N-acetylcysteine as a mitochondrial enhancer: a new class of psychoactive drugs?

Fries, Gabriel R.; Kapczinski, Flávio

doi:10.1590/s1516-44462011000400003

Cited by 14 publications

(10 citation statements)

References 7 publications

(4 reference statements)

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“…All these findings support the view that NAC attenuates the degree of inflammation and oxidative stress caused by chronic ASP administration in rats (Arakawa and Ito, 2007). Whereas several studies have described a biphasic effect of NAC on oxidative stress, ultimately leading to the control of free radicals on neuronal injury (Fries and Kapczinski, 2011).…”

Section: Discussionsupporting

confidence: 81%

“…Disorders of GSH metabolism are common in major neurodegenerative diseases showing GSH depletion and increased levels of oxidative stress in the brain (Aoyama and Nakaki, 2013). The current findings indicate that chronic stress of ASP has been shown to induce inhibition in GSH content and decreased GSH levels may be due to mitochondrial dysfunction and oxidative stress that increase the accumulation of toxic forms of ASP (Fries and Kapczinski, 2011;Ruszkiewicz and Albrecht, 2015). So, the present study suggested that supplementation with NAC could protect against ASP toxicity as well as reverses mitochondrial dysfunctions (Table 3).…”

Section: Discussionmentioning

confidence: 60%

“…NAC is an acetylated variant of the amino acid L-cysteine, is an effective antidote able to increase cell protection to oxidative stress (Fries and Kapczinski, 2011). Moreover, NAC is an effective scavenger of free radicals as it interacts with ROS such as OHÅ and H2O2 as well as a major contributor to maintenance of the cellular GSH status and can minimize the oxidative effect of ROS through correcting or preventing GSH depletion.…”

Section: Introductionmentioning

confidence: 99%

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

Saleh

2015

The Journal of Basic & Applied Zoology

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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/).

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

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

Saleh

2015

The Journal of Basic & Applied Zoology

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“…And also, H 2 O 2 -induced PGC-1α downergulation was inhibited by NAC pre-treatment in H 2 O 2 -treated HK-2 cells. It has been recently reported that NAC plays a role as a mitochondrial enhancer as well as an antioxidant precursor to glutathione (GSH) 40 . In psychiatry and related neurodegenerative diseases, NAC used to increase mitochondrial resilience and prevent allostatic load by inhibiting mechanism of oxidative stress and inflammation 41, 42 .…”

Section: Discussionmentioning

confidence: 99%

PGC-1α attenuates hydrogen peroxide-induced apoptotic cell death by upregulating Nrf-2 via GSK3β inactivation mediated by activated p38 in HK-2 Cells

Choi

Kim

Park

et al. 2017

Sci Rep

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Ischemia/reperfusion injury triggers acute kidney injury (AKI) by aggravating oxidative stress mediated mitochondria dysfunction. The peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) is a master player that regulates mitochondrial biogenesis and the antioxidant response. We postulated that PGC-1α functions as cytoprotective effector in renal cells and that its regulation mechanism is coordinated by nuclear factor erythroid 2-related factor 2 (Nrf-2). In this study, to understand the effect and molecular mechanisms of PGC-1α, we developed an empty vector or PGC-1α-overexpressing stable cell lines in HK-2 cells (Mock or PGC-1α stable cells). PGC-1α overexpression increased the viability of cells affected by H2O2 mediated injury, protected against H2O2-mediated apoptotic events and inhibited reactive oxygen species accumulation in the cytosol and mitochondria as compared to that in Mock cells. The cytoprotective effect of PGC-1α was related to Nrf-2 upregulation, which was counteracted by Nrf-2-specific knockdown. Using inhibitor of p38, we found that regulation of the p38/glycogen synthase kinase 3β (GSK3β)/Nrf-2 axis was involved in the protective effects of PGC-1α. Taken together, we suggest that PGC-1α protects human renal tubule cells from H2O2-mediated apoptotic injury by upregulating Nrf-2 via GSK3β inactivation mediated by activated p38.

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“…69,70 The mitochondria-protective effect is another mechanism that NAC through it can protect brain tissue from oxidative insults during cerebral ischemia. 71 NAC probably by protecting mitochondrial respiratory chain proteins from oxidative damage can maintain mitochondrial bioenergetic capacity. 72 Such findings are in accord with those experimental studies which showed NAC treatment can effectively restore mitochondrial dysfunction in brain tissue.…”

Section: Discussionmentioning

confidence: 99%

<p>Evidence for a Beneficial Effect of Oral N-acetylcysteine on Functional Outcomes and Inflammatory Biomarkers in Patients with Acute Ischemic Stroke</p>

Sabetghadam¹,

Mazdeh²,

Abolfathi³

et al. 2020

NDT

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Purpose: Numerous preclinical studies have demonstrated the potential neuroprotective effects of N-acetylcysteine (NAC) in the treatment of brain ischemia. Accordingly, the present study aimed to assess the potential therapeutic effects of oral NAC in patients with acute ischemic stroke. Patients and Methods: In a randomized, double-blind, placebo-controlled trial study, 68 patients with acute ischemic stroke with the onset of symptoms less than 24 hours were randomly assigned to either the NAC-treated group or placebo-treated group. NAC and matched placebo were administrated by a 72-hour oral protocol (initially 4 grams loading dose and after on, 4 g in 4 equal divided doses for more 2 days). The primary outcomes were quantification of any neurologic deficit by the use of the National Institute of Health Stroke Scale (NIHSS) score and functional disability by the use of the modified Rankin scale (mRS) at 90 days after stroke. Additionally, serum levels of markers of oxidative stress and inflammation as a main mechanism of its action were assessed at baseline and the end of 3-day treatment protocol. Results: NAC-treated patients in comparison with placebo-treated patients showed a significantly lower mean NIHSS scores at day 90 after stroke. A favorable functional outcome which was defined as an mRS score of 0 or 1, also in favor of NAC compared to placebo was noted on day 90 after stroke (57.6% in the NAC-treated group compared with 28.6% in the placebo-treated group). Further, compared to the placebo, NAC treatment significantly decreased serum levels of proinflammatory biomarkers such as interleukin 6 (IL-6), soluble intercellular cell adhesion molecule-1 (sICAM-1), nitric oxide (NO), malondialdehyde (MDA), and neuron-specific enolase (NSE) and significantly increased serum levels of anti-oxidant biomarkers such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and total thiol groups (TTG). Conclusion: The pattern of results suggests that oral NAC administration early after an acute ischemic stroke is associated with a better outcome profile in terms of acute neurological deficit and disability grade compared to placebo. NAC may improve neurological outcomes of patients with stroke at least in part by its antioxidant and anti-inflammatory effects.

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N-acetylcysteine as a mitochondrial enhancer: a new class of psychoactive drugs?

Cited by 14 publications

References 7 publications

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

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

PGC-1α attenuates hydrogen peroxide-induced apoptotic cell death by upregulating Nrf-2 via GSK3β inactivation mediated by activated p38 in HK-2 Cells

<p>Evidence for a Beneficial Effect of Oral N-acetylcysteine on Functional Outcomes and Inflammatory Biomarkers in Patients with Acute Ischemic Stroke</p>

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