BACKGROUND

Postoperative atrial fibrillation (POAF) is the most common arrythmia to occur after cardiovascular surgery. Inflammation being pivotal in POAF perpetuation has been utilized as a therapeutic target. Owing to their anti-inflammatory and anti-oxidant effects, beta-blockers (BB) and N-acetylcysteine (NAC) became research interests in the pursuit for an effective POAF prevention strategy.

To determine the efficacy of NAC plus BB versus BB alone in preventing POAF in cardiac surgery patients.

A literature search using the following search engines: PubMed/Medline, Cochrane Review Central, Clinical Trials Registry, ResearchGate, Mendeley and Google Scholar for relevant randomized trials were conducted. Published and unpublished studies indexed from inception until 2023 were included. Three independent reviewers evaluated the randomized clinical trials (RCTs) for eligibility. The pooled estimates for POAF prevention as primary outcome and MACE, mortality, myocardial infarction, stroke, ICU LOS and hospital LOS as secondary outcomes were measured using the RStudio statistical software.

Seven eligible RCTs allocated 1069 cardiac surgery patients to NAC + BB (n=539) and BB alone (N = 530) treatment arms. The effect estimate using random effect model disclosed significantly reduced POAF events (RR 0.62, 95% CI [0.44, 0.86], p = 0.005) in those on NAC + BB. While no statistical difference between the study arms were demonstrated in reducing mortality (RR 0.63, 95% CI [0.23, 1.73], p = 0.37); myocardial infarction (RR 1.02, 95% CI [0.49, 2.13], p = 0.96); stroke (RR 0.95, 95% CI [0.24, 3.68], p = 0.94); ICU LOS (std. mean difference 0.14, 95% CI [-0.43, 0.70], p = 0.41), and hospital LOS (std. mean difference 0.08, 95% CI [-0.06, 0.21], p = 0.19).

Among cardiac surgery patients, the use of NAC in combination with BB compared with BB alone significantly reduced POAF.

BACKGROUND

Tobacco smoking remains a primary health concern, more significantly in developing countries and continuously exerts a huge impact on global health. Available treatments for smoking cessation are often associated with adverse side effects, thus there is a great need for new therapies for smoking cessation. N-Acetylcysteine (NAC) is a widely available and well tolerated drug that would increase the intracellular levels of glutathione which modulates oxidative, immune-inflammatory, glutamatergic and neurotrophic pathways. There is suggestive evidence for the use of NAC in smoking cessation. Despite promising preclinical and preliminary clinical findings, randomised controlled trials which aim to evaluate NAC’s efficacy for smoking cessation and substance use disorders have shown mixed outcomes. With this gap in literature this study aims to determine the effect of NAC as an adjunctive treatment for smoking cessation.

The main objective of this study was to investigate the effect of NAC as an adjunctive treatment for smoking cessation

The study covered randomised clinical trials published in peer-reviewed journals registered in the Cochrane Central Register of Controlled Trials and PubMed. Study population in the selected studies had patients 18-65 of age years and with tobacco-use disorder or patients who smoke an average of 5 sticks per day. The primary outcome would be the effect of NAC on smoking cessation. The researcher utilised Review Manager 5.4.1 for the analysis of this study.

Initial Search in PubMed and Cochrane Library identified 23 clinical trials (6 PubMed, 17 Cochrane Library). 3 articles were included in the analysis. A total of 238 participants were enrolled in the studies, with 121 enrolled in the treatment group (NAC) and 106 were in the placebo group. The mean age of participants is 36.59 years and treatment duration vary up with the shortest duration of 1 month and longest duration of 3 months. Pooled odds ratio (2.41) shows that the true population odds of smoking cessation were between 1.32 and 4.41 in favor to the participants in the NAC group with 95% confidence interval. Measurement of secondary outcomes showed a significant reduction on carbon monoxide exhaled in the NAC group compared to the placebo group (P-0.0001, MD (95CI) -2.04 (3.09,-0.99). Pooled odds ratio (3.4) shows that there is a higher odds of adverse events between 1.72 and 6.90 higher in the NAC group with 95% confidence interval.

The results of this study showed a favourable effect of NAC as an adjunctive treatment for smoking cessation. NAC has shown a great potential to address the limited access to therapy due to its good safety profile and its wide availability.

Objectives: This study aimed to determine the effectiveness of N-acetylcysteine (NAC) in reversal of liver enzyme abnormalities among pediatric patients with dengue induced liver injury. Materials and Methods: The preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P 2020) declaration was used to create this systematic review. The study population included children (<18 years old) diagnosed with dengue-associated Liver Injury and given NAC. The outcome of interest was full recovery. A search was performed in PubMed/MEDLINE, EMBASE, Google Scholar, HERDIN PLUS, WPRIM, clinicaltrials.gov, and Cochrane databases on March 2023. The New Castle-Ottawa Quality Assessment Scale was adapted for risk of bias assessment for cohort studies. Results: Three case series and one pre-post cohort study published from 2013 to 2022 were included. The studies were of acceptable quality. In two studies with overall 10 pediatric patients given NAC for dengue-related ALF, all recovered without adverse events. In one study with 4 patients given NAC, half survived with their liver function tests returning to normal values. Finally, in one comparative study, the durations of time before the liver function tests returned to normal levels, and the mortality rates between those treated with and without N-acetyl cysteine were not significantly different. All studies reported no occurrence of adverse drug reaction related to NAC. Conclusion This systematic review shows limited evidence on the effectiveness of NAC in the reversal of liver enzymes among pediatric patients because of the low incidence of dengue induced liver injury seen in observational studies. Given that NAC is reported by all four studies to be accessible, effective, and with no attributable adverse events, its use can be considered. However, clinicians must still be cautioned given the limited available evidence.
Acetylcysteine

Objective To evaluate the antagonistic effects of N-acetylcysteine (NAC) on mitogen-activated protein kinases (MAPK) pathway activation, oxidative stress and inflammatory responses in rats with lung injury induced by fine particulate matter (PM_2.5). Methods Forty eight male Wistar rats were randomly divided into six groups: blank control group (C1), water drip control group (C2), PM_2.5 exposed group (P), low-dose NAC treated and PM_2.5 exposed group (L), middle-dose NAC treated and PM_2.5 exposed group (M), and high-dose NAC treated and PM_2.5 exposed group (H). PM_2.5 suspension (7.5 mg/kg) was administered tracheally once a week for four times. NAC of 125 mg/kg, 250 mg/kg and 500 mg/kg was delivered intragastrically to L, M and H group respectively by gavage (10 ml/kg) for six days before PM_2.5 exposure. The histopathological changes and human mucin 5 subtype AC (MUC5AC) content in lung tissue of rats were evaluated. We investigated IL-6 in serum and bronchoalveolar lavage fluid (BALF) by Enzyme-linked immunosorbent assay (ELISA), MUC5AC in lung tissue homogenate by ELISA, glutathione peroxidase (GSH-PX) in serum and BALF by spectrophotometry, and the expression of p-ERK1/2, p-JNK1/2 and p-p38 proteins by Western blot. All the measurements were analyzed and compared statistically. Results Lung tissue of rats exposed to PM_2.5 showed histological destruction and increased mucus secretion of bronchial epithelial cells. Rats receiving NAC treatment showed less histological destruction and mucus secretion. Of P, L, M and H group, MUC5AC in lung tissue, IL-6 in serum and BALF were higher than controls (C1 and C2) (all P<0.05), with the highest levels found in the P group and a decreasing trend with increase of NAC dose. The activity of GSH-PX in serum and BALF of PM_2.5 exposed rats (P, L, M and H) was lower than that of controls (all P<0.05), with higher activities found in NAC treated rats (L, M, and H), and an increasing trend with increase of NAC dose. The expressions of p-ERK1/2, p-JNK1/2 and p-p38 proteins in PM_2.5 exposed lung tissue (P, L, M and H) was higher than controls (all P<0.05), with decreased levels and dose dependent downregulation found in NAC treated rats. Conclusion NAC can antagonize major MAPK pathway activation, lung oxidative stress and inflammatory injury induced by PM_2.5 in rats.
Acetylcysteine/pharmacology* ; Animals ; Bronchoalveolar Lavage Fluid ; Enzyme Activation/drug effects* ; Glutathione Peroxidase/metabolism* ; Inflammation/pathology* ; Interleukin-6/metabolism* ; Lung/pathology* ; Lung Injury/pathology* ; Male ; Mitogen-Activated Protein Kinases/metabolism* ; Mucin 5AC/metabolism* ; Mucus/metabolism* ; Oxidative Stress/drug effects* ; Particle Size ; Particulate Matter/toxicity* ; Phosphorylation/drug effects* ; Rats, Wistar

Curcumin( Cur) is a natural active substance extracted from the roots or tubers of traditional Chinese medicinal materials. It has anti-inflammatory and anti-tumor activities on brain diseases. Due to the poor stability,low solubility,poor absorption and low bioavailability of curcumin,N-acetyl-L-cysteine( NAC) was used as an absorption enhancer and mixed with curcumin to improve the absorption of curcumin in the body. In this paper,curcumin was smashed by airflow pulverization,and Cur-NAC mixtures were prepared by being grinded with liquid. Then,the raw material and the product were analyzed by differential scanning calorimetry( DSC),X-ray diffraction( XRD) for structural characterization. The dissolution was determined by high performance liquid chromatography( HPLC) analysis. The characteristic peaks of the samples prepared by grinding method were similar to those of the raw materials,while the melting temperature and the accumulated dissolution degree were not significantly changed. The crystal forms of the products were not changed,and no new crystal form was formed after grinding. After the administration of intranasal powder,blood samples were collected from the orbit,while the whole brain tissues were removed from the skull and dissected into 10 anatomical regions. The concentrations of curcumin in these samples were determined by UPLC-MS/MS. The concentrations of curcumin in plasma and brain were compared at different time points. After intranasal administration of two drugs,it was found that the concentration of curcumin after sniffing up the mixtures in plasma was high,and the concentration of the drug in the olfactory bulb,hippocampus,and pons was increased significantly. Within 0. 083-0. 5 h,the olfactory bulb,piriform lobe and hippocampus remained high concentrations,the endodermis,striatum,hypothalamus and midbrain reached high concentrations within 1-3 h; and the cerebellum,pons and brain extension maintained relatively high concentrations within 3-7 h. The experiment showed that nasal administration of Cur-NAC mixtures can significantly improve the bioavailability of curcumin,and lead to significant differences in brain tissue distribution.
Acetylcysteine ; pharmacology ; Administration, Intranasal ; Animals ; Biological Availability ; Brain ; Brain Chemistry ; Chromatography, Liquid ; Curcumin ; pharmacokinetics ; Rats ; Tandem Mass Spectrometry ; Tissue Distribution

BACKGROUND: Antinociceptive anti-inflammatory drugs have many adverse effects. The goal of this investigation is to study the probable anti-inflammatory and analgesic effects of verapamil and N-acetylcysteine (NAC) in experimental rats. METHODS: Adult male Wistar rats were randomly divided into 4 groups in the antinociceptive study, each containing 6 rats; the normal control group, which received saline (1 mL/kg); the diclofenac group, which received diclofenac sodium (5 mg/kg); the NAC group, which received NAC (125 mg/kg); and the verapamil group, which received verapamil (8 mg/kg). In the anti-inflammatory study, 5 groups were used, the 4 previous groups with the addition of an edema control group, received saline and were subjected to formalin test. Hot plate latency time was recorded for antinociceptive evaluation. Paw edema thickness and biochemical parameters were recorded for anti-inflammatory evaluation. RESULTS: Administration of NAC showed significant prolongation of hot plate latency time at 1 hour when compared to the control group while verapamil showed a significant prolongation of hot plate latency time at 1 and 2 hours when compared to the control group and NAC group values. Administration of NAC and verapamil significantly decreased paw edema thickness at 2, 4, and 8 hours when compared to edema control values. Regarding biochemical markers, NAC and verapamil significantly decreased serum nitric oxide synthase, C-reactive protein, and cyclooxygenase-2 levels compared to the edema control value. In accordance, a marked improvement of histopathological findings was observed with both drugs. CONCLUSIONS: NAC and verapamil have antinociceptive and anti-inflammatory effects comparable to diclofenac sodium.
Acetylcysteine ; Adult ; Animals ; Anti-Inflammatory Agents ; Biomarkers ; C-Reactive Protein ; Cyclooxygenase 2 ; Diclofenac ; Edema ; Humans ; Male ; Nitric Oxide Synthase ; Pain Measurement ; Rats ; Rats, Wistar ; Verapamil

Based on the reactive oxygen species (ROS) regulatory properties of diphenyleneiodonium (DPI), we investigated the effects of DPI on host-infected T. gondii proliferation and determined specific concentration that inhibit the intracellular parasite growth but without severe toxic effect on human retinal pigment epithelial (ARPE-19) cells. As a result, it is observed that host superoxide, mitochondria superoxide and H2O2 levels can be increased by DPI, significantly, followed by suppression of T. gondii infection and proliferation. The involvement of ROS in anti-parasitic effect of DPI was confirmed by finding that DPI effect on T. gondii can be reversed by ROS scavengers, N-acetyl-L-cysteine and ascorbic acid. These results suggest that, in ARPE-19 cell, DPI can enhance host ROS generation to prevent T. gondii growth. Our study showed DPI is capable of suppressing T. gondii growth in host cells while minimizing the un-favorite side-effect to host cell. These results imply that DPI as a promising candidate material for novel drug development that can ameliorate toxoplasmosis based on ROS regulation.
Acetylcysteine ; Ascorbic Acid ; Humans ; Mitochondria ; Parasites ; Reactive Oxygen Species ; Retinaldehyde ; Superoxides ; Toxoplasma ; Toxoplasmosis

To investigate the effect of N-acetylcysteine(NAC)on cognitive function and nuclear factor erythroid 2 related factor 2/ heme oxygenase-1(Nrf2/HO-1)pathway in mouse models of postoperative cognitive dysfunction. Methods Fifty-four male C57BL/6J mice(3-4 months old)were randomly divided into control group,surgery group,and surgery+NAC group by block randomization.The intramedullary fixation for left tibial fracture surgery was performed to establish postoperative cognitive dysfunction models.NAC(150 mg/kg)was administered intraperitoneally in group surgery+NAC 30 minutes before and 3 hours,6 hours after surgery,while saline was given in control group and surgery group.Six mice in each group were selected randomly underwent Morris water maze test on the third day after surgery.Animals were sacrificed at the first and third postoperative days,and the hippocampus was harvested.Enzyme-linked immunosorbent assay was used to quantify the levels of interleukin-6(IL-6)and malondialdehyde(MDA)in hippocampus.Western blot and real-time polymerase chain reaction were used to measure the expressions of Nrf2 and HO-1 in hippocampus. Results There was no significant difference in swimming speed among three groups(=2.135,=0.114).Compared with control group and surgery+NAC group,the surgery group had prolonged escape latency(<0.01),reduced platform crossing times(<0.01),and shortened time spent in the target quadrant(<0.01).Compared with the control group,the surgery group and the surgery+NAC group had significantly increased levels of IL-6 and MDA in hippocampus at the first postoperative day(all =0.000).On the third postoperative day,there was no significant difference in the levels of IL-6(=0.251)and MDA(=0.103)between control group and surgery+NAC group.The protein expressions of Nrf2 and HO-1 in hippocampus were significantly higher in surgery group and surgery+NAC group than in control group and significantly higher in surgery+NAC group than in surgery group(all =0.000).The mRNA expressions of Nrf2 and HO-1 in hippocampus were significantly higher in surgery group and surgery+NAC group than in control group and significantly higher in surgery+NAC group than in surgery group (all =0.000). Conclusions NAC pretreatment may reduce oxidative stress and inflammatory response in hippocampus and improve cognitive function.Such effect may be relate to the activation of Nrf2/HO-1 pathway.
Acetylcysteine ; pharmacology ; Animals ; Cognition ; drug effects ; Cognitive Dysfunction ; drug therapy ; etiology ; Heme Oxygenase-1 ; metabolism ; Male ; Membrane Proteins ; metabolism ; Mice ; Mice, Inbred C57BL ; NF-E2-Related Factor 2 ; metabolism ; Postoperative Complications ; Random Allocation

PURPOSE: Protease-activated receptor 2 (PAR2) reportedly triggers the immune response in allergic asthma. We aimed to investigate the mechanism on allergic inflammation mediated by PAR2. METHODS: Human lung epithelial cells (A549 cells) were used for in vitro, and the German cockroach extract (GCE)-induced mouse model was developed for in vivo studies. RESULTS: In A549 cells, the levels of reactive oxygen species (ROS) and thymic stromal lymphopoietin (TSLP) were significantly increased by GCE treatment, but were suppressed by PAR2-antagonist (PAR2-ant) or N-acetylcysteine (NAC) treatment. Claudin-1 was degraded by GCE, and was restored by PAR2-ant or NAC in the cells. In the mouse model, the clinical appearance including bronchial hyperresponsiveness, bronchoalveolar lavage fluid analysis and total immunoglobulin E were significantly suppressed by PAR2-ant or NAC. Moreover, TSLP levels in the lung were suppressed by the same treatments in the lung. Claudin-1 was also degraded by GCE, and was restored by PAR2-ant or NAC. CONCLUSIONS: ROS generation and epidermal tight junction degradation are triggered by protease, followed by the induction of TSLP in allergic asthma. Our findings could suggest that PAR2-ant or anti-oxidants could be considered for allergic diseases as preventive alternatives.
Acetylcysteine ; Animals ; Asthma ; Blattellidae ; Bronchoalveolar Lavage Fluid ; Claudin-1 ; Epithelial Cells ; Humans ; Immunoglobulin E ; Immunoglobulins ; In Vitro Techniques ; Inflammation ; Lung ; Mice ; Oxygen ; Reactive Oxygen Species ; Receptor, PAR-2 ; Receptors, Proteinase-Activated ; Tight Junctions

BACKGROUND: NAD(P)H:quinone oxidoreductase-1 (NQO1) is a widely-distributed flavin adenine dinucleotide-dependent flavoprotein that promotes obligatory 2-electron reductions of quinones, quinoneimines, nitroaromatics, and azo dyes. This reduces quinone levels and thereby minimizes generation of excess reactive oxygen species (ROS) formed by redox cycling, and concurrent depletion of intracellular thiol pools. Ajoene is derived from crushed garlic. It is formed by a reaction involving two allicin molecules, and is composed of allyl sulfide and vinyl disulfide. Ajoene is present in two isomers, E- and Z-form. METHODS: Expression of antioxidant enzymes and nuclear factor E2-related factor-2 (Nrf2) was measured by Western blot analysis. NQO1 promoter activity was assessed by the luciferase reporter gene assay. ROS accumulation was monitored by using the fluorescence-generating probe 2′,7′-dichlorofluorescein diacetate. The intracellular glutathione levels were measured by using a commercially available kit. RESULTS: Z-ajoene significantly up-regulated the expression of representative antioxidant enzyme NQO1 in non-tumorigenic breast epithelial MCF-10A cells at non-toxic concentrations. Z-ajoene enhanced up-regulation and nuclear translocation of Nrf2, which plays a pivotal role in the induction of many genes encoding antioxidant enzymes and other cytoprotective proteins. Z-ajoene treatment also increased the activity of nqo1-promoter harboring antioxidant response element consensus sequences in MCF-10A cells. Silencing of Nrf2 by small interfering RNA abrogated ajoene-induced expression of NQO1. Z-ajoene activated extracellular signal-regulated kinase (ERK). Inhibition of ERK activation by U0126 abrogated ability of Z-ajoene to activate Nrf2 and to induce NQO1 expression. Intracellular ROS accumulation was observed after treatment with Z-ajoene, whereas the E-isoform was not effective. The inhibition of ROS by treatment with N-acetylcysteine, a radical scavenger, abrogated Z-ajoene-induced expression of NQO1 as well as activation of ERK and Nrf2, suggesting that Z-ajoene augments the Nrf2-dependent antioxidant defense via ROS generation and ERK activation. CONCLUSIONS: Z-ajoene induces NQO1 expression in MCF-10A cells through ROS-mediated activation of Nrf2.
Acetylcysteine ; Adenine ; Antioxidant Response Elements ; Azo Compounds ; Blotting, Western ; Breast ; Consensus Sequence ; Epithelial Cells ; Flavoproteins ; Garlic ; Genes, Reporter ; Glutathione ; Humans ; Luciferases ; NF-E2-Related Factor 2 ; Oxidation-Reduction ; Phosphotransferases ; Quinones ; Reactive Oxygen Species ; RNA, Small Interfering ; Up-Regulation