A double-blind randomized controlled trial of N-acetylcysteine (NAC) for the treatment of acute exacerbation of chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease with acute exacerbation (AECOPD) being a common sequalae which negatively impact health status, rates of hospitalization and readmission, and disease progression. N-acetylcysteine (NAC) has been studied in COPD in both stable state and acute exacerbations, which has been shown to have small beneficial effects in stable COPD, as well as AECOPD. Yet, there has been lack of study with well-designed protocol to assess the role of NAC in more objective outcomes in AECOPD. Methods: This is a double-blind randomized controlled trial. Patients will be randomized in 1:1 ratio to receive oral NAC at 600 mg twice daily or placebo twice daily with standard of care. Partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2) and the ratio of partial pressure arterial oxygen and fraction of inspired oxygen (PaO2/FiO2) will be measured on days 1 and 7. The following will be measure at baseline and on day 4 and 7: Forced expiratory volume in one second (FEV1), 24-hour sputum volume, oxygen saturation (SaO2), end-tidal CO2, Leicester Cough Questionnaire (LCQ) score, COPD Assessment Test (CAT) score, grading of wheeze and grade of dyspnoea; blood inflammatory markers (leucocyte count, neutrophil count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and high sensitivity CRP (hs-CRP)). Patients will be randomized to oral NAC at 600 mg twice daily or placebo for 7 days. The main outcome measures include: The difference in PaO2 on day 7. Secondary outcome: Change in following parameters on day 4/7 from baseline: FEV1, sputum volume, CAT score, LCQ score, SaO2, grade of wheeze; mMRC Dyspnoea Scale, end-tidal CO2, blood inflammatory marker, change in PaO2/FiO2 ratio from baseline to day 7, PaCO2 on day 7, 28 and 90 days' mortality, time to wean off supplemental oxygen, length of stay.Primary and secondary outcomes will be compared among the two treatment groups with two-sample t-test. Discussion: We hypothesize that NAC use in COPD exacerbation can provide benefits in clinical and laboratory parameters. Trial Registration: Name of the registry : ClinicalTrials.gov Trial registration number : NCT05706402. URL of the trial registry record for this trial : https://classic.clinicaltrials.gov/ct2/show/NCT05706402 Date of registration : Registered on 11th January 2023 Funding of the trial : The Health and Medical Research Fund (HMRF). Name and contact information for the trial sponsor : Wang Chung Kwok, Clinical Assistant Professor, Honorary Associate Consultant, Queen Mary Hospital, The University of Hong Kong, Hong Kong. Role of sponsor : The funder is not involved in the planning of the study, gathering, analysing, and interpreting the data, or in preparing the manuscript.

Anticandidal activity of Croton heliotropiifolius Kunth essential oil is enhanced by N-acetylcysteine and itraconazole.

Aim: Evaluate the anticandidal effect of Croton heliotropiifolius Kunth essential oil and its interaction with azoles and N-acetylcysteine (NAC) against planktonic cells and biofilms. Materials & methods: Broth microdilution and checkerboard methods were used to evaluate the individual and combined activity with fluconazole and itraconazole (ITRA). The antibiofilm effect of the oil was assessed in 96-well plates alone and combined with ITRA and NAC, and cytotoxicity determined by MTT. Results: The oil inhibited all Candida species growth. The activity was enhanced when associated with ITRA and NAC for planktonic cells and biofilms in formation. The effective concentrations were lower than the toxic ones to V79 cells. Conclusion: C. heliotropiifolius Kunth essential oil is an anticandidal alternative, and can be associated with ITRA and NAC.

Candida is a type of fungus that can cause disease in people. In recent years, the number of available drugs to treat this disease have declined. It is important to search for new drugs. Plants are often used to improve health, so we tested the essential oil of a plant called Croton heliotropiifolius to see if it could kill the fungus. We found that the essential oil could kill the fungus, and could be used with other drugs to improve their effects.

Protective effect of N-acetylcysteine against hepatocellular carcinoma in hepatitis B virus carriers.

Hepatitis B virus (HBV) infection is a leading risk factor for hepatocellular carcinoma (HCC), contributing to cancer development through direct genomic integration and chronic inflammation. N-acetylcysteine (NAC), known for its antioxidant properties, is widely utilized in cancer prevention. However, clinical evidence regarding its protective effect against HCC in HBV carriers remains sparse. In this retrospective cohort study spanning 2008 to 2018, we utilized Taiwan's National Health Insurance Research Database (NHIRD) to include 1,061,174 chronic HBV carriers. Participants were stratified into NAC users and non-users using Propensity Score Matching. We assessed the incidence of HCC in both cohorts, examining the relationship between NAC usage duration and HCC incidence, and evaluating the dose-response effect. NAC users exhibited a significantly lower risk of developing HCC (adjusted hazard ratio [aHR]: 0.38; 95% confidence interval [CI]: 0.36-0.40; P < 0.0001). A dose-response relationship was evident, with higher cumulative defined daily doses (cDDDs) of NAC correlating with reduced HCC risk, revealing a significant trend (P < 0.0001). Notably, a daily NAC intensity of > 1.4 DDDs was associated with a decreased risk of HCC in HBV patients. Our results demonstrate that the use of NAC, in a dose-dependent manner, is intricately linked with a diminished incidence of HCC in individuals chronically infected with the HBV.

Effects of N-acetylcysteine on hepatocellular carcinoma in chronic hepatitis C.

Hepatitis C virus (HCV) infection significantly contributes to global hepatocellular carcinoma (HCC) incidence. N-Acetylcysteine (NAC), known for its antioxidant properties, is a potential therapeutic agent. However, evidence on its efficacy in reducing HCC risk among HCV patients is limited. A retrospective cohort analysis using Taiwan's National Health Insurance Research Database (2008-2018) included ≥18-year-old HCV patients. NAC usage (≥28 cumulative defined daily doses [cDDDs]) was assessed for its association with HCC risk using Cox regression models and propensity score matching. The study comprised 269,647 HCV patients, with detailed NAC dosage characterization and hazard ratios (HRs) for HCC risk. Post-matching, NAC usage emerged as the significant predictor of reduced HCC risk (adjusted HR: 0.39, 95% CI: 0.37-0.41, P<0.0001). Dose-response analysis showed reduced HCC risk with increasing cDDDs of NAC (P<0.0001). Higher daily NAC dosage (≥1 DDD) was associated with significantly lower HCC risk (adjusted HR: 0.33, 95% CI: 0.31-0.36, P<0.0001). The study provides compelling evidence for NAC's potential in reducing HCC risk among HCV patients. Insights into dose-dependent effects and optimal daily intensity thresholds offer valuable directions for future therapeutic strategies and clinical trials targeting HCC burden in HCV-infected individuals.

N-acetylcysteine stimulates the proliferation and differentiation in heat-stressed skeletal muscle cells.

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.

Add-on Sodium Benzoate and N-Acetylcysteine in Patients With Early Schizophrenia Spectrum Disorder: A Multicenter, Double-Blind, Randomized Placebo-Controlled Feasibility Trial.

Background and Hypothesis: 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. Study Design: 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. Study Results: 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. Conclusions: 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. Trial Registration: ClinicalTrials.gov: NCT03510741.

N-Acetylcysteine and a Specialized Preventive Intervention for Individuals at High Risk for Psychosis: A Randomized Double-Blind Multicenter Trial.

Background and Hypothesis: 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. Study Design: 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. Study Results: 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 ±â€…13.4%, PSM + NAC: 72.7 ±â€…13.4%) as compared to patients receiving PLC (IPPI + PLC: 56.1 ±â€…15.3%, PSM + PLC: 39.0 ±â€…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. Conclusions: 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.

N-acetylcysteine combined with insulin therapy can reduce myocardial injury induced by type 1 diabetes through the endoplasmic reticulum pathway.

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.

N-acetylcysteine attenuates sodium arsenite-induced oxidative stress and apoptosis in embryonic fibroblast cells.

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.

Efficacy of N-acetylcysteine for Prevention of Postoperative Atrial Fibrillation Following Coronary Artery Bypass Grafting: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Bisphenol P induces increased oxidative stress in renal tissues of C57BL/6 mice and human renal cortical proximal tubular epithelial cells, resulting in kidney injury.

Bisphenol P (BPP) has been detected in human biological samples; however studies on its nephrotoxicity are scarce. Given the susceptibility of kidneys to endocrine-disrupting chemicals, there is an urgent need to investigate the renal toxicity of BPP. This study aimed to evaluate the effects of different concentrations of BPPs on the kidneys of C57BL/6 mice and elucidate the underlying mechanisms of renal damage using a combination of mouse renal transcriptomic data and human renal proximal tubular epithelial cells (HK-2). Mice were exposed to BPP (0, 0.3, 30, 3000 µg/kg bw/d) via gavage for 5 weeks. Renal injury was assessed based on changes in body and kidney weights, serum renal function indices, and histopathological examination. Transcriptomic analysis identified differentially expressed genes and pathways, whereas cellular assays were used to measure cell viability, reactive oxygen species (ROS), apoptosis, and the expression of key genes and proteins. The results show that BPP exposure induces renal injury, as evidenced by increased body weight, abnormal renal function indices, and renal tissue damage. Transcriptomic analysis revealed alterations in genes and pathways related to oxidative stress, p53 signaling, autophagy, and apoptosis. Cellular experiments confirmed that BPP induces oxidative stress and apoptosis. Furthermore, BPP exposure significantly inhibits autophagy, potentially exacerbating apoptosis and contributing to kidney injury. Treatment with a ROS inhibitor (N-Acetylcysteine, NAC) mitigated BPP-induced autophagy inhibition and apoptosis, implicating oxidative stress as a key factor. BPP exposure may lead to renal injury through excessive ROS accumulation, oxidative stress, inflammatory responses, autophagy inhibition, and increased apoptosis. The effects of NAC highlight the role of oxidative stress in BPP-induced nephrotoxicity. These findings enhance our understanding of BPP-induced nephrotoxicity and underscore the need to control BPP exposure to prevent renal disease. This study emphasized the importance of evaluating the safety of new Bisphenol A analogs, including BPP, in environmental toxicology.

Reduced ischemia-reperfusion oxidative stress injury by melatonin and N-acetylcysteine in the male rat brain.

Middle cerebral artery occlusion (MCAO) is a model for inducing ischemic stroke in rodents, leading to devastating brain damage. Oxidative stress (OS) plays a crucial role in the pathogenesis of ischemia. In this study, the effect of melatonin and N-acetylcysteine on ischemia-reperfusion-induced oxidative stress injury in the cerebral cortex of male rats was investigated. 30 male Wistar rats were divided into sham, ischemic, NAC, melatonin and NAC + melatonin groups. All groups, except the sham group, underwent MCAO on the left side, and the treatment groups received intraperitoneal injections of either 50 mg/kg N-acetylcysteine (NAC) or 5 mg/kg melatonin or a combination of both 24 and 48 hours later. At 24 and 72 hours after surgery, the animals were examined for sensory and motor activity. The cerebral cortex was dissected after sacrificing the rats, infarct volume estimated and the concentrations of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nuclear factor erythroid-2 related factor 2 (Nrf2) were analyzed by enzyme-linked immunosorbent assay (ELISA). The results indicate that the NAC + melatonin group exhibited elevated sensory-motor activity and a reduced infarct volume rate in comparison to the ischemic group (p≤ 0.05). Compared to the ischemic group, the NAC + melatonin group showed a significant increase in SOD concentration and a significant decrease in MDA (p≤ 0.05). It can therefore be concluded that the simultaneous administration of NAC and melatonin can reduce the cerebral infarction volume, and improve neurological functions by modulating SOD and MDA.

Insulin combined with N-acetylcysteine attenuates type 1 diabetes-induced splenic inflammatory injury in canines by inhibiting the MAPKs-NF-κB signaling pathway and pyroptosis.

PURPOSE: Type 1 diabetes (T1DM) is a chronic metabolic disorder that can cause damage to multiple organs including the spleen. Sole insulin therapy is not satisfactory. This study aims to investigate the effects and mechanisms of combined treatment with insulin and N-acetylcysteine (NAC) on spleen damage in T1DM canines, in order to identify drugs that may better assist patients in the management of diabetes and its complications. METHODS: The canine model of T1DM was established by intravenous injection of alloxan (ALX) and streptozotocin (STZ). The therapeutic effects of insulin and NAC were evaluated by clinical manifestations, spleen protein and mRNA expression. RESULTS: The results indicate that the combined treatment of insulin and NAC can alleviate hyperglycemia and hematologic abnormalities, improve splenic histopathological changes, prevent fibrous tissue proliferation, and glycogen deposition. In addition, we observed that this combination treatment significantly suppressed the protein expression of p-P65/P65 (17.6 %, P < 0.05), NLRP3 (46.8 %, P < 0.05), and p-P38/P38 (37.1 %, P < 0.05) induced by T1DM when compared to insulin treatment alone. Moreover, it also significantly decreased the mRNA expression of TLR4 (45.0 %, P < 0.01), TNF-α (30.3 %, P < 0.05), and NLRP3 (43.3 %, P < 0.05). CONCLUSIONS: This combination has the potential to mitigate splenic inflammatory injury in T1DM canines by suppressing the activation of MAPKs-NF-κB pathway and pyroptosis. These findings provide a reference for the treatment strategies of diabetes and its complications.

Synthesis of N-acetylcysteine functionalized cholic acid based triarmed poly DL-Lactide and encapsulation of gold nanoparticles: Studies on the antimicrobial activity and biocompatibility for drug delivery applications.

Cholic acid based biodegradable reverse polymeric micelles have been widely utilized as preclinically suitable drug delivery system for poorly water-soluble drugs. In this report, we developed N-acetylcysteine functionalized cholic acid based triarmed poly (Dl-lactide) (ACyCA-triarmed (DLL)n as reversed polymeric micelles for drug delivery studies. ACyCA was synthesized via thiol-yne click reaction and subsequently used as an initiator for the synthesis of ACyCA-triarmed (DLL)n through ring opening polymerization (ROP) using Sn (Oct)2 as a catalyst. The synthesized ACyCA-triarmed (DLL)n was characterized using GPC, FT-IR, 1H NMR, 13C NMR, spectrofluorometer, HR-TEM, DSC, TGA, XRD, DLS, and zeta potential techniques. The reverse critical micellar concentration of the polymer was determined to be 1.99 mg/mL using a spectrofluorometer. The synthesized reverse micelles (RMs) were utilized as a reducing and capping agent for the preparation of AuNPs under sunlight exposure. The formed AuNPs exhibited spherical in shape with an average size of ∼ 23.4 nm and Dh was found to be 86.8 ± 1.3 nm as evidenced by the TEM and DLS analysis. Furthermore, the antimicrobial activity, hemolytic activity, anti-oxidant activity, and in-vitro drug release studies were examined for the RMs-AuNPs and compared with RMs. The hydrophobic nature of RMs and RMs-AuNPs had better haemocompatibility at above the reversed CMC. The antioxidant activity RMs-AuNPs showed better inhibitory effect in a dose-dependent manner as compared to RMs. The RMs-AuNPs formulation act as reservoir for solubilization of hydrophobic doxorubicin (Dox.HCl) drugs and can be used as therapeutic platform for slow and sustained release of drugs in biological medium.

Sinus Irrigation with N-Acetylcysteine after Endoscopic Sinus Surgery for Chronic Rhinosinusitis: A Preliminary Report of a Single-Blind Randomized Controlled Trial.

Nasal irrigation is crucial following endoscopic sinus surgery (ESS), especially for managing chronic rhinosinusitis (CRS). This study assessed the effectiveness of N-acetylcysteine (NAC) irrigation during the post-ESS period of patients with CRS without nasal polyposis. In this prospective, single-blind randomized controlled trial, 49 patients (NAC, n = 24; saline, n = 25) undergoing ESS were assigned to receive either NAC or saline irrigations twice daily for a month. The preoperative and postoperative assessments conducted included Lund-Macka (LM) and Lund-Kennedy (LK) endoscopic scores, the Nasal Obstruction Symptom Evaluation (NOSE) scale, and the Sino-Nasal Outcome Test-20 (SNOT-20). At 2 weeks, 1 month, and 3 months after the operation, endoscopic findings and symptoms were evaluated. Both groups showed no differences in age, sex, LM and LK scores, NOSE scale, and SNOT-20 preoperatively. In terms of the endoscopic findings regarding the sinonasal mucosa after ESS, the NAC group had slightly lower scores 2 weeks, 1 month, and 3 months after the operation, but this difference was not statistically significant. The NAC group showed significant improvement in VAS scores, namely, postnasal drip (1.0, p = 0.041), smell dysfunction (0.8, p = 0.003), and crust (1.5, p = 0.034), compared to the control group's scores of 2.6, 4.7, and 3.6, respectively, 2 weeks after the operation, although no significant differences were observed in VAS scores for any symptoms 1 and 3 months after the operation. NAC was well tolerated, and no adverse events were reported. NAC irrigation showed benefits over saline irrigation in terms of improving postnasal drip, smell dysfunction, and crust after ESS for CRS without nasal polyposis in the immediate postoperative period.

Investigation of the Effects of N-acetylcysteine and Selenium on Vesicoureteral Reflux Nephropathy: An Experimental Study.

INTRODUCTION: This study aimed to investigate the effects of N-acetylcysteine (NAC) and selenium (Se) on vesicoureteral reflux (VUR) nephropathy. METHODS: A total of 44 rabbits in 7 groups, namely group 1 (Control), group 2 (VUR + sterile urine), group 3 (VUR + sterile urine + NAC), group 4 (VUR + sterile urine + Se), group 5 (VUR + infected urine), group 6 (VUR + infected urine + NAC) and group 7 (VUR + infected urine + Se), were used. 99mTc Dimercaptosuccinic acid renal scan (DMSA), cystogram and urine culture were performed both at the beginning and end of the study. Left VUR was created surgically, and E. coli was inoculated in infected urine groups. NAC and Se were administered daily for 21 days. Malondialdehyde (MDA) measurement, inflammatory response scores (IRSs), and cicatrization response scores (CRSs) in renal tissues were evaluated. RESULTS: VUR did not reduce left renal uptake values in neither group 2 nor group 5. MDA levels of the left kidney were significantly higher in group 5 compared to group 1 (p = 0.001). There was no significant difference in MDA levels between group 5 and group 6, and between group 5 and group 7. Left kidney IRSs were found to be higher in all other groups except group 2 compared to the control group (p < 0.001). Left kidney CRSs were significantly higher in group 5 compared to group 2 (p = 0.026), group 6 (p < 0.001) and group 7 (p = 0.006). CONCLUSION: A decrease in renal functions was not observed in VUR, even if there was infection. When CRSs were evaluated, NAC and Se had protective effects in terms of scar formation in VUR nephropathy. TYPE OF STUDY: Experimental animal study. LEVELS OF EVIDENCE: N/A.

Budesonide and N-acetylcysteine inhibit activation of the NLRP3 inflammasome by regulating miR-381 to alleviate acute lung injury caused by the pyroptosis-mediated inflammatory response.

Background: The anti-inflammatory effects of budesonide (BUN) and N-acetylcysteine (NAC) attenuate acute lung injury (ALI). The aim of this study was to investigate the effects of combination therapy consisting of BUN and NAC on ALI and the underlying mechanisms. Methods: In vitro and in vivo models of ALI were generated by LPS induction. Western blotting was used to detect the expression levels of pyroptosis-related proteins and inflammation-related factors, and RT-qPCR was used to detect the expression of miR-381. Cell proliferation and apoptosis were detected by CCK-8 and flow cytometry, respectively. ELISA was used to detect the levels of inflammation-related factors. HE staining was used to detect lung injury. Results: The results showed that LPS effectively induced pyroptosis in cells and promoted the expression of pyroptosis-related proteins (Caspase1, Gasdermin D and NLRP3) and inflammatory cytokines (TNF-α, IL-6 and IL-1ß). The combination of BUN and NAC significantly alleviated LPS-induced pyroptosis and inflammation. In addition, the combination of BUN and NAC effectively promoted miR-381 expression. Transfection of miR-381 mimics effectively alleviated LPS-induced pyroptosis and inflammation, while transfection of miR-381 inhibitors had the opposite effect. miR-381 negatively regulates NLRP3 expression. Treatment with a miR-381 inhibitor or pc-NLRP3 reversed the effects of the combination of BUN and NAC. In a mouse model of ALI, the combination of BUN and NAC effectively improved lung injury, while treatment with a miR-381 inhibitor or pc-NLRP3 effectively reversed this effect. Conclusion: Overall, this study revealed that BUN + NAC inhibits the activation of NLRP3 by regulating miR-381, thereby alleviating ALI caused by pyroptosis-mediated inflammation.

Low dose rifaximin combined with N-acetylcysteine is superior to rifaximin alone in a rat model of IBS-D: a randomized trial.

Rifaximin is FDA-approved for treatment of irritable bowel syndrome with diarrhea (IBS-D), but poor solubility may limit its efficacy against microbes in the mucus layer, e.g. Escherichia coli. Here we evaluate adding the mucolytic N-acetylcysteine (NAC) to improve rifaximin efficacy. In a resazurin checkerboard assay, combining rifaximin with NAC had significant synergistic effects in reducing E. coli levels. The optimal rifaximin + NAC combination was then tested in a validated rat model of IBS-D (induced by cytolethal distending toxin [CdtB] inoculation). Rats were inoculated with vehicle and treated with placebo (Control-PBS) or rifaximin + NAC (Control-Rif + NAC, safety), or inoculated with CdtB and treated with placebo (CdtB-PBS), rifaximin (CdtB-Rifaximin), or rifaximin + NAC (CdtB-Rif + NAC) for 10 days. CdtB-inoculated rats (CdtB-PBS) developed wide variability in stool consistency (P = 0.0014) vs. controls (Control-PBS). Stool variability normalized in rats treated with rifaximin + NAC (CdtB-Rif + NAC) but not rifaximin alone (CdtB-Rifaximin). Small bowel bacterial levels were elevated in CdtB-PBS rats but normalized in CdtB-Rif + NAC but not CdtB-Rifaximin rats. E. coli and Desulfovibrio spp levels (each associated with different IBS-D microtypes) were also elevated in CdtB-inoculated (CdtB-PBS) but normalized in CdtB-Rif + NAC rats. Cytokine levels normalized only in CdtB-Rif + NAC rats, in a manner predicted to be associated with reduced diarrhea driven by reduced E. coli. These findings suggest that combining rifaximin with NAC may improve the percentage of IBS-D patients responding to treatment.

The role of N-acetylcysteine in osteogenic microenvironment for bone tissue engineering.

Bone defect is a common clinical symptom which can arise from various causes. Currently, bone tissue engineering has demonstrated positive therapeutic effects for bone defect repair by using seeding cells such as mesenchymal stem cells and precursor cells. N-acetylcysteine (NAC) is a stable, safe and highly bioavailable antioxidant that shows promising prospects in bone tissue engineering due to the ability to attenuate oxidative stress and enhance the osteogenic potential and immune regulatory function of cells. This review systematically introduces the antioxidant mechanism of NAC, analyzes the advancements in NAC-related research involving mesenchymal stem cells, precursor cells, innate immune cells and animal models, discusses its function using the classic oral microenvironment as an example, and places particular emphasis on the innovative applications of NAC-modified tissue engineering biomaterials. Finally, current limitations and future prospects are proposed, with the aim of providing inspiration for targeted readers in the field.

Three consecutive cases of acute liver failure in young women due to acetaminophen overdose: insights into Japanese social issues and transplantation landscape.

Acetaminophen (APAP) is an over-the-counter (OTC) drug known worldwide for its safety and efficacy. However, in Japan, OTC drug overdose has become a prominent social problem in recent years due to stricter regulations for other drugs, especially among young people, and APAP is an increasing cause of acute liver injury due to overdose. This report describes three consecutive cases of acute liver failure in young women (22, 22 and 19 years old) due to APAP overdose in December 2023. Despite severe liver injury, indicated by high ALT levels and coagulopathy, these cases recovered without requiring liver transplantation. This report discusses three cases of acute liver failure in young Japanese women following APAP overdose, reflecting a national increase in such cases due to increased misuse of OTC drugs and societal factors. Key findings include the need for early treatment with N-acetylcysteine (NAC) and the importance of mental health assessment in the management of overdose patients. The cases underscore the need for prompt team-based care to prevent serious outcomes and highlight the complexity of liver transplantation decisions in Japan, highlighting the need for comprehensive strategies to address the escalating problem of APAP overdose.