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![Mechanism of molecular action of N-acetylcysteine. Adapted from Aldini et al. (2018) [3].](publication/352474742/figure/fig1/AS:1035521220435969@1623898906585/Mechanism-of-molecular-action-of-N-acetylcysteine-Adapted-from-Aldini-et-al-2018-3.png)
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N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several dis...
Contexts in source publication
Context 1
... is a thiol that acts as an acetylated precursor to the amino acid L-cysteine; it can reduce various radicals, by donating one electron, or acts as a nucleophile by donating one or two electrons (Figure 1) [33,34]. Its chemical structure, formed by the sulfhydryl functional group (-SH) plus an acetyl group (-COCH3) linked to the amino group (NH2), is responsible for its metabolic activities related to the direct and indirect antioxidant action and mucolytic action [35]. ...
Context 2
... the study suggested that the use of NAC may be a potential strategy (alone or combined with insulin) to prevent congenital heart defects in newborns of diabetic mothers [199]. From this perspective, a clinical trial that aims to analyze the results of pregnancy and the metabolic profile of women with gestational diabetes mellitus supplemented with oral NAC (600 mg/three times daily/for 6 weeks) is registered in the Cochrane Central Register of Controlled Trials (ID CN-02170464). ...
Citations
... This property makes NAC a widely employed drug for paracetamol overdose treatment. [5][6][7] Aside from its antioxidant properties, NAC is also a potent reducing agent for protein disulfide cross-links, utilizing the classic thiol-disulfide interchange mechanism. This attribute is responsible for its mucolytic activity, as it disrupts disulfide links present in mucoproteins, reducing mucus viscosity. ...
... Consequently, NAC has practical application in the treatment of chronic bronchopulmonary disorders. [5][6][7] Additionally, NAC demonstrates promising anti-inflammatory and metal-chelating activities. Regarding anti-inflammatory properties, NAC functions by inhibiting NF-kB, a key player in the inflammatory and immune response triggered by oxidative stress. ...
... This results in the formation of easily excretable complexes for the body. [7] Due to these multifaceted properties, ongoing clinical studies are exploring the potential of NAC in treating various psychiatry/neurology disorders such as Alzheimer's, anxiety, bipolar disorder, metabolic syndrome (including diabetes), and other health conditions. [7][8][9][10] Considering the crucial role that the thiol (sulfhydryl) group in NAC has in explaining its antioxidant effects, and in establishing protein disulfide cross-links or binding to active redox metal ions a critical aspect is to determine the structure of NAC to understand its biological processes. ...
Herein, we report a spectroscopic study of N‐acetyl‐L‐cysteine, an important antioxidant drug, using Fourier‐transform microwave techniques and in isolated conditions. Two conformers are observed, where most stable structure adopts a cis disposition, and the second conformer has a lower abundance and adopts a trans disposition. The rotational constants and the barriers to methyl internal rotation are determined for each conformer, allowing a precise conformation identification. The results show that the cis form adopts an identical structure in the crystal, solution, and gas phases. Additionally, the structures are contrasted against those of cysteine.
... This reduction is achieved through the suppression of NF-κB activity. Despite numerous in vivo and ex vivo investigations demonstrating the significant biological effects of NAC and its potential therapeutic benefits, the efficacy of NAC in clinical research for various pathological disorders remains controversial [68][69][70]. ...
Background
There is a consistent association between exposure to air pollution and elevated rates of cardiopulmonary illnesses. As public health activities emphasize the paramount need to reduce exposure, it is crucial to examine strategies like the antioxidant diet that could potentially protect individuals who are unavoidably exposed.
Methods
A systematic search was performed in PubMed/Medline, EMBASE, CENTRAL, and ClinicalTrials.gov up to March 31, 2023, for clinical trials assessing dietary supplements against cardiovascular (blood pressure, heart rate, heart rate variability, brachial artery diameter, flow-mediated dilation, and lipid profile) or pulmonary outcomes (pulmonary function and airway inflammation) attributed to air pollution exposure.
Results
After reviewing 4681 records, 18 studies were included. There were contradictory findings on the effects of fish oil and olive oil supplementations on cardiovascular outcomes. Although with limited evidence, fish oil offered protection against pulmonary dysfunction induced by pollutants. Most studies on vitamin C did not find protective cardiovascular effects; however, the combination of vitamin C and E offered protective effects against pulmonary dysfunction but showed conflicting results for cardiovascular outcomes. Other supplements like sulforaphane, L-arginine, n-acetylcysteine, and B vitamins showed potential beneficial effects but need further research due to the limited number of existing trials.
Conclusions
Although more research is needed to determine the efficacy and optimal dose of anti-inflammatory and antioxidant dietary supplements against air pollution toxicity, this low-cost preventative strategy has the potential to offer protection against outcomes of air pollution exposure.
... N-acetylcysteine (NAC) is a mucolytic drug, also used in the treatment of acetaminophen overdose, which has been listed by the World Health Organization as an essential medicine [1,2]. The route of administration of NAC depends on the condition that is being treated; the modes ...
... As presented previously, an interaction between RSV and air pollution, which potentially enhances the pathological effects of both infection and pollution, may be divided into 3 main areas of interest, and so are the results presented. The directions of interaction are: (1) a facilitated viral entry (caused by the enhanced RSV adherence or damage to the host protective barriers), (2) an increased viral load (due to the increased RSV virulence, or the increased release from infected cells, or the decreased host immune response that impedes virus clearance), and (3) an exaggerated host response (a prolonged or inadequate inflammatory response that may lead to hyperreactivity reactions and histopathologic changes) [15]. We aimed to generalize the results in order to make it easier for the reader to understand the possible pathomechanisms involved, but it must be emphasized that: 1. the pathomechanisms present in humans may differ from those studied in animal or cell models, although the mechanisms are expected to be common and the choice of models is dictated by the potential reflection of those present in humans; 2. the mechanisms may differ significantly between the pollutants, so the pollutant studied is mentioned in the table that describes the included publications; 3. the mechanisms may vary with time, dose, or situation, e.g., in the majority of cases, the type of response would be stopped in a relatively short period of time, although in some particularly susceptible populations, it may be prolonged (e.g., patients with asthma); 4. the direction and magnitude of the mechanism activation or deactivation may vary, and the same mechanism may be activated or blocked, depending on the stage of infection or response to infection; and 5. studies demonstrating the effects of NAC have mostly been performed in cellular or animal models, and the effects in humans may vary. ...
... All three main routes of administration are available for NAC treatment in humans; NAC may be administered orally, intravenously, or by inhalation [2]. The series of experiments in human type II pulmonary epithelial cell line derived from human lung adenocarcinoma (A549) showed a dose-dependent antiviral activity and cytotoxicity of NAC [42]. ...
N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. The respiratory syncytial virus (RSV) is one of the most important etiological factors of lower respiratory tract infections, and exposure to air pollution appears to be additionally associated with higher RSV incidence and disease severity. We aimed to systematically review the existing literature to determine which molecular mechanisms mediate the effects of NAC in an RSV infection and air pollution, and to identify the knowledge gaps in this field. A search for original studies was carried out in three databases and a calibrated extraction grid was used to extract data on the NAC treatment (dose, timing), the air pollutant type, and the most significant mechanisms. We identified only 28 studies conducted in human cellular models (n = 18), animal models (n = 7), and mixed models (n = 3). NAC treatment improves the barrier function of the epithelium damaged by RSV and air pollution, and reduces the epithelial permeability, protecting against viral entry. NAC may also block RSV-activated phosphorylation of the epidermal growth factor receptor (EGFR), which promotes endocytosis and facilitates cell entry. EGFR also enhances the release of a mucin gene, MUC5AC, which increases mucus viscosity and causes goblet cell metaplasia; the effects are abrogated by NAC. NAC blocks virus release from the infected cells, attenuates the cigarette smoke-induced shift from necrosis to apoptosis, and reverses the block in IFN-γ-induced antiviral gene expression caused by the inhibited Stat1 phosphorylation. Increased synthesis of pro-inflammatory cytokines and chemokines is induced by both RSV and air pollutants and is mediated by the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways that are activated in response to oxidative stress. MCP-1 (monocyte chemoattractant protein-1) and RANTES (regulated upon activation, expressed and secreted by normal T cells) partially mediate airway hyperresponsiveness (AHR), and therapeutic (but not preventive) NAC administration reduces the inflammatory response and has been shown to reduce ozone-induced AHR. Oxidative stress-induced DNA damage and cellular senescence, observed during RSV infection and exposure to air pollution, can be partially reversed by NAC administration, while data on the emphysema formation are disputed. The review identified potential common molecular mechanisms of interest that are affected by NAC and may alleviate both the RSV infection and the effects of air pollution. Data are limited and gaps in knowledge include the optimal timing or dosage of NAC administration, therefore future studies should clarify these uncertainties and verify its practical use.
... N-acetylcysteine (NAC) stands out as a promising therapeutic candidate due to its safety profile, affordability, and multifaceted pharmacological properties. Approved by the FDA for treating acetaminophen overdose and serving as a mucolytic agent, NAC has garnered attention for its pleiotropic effects, including antioxidant, anti-inflammatory, and anti-apoptotic activities [12]. Moreover, it has demonstrated protective benefits against disorders associated with oxidative stress and mitochondrial dysfunction across various organ systems, including the kidneys [4,12,13]. ...
... Approved by the FDA for treating acetaminophen overdose and serving as a mucolytic agent, NAC has garnered attention for its pleiotropic effects, including antioxidant, anti-inflammatory, and anti-apoptotic activities [12]. Moreover, it has demonstrated protective benefits against disorders associated with oxidative stress and mitochondrial dysfunction across various organ systems, including the kidneys [4,12,13]. Of particular interest is the evidence proving that NAC can act directly within the mitochondria, underscoring its potential in mitigating cellular damage [14]. ...
... The findings further indicated that NAC prevented upregulation of these proinflammatory cytokines by suppressing the activity of NF-κB. The anti-inflammatory effects of NAC via inhibition of NF-κB have been well established, in addition to its antioxidant activity [12]. Interestingly, SIRT3 has also been proven to inhibit inflammation by interfering with the NF-κB p65 subunit [45]. ...
Bisphenol A (BPA) and high-fat diets (HFD) are known to adversely affect the kidneys. However, the combined effects of both cases on kidney health and the potential benefits of N-acetylcysteine (NAC) in mitigating these effects have not been investigated. To explore these aspects, male Wistar rats were fed with HFD and allocated to receive a vehicle or BPA. At week twelve, the BPA-exposed rats were subdivided to receive a vehicle or NAC along with BPA until week sixteen. Rats fed HFD and exposed to BPA showed renal dysfunction and structural abnormalities, oxidative stress, inflammation, and mitochondrial dysfunction, with alterations in key proteins related to mitochondrial oxidative phosphorylation (OXPHOS), bioenergetics, oxidative balance, dynamics, apoptosis, and inflammation. Treatment with NAC for 4 weeks significantly improved these conditions. The findings suggest that NAC is beneficial in protecting renal deterioration brought on by prolonged exposure to BPA in combination with HFD, and modulation of sirtuin 3 (SIRT3) signaling by NAC appears to play a key role in the preservation of homeostasis and integrity within the mitochondria by enhancing OXPHOS activity, maintaining redox balance, and reducing inflammation. This study provides valuable insights into potential therapeutic strategies for preserving kidney health in the face of environmental and dietary challenges.
... In addition, NAC affects dopaminergic metabolism and regulates dopamine levels, which is promising in the context of addiction therapy. (4) NAC is also characterized by anti-inflammatory properties. NAC has been shown to reduce the levels of cytokines associated with inflammatory processes: interleukin-6 (IL-6), interleukin-1 (IL-1β) and tumor necrosis factor (TNF-α). ...
... The lack of effective treatment for addiction has prompted researchers to continue their search for safe and effective addiction therapy. (3)(4) ...
Introduction and purpose N-acetylcysteine (NAC) is one of the more popular drugs, widely available in pharmacies, used to treat wet cough. NAC's diverse mechanism of action has drawn the attention of researchers for its great potential in the treatment of many conditions. Indeed, it has been noted that administration of NAC allows indirect modulation of the central nervous system, which may be important in the treatment of psychiatric diseases. The following review focuses on recent reports of NAC's potentially beneficial effects on psychiatric conditions such as depression, schizophrenia, obsessive-compulsive disorder, and addiction. Description of the state of knowledge Based on studies conducted on animals (rats), a positive effect of NAC has been proven, observing a reduction in the severity of depressive symptoms. Based on the above data, more and more human studies are being conducted, where the effect of NAC on the symptoms of various mental conditions is being investigated. In recent years, the antioxidant, anti-inflammatory and neurotransmitter function modulating effects of NAC on the brain have been proven, with significant potential in the treatment of mental illness. Conclusions The potential impact of NAC on the treatment of mental illness is a rapidly developing topic in recent years. On the basis of available scientific data, partial reduction of symptoms of mental illnesses through the use of NAC has been confirmed. It is a very promising drug, which in this indication requires additional studies to unequivocally confirm its beneficial effects on the functioning of the central nervous system.
... In addition, NAC affects dopaminergic metabolism and regulates dopamine levels, which is promising in the context of addiction therapy. (4) NAC is also characterized by anti-inflammatory properties. NAC has been shown to reduce the levels of cytokines associated with inflammatory processes: interleukin-6 (IL-6), interleukin-1 (IL-1β) and tumor necrosis factor (TNF-α). ...
... The lack of effective treatment for addiction has prompted researchers to continue their search for safe and effective addiction therapy. (3)(4) ...
Introduction Cardiovascular diseases are the most numerous group of diseases prevalent in the world. They are a challenge for many health systems, in terms of keeping life comfortable and also economics. The cause of selected disease entities is too much cholesterol in the blood. The most popular treatment for hypercholesterolemia is based on statins. Many patients are affected by intolerance to these drugs, so an important issue is the discovery and improvement of alternatives to statins. Purpose of work The purpose of this review is to collect literature data on the latest treatments for hypercholesterolemia with drugs other than statins and ezetimibe. Materials and methods Materials are from a review of recent literature available in PubMed. To search for articles, we used keywords such as: bempedoic acid, non-statin therapy, cardiovascular risk, inclisiran, alirocumab, cardiovascular disease, dyslipidemia, evolocumab. Summary Treatment of hypercholesterolemia with statins remains the most popular management strategy. Intolerance to treatment with these drugs creates serious clinical problems for patients. Recently, we could see the emergence of new drugs as alternatives to statins. As the results show, the new drugs can effectively replace statins in the hypolipemic treatment especially of patients who cannot be treated with them.
... Therefore, it could potentially be used in the treatment of disorders associated with oxidative stress and inflammation [36] [37] . NAC has important direct antioxidant activity as it is able to increase the intracellular concentration of glutathione. ...
... (NF-κB) [37]. ...
Introduction and purpose: Polycystic ovary syndrome is the most common endocrinopathy in women, with a prevalence ranging from 10% to 13%. Oxidative stress and decreased antioxidant levels contribute to the development of various diseases, and one of them is polycystic ovary syndrome. The aim of this review is to provide an overview of the current knowledge about the effects of antioxidant administration in PCOS treatment.
A brief description of the state of knowledge: Oxidative stress is an imbalance between increased levels of reactive oxygen species and a decreased efficiency of antioxidant mechanisms, which can potentially cause damage. The harmful effects of free radicals might be neutralized by antioxidants obtained from the diet, such as polyphenols, vitamins C, and E. These compounds improve several aspects of the PCOS pathomechanism, including hormonal imbalance, glucose metabolism, lipid profile, and ovarian functionality.
Conclusions: The outcomes of all the reviewed studies in this paper indicate that antioxidants such as resveratrol, curcumin, vitamin C and E, N-acetylcysteine, and melatonin have therapeutic potential in the management of PCOS. However, currently antioxidant therapies cannot be recommended in PCOS therapy since there is a need for more prospective randomized clinical trials on a larger sample to establish a long-term effects of antioxidants supplementation in PCOS, the optimal dosage, and finally to assess which antioxidant is the most efficient in PCOS treatment.
... N-acetylcysteine (NAC) is a modified form of the amino acid cysteine, enhanced by the addition of an acetyl group, making it an antioxidant agent that plays a role in the oxidation and formation of disulfide bonds [18,144]. These processes are vital for stabilizing protein structures and preventing cellular damage. ...
Bacterial infections trigger a multifaceted interplay between inflammatory mediators and redox regulation. Recently, accumulating evidence has shown that redox signaling plays a significant role in immune initiation and subsequent immune cell functions. This review addresses the crucial role of the thioredoxin (Trx) system in the initiation of immune reactions and regulation of inflammatory responses during bacterial infections. Downstream signaling pathways in various immune cells involve thiol-dependent redox regulation, highlighting the pivotal roles of thiol redox systems in defense mechanisms. Conversely, the survival and virulence of pathogenic bacteria are enhanced by their ability to counteract oxidative stress and immune attacks. This is achieved through the reduction of oxidized proteins and the modulation of redox-sensitive signaling pathways, which are functions of the Trx system, thereby fortifying bacterial resistance. Moreover, some selenium/sulfur-containing compounds could potentially be developed into targeted therapeutic interventions for pathogenic bacteria. Taken together, the Trx system is a key player in redox regulation during bacterial infection, and contributes to host-pathogen interactions, offering valuable insights for future research and therapeutic development.
... N-acetylcysteine (NAC) is a drug approved by both the FDA and the WHO that is essential for treating acetaminophen overdose and, more recently, has been used as a mucolytic agent in respiratory diseases [17][18][19]. As a nutritional supplement, NAC is widely available without a prescription in several countries due to its antioxidant properties and commercial appeal as a nutraceutical [17]. ...
... N-acetylcysteine (NAC) is a drug approved by both the FDA and the WHO that is essential for treating acetaminophen overdose and, more recently, has been used as a mucolytic agent in respiratory diseases [17][18][19]. As a nutritional supplement, NAC is widely available without a prescription in several countries due to its antioxidant properties and commercial appeal as a nutraceutical [17]. Its primary function lies in its antioxidant and anti-inflammatory capabilities, crucial for maintaining cellular redox balance and providing therapeutic potential for diseases associated with oxidative stress [1,13,20,21]. ...
This study investigates the efficacy of a thermo-responsive N-acetylcysteine (NAC) hydrogel on wound healing and oral ulcer recovery. Formulated by combining NAC with methylcellulose, the hydrogel’s properties were assessed for temperature-induced gelation and cell viability using human fibroblast cells. In vivo experiments on Sprague Dawley rats compared the hydrogel’s effects against saline, NAC solution, and a commercial NAC product. Results show that a 5% NAC and 1% methylcellulose solution exhibited optimal outcomes. While modest improvements in wound healing were observed, significant enhancements were noted in oral ulcer recovery, with histological analyses indicating fully regenerated mucosal tissue. The study concludes that modifying viscosity enhances NAC retention, facilitating tissue regeneration. These findings support previous research on the beneficial effects of antioxidant application on damaged tissues, suggesting the potential of NAC hydrogels in improving wound care and oral ulcer treatment.
... A more recent 2019 meta-analysis corroborated these findings, analyzing 29 RCTs with 2,486 participants and demonstrating that NAC use resulted in a non-statistically significant reduction in arrhythmia or mortality [70]. Since NAC has antioxidant and anti-inflammatory properties through its ability to replenish cellular glutathione stores, theoretically it may reduce the oxidative stress associated with increased rates of AFib and other postoperative ischemic-reperfusion cardiac injury, but data at the moment does not definitely support its use [71]. ...
Antiarrhythmic drugs play a pivotal role in managing and preventing arrhythmias. Amiodarone, classified as a class III antiarrhythmic, has been used prophylactically to effectively prevent atrial fibrillation postoperatively in cardiac surgeries. However, there is a lack of consensus on the use of amiodarone and other antiarrhythmic drugs as prophylaxis to reduce the occurrence of all types of postoperative arrhythmias in cardiac and non-cardiac surgeries. A comprehensive PubMed query yielded 614 relevant papers, of which 52 clinical trials were analyzed. The data collection included the class of antiarrhythmics, timing or method of drug administration, surgery type, type of arrhythmia and its incidence, and hospitalization length. Statistical analyses focused on prophylactic antiarrhythmics and their respective reductions in postoperative arrhythmias and hospitalization length.
Prophylactic amiodarone alone compared to placebo demonstrated a significant reduction in postoperative arrhythmia incidence in cardiac and non-cardiac surgeries (24.01%, p<0.0001), and it was the only treatment group to significantly reduce hospitalization length versus placebo (p = 0.0441). Prophylactic use of class 4 antiarrhythmics versus placebo also demonstrated a significant reduction in postoperative arrhythmia incidence (28.01%, p<0.0001), and while there was no significant statistical reduction compared to amiodarone (4%, p=0.9941), a lack of abundant data provides a case for further research on the prophylactic use of class 4 antiarrhythmics for this indication.
Amiodarone prophylaxis remains a prime cornerstone of therapy in reducing postoperative arrhythmia incidence and hospitalization length. Emerging data suggests a need for a broader exploration of alternative antiarrhythmic agents and combination therapies, particularly class 4 antiarrhythmics, in both cardiac and non-cardiac surgeries. This meta-analysis depicts the effectiveness of amiodarone, among other antiarrhythmics, in postoperative arrhythmia incidence and hospitalization length reduction in cardiac and non-cardiac surgeries.
