Oxidative stress evoked damages leading to attenuated memory and inhibition of NMDAR–CaMKII–ERK/CREB signalling on consumption of aspartame in rat model (original) (raw)
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Neurochemical Research, 2014
Long-term intake of aspartame at the acceptable daily dose causes oxidative stress in rodent brain mainly due to the dysregulation of glutathione (GSH) homeostasis. N-Acetylcysteine provides the cysteine that is required for the production of GSH, being effective in treating disorders associated with oxidative stress. We investigated the effects of N-acetylcysteine treatment (150 mg kg -1 , i.p.) on oxidative stress biomarkers in rat brain after chronic aspartame administration by gavage (40 mg kg -1 ). N-Acetylcysteine led to a reduction in the thiobarbituric acid reactive substances, lipid hydroperoxides, and carbonyl protein levels, which were increased due to aspartame administration. N-Acetylcysteine also resulted in an elevation of superoxide dismutase, glutathione peroxidase, glutathione reductase activities, as well as nonprotein thiols, and total reactive antioxidant potential levels, which were decreased after aspartame exposure. However, N-acetylcysteine was unable to reduce serum glucose levels, which were increased as a result of aspartame administration. Furthermore, catalase and glutathione S-transferase, whose activities were reduced due to aspartame treatment, remained decreased even after N-acetylcysteine exposure. In conclusion, N-acetylcysteine treatment may exert a protective effect against the oxidative damage in the brain, which was caused by the longterm consumption of the acceptable daily dose of aspartame by rats.
Toxicology, 2007
Studies have implicated aspartame (ASP) ingestion in neurological problems. The aim of this study was to evaluate hippocampal Na + ,K +-ATPase and Mg 2+-ATPase activities after incubation with ASP or each of ASP metabolites, phenylalanine (Phe), methanol (MeOH) and aspartic acid (asp) separately. Suckling rat hippocampal homogenates or pure Na + ,K +-ATPase were incubated with ASP metabolites. Na + ,K +-ATPase and Mg 2+-ATPase activities were measured spectrophotometrically. Incubation of hippocampal or pure Na + ,K +-ATPase with ASP concentrations (expected in the cerebrospinal fluid (CSF)) after ASP consumption of 34, 150 or 200 mg/kg resulted in hippocampal enzyme activity reduction of 26%, 50% or 59%, respectively, whereas pure enzyme was remarkably stimulated. Moreover, incubation with hippocampal homogenate of each one of the corresponding in the CSF ASP metabolites related to the intake of common, high/abuse doses of the sweetener, inhibited Na + ,K +-ATPase, while pure enzyme was activated. Hippocampal Mg 2+-ATPase remained unaltered. Addition of l-cysteine (cys) or reduced glutathione (GSH) in ASP mixtures, related with high/toxic doses of the sweetener, completely or partially restored the inactivated membrane Na + ,K +-ATPase, whereas the activated pure enzyme activity returned to normal. CSF concentrations of ASP metabolites related to common, abuse/toxic doses of the additive significantly reduced rat hippocampal Na + ,K +-ATPase activity, whereas pure enzyme was activated. Cys or GSH completely or partially restored both enzyme activities.
https://www.ijhsr.org/IJHSR\_Vol.6\_Issue.3\_March2016/40.pdf, 2016
Aspartame is one of the most common artificial sweeteners in use today worldwide. It has a wide acceptance as an additive in liquid beverages and food. Aspartame has been implicated in many health problems. The study aimed to investigate whether aspartame consumption induces oxidative stress and whether it can threaten the antioxidant defense system in hepatic and renal tissues. The experiment was performed on adult male albino rats. They were distributed into 4 groups, group I represented the control animals and received orally water. The rest were given aspartame in a dose 50 mg/kg for 15, 30 and 60 days respectively. Blood was collected and centrifuged to obtain serum for the determination of serum enzymes. The tissue samples were homogenized, centrifuged and the clear supernatant was collected and used for further biochemical analysis. The results showed a significant increase in lipid peroxidation (LPO) level in liver and kidney. A remarkable reduction in glutathione (GSH) content was also observed in both hepatic and renal tissues. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) were significantly reduced in both liver and kidney. In addition, the results also indicated a significant increase in activities of serum marker enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT). The data provided in this study clearly point out that aspartame consumption at a dose of 50 mg/kg induces oxidative stress in hepatic and renal tissues by generation of free radicals.
Eff ect of aspartame in spinal cord and motor behavior in Wistar albino rats
Introduction: More than 90 countries have given the artificial sweetener aspartame the green light to be used in thousands of food and beverage products. Two hundred times sweeter than sugar, aspartame allows food manufacturers to produce sweet foods they can market as “low calorie,” “diet,” or sugar-free,” appealing to hundreds of millions of consumers looking to cut sugar from their diets. Concern relating to the possible adverse effect has been raised due to aspartames metabolic components. Aspartame is rapidly and completely metabolized in humans and experimental animals to aspartic acid (40%), phenylalanine (50%) and methanol (10%). Methanol, a toxic metabolite is primarily metabolized by oxidation to formaldehyde and then to formate these processes are accompanied by the formation of superoxide anion and hydrogen peroxide. Lacuna and Method: This study focus is to understand whether the oral administration of aspartame (40mg/kg.bw) for 90 days, has any effect on membrane bound ATPases, antioxidant status(both enzymatic and non-enzymatic) in spinal cord and motor behavior of Wistar albino rats. To mimic human methanol metabolism, folate deficient rats were used. Result: After 90 days of aspartame administration, showed a significant alteration in membrane bound ATPases, decrease in both enzymatic and non-enzymatic antioxidant level while there was no significant change was observed in motor behavior. Conclusion: This study concludes that oral administration of aspartame (40mg/kg.bw) for longer duration may cause oxidative stress in spinal cord, which didn’t have any consequence on motor behavior, but which may be the root of other neuronal complication because oxidative stress in spinal cord can’t be ignored.
Redox biology, 2017
No-caloric sweeteners, such as aspartame, are widely used in various food and beverages to prevent the increasing rates of obesity and diabetes mellitus, acting as tools in helping control caloric intake. Aspartame is metabolized to phenylalanine, aspartic acid, and methanol. Our aim was to study the effect of chronic administration of aspartame on glutathione redox status and on the trans-sulphuration pathway in mouse liver. Mice were divided into three groups: control; treated daily with aspartame for 90 days; and treated with aspartame plus N-acetylcysteine (NAC). Chronic administration of aspartame increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase activities and caused liver injury as well as marked decreased hepatic levels of reduced glutathione (GSH), oxidized glutathione (GSSG), γ-glutamylcysteine (γ-GC), and most metabolites of the trans-sulphuration pathway, such as cysteine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH). Aspa...
Current Nutrition & Food Science, 2015
Aspartame is rapidly and completely metabolized in humans and experimental animals to aspartic acid (40%), phenylalanine (50%) and methanol (10%). Methanol, a toxic metabolite is primarily metabolized by oxidation to formaldehyde and then to formate these processes are accompanied by the formation of superoxide anion and hydrogen peroxide. This study focuses on whether the oral administration of aspartame (40 mg/kg.bw/day) for 15-days and 30-days, has any effect on membrane bound ATPase, 'Marker' enzymes (ALP, ALT, ACP, AST &LDH) some selective liver and kidney function parameter and antioxidant status in liver and kidney of rats. To mimic human methanol metabolism, folate deficient rats were used. After 15-days of aspartame administration, there was no change observed in kidney, however liver showed a significant decrease in membrane bound ATPase enzyme (Na + /k + , Mg 2+ & Ca 2+ ), marker enzymes (ALP, ALT, AST & LDH) and significant increase in marker enzymes (ACP), antioxidant enzyme level. However, after aspartame administration for30-days, liver and kidney both showed a significant decrease in membrane bound ATPase enzyme(Na + k + , Mg 2+ & Ca 2+ ), marker enzymes (ALP, ALT, AST & LDH) and decrease of antioxidant enzyme level in liver and significant increase in marker enzymes (ACP) and antioxidant enzyme level in kidney. This study concludes that oral administration of aspartame (40mg/kg.bw/day) for longer duration may induce oxidative stress by aspartame metabolite methanol and can damage both liver and kidney. The liver was found to be more sensitive than kidney to oxidative stress, as also reflected by the histology of liver and kidney.
2016
Object: Food additives have been used widely for promotion of food safety, flavoring and coloring. We aimed to investigate the effects of Monosodium Glutamate and Aspartame on hippocampal N-methyl D-aspartate receptor subunits and serum antioxidant enzymes and total oxidative stress indices. Materials and methods: Rats were randomly divided into four groups: Control, MSG (Monosodium Glutamate: 120 mg/kg), ASP (Aspartame: 40 mg/kg) and MSG + ASP for 8 weeks. NMDA receptor subunits, the oxidative stress indices and serum parameters were measured in hippocampal tissue and serum. Results: MSG and ASP consumption significantly increased MDA and NMDA receptor subunit levels (NR1, NR2A and NR2B) in hippocampus and decreased serum SOD and GSH-Px activities. There was no significant difference in serum MDA levels and total oxidative stress indices. Conclusion: MSG and ASP consumption alters NMDA receptor levels and may contribute to the pathogenesis of some neurodegenerative disorders via ex...
The artificial dipeptide sweetner aspartame [APM; L- aspartyl-L- phenylalanine methyl ester] is present in many products especially unsweetened and sugar products. These products are frequently utilized by people trying to lose weight or patients with diabetes. Concern relating to the possible adverse effect has been raised due to aspartames metabolic components. Aspartame is rapidly and completely metabolized in humans and experimental animals to aspartic acid (40%), phenylalanine (50%) and methanol (10%). Methanol, a toxic metabolite is primarily metabolized by oxidation to formaldehyde and then to formate these processes are accompanied by the formation of superoxide anion and hydrogen peroxide. This study focus is to understand whether the oral administration of aspartame (40 mg/kg b.w) for 90 days, have any effect on membrane bound ATPases in RBC, antioxidant status in blood cell and neutrophil function of rats. To mimic human methanol metabolism, folate deficient rats were used. After 90 days of aspartame administration, shows a significant change in membrane bound ATPases, antioxidant level and immune response. This study concludes that oral administration of aspartame (40mg/kg b.w) for longer duration may cause oxidative stress in blood cell and altered the neutrophil function
Serum biochemical responses under oxidative stress of aspartame in wistar albino rats
Objective: To study whether the oral administration of aspartame (40 mg/kg body d, 30 d and 90 d have any effect on marker enzymes, some selective liver and k iwdneiegyh tf)u nfcotri o1n5 mpaertaamboeltiesmr, , lfiopliadte p deerfoicxiiednatt iaonnim aanlds waenrteio uxsiedda.n t status in serum. To mimic human methanol Method: Animal weight, complete hemogram, marker enzyme in serum, some selected serum pperorofixlied arteioflne,c nt itlriivce ro xaidned, eknidzynmeya tficu nacntdi onno,n p-leanszmyma actoicr taincotisotxeirdoannet lleevveell w, aasn md eians usererdu m. , lipid Result: After 15 d of aspartame administration animals showed a significant change in marker sehnozywmede sa, asnigdn aifnictiaonxti dcahnatn lgeev eiln. Hsoomwee vseerl,e acftteedr sreepruemat epdr olofinleg rteerfmle catsd mliivneirs tarantdio kni d(3n0e dy afunndc 9ti0o nd,) along with marker enzymes, and antioxidant level. Conclusions: This study concludes that oral administration of aspartame (40 mg/kg body weight) causes oxidative stress in Wistar albino rats by altering their oxidant/antioxidant balance.
More than 90 countries have given the artificial sweetener aspartame the green light to be used in thousands of food and beverage products. The artificial dipeptide sweetener aspartame [APM; Laspartyl- L- phenylalanine methyl ester] is present in many products especially unsweetened and sugar products. These products are frequently utilized by people trying to lose weight or patients with diabetes. Concern relating to the possible adverse effect has been raised due to aspartames metabolic components. Aspartame is rapidly and completely metabolized in humans and experimental animals to aspartic acid (40%), phenylalanine (50%) and methanol (10%). Methanol, a toxic metabolite is primarily metabolized by oxidation to formaldehyde and then to formate these processes are accompanied by the formation of superoxide anion and hydrogen peroxide. This study focus is to understand whether the oral administration of aspartame (40 mg/kg b.w.) for 90 days, have any effect on membrane bound ATPase’s, antioxidant status and immune response (cell and humoral) of rats. To mimic human methanol metabolism, folate deficient rats were used. After 90 days of aspartame administration, shows free radical production by a significant increase in LPO and nitric oxide (NO) level and decrease in both enzymatic and nonenzymatic antioxidant level which alters the immune response. This study concludes that oral administration of aspartame (40mg/kg b.w) for longer duration may cause oxidative stress on immune organs and altered the immune response (cell and humoral) in wistar albino rats.