Anxiolytic properties of N -acetylcysteine in mice

Santos, Patricia C. Dos; Herrmann, Ana Paula; Benvenutti, Radharani; Noetzold, Guilherme; Giongo, F; Gama, Clarissa Severino; Piato, Ângelo; Elisabetsky, Elaine

doi:10.1016/j.bbr.2016.10.010

Cited by 29 publications

(15 citation statements)

References 58 publications

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“…In zebrafish, NAC treatment, at concentrations of 0.1-10 mg/L (provided in the water tank for 10 min), prevented acute stress-induced anxiety-like behavior (Mocelin, Herrmann et al 2015) and, when given at dose of 1 mg/L per day for 7 days, reversed the anxiogenic effects and increased ROS induced by chronic unpredictable stress (Mocelin, Marcon et al 2018). In mice, treatment with NAC, acutely (60-150 mg/kg) or subchronically (10-100 mg/kg i.p for four consecutive days) reduced anxiety and increased social preference (Santos, Herrmann et al 2017). Interestingly, in another mouse model, even though a single NAC treatment (30-120 mg/kg, i.p.)…”

Section: N-acetyl-cysteine N-acetyl-cysteine (Nac)mentioning

confidence: 99%

Therapeutic potential of glutathione-enhancers in stress-related psychopathologies

Zalachoras

Hollis

Ramos-Fernández

et al. 2020

Neuroscience & Biobehavioral Reviews

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Section: N-acetyl-cysteine N-acetyl-cysteine (Nac)mentioning

confidence: 99%

Therapeutic potential of glutathione-enhancers in stress-related psychopathologies

Zalachoras

Hollis

Ramos-Fernández

et al. 2020

Neuroscience & Biobehavioral Reviews

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“…NAC prevented rhythm disruption-induced anxiety in mice 69. The anxiolytic effects of NAC have also been documented in the light/dark model and in stress-induced anxiety behavior in zebrafish,70 as well as in the hole-board test, the light/dark model, the open field test, social interaction, and stress-induced hyperthermia in mice 71. One report suggested that NAC may have anxiogenic properties, but this conclusion is questionable since it was based only on decreased time spent in the center of an open field, which was also accompanied by decreased locomotion 84…”

Section: Resultsmentioning

confidence: 85%

Anxiolytic properties of compounds that counteract oxidative stress, neuroinflammation, and glutamatergic dysfunction: a review

Santos

Herrmann

Elisabetsky

et al. 2019

Braz. J. Psychiatry

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Objective:Anxiety disorders are highly prevalent and the efficacy of the available anxiolytic drugs is less than desired. Adverse effects also compromise patient quality of life and adherence to treatment. Accumulating evidence shows that the pathophysiology of anxiety and related disorders is multifactorial, involving oxidative stress, neuroinflammation, and glutamatergic dysfunction. The aim of this review was to evaluate data from animal studies and clinical trials showing the anxiolytic effects of agents whose mechanisms of action target these multiple domains.Methods:The PubMed database was searched for multitarget agents that had been evaluated in animal models of anxiety, as well as randomized double-blind placebo-controlled clinical trials of anxiety and/or anxiety related disorders.Results:The main multitarget agents that have shown consistent anxiolytic effects in various animal models of anxiety, as well in clinical trials, are agomelatine, N-acetylcysteine (NAC), and omega-3 fatty acids. Data from clinical trials are preliminary at best, but reveal good safety profiles and tolerance to adverse effects.Conclusion:Agomelatine, NAC and omega-3 fatty acids show beneficial effects in clinical conditions where mainstream treatments are ineffective. These three multitarget agents are considered promising candidates for innovative, effective, and better-tolerated anxiolytics.

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“…Studies have indicated NAC effects as an anxiolytic ( Mocelin et al, 2015 ; Santos et al, 2017 ) and antidepressant drug ( Magalhães et al, 2011 ; Berk et al, 2013 ; Costa-Campos et al, 2013 ; Pilz et al, 2015 ). Therefore, NAC has advantages over the existing therapies since, besides having a potential preventive effect, it may be able to treat the non-motor aspects of PD, which include depression, anxiety, cognitive impairment and sleep disturbances ( Klockgether, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae

Benvenutti

Marcon

Reis

et al. 2018

PeerJ

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BackgroundParkinson’s disease (PD) is the second most common neurodegenerative disorder. In addition to its highly debilitating motor symptoms, non-motor symptoms may precede their motor counterparts by many years, which may characterize a prodromal phase of PD. A potential pharmacological strategy is to introduce neuroprotective agents at an earlier stage in order to prevent further neuronal death. N-acetylcysteine (NAC) has been used against paracetamol overdose hepatotoxicity by restoring hepatic concentrations of glutathione (GSH), and as a mucolytic in chronic obstructive pulmonary disease by reducing disulfide bonds in mucoproteins. It has been shown to be safe for humans at high doses. More recently, several studies have evidenced that NAC has a multifaceted mechanism of action, presenting indirect antioxidant effect by acting as a GSH precursor, besides its anti-inflammatory and neurotrophic effects. Moreover, NAC modulates glutamate release through activation of the cystine-glutamate antiporter in extra-synaptic astrocytes. Its therapeutic benefits have been demonstrated in clinical trials for several neuropsychiatric conditions but has not been tested in PD models yet.MethodsIn this study, we evaluated the potential of NAC to prevent the damage induced by 6-hydroxydopamine (6-OHDA) on motor, optomotor and morphological parameters in a PD model in larval zebrafish.ResultsNAC was able to prevent the motor deficits (total distance, mean speed, maximum acceleration, absolute turn angle and immobility time), optomotor response impairment and morphological alterations (total length and head length) caused by exposure to 6-OHDA, which reinforce and broaden the relevance of its neuroprotective effects.DiscussionNAC acts in different targets relevant to PD pathophysiology. Further studies and clinical trials are needed to assess this agent as a candidate for prevention and adjunctive treatment of PD.

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Anxiolytic properties of N -acetylcysteine in mice

Cited by 29 publications

References 58 publications

Therapeutic potential of glutathione-enhancers in stress-related psychopathologies

Therapeutic potential of glutathione-enhancers in stress-related psychopathologies

Anxiolytic properties of compounds that counteract oxidative stress, neuroinflammation, and glutamatergic dysfunction: a review

N-acetylcysteine protects against motor, optomotor and morphological deficits induced by 6-OHDA in zebrafish larvae

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