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Biomolecules Sep 2015This review on recent research advances of the lipid peroxidation product 4-hydroxy-nonenal (HNE) has four major topics: I. the formation of HNE in various organs and... (Review)
Review
This review on recent research advances of the lipid peroxidation product 4-hydroxy-nonenal (HNE) has four major topics: I. the formation of HNE in various organs and tissues, II. the diverse biochemical reactions with Michael adduct formation as the most prominent one, III. the endogenous targets of HNE, primarily peptides and proteins (here the mechanisms of covalent adduct formation are described and the (patho-) physiological consequences discussed), and IV. the metabolism of HNE leading to a great number of degradation products, some of which are excreted in urine and may serve as non-invasive biomarkers of oxidative stress.
Topics: Acetylcysteine; Animals; Fatty Acids, Unsaturated; Humans; Lipid Peroxidation; Oxidative Stress
PubMed: 26437435
DOI: 10.3390/biom5042247 -
Cellular Microbiology Feb 2021Viruses confiscate cellular components of the ubiquitin-proteasome system (UPS) to facilitate many aspects of the infectious cycle. The 26S proteasome is an... (Review)
Review
Viruses confiscate cellular components of the ubiquitin-proteasome system (UPS) to facilitate many aspects of the infectious cycle. The 26S proteasome is an ATP-dependent, multisubunit proteolytic machine present in all eukaryotic cells. The proteasome executes the controlled degradation of functional proteins, as well as the hydrolysis of aberrantly folded polypeptides. There is growing evidence for the role of the UPS in viral entry. The UPS assists in several steps of the initiation of infection, including endosomal escape of the entering virion, intracellular transport of incoming nucleocapsids and uncoating of the viral genome. Inhibitors of proteasome activity, including MG132, epoxomicin, lactacystin and bortezomib have been integral to developments in this area. Here, we review the mechanistic details of UPS involvement in the entry process of viruses from a multitude of families. The possibility of proteasome inhibitors as therapeutic antiviral agents is highlighted.
Topics: Acetylcysteine; Animals; Antiviral Agents; Bortezomib; Host Microbial Interactions; Humans; Leupeptins; Nucleocapsid; Oligopeptides; Proteasome Endopeptidase Complex; Proteasome Inhibitors; Proteolysis; Ubiquitin; Virion; Virus Internalization; Virus Physiological Phenomena; Viruses
PubMed: 33037857
DOI: 10.1111/cmi.13276 -
Nihon Shinkei Seishin Yakurigaku Zasshi... Apr 2016Oxidative stress and neuroinflammation have recently been focused on the pathological hypotheses of schizophrenia. N-acetylcysteine (NAC) is a precursor of endogenous... (Review)
Review
Oxidative stress and neuroinflammation have recently been focused on the pathological hypotheses of schizophrenia. N-acetylcysteine (NAC) is a precursor of endogenous antioxidant glutathione and has antioxidant, anti-inflammatory, and neuroprotective properties. NAC is widely available as an over-the-counter nutritional supplement. Increasing lines of evidence suggest that NAC is effective for various mental disorders. In randomized controlled trials, treatment with NAC as an add-on to antipsychotics showed beneficial effects and safety profiles in patients with chronic schizophrenia. The results of a recent preclinical study using a neurodevelopmental model of schizophrenia suggest that NAC may have promising effects in an early stage of schizophrenia and an at-risk mental state. However, there is little clinical evidence for the efficacy and safety of NAC at these stages of schizophrenia. In this review, we summarize the evidence regarding the effectiveness of NAC for the treatment of schizophrenia and its prodromal stage. We also introduce the preliminary results of our research on NAC.
Topics: Acetylcysteine; Animals; Anti-Inflammatory Agents; Antioxidants; Clinical Trials as Topic; Disease Models, Animal; Glutathione; Humans; Microglia; Neuroprotective Agents; Oxidative Stress; Schizophrenia
PubMed: 27333656
DOI: No ID Found -
Advanced Emergency Nursing Journal 2016This article will review the available evidence related to the management of non-acetaminophen induced acute liver failure with N-acetylcysteine. Randomized controlled... (Meta-Analysis)
Meta-Analysis Review
This article will review the available evidence related to the management of non-acetaminophen induced acute liver failure with N-acetylcysteine. Randomized controlled trials and a meta-analysis were included in this review. The efficacy of N-acetylcysteine in the treatment of acute liver failure from causes other than acetaminophen toxicity was evaluated. The efficacy of N-acetylcysteine in non-acetaminophen-induced acute liver failure is limited to specific patient populations. Patients classified as Coma Grade I or II are more likely to benefit from the use of this agent. The use of N-acetylcysteine is associated with improved transplant-free survival, not overall survival, in adults. N-Acetylcysteine does not improve the overall survival of patients with non-acetaminophen-induced acute liver failure but may be beneficial in those patients with Coma Grades I-II. Liver transplantation remains the only definitive therapy in advanced disease.
Topics: Acetylcysteine; Humans; Liver Failure, Acute; Liver Transplantation; Patient Selection; Survival Analysis
PubMed: 27482990
DOI: 10.1097/TME.0000000000000116 -
Survey of Ophthalmology 2022N-acetylcysteine (NAC) was first discovered as a mucolytic agent in 1960. We investigate the role of topical NAC in ocular therapeutics, including its mechanism of... (Review)
Review
N-acetylcysteine (NAC) was first discovered as a mucolytic agent in 1960. We investigate the role of topical NAC in ocular therapeutics, including its mechanism of action, current applications, and adverse effects. A systematic search of peer-reviewed articles identified 106 references including in vitro, in vivo and clinical studies on the use of NAC in the treatment of ocular diseases. NAC can be synthetically manufactured, and its mechanisms of action include mucolysis, scavenging hydroxyl radicals, and modulation of inflammatory cascades. These unique properties contribute to the diverse applications of NAC, including its steroid-sparing potential. NAC has been used topically in the treatment of corneal wounds, chemical injuries, keratitis, dry eye disease and meibomian gland dysfunction. The clinical benefits of NAC are evident over a wide range of concentrations, the most common being 5-10% topical NAC applied four times daily. Adverse effects such as corneal necrosis are rare, but have been reported with higher doses. NAC also has potential applications in laser epithelial keratomileusis, diabetic eye disease, retinitis pigmentosa, senile nuclear cataracts, macular degeneration, and cigarette smoke-induced corneal damage. Recently, chitosan-NAC has been used as a nanocarrier for the topical administration of medications to the ocular surface. Owing to its potent antioxidant, anti-inflammatory and mucolytic properties, topical NAC has had extensive use in the treatment of ocular pathology.
Topics: Acetylcysteine; Administration, Topical; Chitosan; Cornea; Dry Eye Syndromes; Humans
PubMed: 34339721
DOI: 10.1016/j.survophthal.2021.07.008 -
The European Respiratory Journal May 2023Mucin disulfide cross-links mediate pathologic mucus formation in muco-obstructive lung diseases. MUC-031, a novel thiol-modified carbohydrate compound, cleaves...
BACKGROUND
Mucin disulfide cross-links mediate pathologic mucus formation in muco-obstructive lung diseases. MUC-031, a novel thiol-modified carbohydrate compound, cleaves disulfides to cause mucolysis. The aim of this study was to determine the mucolytic and therapeutic effects of MUC-031 in sputum from patients with cystic fibrosis (CF) and mice with muco-obstructive lung disease (βENaC-Tg mice).
METHODS
We compared the mucolytic efficacy of MUC-031 and existing mucolytics (N-acetylcysteine (NAC) and recombinant human deoxyribonuclease I (rhDNase)) using rheology to measure the elastic modulus (G') of CF sputum, and we tested effects of MUC-031 on airway mucus plugging, inflammation and survival in βENaC-Tg mice to determine its mucolytic efficacy .
RESULTS
In CF sputum, compared to the effects of rhDNase and NAC, MUC-031 caused a larger decrease in sputum G', was faster in decreasing sputum G' by 50% and caused mucolysis of a larger proportion of sputum samples within 15 min of drug addition. Compared to vehicle control, three treatments with MUC-031 in 1 day in adult βENaC-Tg mice decreased airway mucus content (16.8±3.2 7.5±1.2 nL·mm, p<0.01) and bronchoalveolar lavage cells (73 833±6930 47 679±7736 cells·mL, p<0.05). Twice-daily treatment with MUC-031 for 2 weeks also caused decreases in these outcomes in adult and neonatal βENaC-Tg mice and reduced mortality from 37% in vehicle-treated βENaC-Tg neonates to 21% in those treated with MUC-031 (p<0.05).
CONCLUSION
MUC-031 is a potent and fast-acting mucolytic that decreases airway mucus plugging, lessens airway inflammation and improves survival in βENaC-Tg mice. These data provide rationale for human trials of MUC-031 in muco-obstructive lung diseases.
Topics: Adult; Humans; Mice; Animals; Expectorants; Sulfhydryl Compounds; Cystic Fibrosis; Acetylcysteine; Sputum; Lung Diseases, Obstructive; Inflammation; Carbohydrates; Lung
PubMed: 37080569
DOI: 10.1183/13993003.02022-2022 -
Nutrients May 2023Administering N-acetylcysteine (NAC) could counteract the effect of free radicals, improving the clinical evolution of patients admitted to the Intensive Care Unit... (Randomized Controlled Trial)
Randomized Controlled Trial
Administering N-acetylcysteine (NAC) could counteract the effect of free radicals, improving the clinical evolution of patients admitted to the Intensive Care Unit (ICU). This study aimed to investigate the clinical and biochemical effects of administering NAC to critically ill patients with COVID-19. A randomized controlled clinical trial was conducted on ICU patients ( 140) with COVID-19 and divided into two groups: patients treated with NAC (NAC-treated group) and patients without NAC treatment (control group). NAC was administered as a continuous infusion with a loading dose and a maintenance dose during the study period (from admission until the third day of ICU stay). NAC-treated patients showed higher PaO/FiO ( 0.014) after 3 days in ICU than their control group counterparts. Moreover, C-reactive protein ( 0.001), D-dimer ( 0.042), and lactate dehydrogenase ( 0.001) levels decreased on the third day in NAC-treated patients. Glutathione concentrations decreased in both NAC-treated ( 0.004) and control ( 0.047) groups after 3 days in ICU; whereas glutathione peroxidase did not change during the ICU stay. The administration of NAC manages to improve the clinical and analytical response of seriously ill patients with COVID-19 compared to the control group. NAC is able to stop the decrease in glutathione concentrations.
Topics: Humans; Acetylcysteine; COVID-19; Critical Illness; Glutathione; Dietary Supplements
PubMed: 37405379
DOI: 10.3390/nu15092235 -
The Journal of Prevention of... 2017Alzheimer's disease is a progressive neurodegenerative disease for which there is no cure and only a few treatments providing little relief. Increased oxidative stress... (Review)
Review
Alzheimer's disease is a progressive neurodegenerative disease for which there is no cure and only a few treatments providing little relief. Increased oxidative stress that is associated with aging is strongly implicated in the pathogenesis and progression of Alzheimer's disease. Studies have shown that levels of the endogenous antioxidant glutathione decline at an early stage of Alzheimer's disease with decreased levels correlating with worse cognitive functions. N-acetylcysteine, a drug also widely available as a dietary supplement, is a precursor of L-cysteine, which in turn is a component of glutathione. Because cysteine availability is a limiting factor for glutathione synthesis, treatment with N-acetylcysteine may increase glutathione levels and thereby counter oxidative stress, promote redox -regulated cell signaling, and improve immune responses. In this review, we evaluate the existing literature and the potential of N-acetylcysteine in promoting cognitive health and alleviating cognitive decline associated with dementia. Discussion will also include possible mechanisms of action of N-acetylcysteine, its effects on aging biology, and safety of long-term use. Based on the available literature, a nutraceutical formulation containing N-acetylcysteine among other compounds has shown some pro-cognitive benefits in Alzheimer's patients and older adults, but the evidence for N-acetylcysteine alone is less robust. Although N-acetylcysteine crosses the blood-brain-barrier, low bioavailability is an obstacle. One promising avenue of research may be to explore derivatives of N-acetylcysteine such as N-acetylcysteine amide, which has been reported in preclinical studies to have higher permeability through cellular and mitochondrial membranes with increased central nervous system bioavailability compared to N-acetylcysteine.
Topics: Acetylcysteine; Cognitive Aging; Dementia; Humans; Neuroprotective Agents; Nootropic Agents
PubMed: 29182711
DOI: 10.14283/jpad.2017.22 -
European Review For Medical and... Jun 2023Evidence for the mucolytic and expectorant efficacy of intravenous (IV) N-acetylcysteine (NAC) is limited. This study aimed to evaluate in a large, multicenter,... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Evidence for the mucolytic and expectorant efficacy of intravenous (IV) N-acetylcysteine (NAC) is limited. This study aimed to evaluate in a large, multicenter, randomized, controlled, subject, and rater-blinded study whether IV NAC is superior to placebo and non-inferior to ambroxol in improving sputum viscosity and expectoration difficulty.
PATIENTS AND METHODS
A total of 333 hospitalized subjects from 28 centers in China with respiratory disease (such as acute bronchitis, chronic bronchitis and exacerbations, emphysema, mucoviscidosis, and bronchiectasis) and abnormal mucus secretion were randomly allocated in a 1:1:1 ratio to receive NAC 600 mg, ambroxol hydrochloride 30 mg, or placebo as an IV infusion twice daily for 7 days. Mucolytic and expectorant efficacy was assessed by ordinal categorical 4-point scales and analyzed by stratified and modified Mann-Whitney U statistics.
RESULTS
NAC showed consistent and statistically significant superiority to placebo and non-inferiority to ambroxol in change from baseline to day 7 in both sputum viscosity scores [mean (SD) difference 0.24 (0.763), p<0.001 vs. placebo] and expectoration difficulty score [mean (SD) difference 0.29 (0.783), p=0.002 vs. placebo]. Safety findings confirm the good tolerability profile of IV NAC reported from previous small studies, and no new safety concerns were identified.
CONCLUSIONS
This is the first large, robust study of the efficacy of IV NAC in respiratory diseases with abnormal mucus secretion. It provides new evidence for IV NAC administration in this indication in clinical situations where the IV route is preferred.
Topics: Humans; Acetylcysteine; Expectorants; Ambroxol; Respiration Disorders; Mucus; Double-Blind Method
PubMed: 37318485
DOI: 10.26355/eurrev_202306_32628 -
Nutrients May 2023N-acetylcysteine (NAC) is used as a sports supplement for its ability to modulate exercise-induced oxidative damage through its antioxidant actions and maintenance of... (Review)
Review
N-acetylcysteine (NAC) is used as a sports supplement for its ability to modulate exercise-induced oxidative damage through its antioxidant actions and maintenance of glutathione homeostasis, positioning NAC as a strategy to improve physical performance. We aimed to evaluate the current evidence on the benefits of NAC supplementation on physical performance and laboratory biomarkers in adult men. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically reviewed studies indexed in the Web of Science, Scopus, and PubMed to assess the effects of NAC on physical performance, laboratory biomarkers, and adverse effects in adult men. Original articles published up to 30 April 2023 with a controlled trial design comparing NAC supplementation with a control group were included. The modified McMaster Critical Review Form for Quantitative Studies was used as an assessment tool and the Cochrane Risk of Bias was applied. Of the 777 records identified in the search, 16 studies met the inclusion and exclusion criteria. Overall, most of the trials reported beneficial effects of NAC supplementation and no serious adverse events were reported. Participants supplemented with NAC showed significant improvements in exercise performance, antioxidant capacity, and glutathione homeostasis. However, there was no clear evidence of beneficial effects of NAC supplementation on haematological markers, inflammatory response, and muscle behaviour. NAC supplementation appears to be safe and may regulate glutathione homeostasis, have antioxidant effects, and improve exercise performance. However, further studies are needed to clarify the relevance of its use.
Topics: Male; Adult; Humans; Acetylcysteine; Antioxidants; Dietary Supplements; Glutathione; Physical Functional Performance; Biomarkers; Randomized Controlled Trials as Topic
PubMed: 37299425
DOI: 10.3390/nu15112463