298, 308 and 318 K). Combining above results and those of spectrofluorometric competition experiment and circular dichroism (CD), indicated that APM binds to HSA via Sudlow's site I. Furthermore, the study of molecular docking on HSA binding also indicated that APM can strongly bind to the site I (subdomain IIA) of HSA mainly by hydrophobic interaction and hydrogen bond interactions exist between APM and HSA.


Assuntos
Aspartame/metabolismo , Albumina Sérica Humana/metabolismo , Análise Espectral , Ligação Competitiva , Humanos , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Albumina Sérica Humana/química
13.
ACS Appl Mater Interfaces ; 13(1): 1398-1412, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33398990

RESUMO

Nanotechnology-based packaging may improve food quality and safety, but packages manufactured with polymer nanocomposites (PNCs) could be a source of human dietary exposure to engineered nanomaterials (ENMs). Previous studies showed that PNCs release ENMs to foods predominantly in a dissolved state, but most of this work used food simulants like dilute acetic acid and water, leaving questions about how substances in real foods may influence exposure. Here, we demonstrate that food and beverage ingredients with reducing properties, like sweeteners, may alter exposure by inducing nanoparticle formation in foods contacting silver nanotechnology-enabled packaging. We incorporated 12.8 ± 1.4 nm silver nanoparticles (AgNPs) into polyethylene and stored media containing reducing ingredients in packages manufactured from this material under accelerated room-temperature and refrigerated conditions. Analysis of the leachates revealed that reducing ingredients increased the total silver transferred to foods contacting PNC packaging (by as much as 7-fold) and also induced the (re)formation of AgNPs from this dissolved silver during storage. AgNP formation was also observed when Ag+ was introduced to solutions of natural and artificial sweeteners (glucose, sucrose, aspartame), commercial beverages (soft drinks, juices, milk), and liquid foods (yogurt, starch slurry), and the amount and morphology of reformed AgNPs depended on the ingredient formulation, silver concentration, storage conditions, and light exposure. These results imply that food and beverage ingredients may influence dietary exposure to nanoparticles when PNCs are used in packaging applications, and the practice of using food simulants may in certain cases underpredict the amount of ENMs likely to be found in foods stored in these materials.


Assuntos
Bebidas , Embalagem de Alimentos , Nanopartículas Metálicas/química , Prata/química , Animais , Aspartame/química , Temperatura Baixa , Contaminação de Alimentos/análise , Glucose/química , Nanopartículas Metálicas/análise , Oxirredução , Polietileno/química , Prata/análise , Amido/química , Sacarose/química , Edulcorantes/química , Iogurte
14.
Birth Defects Res ; 113(1): 90-107, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33128303

RESUMO

BACKGROUND: Caffeine and aspartame (ASP) are mostly used as a diet regimen to reduce overweight. The risk increase if used during critical life periods that may affect the development of fetal organs. OBJECTIVE: To evaluate the individual and combined effects of maternal exposure to caffeine and ASP during gestation and lactation on the kidneys' development of rats' offspring. METHODS: Pregnant rats were divided randomly into four groups; Group I (control group). Group II (ASP group): ASP was given at a dose of 40 mg of /kg/day. Group III (Caffeine group): caffeine was given at a dose of 80 mg/kg/day. Group IV (ASP & caffeine group); where previous doses of ASP and caffeine were given at the same time. All the treatments were given by oral gavage from the first day of pregnancy until postnatal day 30. Kidneys of rats' offspring were dissected and tested for detection of oxidative stress markers and for histopathological & immunohistochemical examination. RESULTS: This study showed a high significant increase in oxidative load (malondialdehyde) in renal tissues in group IV associated with decreased activities of total glutathione and antioxidant enzymes (superoxide dismutase and glutathione peroxidase). Histological and morphometric examination results showed delayed maturation of renal tissues in Group II and III, but more deleterious effects were observed in group IV with a lot of pathological changes in renal tissues. CONCLUSION: The extensive use of caffeine and ASP should be controlled to avoid the risk of their toxicity.


Assuntos
Aspartame , Cafeína , Animais , Antioxidantes , Aspartame/toxicidade , Cafeína/toxicidade , Feminino , Humanos , Rim , Exposição Materna/efeitos adversos , Gravidez , Ratos
15.
Environ Toxicol ; 36(2): 223-237, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32951320

RESUMO

Aspartame is one of the most common consumed artificial sweeteners utilized in many food products and beverages. It has been indicated that long-term consumption of aspartame leads to reproductive toxicity but its mechanism is not well-clear. In this study we investigated mechanism of aspartame-induced reproductive toxicity in male mice. For this purpose, 36 NMRI mature male mice received three doses of 40, 80, and 160 mg/kg body weight of aspartame, respectively per day by gavage for 90 days and also a control group was considered which received 0.5 mL of normal saline as the same route. The results revealed that long-term administration of aspartame at high doses significantly (P < .05) reduced gonadosomatic index, serum concentration of pituitary-testicular axis hormones (FSH, LH, and testosterone). It also decreased sperm parameters and total antioxidant capacity, antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), while it caused increase in nitric oxide and malondialdehyde levels in testis tissue and sperm samples. Also, it decreased attenuated testicular histomorphometric indices (tubular differentiation index, spermiogenesis index, and repopulation index), and steroidogenic foci, while increased mRNA damages and apoptosis rate, downregulated antiapoptotic (Bcl-2) and upregulated proapoptotic (P53, BAX, and caspase-3) mediators respectively in testis. These findings indicated that consumption of aspartame for a long period results in male reproductive toxicity by decrease in serum concentration of pituitary-testis axis hormones and induction of oxidative stress and apoptosis in testis.


Assuntos
Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Aspartame/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Aspartame/administração & dosagem , Proteínas Relacionadas à Autofagia/metabolismo , Caspases/metabolismo , Relação Dose-Resposta a Droga , Glutationa Peroxidase/metabolismo , Masculino , Malondialdeído/metabolismo , Camundongos , Espermatogênese/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Testículo/metabolismo , Testosterona/sangue
16.
Int J Pharm ; 593: 120171, 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33321170

RESUMO

Osteoporosis therapy consists of inhibiting the osteoclasts' activity and promoting osteoblasts' osteogenesis. Salmon calcitonin (sCT) could realize both requirements, however, it is limited by the low bioavailability caused by fibrillation. Supramolecular assembly of sCT and biocompatible agents into nanoassemblies provides an opportunity to overcome these shortcomings. Herein, we used a facile method to fabricate salmon calcitonin-aspartame (sCT-APM) nanoassemblies. Supramolecular interactions could not only delay fibrillation time (from 36.9 h to 50.4 h), but also achieve sustained sCT release. Moreover, sCT-APM showed good biocompatibility and higher osteoinductive capacity than free sCT, revealing an osteogenesis improvement effect. Moreover, in vivo studies showed that sCT-APM has enhanced relative bioavailability (2.42-fold of sCT) and increased relative therapeutic efficacy (3.55-fold of sCT) through subcutaneous injection. These findings provide a convenient alternative strategy for osteoporosis therapy via supramolecular assemblies.


Assuntos
Osteogênese , Osteoporose , Aspartame , Calcitonina , Humanos
17.
Can J Diet Pract Res ; 82(2): 90-94, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33320777

RESUMO

Purpose: To compare the perceived healthiness of different sweeteners relative to table sugar and examine efforts to consume less sugars and sweeteners.Methods: As part of the 2017 Canada Food Study online survey, 1000 youth and young adults were randomized to rate the healthiness of 1 of 6 sweeteners (aspartame, sucralose, stevia, agave, high-fructose corn syrup, "raw" sugar) or 1 sweetener brand name (Splenda) compared with "table sugar".Results: Perceptions of sweeteners varied widely. For example, the majority of respondents perceived high-fructose corn syrup (63.9%) and aspartame (52.4%) as less healthy than table sugar, whereas almost half (47.8%) perceived raw sugar as being healthier than table sugar. No assessed socio-demographic variables were significantly associated with perceived healthiness of sweeteners compared with table sugar (P ≥ 0.05). More consumers had attempted to consume less sugar (65.4%) compared with less "artificial" (31.2%) or "natural" (24.0%) low-calorie sweeteners.Conclusions: Perceptions of sweetener healthiness may be related to sweeteners' perceived level of "naturalness" rather than energy content. This has important implications for understanding consumer preferences, particularly given greater use of low-calorie sweeteners in the food supply and policy developments such as sugar taxes and enhanced sugar labelling.


Assuntos
Stevia , Edulcorantes , Adolescente , Aspartame , Comportamento do Consumidor , Ingestão de Energia , Humanos , Adulto Jovem
18.
PLoS One ; 15(12): e0232916, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33264281

RESUMO

Automated, homecage behavioral training for rodents has many advantages: it is low stress, requires little interaction with the experimenter, and can be easily manipulated to adapt to different experimental conditions. We have developed an inexpensive, Arduino-based, homecage training apparatus for sensory association training in freely-moving mice using multiwhisker air current stimulation coupled to a water reward. Animals learn this task readily, within 1-2 days of training, and performance progressively improves with training. We examined the parameters that regulate task acquisition using different stimulus intensities, directions, and reward valence. Learning was assessed by comparing anticipatory licking for the stimulus compared to the no-stimulus (blank) trials. At high stimulus intensities (>9 psi), animals showed markedly less participation in the task. Conversely, very weak air current intensities (1-2 psi) were not sufficient to generate rapid learning behavior. At intermediate stimulus intensities (5-6 psi), a majority of mice learned that the multiwhisker stimulus predicted the water reward after 24-48 hrs of training. Both exposure to isoflurane and lack of whiskers decreased animals' ability to learn the task. Following training at an intermediate stimulus intensity, mice were able to transfer learning behavior when exposed to a lower stimulus intensity, an indicator of perceptual learning. Mice learned to discriminate between two directions of stimulation rapidly and accurately, even when the angular distance between the stimuli was <15 degrees. Switching the reward to a more desirable reward, aspartame, had little effect on learning trajectory. Our results show that a tactile association task in an automated homecage environment can be monitored by anticipatory licking to reveal rapid and progressive behavioral change. These Arduino-based, automated mouse cages enable high-throughput training that facilitate analysis of large numbers of genetically modified mice with targeted manipulations of neural activity.


Assuntos
Aprendizagem por Discriminação , Abrigo para Animais , Vibrissas/fisiologia , Ar , Animais , Antecipação Psicológica/efeitos dos fármacos , Antecipação Psicológica/fisiologia , Aspartame , Automação , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Aprendizagem por Discriminação/efeitos dos fármacos , Remoção de Cabelo , Isoflurano/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Estimulação Física , Recompensa , Sensação/fisiologia , Água
19.
Nutrients ; 12(12)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255204

RESUMO

Aspartame (ASP), an artificial sweetener abundantly consumed in recent years in an array of dietary products, has raised some concerns in terms of toxicity, and it was even suggested a link with the risk of carcinogenesis (colorectal cancer), though the present scientific data are rather inconclusive. This study aims at investigating the potential role of aspartame in colorectal cancer by suggesting two experimental approaches: (i) an in vitro cytotoxicity screening in HT-29 human colorectal carcinoma cells based on cell viability (Alamar blue assay), cell morphology and cell migration (scratch assay) assessment and (ii) an in ovo evaluation in terms of angiogenic and irritant potential by means of the chorioallantoic membrane method (CAM). The in vitro results showed a dose-dependent cytotoxic effect, with a significant decrease of viable cells at the highest concentrations tested (15, 30 and 50 mM) and morphological cellular changes. In ovo, aspartame (15 and 30 mM) proved to have a pro-angiogenic effect and a weak irritant potential at the vascular level. These data suggest new directions of research regarding aspartame's role in colorectal cancer.


Assuntos
Indutores da Angiogênese/farmacologia , Aspartame/metabolismo , Aspartame/farmacologia , Neoplasias Colorretais/metabolismo , Citotoxinas/farmacologia , Edulcorantes/farmacologia , Indutores da Angiogênese/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citotoxinas/metabolismo , Células HT29/metabolismo , Humanos , Técnicas In Vitro , Edulcorantes/metabolismo
20.
Artigo em Inglês | MEDLINE | ID: mdl-33291649

RESUMO

There is an association between the consumption of artificial sweeteners and Type 2 diabetes in cohort studies, but intervention studies do not show a clear elevation of blood glucose after the use of artificial sweeteners. The objective of this study was to examine whether two commonly used artificial sweeteners had an adverse effect on glucose control in normal-weight subjects, and in overweight and obese subjects when consumed for 2 weeks. In the study, 39 healthy subjects (body-mass index, kg/m2) (18-45) without Type 2 diabetes with an age of 18-75 years were randomly assigned to 0.6 L/day of an artificially sweetened soft drink containing acesulfame K (950) and aspartame (951) or 0.6 L/day of mineral water for 2 weeks each in a crossover study. There was a 4 week washout period with no drinks consumed. Glucose levels were read by a continuous glucose monitor (CGM) during each 2 week period. A 75 g oral glucose-tolerance test (OGTT) was performed at the beginning and end of each intervention period. Blood samples were collected at baseline, and 1 and 2 h for glucose and insulin. A 2 week intake of artificially sweetened beverage (ASB) did not alter concentrations of fasting glucose and fasting insulin, the area under the curve (AUC) for OGTT glucose and insulin, the incremental area under the curve (iAUC) for OGTT glucose and insulin, the homeostatic model assessment for insulin resistance (HOMA-IR), and the Matsuda index compared with the baseline and with the changes after a 2 week intake of mineral water. Continuous 2 week glucose concentrations were not significantly different after a 2 week intake of ASB compared with a 2 week intake of mineral water. This study found no harmful effect of the artificially sweetened soft drink containing acesulfame K (950) and aspartame (951) on glucose control when consumed for 2 weeks by people without Type 2 diabetes.


Assuntos
Aspartame , Glicemia , Diabetes Mellitus Tipo 2 , Edulcorantes , Tiazinas , Adulto , Aspartame/efeitos adversos , Bebidas , Estudos Cross-Over , Feminino , Glucose , Humanos , Insulina , Masculino , Edulcorantes/efeitos adversos , Tiazinas/efeitos adversos
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