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1.
BMC Res Notes ; 17(1): 155, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840123

ABSTRACT

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.


Subject(s)
Aspartame , Kidney , Mice, Inbred ICR , Oxidative Stress , Sweetening Agents , Animals , Aspartame/pharmacology , Kidney/drug effects , Kidney/metabolism , Sweetening Agents/pharmacology , Sweetening Agents/administration & dosage , Mice , Male , Oxidative Stress/drug effects , Antioxidants/pharmacology , Antioxidants/metabolism , Superoxide Dismutase/metabolism , Blood Urea Nitrogen
2.
Int Immunopharmacol ; 135: 112295, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38776852

ABSTRACT

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.


Subject(s)
Aspartame , Cognitive Dysfunction , Microglia , Microglia/drug effects , Microglia/immunology , Humans , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/drug therapy , Animals , Neuroinflammatory Diseases/immunology , Neuroinflammatory Diseases/drug therapy , Neuroinflammatory Diseases/chemically induced , Sweetening Agents , Brain/drug effects , Brain/pathology , Brain/metabolism , Brain/immunology
3.
Sci Rep ; 14(1): 11492, 2024 05 20.
Article in English | MEDLINE | ID: mdl-38769413

ABSTRACT

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.


Subject(s)
Aspartame , Carcinogens , Molecular Docking Simulation , Aspartame/chemistry , Aspartame/adverse effects , Aspartame/metabolism , Aspartame/toxicity , Humans , Carcinogens/toxicity , Carcinogens/chemistry , Sweetening Agents/chemistry , Sweetening Agents/adverse effects , Sweetening Agents/toxicity , Stomach Neoplasms/chemically induced
4.
Diabetes Obes Metab ; 26(7): 2645-2651, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38558517

ABSTRACT

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.


Subject(s)
Blood Glucose , Caffeine , Cross-Over Studies , Diabetes Mellitus, Type 1 , Exercise , Hypoglycemia , Insulin, Long-Acting , Humans , Insulin, Long-Acting/administration & dosage , Insulin, Long-Acting/therapeutic use , Double-Blind Method , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/complications , Male , Female , Caffeine/administration & dosage , Adult , Hypoglycemia/prevention & control , Hypoglycemia/chemically induced , Blood Glucose/metabolism , Blood Glucose/drug effects , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/administration & dosage , Glucose/metabolism , Middle Aged , Aspartame/administration & dosage , Aspartame/adverse effects
5.
Neurotoxicology ; 102: 37-47, 2024 May.
Article in English | MEDLINE | ID: mdl-38499183

ABSTRACT

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 80 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.


Subject(s)
Aspartame , Body Weight , Corticosterone , Cytokines , Depression , Mice, Inbred C57BL , Sweetening Agents , Animals , Corticosterone/blood , Aspartame/toxicity , Depression/chemically induced , Depression/blood , Male , Mice , Body Weight/drug effects , Cytokines/blood , Cytokines/metabolism , Sweetening Agents/administration & dosage , Sweetening Agents/toxicity , Brain/drug effects , Brain/metabolism , Circadian Rhythm/drug effects , Circadian Rhythm/physiology , Behavior, Animal/drug effects
8.
Nutrients ; 16(4)2024 Feb 08.
Article in English | MEDLINE | ID: mdl-38398814

ABSTRACT

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.


Subject(s)
Aspartame , Sweetening Agents , Rats , Male , Animals , Aspartame/adverse effects , Rats, Wistar , Sweetening Agents/adverse effects , RNA, Messenger/genetics , Potassium
9.
J. physiol. biochem ; 80(1): 53-65, Feb. 2024. ilus, graf
Article in English | IBECS | ID: ibc-229940

ABSTRACT

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 β-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. (AU)


Subject(s)
Aspartame , Apoptosis , Caspase 3
10.
J. physiol. biochem ; 80(1): 53-65, Feb. 2024. ilus, graf
Article in English | IBECS | ID: ibc-EMG-565

ABSTRACT

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 β-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. (AU)


Subject(s)
Aspartame , Apoptosis , Caspase 3
11.
Mol Nutr Food Res ; 68(5): e2300270, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38389198

ABSTRACT

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.


Subject(s)
Kisspeptins , Puberty, Delayed , Humans , Rats , Female , Animals , Kisspeptins/metabolism , Kisspeptins/pharmacology , Aspartame/adverse effects , Aspartame/metabolism , Puberty, Delayed/metabolism , Rats, Sprague-Dawley , Sexual Maturation/physiology , Gonadotropin-Releasing Hormone/genetics , Hypothalamus/metabolism , Puberty , RNA, Messenger/metabolism
12.
Nutrients ; 16(1)2024 Jan 02.
Article in English | MEDLINE | ID: mdl-38201980

ABSTRACT

(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.


Subject(s)
High Fructose Corn Syrup , Insulin Resistance , Young Adult , Humans , Glucose , Glucose Tolerance Test , Aspartame/pharmacology , Zea mays , Sucrose/pharmacology , Fructose/adverse effects , High Fructose Corn Syrup/adverse effects , Beverages , Insulin
13.
Recenti Prog Med ; 115(2): 82-84, 2024 Feb.
Article in Italian | MEDLINE | ID: mdl-38291933

ABSTRACT

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.


Subject(s)
Dietary Supplements , Sweetening Agents , Humans , Prevalence , Vitamins , Aspartame
14.
Br J Nutr ; 131(1): 63-72, 2024 01 14.
Article in English | MEDLINE | ID: mdl-37424288

ABSTRACT

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.


Subject(s)
Endometrial Neoplasms , Non-Nutritive Sweeteners , Female , Humans , Aspartame/adverse effects , Endometrial Neoplasms/epidemiology , Endometrial Neoplasms/etiology , Non-Nutritive Sweeteners/adverse effects , Saccharin/adverse effects , Sucrose/adverse effects , Sweetening Agents/adverse effects , Observational Studies as Topic
15.
Nutr Neurosci ; 27(5): 506-519, 2024 May.
Article in English | MEDLINE | ID: mdl-37395401

ABSTRACT

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.


Subject(s)
Aspartame , Parkinson Disease , Animals , Humans , Cognition , Oxidative Stress , Neurotransmitter Agents
16.
J Physiol Biochem ; 80(1): 53-65, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37906422

ABSTRACT

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.


Subject(s)
Apoptosis , Aspartame , Islets of Langerhans , Animals , Mice , Apoptosis/drug effects , Aspartame/adverse effects , Aspartame/metabolism , Caspase 3/metabolism , Death-Associated Protein Kinases/drug effects , Death-Associated Protein Kinases/pharmacology , Islets of Langerhans/drug effects , Islets of Langerhans/metabolism , Phosphorylation , Signal Transduction , STAT3 Transcription Factor/metabolism , Sucrose/metabolism , Sucrose/pharmacology , Transcription Factors/metabolism
17.
J Nanobiotechnology ; 21(1): 409, 2023 Nov 06.
Article in English | MEDLINE | ID: mdl-37932843

ABSTRACT

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.


Subject(s)
Anti-Infective Agents , Carbapenem-Resistant Enterobacteriaceae , Metal Nanoparticles , Animals , Mice , Gold/chemistry , Metal Nanoparticles/chemistry , Sweetening Agents , Aspartame , Reactive Oxygen Species , Anti-Bacterial Agents/pharmacology , Bacteria , Microbial Sensitivity Tests
18.
Food Res Int ; 173(Pt 1): 113365, 2023 11.
Article in English | MEDLINE | ID: mdl-37803662

ABSTRACT

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.


Subject(s)
Aspartame , Sweetening Agents , Aspartame/analysis , Sweetening Agents/toxicity , Sweetening Agents/analysis , Carbonated Beverages/analysis , Beverages/analysis
19.
Food Res Int ; 173(Pt 2): 113406, 2023 11.
Article in English | MEDLINE | ID: mdl-37803739

ABSTRACT

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.


Subject(s)
Aspartame , Sugar-Sweetened Beverages , Humans , Sweetening Agents , Insulin , Single-Blind Method , alpha-Amylases , Sucrose , Water
20.
Article in English | MEDLINE | ID: mdl-37695976

ABSTRACT

Government regulatory actions and public policies have been recently implemented in Brazil due to the excessive consumption of sugar. Therefore, it becomes relevant to determine the levels of high-intensity sweeteners in tabletop sweeteners consumed by the Brazilian population. Thus, an analytical method was developed and validated for the simultaneous determination of nine sweeteners (acesulfame potassium, aspartame, advantame, sodium cyclamate, neotame, saccharin, sucralose, stevioside, and rebaudioside A) by using ultra-high performance liquid chromatography coupled to mass spectrometry in tandem. The sample preparation encompassed only dilution steps. The method was validated taking into account the parameters of linearity, precision, accuracy, and matrix effects. The analytes were determined in two different batches of 21 commercial liquid and powder tabletop sweeteners available on the local market, totaling 42 samples. A minimum of one and a maximum of four sweeteners were found in the analyzed products and sweeteners that were not described on the label were not detected. It is expected that the established method can be used in monitoring programs and that the presented results can contribute to exposure assessments performed nationally.


Subject(s)
Non-Nutritive Sweeteners , Sweetening Agents , Sweetening Agents/analysis , Non-Nutritive Sweeteners/analysis , Powders , Aspartame/analysis , Food Additives
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