The Protective Effect of N-Acetylcysteine on Oxidative Stress in the Brain Caused by the Long-Term Intake of Aspartame by Rats

Finamor, Isabela; Ourique, Giovana M.; Pês, Tanise S.; Saccol, Etiane M.H.; Bressan, Caroline A.; Scheid, Taina; Baldisserotto, Bernardo; Llesuy, Susana; Partata, Wania Aparecida; Pavanato, María A.

doi:10.1007/s11064-014-1360-9

Cited by 19 publications

(13 citation statements)

References 45 publications

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“…Glutathione peroxidase converts H 2 O 2 and organic hydroperoxides to less reactive products [33]. Hence, it is hypothesized that the decrease in the GPx activity might cause the H 2 O 2 accumulation and a further inactivation in its activities [34]. Consequently, the brain becomes even more susceptible to oxidative processes.…”

Section: Discussionmentioning

confidence: 99%

Prophylactic and Ameliorative Effect of N-Acetylcysteine on Doxorubicin-Induced Neurotoxicity in Wister Rats

Mohammed

Radwan

Elsayed

2019

Egyptian Journal of Basic and Clinical Pharmacology

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Doxorubicin (DOX) is an anthracycline antibiotic and a quinone-containing chemotherapeutic drug used for various types of cancers. However, as with most anticancer drugs, it causes many toxic effects, one of them is cognitive impairment. The present study investigated the prophylactic and ameliorative effect of n-acetylcysteine (NAC) against DOX-induced neurotoxicity in rats. Rats were divided into four groups. Control group: rats received saline. NAC treated group: rats received NAC (100 mg/kg, p.o.) daily for 35 days. DOX-treated group: rats received DOX (4 mg/kg, i.p.) for four weeks on day 7, 14, 21 and 28. DOX+NAC treated group 1: rats received NAC (100 mg/kg, p.o.) daily for 35 days and DOX (4 mg/kg, i.p.) for four weeks on day 7, 14, 21 and 28). DOX+NAC treated group 2: rats received NAC (100 mg/kg, p.o.) daily started at the 7th day of the experiment till the end of the experiment and DOX (4 mg/kg, i.p.) for four weeks on day 7, 14, 21 and 28. The present results showed a significant reduction in the body weight, which was associated with a significant increase in brain to body weight ratio in DOX-treated rats. Tumor necrosis factor (TNF-α) level, malondialdehyde (MDA) and total protein levels were significantly elevated. Whilst, reduced glutathione (GSH) and glutathione peroxidase (GPx) levels were significantly decreased. Moreover, there were histopathological abnormalities in the brain tissue of DOX-treated rats, as most of the neurons degenerated and the blood vessels surrounded with wide perivascular spaces. In addition, the neuropil was vacuolated. The present study demonstrated that NAC has a neuroprotective effect on the brain damage induced by DOX, through inhibition of inflammation and oxidative stress. This neuroprotective effect was more pronounced in DOX+NAC treated group 1, as it produced a significant increase in brain GSH and GPx levels and more improvement in the histopathological abnormality compared to DOX+NAC treated group 2.

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Section: Discussionmentioning

confidence: 99%

Prophylactic and Ameliorative Effect of N-Acetylcysteine on Doxorubicin-Induced Neurotoxicity in Wister Rats

Mohammed

Radwan

Elsayed

2019

Egyptian Journal of Basic and Clinical Pharmacology

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“…The pathogenesis of stroke and several neurodegenerative diseases could be attributed to neuronal apoptosis induced by oxidative stress (Xu et al, 2002;Agar and Durham, 2003;Barnham et al, 2004). Oxidants, such as free radicals and hydrogen peroxide, induce inflammation and synthesis of reactive oxygen species resulting in cell injury (Zahler et al, 2000;Finamor et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective and Ameliorating Impacts of Omega‐3 Against Aspartame‐induced Neuronal and Astrocytic Degeneration

Ali

Sonpol

2017

The Anatomical Record

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Aspartame (ASP) is one of the commonest artificial sweetener used all over the world and considered as an extremely risky compound and raises a lot of controversy. Therefore, this study was designed to investigate cellular damage of the anterior horn cells in the spinal cord of albino male rats and the possibility of hindering these changes by using omega-3 (OM3).Thirty seven adult male albino rats were divided into three groups: Control, ASP-treated and ASP + OM3-treated groups. Spinal cord sections were prepared and stained with Hx&E, caspase-3 and GFAP immunostaining. All data were morphometrically and statistically analyzed. In ASP-treated group, the cell body of some degenerated neurons was swollen and its cytoplasm was vacuolated. Their nuclei were eccentric and pyknotic. Moreover, other neurons were of a heterogeneous pattern in the form of cell body shrinkage, loss of Nissl substance, intensely stained eosinophilic cytoplasm and a small darkly stained nucleus that may eventually fragment. However, the cells were apparently normal in ASP+ OM3-treated group. Strong +ve caspase-3 stained neurons were detected in ASP-treated group. Furthermore, the immunoreaction was faint on treating the rats with both ASP and OM3. Few number of +ve GFAP- stained astrocytes were observed in ASP-treated rats. On the other hand, the immunoreactivity for GFAP was found to be intense in the ASP + OM3-treated group. Additionally, there was a significant decrease in the surface area percentage of the +ve GFAP-stained astrocytes of the ASP-treated group compared to the control and the ASP + OM3-treated groups. Anat Rec, 300:1290-1298, 2017. © 2017 Wiley Periodicals, Inc.

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“…ASP ingestion has been associated with an increase in brain oxidative stress [ 88 , 89 ]. We found a number of stress-associated and neuroinflammatory hypothalamic ASP-responsive DEGs including resistin, Cyp2e1 , Tspo , Pomc and Ly6D , adiponectin, Fabp4 , Scarb1 and Cd36 .…”

Section: Methodsmentioning

confidence: 99%

Effect of developmental NMDAR antagonism with CGP 39551 on aspartame-induced hypothalamic and adrenal gene expression

et al. 2018

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RationaleAspartame (L-aspartyl phenylalanine methyl ester) is a non-nutritive sweetener (NNS) approved for use in more than 6000 dietary products and pharmaceuticals consumed by the general public including adults and children, pregnant and nursing mothers. However a recent prospective study reported a doubling of the risk of being overweight amongst 1-year old children whose mothers consumed NNS-sweetened beverages daily during pregnancy. We have previously shown that chronic aspartame (ASP) exposure commencing in utero may detrimentally affect adulthood adiposity status, glucose metabolism and aspects of behavior and spatial cognition, and that this can be modulated by developmental N-methyl-D-aspartate receptor (NMDAR) blockade with the competitive antagonist CGP 39551 (CGP). Since glucose homeostasis and certain aspects of behavior and locomotion are regulated in part by the NMDAR-rich hypothalamus, which is part of the hypothalamic-pituitary-adrenal- (HPA) axis, we have elected to examine changes in hypothalamic and adrenal gene expression in response to ASP exposure in the presence or absence of developmental NMDAR antagonism with CGP, using Affymetrix microarray analysis.ResultsUsing 2-factor ANOVA we identified 189 ASP-responsive differentially expressed genes (DEGs) in the adult male hypothalamus and 2188 in the adrenals, and a further 23 hypothalamic and 232 adrenal genes significantly regulated by developmental treatment with CGP alone. ASP exposure robustly elevated the expression of a network of genes involved in hypothalamic neurosteroidogenesis, together with cell stress and inflammatory genes, consistent with previous reports of aspartame-induced CNS stress and oxidative damage. These genes were not differentially expressed in ASP mice with CGP antagonism. In the adrenal glands of ASP-exposed mice, GABA and Glutamate receptor subunit genes were amongst those most highly upregulated. Developmental NMDAR antagonism alone had less effect on adulthood gene expression and affected mainly hypothalamic neurogenesis and adrenal steroid metabolism. Combined ASP + CGP treatment mainly upregulated genes involved in adrenal drug and cholesterol metabolism.ConclusionASP exposure increased the expression of functional networks of genes involved in hypothalamic neurosteroidogenesis and adrenal catecholamine synthesis, patterns of expression which were not present in ASP-exposed mice with developmental NMDAR antagonism.

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The Protective Effect of N-Acetylcysteine on Oxidative Stress in the Brain Caused by the Long-Term Intake of Aspartame by Rats

Cited by 19 publications

References 45 publications

Prophylactic and Ameliorative Effect of N-Acetylcysteine on Doxorubicin-Induced Neurotoxicity in Wister Rats

Prophylactic and Ameliorative Effect of N-Acetylcysteine on Doxorubicin-Induced Neurotoxicity in Wister Rats

Neuroprotective and Ameliorating Impacts of Omega‐3 Against Aspartame‐induced Neuronal and Astrocytic Degeneration

Effect of developmental NMDAR antagonism with CGP 39551 on aspartame-induced hypothalamic and adrenal gene expression

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