Nausea serves as a protective mechanism in organisms to prevent excessive consumption of toxic substances. Due to the adverse effects of chemical anti-nausea drugs, there is a growing interest in using herbal remedies and natural antioxidants. In this study, we evaluated the neuroprotective effects of quercetin (QU) and N-acetylcysteine (NAC) against oxidative damage induced by nausea. Emesis was induced in chickens using ipecac and copper sulfate (600 and 60 mg/kg, orally, respectively). QU and NAC (with doses of 50, 100, 200 mg/kg), and their combination were administered, along with a standard therapy (metoclopramide; MET 2 mg/kg) for one-time. Mitochondrial function, lipid peroxidation (LPO), protein carbonyl (PC), glutathione level (GSH), and reactive oxygen species (ROS) as oxidative damage biomarkers were evaluated in the chicken\'s brain mitochondria. QU and NAC significantly reduced emesis induced by copper sulfate and ipecac compared to the control group (P < 0.001). Significant differences in oxidative damage were observed in the groups received of copper sulfate and ipecac compared with control group. Levels of LPO, ROS, and PC were significantly decreased after the administration of QU and NAC in emesis induced by copper sulfate and ipecac. While, mitochondrial function and GSH levels were increased after the administration of QU and NAC. Combination therapy with QU and NAC yielded the most effective results. This study suggests that QU and NAC possess antiemetic effects through both peripheral and central mechanisms and exhibit neuroprotective effects against oxidative brain damage induced by emesis by increasing plasma antioxidants or scavenging free radicals.

Bacterial resistance poses a significant threat to both human and animal health. N-acetylcysteine (NAC), which is used as an anti-inflammatory, has been shown to have distinct and contrasting impacts on bacterial resistance. However, the precise mechanism underlying the relationship between NAC and bacterial resistance remains unclear and requires further investigation. In this study, we study the effect of NAC on bacterial resistance and the underlying mechanisms. Specifically, we examine the effects of NAC on Edwardsiella tarda ATCC15947, a pathogen that exhibits resistance to many antibiotics. We find that NAC can promote resistance of E. tarda to many antibiotics, such as doxycycline, resulting in an increase in the bacterial survival rate. Through proteomic analysis, we demonstrate that NAC activates the amino acid metabolism pathway in E. tarda, leading to elevated intracellular glutathione (GSH) levels and reduced reactive oxygen species (ROS). Additionally, NAC reduces antibiotic influx while enhancing efflux, thus maintaining low intracellular antibiotic concentrations. We also propose that NAC promotes protein aggregation, thus contributing to antibiotic resistance. Our study describes the mechanism underlying E. tarda resistance to doxycycline and cautions against the indiscriminate use of metabolite adjuvants.

BACKGROUND: Phlegm is prevalent symptom in patients with chronic obstructive pulmonary disease (COPD). Few studies have investigated the effectiveness of N-acetylcysteine (NAC) nebulizer therapy in COPD patients. We evaluated the effect of nebulized NAC on the improvement of phlegm symptom in COPD patients.
METHODS: This was a 12-week, prospective, single-arm, open-label, phase IV multi-center trial (NCT05102305, Registration Date: 20-October-2021). We enrolled patients aged ≥ 40 years with post bronchodilator forced expiratory volume in one second/forced vital capacity (FEV1/FVC) < 0.7 and COPD assessment test (CAT) phlegm score ≥ 2; the patients were current or ex-smoker with smoking pack-years ≥ 10. The primary endpoint was to determine the change in CAT phlegm score at 12 weeks compared to the baseline. Patients were assessed at baseline, 4, 8, and 12 weeks of treatment using the CAT score.
RESULTS: In total, 100 COPD patients were enrolled from 10 hospitals. The mean age of the patients was 71.42 ± 8.20 years, with 19.78% being current-smokers and 80.22% being ex-smokers. The mean smoking pack-years was 40.32 ± 35.18. The mean FVC, FEV1, and FEV1/FVC were 3.94 L (75.44%), 2.22 L (58.50%), and 0.53, respectively. The CAT phlegm score at baseline was 3.47 ± 1.06, whereas after 12 weeks of nebulized NAC it significantly decreased to 2.62 ± 1.30 (p < 0.01). More than half (53.5%) of the patients expressed satisfaction with the effects of nebulized NAC therapy. Adverse events occurred in 8 (8.0%) patients. Notably, no serious adverse drug reactions were reported.
CONCLUSIONS: In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks.

This study investigated the effects of N-Acetylcysteine (NAC) combined with Ambroxol Hydrochloride (AH) on clinical symptoms, C-Reactive Protein (CRP), and Procalcitonin (PCT) levels in children with pneumonia.
A total of 98 children with pneumonia were assigned to the control group and observation group by random number table method. NAC was administered to the observation group and AH was given to the control group. The therapeutic effect was observed, the disappearance time of clinical symptoms and levels of inflammatory factors, lung function parameters, blood gas analysis parameters, and immunoglobulin were measured. The incidence of adverse reactions was statistically analyzed.
A higher effective rate was observed in the observation group than in the control group (p < 0.05). Antipyretic time, cough disappearance time, and lung rale disappearance time in the observation group were shorter than those in the control group (p < 0.05). After treatment, CRP and PCT were lower (p < 0.05), FVC, FEV1, and FEV1/FVC were higher, PaCO2 was lower, PaO2 and SaO2 were higher, and IgA, IgG, IgM, and C3 were higher in the observation group than those in the control group (p < 0.05). The incidence of adverse reactions between the two groups was not significantly different (p > 0.05).
NAC combined with AH is effective in the treatment of pediatric pneumonia by effectively alleviating clinical symptoms, reducing inflammatory factors, and improving lung function and immune function.

N-acetylcysteine (NAC) is known for its beneficial effects on health due to its antioxidant and antiapoptotic properties. This study explored the protective effects of NAC against oxidative stress in heat-stressed (HS) skeletal muscle cells and its role in promoting muscle development. NAC reduced the heat shock response by decreasing the expression of heat shock protein 70 (HSP70) in HS-induced muscle cells during proliferation and differentiation. NAC also mitigated HS-induced oxidative stress via increasing the antioxidant enzyme levels and reducing oxidant enzyme levels. Treatment with NAC at 2 mM increased cell viability from 43.68% ± 5.14%-66.69% ± 14.43% and decreased the apoptosis rate from 7.89% ± 0.53%-5.17% ± 0.11% in skeletal muscle cells. Additionally, NAC promoted the proliferation and differentiation of HS-induced skeletal muscle cells by upregulating the expression of PAX7, MYF5, MRF4 and MYHC. These findings suggest that NAC alleviates HS-induced oxidative damage in skeletal muscle cells and support muscle development.

With the development of Type 1 diabetes mellitus (T1DM), various complications can be caused. Hyperglycemia affects the microenvironment of cardiomyocytes, changes endoplasmic reticulum homeostasis, triggers unfolding protein response and eventually promotes myocardial apoptosis. However, insulin therapy alone cannot effectively combat the complications caused by T1DM. Forty adult beagles were randomly divided into five groups: control group, diabetes mellitus group, insulin group, insulin combined with NAC group, and NAC group. 24-hour blood glucose, 120-day blood glucose, 120-day body weight, and serum FMN content were observed, furthermore, hematoxylin-eosin staining, Periodic acid Schiff reagent staining, and Sirius red staining of the myocardium were evaluated. The protein expressions of GRP78, ATF6, IRE1, PERK, JNK, CHOP, caspase 3, Bcl2, and Bax were detected. Results of the pathological section of myocardial tissue indicated that insulin combined with NAC therapy could improve myocardial pathological injury and glycogen deposition. Additionally, insulin combined with NAC therapy down-regulates the expression of GRP78, ATF6, IRE1, PERK, JNK, CHOP, caspase3, and Bax. These findings suggest that NAC has a phylactic effect on myocardial injury in beagles with T1DM, and the mechanism may be related to the improvement of endoplasmic reticulum stress-induced apoptosis.

UNASSIGNED: Oxidative stress pathways may play a role in schizophrenia through direct neuropathic actions, microglial activation, inflammation, and by interfering with NMDA neurotransmission. N-acetylcysteine (NAC) has been shown to improve negative symptoms of schizophrenia, however, results from trials of other compounds targeting NMDA neurotransmission have been mixed. This may reflect poor target engagement but also that risk mechanisms act in parallel. Sodium Benzoate (NaB) could have an additive with NAC to act on several pathophysiological mechanisms implicated in schizophrenia.
UNASSIGNED: A multicenter, 12 weeks, 2 × 2 factorial design, randomized double-blind placebo-controlled feasibility trial of NaB and NAC added to standard treatment in 68 adults with early schizophrenia. Primary feasibility outcomes included recruitment, retention, and completion of assessments as well as acceptability of the study interventions. Psychosis symptoms, functioning, and cognitive assessments were also assessed.
UNASSIGNED: We recruited our desired sample (n = 68) and retained 78% (n = 53) at 12 weeks, supporting the feasibility of recruitment and retention. There were no difficulties in completing clinical outcome schedules. Medications were well tolerated with no dropouts due to side effects. This study was not powered to detect clinical effect and as expected no main effects were found on the majority of clinical outcomes.
UNASSIGNED: We demonstrated feasibility of conducting a clinical trial of NaB and NAC. Given the preliminary nature of this study, we cannot draw firm conclusions about the clinical efficacy of either agent, and a large-scale trial is needed to examine if significant differences between treatment groups emerge.
UNASSIGNED: ClinicalTrials.gov: NCT03510741.

UNASSIGNED: Clinical high risk for psychosis (CHR-P) offers a window of opportunity for early intervention and recent trials have shown promising results for the use of N-acetylcysteine (NAC) in schizophrenia. Moreover, integrated preventive psychological intervention (IPPI), applies social-cognitive remediation to aid in preventing the transition to the psychosis of CHR-P patients.
UNASSIGNED: In this double-blind, randomized, controlled multicenter trial, a 2 × 2 factorial design was applied to investigate the effects of NAC compared to placebo (PLC) and IPPI compared to psychological stress management (PSM). The primary endpoint was the transition to psychosis or deterioration of CHR-P symptoms after 18 months.
UNASSIGNED: While insufficient recruitment led to early trial termination, a total of 48 participants were included in the study. Patients receiving NAC showed numerically higher estimates of event-free survival probability (IPPI + NAC: 72.7 ± 13.4%, PSM + NAC: 72.7 ± 13.4%) as compared to patients receiving PLC (IPPI + PLC: 56.1 ± 15.3%, PSM + PLC: 39.0 ± 17.4%). However, a log-rank chi-square test in Kaplan-Meier analysis revealed no significant difference of survival probability for NAC vs control (point hazard ratio: 0.879, 95% CI 0.281-2.756) or IPPI vs control (point hazard ratio: 0.827, 95% CI 0.295-2.314). The number of adverse events (AE) did not differ significantly between the four groups.
UNASSIGNED: The superiority of NAC or IPPI in preventing psychosis in patients with CHR-P compared to controls could not be statistically validated in this trial. However, results indicate a consistent pattern that warrants further testing of NAC as a promising and well-tolerated intervention for CHR patients in future trials with adequate statistical power.

UNASSIGNED: As the prevalence of coronary artery disease rises, the demand for coronary artery bypass grafting (CABG) increases. A common complication after CABG is postoperative atrial fibrillation (POAF), which is linked to adverse clinical outcomes. N-acetylcysteine (NAC), an antioxidant, may mitigate oxidative stress and reduce the incidence of POAF. This meta-analysis aims to investigate the efficacy of NAC in preventing POAF after CABG.
UNASSIGNED: The meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We systematically searched multiple databases, including PubMed, Cochrane Library, ProQuest, and ScienceDirect, to identify relevant randomized controlled trials (RCTs). The intervention groups received perioperative NAC therapy, while the control groups received a placebo. The outcomes assessed were POAF incidence, all-cause mortality, and hospital length of stay (LOS). Review Manager 5.3 was used to conduct the meta-analysis.
UNASSIGNED: Eleven RCTs involving 648 patients were included. The NAC group comprised 326 patients, while the control group comprised 322 patients. In the pooled analysis, patients in the NAC group had a significantly lower incidence of POAF (odds ratios (OR) = 0.57; 95% confidence intervals (CI) = 0.33 to 0.97; p = 0.04) and a shorter hospital LOS (weighted mean differences (WMD) = -0.66; 95% CI = -1.22 to -0.10; p = 0.02) compared to the control group. However, there was no significant difference in all-cause mortality.
UNASSIGNED: The perioperative administration of NAC can effectively reduce the incidence of POAF and hospital LOS in CABG patients. However, larger RCTs are needed to confirm these findings.

In recent years, the increase in environmental pollutants has been one of the most important factors threatening human and environmental health. Arsenic, a naturally occurring element found in soil, water, and air, easily enters the human body and leads to many metabolic disorders. In this study, we focused on the possible protective effects of N-acetylcysteine (NAC) against sodium arsenite (As)-induced toxic effects on embryonic fibroblast cells. The effects of As and NAC treatment on cells were evaluated, including cytotoxicity, oxidative stress, and apoptosis. Embryonic fibroblast cells were exposed to As (ranging from 0.01 μM to 10 μM) and NAC (at a concentration of 2 mM) for 24 h. The assessment of cytotoxicity markers, such as cell viability and lactate dehydrogenase (LDH), showed that As significantly reduced cell viability and increased LDH levels. Furthermore, we observed that As increased the amount of reactive oxygen species (ROS) in the cell, decreased the activity of antioxidant enzymes, and triggered apoptosis in cells. Additionally, our research revealed that the administration of NAC mitigates the detrimental effects of As. The results showed that As exerted hazardous effects on embryonic fibroblast cells through the induction of oxidative stress and apoptosis. In this context, our study provides evidence that NAC may have a protective effect against the toxicity of As in embryonic fibroblast cells.