Anti-neuroinflammatory and antioxidant effects of N-acetyl cysteine in long-term consumption of artificial sweetener aspartame in the rat cerebral cortex

Abstract

This study specifically focuses to investigate whether N-acetyl cysteine (NAC) has potential ameliorative effects against aspartame-induced brain pathophysiology in rats. Thirty adult male Wistar rats weighing 200-220 g were randomly divided into three groups as follows: the first group was administered with distilled water and served as the control group; the second group was given aspartame at a dose of 75 mg/kg b.wt. and the third group was given both aspartame and N-acetyl cysteine at dose of 75 mg/kg b.wt. and 600 mg/kg b.wt. respectively. Oral administration was done in the morning daily for 90 days.Long term consumption of the artificial sweetener aspartame (ASP) induced large increments in cortical inflammation and oxidative stress. Daily oral NAC administration can significantly reverse brain-derived neurotrophic factor (BDNF) levels, blocked the cyclooxygenase-2 (COX-2) and prostaglandin E 2 (PGE 2 ) production with selective attenuation in expression of proinflammatory cytokines of interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a) in the rat cerebral cortex. Also, NAC can significantly replenish and correct intracellular glutathione (GSH) levels, modulate the elevated levels of total nitric oxide (TNO) and lipid peroxidation (LPO). Conclusions: The present results amply support the concept that the brain oxidative stress and inflammation coexist in experimental animals chronically treated with aspartame and they represent two distinct therapeutic targets in ASP toxicity. The present data propose that NAC attenuated ASP neurotoxicity and improved neurological functions, suppressed brain inflammation, and oxidative stress responses and may be a useful strategy for treating ASP-induced neurotoxicity. ª 2015 The Egyptian German Society for Zoology. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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

“…However, it significantly prevented all DOX-induced brain injuries possibly due to its anti-inflammatory and neuroprotective effects [40]. The administration of NAC produced a statistically significant decrease in TNF-α level compared to the DOX group, which agreed with the results of Saleh [41] who reported that NAC in a dose of 75 mg/kg and 600 mg/kg improved neurological functions, prevented brain inflammation and oxidative stress responses in aspartame-induced neurotoxicity. Also, Palacio et al [13] revealed that NAC inhibits the inflammatory cytokines TNF-α, IL-1b and IL-6 in lipopolysaccharide-activated macrophages cell line under mild oxidative conditions.…”

l-Cysteine augments microtubule-associated protein 2 levels and enhances antioxidant activity in rats following traumatic brain injury

“…Bavarsad Shahripour et al (2014) have reported that the therapeutic potential of N-acetylcysteine in neurological disorder recovery. Hasegawa et al (2012) demonstrated the anti-inflammatory activities of cysteine in human endothelial cells, and other researchers have reported that N-acetyl-cysteine induced antioxidant and anti-inflammatory activities in the cerebral cortex of aspartame-treated rats (Saleh 2015). MAP2 is a well-known cytoskeletal protein that is present in neuronal perikarya and dendrites (Buddle et al 2003) and serves as a marker for neuronal damage (Miyazawa et al 1993;Buddle et al 2003;Fontaine-Lenoir et al 2006).…”

“…Furthermore, Li et al (2016) reported that rats treated with N-acetyl-cysteine exhibited reductions in neuropathic pain via the inhibition of matrix metalloproteinases (MMPs), and Eakin et al (2014) showed that supplementation with N-acetyl-cysteine improves behavioral parameters following brain injury. Additionally, N-acetyl-cysteine exerts antioxidant and anti-inflammatory activities in the cerebral cortex of aspartame-treated rats (Saleh 2015).…”

Simultaneous determination of total homocysteine, cysteine, glutathione, and N‐acetylcysteine in brain homogenates by HPLC

“…NAC, an N ‐acetyl derivative of Cys, is widely available as a nutritional supplement with antioxidant properties. NAC is of considerable therapeutic importance as a mucolytic drug in the treatment of bronchitis . NAC acts directly by detoxifying free radicals and indirectly by augmenting the level of reduced GSH under oxidative stress.…”