Aspartame induced cardiac oxidative stress in Wistar albino rats

Aspartame (non-nutritive sweetener) is consumed by millions of people in products like beverages, instant breakfasts, desserts, breathe mints, sugar free chewing gum, vitamins, and pharmaceutical. On a weight basis, metabolism of aspartame generates approximately 50% phenylalanine, 40% aspartic acid and 10% methanol. The detailed mechanisms of their effects on cardiac tissue are still unclear. The present study aimed to clarify whether longer time aspartame consumption has any effect on heart of Wistar albino rats. Animals were randomly divided into 4 groups of 6 animals (group-1: control, group-2: folate deficient diet fed animals, group-3: control animals treated with aspartame, group-4: folate deficient diet fed animals treated with aspartame). Aspartame was given orally (40 mg/kg·bw/day), dissolved in normal saline and for 90 days. Since human beings have very low hepatic folate content, the folate deficient diet fed animals were used to mimic the human methanol metabolism. Aspartame consumption increased significantly plasma corticosterone level, suggesting that aspartame may act as a chemical stressor. There was a significant increase in lipid peroxidation, nitric oxide and protein carbonyl, and significant decrease in protein thiol, cardiac membrane bound ATPases (Na⁺, K⁺, Ca⁺⁺, Mg⁺⁺), enzymatic (SOD, CAT, GPX, G6PD, GR) and non-enzymatic antioxidants (GSH, Vit-C, Vit-E) as well as a significant increase in heart rate and heart marker enzymes (CK and CK-MB). It may be due to excessive generation of free radicals, which impairs cardiac function. Aspartame metabolite methanol or formaldehyde may be the causative factors behind these changes. However, up regulation of Hsp70 in immunohistochemical analysis of cardiac tissue might be a protective response to oxidative stress induced by aspartame metabolites and structural damages in cardiac tissue.     

Artificial sweetener consumption and urinary tract tumors in Cordoba, Argentina

OBJECTIVE: To determine the role of the habitual use of the most common artificial sweeteners (AS) in the development of urinary tract tumors (UTT) in Argentina. METHODS: Case-control study of 197 patients with histologically confirmed UTT of transitional varieties, and 397 controls with acute, non-neoplastic, and non-urinary tract diseases, admitted to the same hospitals in Córdoba (Argentina) between 1999 and 2006. All subjects were interviewed about their use of AS and their exposure to other known or suspected risk factors for UTT. RESULTS: Fifty-one UTT patients (26%) and 87 controls (22%) used AS. The risk of UTT was significantly increased in long-term (> or =10 years) AS users compared with none-AS users. The OR (95% CI) for long-term consumers was 2.18 (1.22-3.89) and for short-term users was 1.10 (0.61-2.00) after adjustment for age, gender, BMI, social status. and years of tobacco use. CONCLUSION: Regular use of AS for 10 years or more was positively associated with UTT.     

In vitro effect of aspartame in angiogenesis induction

Aspartame (APM) is the most widely used artificial sweetener and is added to a wide variety of foods, beverages, drugs, and hygiene products. In vitro and in vivo tests have reported contradictory data about APM genotoxicity. We evaluated the angiogenic effect of APM in an in vitro model using blood vessel development assay (Angio-Kit), cultured endothelial cells and fibroblasts. The release of IL-6, VEGF-A, and their soluble receptors sIL-R6 and sVEGFR-2 were determined over time in the conditioned medium of the Angio-Kit system, endothelial cells and cell lines with fibroblast properties after APM treatment. Reactive oxygen species (ROS) formation, cell viability, and stimulation of the extracellular signal-regulated kinases (erk1/2) and protein p38 were also evaluated. Exposure to APM induced blood vessel formation. ROS production was observed in endothelial cells after APM treatment, which was associated with a slight cell cytotoxicity. Neither intracellular ROS formation nor cell death was observed in fibroblasts. APM increases the levels of inflammatory mediator IL-6, VEGF and their soluble receptors released from endothelial cells into the medium. APM treatment induces VEGF-pathway activation by erk1/2 and p38 phosphorylation. APM at low doses is an angiogenic agent that induces regenerative cytokine production leading to the activation of MAPKs and resulting in the formation of new blood vessels.     

The effect of aspartame metabolites on the suckling rat frontal cortex acetylcholinesterase. An in vitro study

Aspartame (ASP) consumption is suggested to be implicated with muscarinic dysfunction. The aim of this work was to evaluate the effect of ASP and its metabolites on acetylcholinesterase (AChE) activity in rat frontal cortex and pure enzyme. Rat frontal cortex homogenate or pure enzyme AChE (eel E. Electricus) were incubated with ASP and each of ASP components, phenylalanine (Phe), aspartic acid (asp), and methanol (MeOH) for 1 h at 37 °C. AChE was measured spectrophotometrically. The results showed that incubation of rat tissue or pure enzyme with the sum of ASP metabolites, as reported to be found in the CSF after 150 or 200 mg/kg ASP consumption, inhibited frontal cortex and pure AChE about −11% to −29% (p < 0.001). Asp, Phe or MeOH concentrations related to their CSF levels after ingestion of abuse or toxic ASP doses, when separately incubated with frontal cortex or pure AChE, resulted in a significant decrease of the enzyme activities. In conclusion:

ASP compounds may directly and/or indirectly act on the frontal cortex AChE. High or toxic doses of the sweetener remarkably decreased the enzyme activity. If this in vitro finding comes into human reality, it may be suggested that cholinergic symptoms are related to the consumption of the above ASP doses.     

十味益脾颗粒矫味的模糊数学综合评价

目的:优选十味益脾颗粒最佳口味配方。方法:采用添加甜味剂和香精法优化十味益脾颗粒口味,运用模糊数学法综合评价不同矫味配方效果,确定最佳配方。结果:阿司帕坦和甜橙香精配合应用对十味益脾颗粒的矫味效果最好,矫味配方为每千克十味益脾颗粒中含阿司帕坦10.0g和甜橙香精5.0g。结论:模糊数学综合评价可用于十味益脾颗粒矫味配方筛选。本实验得到的矫味配方可为该制剂的工业化生产提供参考。     

高效液相色谱同时测定食品中5种添加剂

[目的]建立高效液相色谱(HPLC)同时测定食品中安赛蜜、糖精钠、苯甲酸、山梨酸和阿斯巴甜的方法。[方法]样品经去蛋白、脱色、超声提取、过滤膜等预处理,采用HPLC二极管分段多波长同时测定。[结果]方法线性良好,相关系数为0.9995~0.9999,回收率为90.70%~98.20%,相对标准偏差为0.41%~2.40%。[结论]方法准确可靠、简便快速、易于掌握、便于推广。     

Characterization of aspartame–cyclodextrin complexation

The inclusion complex formation of aspartame (guest) and various cyclodextrins (host) were examined using ¹H NMR titration and capillary electrophoresis. Initially the protonation constants of aspartame were determined by NMR-pH titration with in situ pH measurement to yield log K₁ = 7.83 and log K₂ = 2.96. Based on these values the stability of the complexes formed by aspartame and 21 different cyclodextrins (CDs) were studied at pH 2.5, pH 5.2 and pH 9.0 values where aspartame exists predominantly in monocationic, zwitterionic and monoanionic form, respectively. The host cyclodextrin derivatives differed in various sidechains, degree of substitution, charge and purity so that the effect of these properties could be examined systematically. Concerning size, the seven-membered beta-cyclodextrin and its derivatives have been found to be the most suitable host molecules for complexation. Highest stability was observed for the acetylated derivative with a degree of substitution of 7. The purity of the CD enhanced the complexation while the degree of substitution did not provide obvious consequences. Finally, geometric aspects of the inclusion complex were assessed by 2D ROESY NMR and molecular modelling which proved that the guest's aromatic ring enters the wider end of the host cavity.     

灰色系统理论在工艺考察中的应用——天冬甜素合成工艺的关联度分析

依据灰色系统理论对影响甲酰天冬酸酐(合成天冬甜素的中间体)收率的因素进行了关联度分析。分析结果表明:加料时间为影响收率的次要因素,而原料配比、反应温度和反应时间为主要因素。关联度分析运算简单,样本数不受限制,是一种有效的因素分析方法。     

l-Cysteine and glutathione restore the modulation of rat frontal cortex Na, K-ATPase activity induced by aspartame metabolites

BACKGROUND: Studies have suggested that aspartame (ASP) ingestion is implicated in neurological problems. AIM: The aim of this study was to evaluate rat frontal cortex Na+, K+ -ATPase and Mg2+ -ATPase activities after incubation with ASP or each of its metabolites, phenylalanine (Phe), methanol (MeOH) and aspartic acid (asp) separately. METHOD: Suckling rat frontal cortex homogenates or pure Na+, K+ -ATPase were incubated with ASP metabolites. Na+, K+ -ATPase and Mg2+ -ATPase activities were measured spectrophotometrically. RESULTS: Incubation of frontal cortex homogenate or pure Na+, K+ -ATPase with various ASP concentrations as expected in the cerebrospinal fluid (CSF) after ASP consumption of 34, 150 or 200mg/kg, decreased the frontal cortex enzyme activity by 33%, 53% or 57%, respectively, whereas pure enzyme was remarkably stimulated. Moreover, incubation of frontal cortex homogenate with each one of the expected ASP metabolites in the CSF, except MeOH, which are related to the intake of the above mentioned doses of the sweetener, resulted in an activation of the membrane Na+, K+ -ATPase, as well as pure enzyme. Frontal cortex Mg2+-ATPase remained unaltered. Addition of l-cysteine (cys) or reduced glutathione (GSH) to ASP metabolites mixtures, corresponding to 150 or 200mg/kg doses of the sweetener, completely or partially restored to normal the modulated membrane and pure Na+, K+ -ATPase activities. CONCLUSION: CSF concentrations of the sum of ASP metabolites corresponding to the intake of common, abuse or toxic doses (34 or 150 or 200mg/kg, respectively) of the additive significantly increased rat frontal cortex Na+, K+ -ATPase and pure enzyme activities. Cys or GSH completely or partially restored to normal both enzyme activities, possibly due to amelioration of the cellular GSH reduction from the action of MeOH, a metabolite of the sweetener and/or by their scavenging effect.     

Effects of chewing gum on responses to routine painful procedures in children

In infants, sweet taste and sucking on a pacifier both have analgesic effects. Animal studies suggest that sweet taste may involve opioids, while rhythmic oral movements, as with a pacifier, increase the release of serotonin, which is involved in the gating of nociceptive afferents. The present study was designed to see if these effects produce an analgesic effect in children. Two studies were performed, during blood draws in a pediatric test center in 7- to 12-year-old children, and during vaccination at school in 9- to 11-year-old children. Using unsweetened or sweetened chewing gum, there were four groups: control, sweet, chew, and sweet plus chew. Overall, there was no effect of either sweet taste or chewing on pain responses. However, in boys sweet taste tended to increase pain ratings, but only in conjunction with chewing, while in girls sweet taste tended to decrease pain ratings in conjunction with chewing and increased them in the absence of chewing. Ratings of pain intensity and affective state were correlated. Affective state before the painful stimulus was related to pain response in the girls and in the boys in the test center, but not in the schools. In the schools, the presence of peers may have influenced the ratings.