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The main objective of this study was to assess the ergogenic effect of N-acetylcysteine (NAC) on myotendinous isometric force production in physically active people after being subjected to a fatigue protocol. Twenty-three physically active people were randomly divided into the following two groups: NAC (n = 12; age = 26.8 ± 4.5 years, height = 173.1 ± 7.2 cm, and weight = 75.5 ± 7.5 kg), who received 2400 mg oral NAC, and control (n = 11; age = 23.4 ± 5.8 years, height = 175.9 ± 4.5 cm, and weight = 72.3 ± 9.9 kg), who received a placebo, for eight days. The isometric force production was assessed pre- and post-NAC supplementation during a maximal voluntary contraction test (MVC) and also during a fatigue protocol composed of seven sets of ten maximal isometric contraction repetitions of 5 s, with 5 s of rest between repetitions and 20 s between sets. No differences were observed between the groups in the force production values at any moment, and no side effects were found after NAC supplementation. After supplementation, a significant decrease in force was observed in both groups, but this significant loss of force started one set later in the NAC group compared to the control group (4th set vs. 5th set), which could be an ergogenic effect of the treatment. Therefore, oral daily supplementation with 2400 mg of NAC for eight days, could delay the decrease in force production during an isometric exercise protocol and without adverse side effects. [ABSTRACT FROM AUTHOR]

N‐acetylcysteine (NAC) may serve as a novel pharmacotherapy for substance use and substance craving in individuals with substance use disorders (SUDs), possibly through its potential to regulate glutamate. Though prior meta‐analyses generally support NAC's efficacy in reducing symptoms of craving, individual trials have found mixed results. The aims of this updated meta‐analysis were to (1) examine the efficacy of NAC in treating symptoms of craving in individuals with SUD and (2) explore subgroup differences, risk of bias and publication bias across trials. Database searches of PubMed, Cochrane Library and ClinicalTrials.gov were conducted in June and July of 2023 to identify relevant randomized control trials (RCTs). The meta‐analysis consisted of 9 trials which analysed data from a total of 623 participants. The most targeted substance in the clinical trials was alcohol (3/9; 33.3%), followed by tobacco (2/9; 22.2%) and multiple substances (2/9; 22.2%). Meta‐analysis, subgroup analyses and leave‐one‐out analyses were conducted to examine the treatment effect on craving symptoms and adverse events (AEs). Risk of bias assessments, Egger's tests and funnel plot tests were conducted to examine the risk of bias and publication bias. NAC did not significantly outperform placebo in reducing symptoms of craving in the meta‐analysis (SMD = 0.189, 95% CI = −0.015–0.393). Heterogeneity was very high in the meta‐analysis (99.26%), indicating that findings may have been influenced by clinical or methodological differences in the study protocols. Additionally, results indicate that there may be publication bias present. Overall, our findings are contrary to those of prior meta‐analyses, suggesting a limited impact of NAC on substance craving. However, the high heterogeneity and presence of publication bias identified warrants cautious interpretation of the meta‐analytic outcomes. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor-Natural Killer-92 (CAR-NK-92) cell therapy has broad prospects as an effective cellular immunotherapy. Efficient CAR-NK-92 cell expansion ex vivo is crucial for its development and wide use. Unlike NK-92 cells, CAR-NK-92 cells need to maintain the stability of CAR expression during culture, besides keeping cell function. This work compared the growth and metabolism between NK-92 cells and CAR-NK-92 cells and found that the expansion efficiency of CAR-NK-92 cells was significantly lower than that of NK-92 cells. Meanwhile, the amino acid metabolism related to reducing agent production in CAR-NK-92 cells was weaker than in NK-92 cells, resulting in higher intracellular oxidation levels. The antioxidant N-acetylcysteine (NAC) was used to regulate the intracellular redox status of CAR-NK-92 cells. Under 1 mM NAC, the intracellular reactive oxygen species (ROS) level of CAR-NK-92 cells was down-regulated, and the cell expansion ability was improved. Furthermore, the addition of NAC has increased the levels of GSH and NADPH in CAR-NK-92 cells, elevated GSH/GSSG ratio and NADPH/NADP+ ratio, enhanced the antioxidant capacity and mitochondrial function of cells, and promoted cell expansion. This study aims to promote CAR-NK-92 cell expansion ex vivo by regulating intracellular redox levels to facilitate its clinical application. [Display omitted] • The proliferation and redox-related amino acids metabolism of CAR-NK-92 cells were significantly weaker than NK-92 cells. • N-acetylcysteine regulates the intracellular redox state by reducing the level of ROS in CAR-NK-92 cells. • 1 mM NAC can promote CAR-NK-92 cell expansion ex vivo. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) affects 6–20% of women worldwide, with insulin resistance and hyperinsulinemia occurring in 50-70% of patients. Hyperinsulinemia exacerbates oxidative stress, contributing to PCOS pathogenesis. N-acetylcysteine (NAC) is an antioxidant and insulin sensitizer that shows promise as a therapeutic for PCOS. Our current study aimed to investigate the effects of NAC supplementation on endocrine-metabolic parameters in PCOS mice and its effect on ovulation induction (OI) efficacy in women with PCOS. Methods: Female C57BL/6 mice were orally administered letrozole (LE) to induce PCOS and then randomly divided into groups receiving daily oral administration of 160 mg/kg NAC (PCOS + NAC group), 200 mg/kg metformin (PCOS + Met group), or 0.5% carboxymethyl cellulose (drug solvent) (pure PCOS group) for 12 days. Healthy female mice served as pure controls. Estrous cycles were monitored during the intervention. Metabolic and hormone levels, ovarian phenotypes, antioxidant activity in ovarian tissues, and oxidative stress levels in oocytes were assessed post-intervention. Furthermore, a pragmatic, randomized, controlled clinical study was conducted with 230 PCOS women, randomly assigned to the NAC group (1.8 g/day oral NAC, n = 115) or the control group (n = 115). Patients in both groups underwent ≤ 3 cycles of OI with sequential LE and urinary follicle-stimulating hormone (uFSH). Cycle characteristics and pregnancy outcomes were compared between groups. Results: Similar to metformin, NAC supplementation significantly improved the estrous cycles and ovarian phenotypes of PCOS mice; reduced the LH concentration, LH/FSH ratio, and T level; and increased glucose clearance and insulin sensitivity. Notably, NAC significantly reduced oocyte ROS levels and increased the mitochondrial membrane potential in PCOS mice. Additionally, NAC significantly enhanced enzymatic and nonenzymatic antioxidant activities in PCOS mouse ovaries, whereas metformin had no such effect. In the clinical trial, compared to women in the control group, women receiving NAC had significantly lower average uFSH dosage and duration (p < 0.005) and significantly greater clinical pregnancy rates per OI cycle and cumulative clinical pregnancy rates per patient (p < 0.005). Conclusion: NAC supplementation improved endocrine-metabolic parameters in PCOS mice and significantly enhanced OI efficacy with sequential LE and uFSH in women with PCOS. Therefore, NAC could be a valuable adjuvant in OI for women with PCOS. [ABSTRACT FROM AUTHOR]

BACKGROUND: Heat stress (HS) has been shown to affect reproductive performance and muscle development negatively in animals. N‐Acetylcysteine (NAC) plays a pivotal role in enhancing the antioxidant performance in animals as a recognized antioxidant. The present study assesses the potential of NAC to modulate the reproductive performance and antioxidant function in pregnant mice exposed to HS. The role of NAC in muscle development of offspring mice was also explored. RESULTS: The results showed that NAC supplementation from day 12 to day 18 of gestation increased the number of litters and enhanced the antioxidant function in pregnant mice under HS exposure. It improved the weight and body condition significantly in the offspring mice (P < 0.05). The alleviation of HS‐induced muscle impairment with NAC was consistent with the alleviation of apoptosis, the enrichment of the proliferation and differentiation in the offspring mice muscle. N‐Acetylcysteine also reversed HS‐induced reduction in the cross‐sectional area of the leg muscle and increased the proportion of myosin heavy chain IIx (MYHCIIx) in the muscle fiber. CONCLUSION: The results of the present study support the use of NAC at a dose of 100 mg kg−1 body weight as supplement for protecting the offspring derived from pregnant mice exposed to HS from muscle impairment by accelerating proliferation and differentiation. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

This document is a compilation of summaries of four different articles from various medical journals. The first article discusses the use of a two-bag N-acetylcysteine (NAC) system for acetaminophen poisoning, comparing its effectiveness and safety to the FDA-approved three-bag system. The second article examines the use of physostigmine in the treatment of anticholinergic toxicity, finding that patients treated with physostigmine alone were less likely to be intubated. The third article explores the use of dexmedetomidine in non-intubated patients, concluding that it is a safe and useful adjunct in the care of agitated toxicological patients. The fourth article compares the acute effects of mescaline, lysergic acid diethylamide (LSD), and psilocybin in a randomized, double-blind, placebo-controlled study, finding that the subjective experiences were similar at the studied doses. These articles provide valuable insights for toxicologists and poison centers in the treatment of various toxicological conditions. [Extracted from the article]

Background: Acetaminophen toxicity remains one of the most common causes of liver failure and is treated with a course of n-acetylcysteine (NAC). This exceptionally effective medication is traditionally administered using a complicated three-bag protocol that is prone to administration errors. Objective: We aimed to assess whether switching to a novel two-bag protocol (150 mg/kg over 1 h followed by 150 mg/kg over 20 h) reduced administration errors while not increasing liver injury or anaphylactoid reactions. Methods: This was a retrospective chart review of hospital encounters for patients with acetaminophen toxicity, comparing outcomes before and after the change from a three-bag protocol to a two-bag protocol at two affiliated institutions. The primary outcome was incidence of medication errors with secondary outcomes including acute liver injury (ALI) and incidence of non-anaphylactoid allergic reactions (NAAR). The study was approved by the health system's Institutional Review Board. Results: 483 encounters were included for analysis (239 in the three-bag and 244 in the two-bag groups). NAAR were identified in 11 patients with no difference seen between groups. Similarly, no differences were seen in ALI. Medication administration errors were observed significantly less often in the two-bag group (OR 0.24) after adjusting for confounders. Conclusion: Transitioning to a novel two-bag NAC regimen decreased administration errors. This adds to the literature that two-bag NAC regimens are not only safe but also may have significant benefits over the traditional NAC protocol. [ABSTRACT FROM AUTHOR]

Background: The management of endodontic infections is a complex challenge, mainly due to the involvement of diverse microorganisms and their by-products. This study aimed to evaluate the efficacy of N-acetylcysteine (NAC), calcium hydroxide (Ca(OH)2), and their combined application as intracanal medications in combating Enterococcus faecalis, Escherichia coli, and lipopolysaccharides (LPS) from E. coli. Methods: A total of 60 single-rooted human teeth were carefully selected and divided into six groups. These tooth canals were deliberately exposed to E. faecalis (ATCC 29212) and E. coli (ATCC 25922) to induce biofilm formation. Subsequently, the specimens were treated with NAC, Ca(OH)2, or a combination of both substances. Three samples of the root canals were collected at three moments: the first sample (S1) was to confirm the initial contamination, the second sample (S2) was immediately post-instrumentation, and the third sample (S3) was collected after the use of the intracanal medication. The antimicrobial efficacy of these intracanal medications was assessed by enumerating colony-forming units per milliliter (CFU/mL). In addition to this, the kinetic chromogenic Limulus Amebocyte Lysate (LAL) assay by Lonza was used to quantify LPS from E. coli. Data tested for normality; then, Kruskal-Wallis and Friedman tests were used, and Dunn's for multiple comparisons. Results: The findings of this study showed significant reductions in the microbial load of E. faecalis and E. coli by S3. Notably, there were no statistically significant differences among the treatment groups concerning these microorganisms. However, it was observed that only the combination of NAC and Ca(OH)2 led to a noteworthy decrease in the quantity of E. coli's LPS after 7-days, demonstrating a statistically significant difference from the other treatment groups. NAC + Ca(OH)2 combination, applied for a duration of 7-days, proved to be more suitable in reducing the presence of E. faecalis, E. coli, and LPS from E. coli within the context of endodontic infections. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Aims: Several studies have highlighted the potent antioxidant properties of N‐acetyl cysteine (NAC). This review aimed to assess the impact of NAC on oxidative stress biomarkers in patients with β‐thalassemia. Methods: The review included articles published before 2024 that investigated the effects of NAC on oxidative stress in individuals with β‐thalassemia. A comprehensive search was conducted across various databases, including Scopus, PubMed, Web of Science, Trip, and CENTRAL. Only English‐language clinical trials were considered for inclusion in this review. Besides, the number needed to treat (NNT) was calculated based on the included studies. Results: Ninety‐nine articles were retrieved from electronic databases, and after a thorough review, eight articles were selected for comprehensive text analysis. The highest dose of NAC administered was 10 mg/kg/day (equivalent to 600 mg/day) over a period of 3–6 months. All the studies assessing the impact of NAC on oxidative stress indicators in β‐thalassemia patients demonstrated positive effects during the 3‐month follow‐up period. Most estimated NNTs fell into 1–5, suggesting significant clinical therapeutic value in this context. Conclusion: The current potency of NAC alone appears to be effective in ameliorating oxidative stress in patients with β‐thalassemia major. While a 3‐month duration seems adequate to demonstrate the antioxidant properties of NAC in this population, larger and well‐designed clinical trials are warranted. Current clinical evidence possesses a high risk of bias. [ABSTRACT FROM AUTHOR]

Objective This study aimed to assess the beneficial effects of N-acetylcysteine (NAC) in the treatment of contrast-induced nephropathy (CIN). Materials and Methods A prospective study was conducted in the department of cardiology of a tertiary health care hospital. A sample of 100 patients who had developed CIN through coronary angioplasty were categorized into two groups: one group treated with intravenous fluids (IVF) monotherapy and the other group treated with the combination of IVF and NAC therapy. Statistical Analysis The data were analyzed using statistical software SPSS software version 26 and statistical significance was set at p < 0.05. Independent t -test and paired t -test were used to analyze the parameters. Results The rate of incidence of CIN was found to be 10%. We observed that the IVF + NAC combination therapy significantly decreases the serum creatinine compared to IVF monotherapy (p = 0.004). Both therapies show similar treatment outcomes with no significant difference (p = 0.556) in the case of estimated glomerular filtration rate (eGFR). Based on creatinine clearance, the results show adding NAC does not impact any additional benefits (p = 000). The duration of hospital stay of the NAC group was reduced significantly (p = 0.000). Conclusion At present, we found that the treatment outcomes which we analyzed based on factors such as serum creatinine, eGFR, and creatinine clearance, are too inconsistent to conclude the beneficial effect of NAC in the management of CIN. [ABSTRACT FROM AUTHOR]

Background/Objectives: Urinary tract infections (UTIs) are infections that involve the urethra, bladder, and, in much more severe cases, even kidneys. These infections represent one of the most common diseases worldwide. Various pathogens are responsible for this condition, the most common being Escherichia coli (E. coli). Bromelain is a proteolytic complex obtained from the stem and stalk of Ananas comosus (L.) Merr. showing several beneficial activities. In addition to bromelain, N-acetylcysteine (NAC) has also been used. Methods: The purpose of this experiment was to evaluate the antibacterial, anti-motility, and anti-biofilm effects of a new polyenzymatic complex (DIF17BRO®) in combination with NAC (the Formulation) on various strains of E. coli isolated from patients with UTIs. Subsequently, the anti-inflammatory and antioxidant effects of the Formulation were studied in an ex vivo model of cystitis, using bladder samples from mice exposed to E. coli lipopolysaccharide (LPS). Results: Our results showed that the Formulation significantly affects the capability of bacteria to form biofilm and reduces the bacteria amount in the mature biofilm. Moreover, it combines the interesting properties of NAC and a polyenzyme plant complex based on bromelain in a right dose to affect the E. coli adhesion capability. Finally, the Formulation exhibited protective effects, as confirmed by the inhibitory activities on multiple inflammatory and oxidative stress-related pathways on bladder specimens exposed to LPS. Conclusions: This blend of active compounds could represent a promising and versatile approach to use to overcome the limitations associated with conventional therapies. [ABSTRACT FROM AUTHOR]

Carbapenem-resistant (CR) Gram-negative bacteria have become a significant public health problem in the last decade. In recent years, the prevalence of CR bacteria has increased. The resistance to carbapenems could result from different mechanisms such as loss of porin, penicillin-binding protein alteration, carbapenemase, efflux pump, and biofilm community. Additionally, genetic variations like insertion, deletion, mutation, and post-transcriptional modification of corresponding coding genes could decrease the susceptibility of bacteria to carbapenems. In this regard, scientists are looking for new approaches to inhibit CR bacteria. Using bacteriophages, natural products, nanoparticles, disulfiram, N-acetylcysteine, and antimicrobial peptides showed promising inhibitory effects against CR bacteria. Additionally, the mentioned compounds could destroy the biofilm community of CR bacteria. Using them in combination with conventional antibiotics increases the efficacy of antibiotics, decreases their dosage and toxicity, and resensitizes CR bacteria to antibiotics. Therefore, in the present review article, we have discussed different aspects of non-antibiotic approaches for managing and inhibiting the CR bacteria and various methods and procedures used as an alternative for carbapenems against these bacteria. [ABSTRACT FROM AUTHOR]

We report a case of a 17 year old lady who presented with severe abdominal pain for 4 days. Patient developed fulminant hepatitis and disseminated intravascular coagulation during her hospital stay. History of Ratol (3% yellow phosphorus) ingestion was revealed on the second day of admission. She was managed with NAC infusion for 3 days along with supportive treatment and was discharged on the 10th day of admission. Accidental ingestion of Ratol is common in rural India. Early diagnosis and management of yellow phosphorus can improve the outcome of the patient. It is important to identify predictors of outcome of patients with toxin-induced liver injury. [ABSTRACT FROM AUTHOR]

Empagliflozin (EMPA) is a glucose-lowering agent that is widely used for treatment of diabetes mellitus and diabetic nephropathy. This work aimed to evaluate the therapeutic and prophylactic effects of EMPA and NAC in treating nephrotoxicity caused by 5-Fluorouracil (5-FU) in male Albino Wistar rats. 48 rats were divided into 6 groups: The first group used as negative control. The second received 20 mg/kg of 5-FU intraperitoneally for 6 days. The third group received 5-FU plus 10 mg/kg EMPA orally for 10 days. The fourth group received EMPA 10 days before the injection of 5-FU. The fifth group received 5-FU plus N-acetylcysteine (NAC) 40 mg/kg. The sixth group received 5-FU, NAC plus EMPA. Biochemical evaluation for urea, creatinine, uric acid, albumin, TNF-a and IL-1ß in serum and GSH and MDA in renal homogenate were done. Histopathological examination of kidneys was done with immunohistochemical analysis of caspase-3. The nephrotoxic effect of 5-FU was characterized by elevation of creatinine, urea, uric acid, MDA, TNF-a and IL-1ß with reduction of albumin and GSH. EMPA caused improvement in kidney status especially when used therapeutically or with NAC. The immunohistochemical analysis showed that EMPA caused a reduction in the expression of caspase-3. EMPA is an effective drug in cases of 5-FU induced nephrotoxicity. It is more effective when used as a treatment rather than a prophylactic strategy. The effect of EMPA is enhanced when combined with NAC. EMPA nephroprotective effect is mediated via antioxidant, antiinflammatory effects and by decreasing the expression of renal caspase-3. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Huppke–Brendel syndrome (HBS) is an autosomal recessive disorder caused by SLC33A1 mutations, a gene coding for the acetyl‐CoA transporter‐1 (AT‐1). So far it has been described in nine pediatric and one adult patient. Therapeutic trials with copper histidinate failed to achieve any clinical improvement. Here, we describe the clinical characteristics of two novel patients, one of them diagnosed by gene analysis and his sib postmortally based on clinical characteristics. We demonstrate a therapeutic trial with acetylation therapy, consisting of N‐acetylcysteine and ketogenic diet, in one of them. We provide biochemical data on N‐acetylated amino acids in cerebrospinal fluid (CSF) and plasma before and after starting this treatment regimen. Our results indicate that ketogenic diet and N‐acetylcysteine do not seem to normalize the concentrations of N‐acetylated amino acids in CSF or plasma. The overall metabolic pattern shows a trend toward lowered levels of N‐acetylated amino acids in CSF and to a lesser extent in plasma. Although there are some assumptions, the function of AT‐1 is still not clear and further studies are needed to better understand mechanisms underlying this complex disorder.

Background: Ischemic stroke (IS) is still a major cause of neurological disability. This study aimed to ascertain potential markers closely related to IS diagnosis and treatment and then we examined the neuroprotective effect of N-acetylcysteine (NAC) in a transient cerebral ischemia. Methods: Male Wistar rats were randomly divided into three groups (n=6), including sham, IR (ischemia-reperfusion), IR+NAC (150 mg/kg, ip; intraperitoneally, 1 hour prior to ischemia and 5 min before reperfusion). The infarct volume was evaluated by 2,3,5-triphenyl tetrazolium chloride staining. H&E and Nissle staining were performed to evaluate cerebral ischemia-reperfusion injury. miR-374a-5p gene expression, MAPK6, NLRP3, smad6, TNF-α, and IL-1β protein levels were determined by Real-time PCR, Western blot, and Elisa in the cerebral cortex exposed to IR. Results: Herein, we found that IR increased infarct volume and pathological damage to the cerebral cortex after global cerebral artery occlusion/reperfusion. In addition, miR-374a-5p gene expression decreased, while MAPK6, NLRP3, and smad6 protein expressions increased in the IR group. TNF-α and IL-1β protein levels increased in the ischemic cortex. Treatment with NAC significantly attenuated infarct size, inflammation and reversed aforementioned molecule levels. Conclusion: Taken together, these results suggested that ischemic insult can increase infarct size, neuronal damage, and inflammation may in part by modulating miR-374a-5p, MAPK6, NLRP3, and smad6 pathway in the brain cortex after cerebral IR insult and providing new clues to molecular mechanisms and treatment targets in IS. It can be alleviated by NAC as a potential therapy for someone afflicted with ischemia.

Aims and Objectives: The incidence of postoperative liver dysfunction is high in patients undergoing double-valve replacement – mitral and aortic valve replacement (DVR). This study aims to evaluate N-acetylcysteine’s free radical scavenging property (NAC) to prevent postoperative liver dysfunction in these patients, thus affecting overall clinical outcomes. Methods: A single-center, prospective, randomized, double-blinded interventional study of 60 patients divided into two groups of 30 each. Group N received prophylactic intravenous NAC, and Group C received volume-matched 5% dextrose. Data comprised demographics, liver function tests (LFT), renal function tests (RFT), vasoactive-inotropic scores (VIS) score, and C-reactive protein (CRP) at various time intervals. Postoperative parameters such as ventilation duration, length of stay in ICU (LOS-ICU), length of hospital stay (LOHS), atrial fibrillation (AF), acute kidney injury (AKI) requiring hemodialysis, and mortality were noted. Statistical analysis was performed with the Student’s t-test and Chi-square test (SPSS 22 software). Results: All postoperative LFT parameters (total bilirubin, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate transaminase (SGPT), and alkaline phosphatase (ALP)) were significantly lower (P < 0.05) at 24, 48, and 72 hours in Group N compared to Group C. RFT and VIS scores were lower in Group N; however, were not statistically significant except for Serum Creatinine at 48 hours (P = 0.0478). Ventilation duration (P = 0.0465) and LOS-ICU (P = 0.0431) were significantly lower in Group N. Other outcomes like AF, LOHS, and mortality were lower in Group N but were not statistically significant. Conclusion: Our study showed that prophylactic administration of NAC in patients undergoing DVR is associated with a reduction in the incidence of postoperative liver dysfunction with a positive impact on postoperative outcomes.

Paola Rogliani,1 Gian Marco Manzetti,1 Shima Gholamalishahi,1 Mario Cazzola,1 Luigino Calzetta2 1Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Rome, Italy; 2Respiratory Disease and Lung Function Unit, Department of Medicine and Surgery, University of Parma, Parma, ItalyCorrespondence: Paola Rogliani, Unit of Respiratory Medicine, Department of Experimental Medicine, University of Rome “Tor Vergata”, Via Montpellier 1, Rome, 00133, Italy, Email paola.rogliani@uniroma2.itAbstract: Mucus clearance is crucial for airway protection, and its dysfunction leads to chronic obstructive pulmonary disease (COPD) characterized by mucus hypersecretion (MHS) and impaired clearance. MUC5AC and MUC5B mucin proteins are key components of airway mucus, with MUC5AC being particularly responsive to environmental stimuli, making it a potential COPD biomarker. N-acetylcysteine (NAC) is a mucolytic agent with known effects on mucus viscosity and clearance, but its precise mechanisms in COPD remain unclear. This systematic review evaluated the impact of NAC on MHS in the airways, reporting significant inhibitory effects on MUC5AC and MUC5B gene and protein expression, as well as a reduction in the number of goblet cells. NAC has demonstrated efficacy in vitro and in animal models of MHS, including COPD models, but data on human bronchial tissue are lacking. This systematic review suggests that NAC acts as a mucolytic and a mucoregulator, directly inhibiting mucus secretion and goblet cell hyperplasia. Given the critical role of MHS in COPD progression, exacerbations, and mortality, these findings highlight the potential of NAC as a targeted therapy for hypersecretion COPD phenotypes. However, further studies are needed to confirm the results of this systematic review, even in human bronchial tissue, to provide translatable evidence in clinical settings. Understanding the intimate mechanism of NAC versus MHS regulation may pave the way for more effective treatments targeting airway mucus dysfunction in COPD, ultimately improving patient outcomes and reducing morbidity and mortality associated with chronic mucus hypersecretion.Keywords: COPD, mucus hypersecretion, N-acetylcysteine, systematic review

Abstract Background Polycystic ovary syndrome (PCOS) affects 6–20% of women worldwide, with insulin resistance and hyperinsulinemia occurring in 50-70% of patients. Hyperinsulinemia exacerbates oxidative stress, contributing to PCOS pathogenesis. N-acetylcysteine (NAC) is an antioxidant and insulin sensitizer that shows promise as a therapeutic for PCOS. Our current study aimed to investigate the effects of NAC supplementation on endocrine-metabolic parameters in PCOS mice and its effect on ovulation induction (OI) efficacy in women with PCOS. Methods Female C57BL/6 mice were orally administered letrozole (LE) to induce PCOS and then randomly divided into groups receiving daily oral administration of 160 mg/kg NAC (PCOS + NAC group), 200 mg/kg metformin (PCOS + Met group), or 0.5% carboxymethyl cellulose (drug solvent) (pure PCOS group) for 12 days. Healthy female mice served as pure controls. Estrous cycles were monitored during the intervention. Metabolic and hormone levels, ovarian phenotypes, antioxidant activity in ovarian tissues, and oxidative stress levels in oocytes were assessed post-intervention. Furthermore, a pragmatic, randomized, controlled clinical study was conducted with 230 PCOS women, randomly assigned to the NAC group (1.8 g/day oral NAC, n = 115) or the control group (n = 115). Patients in both groups underwent ≤ 3 cycles of OI with sequential LE and urinary follicle-stimulating hormone (uFSH). Cycle characteristics and pregnancy outcomes were compared between groups. Results Similar to metformin, NAC supplementation significantly improved the estrous cycles and ovarian phenotypes of PCOS mice; reduced the LH concentration, LH/FSH ratio, and T level; and increased glucose clearance and insulin sensitivity. Notably, NAC significantly reduced oocyte ROS levels and increased the mitochondrial membrane potential in PCOS mice. Additionally, NAC significantly enhanced enzymatic and nonenzymatic antioxidant activities in PCOS mouse ovaries, whereas metformin had no such effect. In the clinical trial, compared to women in the control group, women receiving NAC had significantly lower average uFSH dosage and duration (p

Abstract 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)

Due to the shared phenomenology and research findings related to disorders like obsessive-compulsive disorder (OCD), trichotillomania (TTM), body dysmorphic disorder (BDD), skin picking disorder (SPD), hoarding disorder (HD), and OCD, these conditions are collectively classified as Obsessive-Compulsive and Related Disorders (OCRDs) in the DSM-5. Despite having distinct features from OCD in terms of course and treatment outcomes, they are categorized together. The etiology of OCRDs remains incompletely understood, and information on their treatment is limited. Traditional pharmacological approaches often fall short in addressing the needs of many OCRD patients, necessitating alternative strategies. Recent research has shed light on a potential imbalance in glutamate, a crucial excitatory neurotransmitter in the brain, among certain patients with OCRDs. Findings from these studies suggest that glutamate modulators may be beneficial for individuals who do not respond to standard pharmacotherapeutic interventions. While no glutamate modulator has conclusively proven effective for OCD, promising results have been noted for memantine and riluzole. The evidence surrounding N-acetylcysteine (NAC) also positions it as a reasonable consideration for some patients. Noteworthy research on D-cycloserine (DCS) and ketamine has indicated potential benefits, and investigations into the off-label use of these pharmacological agents, originally approved for other indications, have been particularly focused on refractory OCRDs. It is essential to highlight that these drugs operate through diverse and, in some cases, opposing mechanisms. However, it is crucial to acknowledge that the existing studies on the use of these drugs in OCRDs are still insufficient. A more in-depth exploration of glutamate imbalance in the etiology of OCRDs is needed to better understand the role of glutamate modulators in treatment.

Abstract 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.

Urinary tract infections (UTIs) are the most common bacterial infections in children, occurring both in children with normal urinary tracts and in ones with urinary tract abnormalities. Children with UTIs can present relevant clinical symptoms and risk long-term consequences. Current recommended preventive measures include chemoprophylaxis and dietary supplements such as cranberry, probiotics and vitamins A and E. Although chemoprophylaxis still represents the gold standard, it raises concerns about antimicrobial resistance. N-acetylcysteine (NAC), a precursor of the antioxidant glutathione, has been proven both to inhibit biofilm formation and to destroy developed biofilms. In adults, NAC has been demonstrated to prevent UTIs and to improve the effect of antibiotics, but so far it has not been analyzed as an antimicrobial option for pediatric UTIs. In this work, we aim to discuss the current applications of NAC in adult urology and its future possible evolutions in pediatric urology.

Objective(s): To investigate the protective effect of N-acetylcysteine (NAC) on septic acute kidney injury (SAKI) via regulating Sirtuin3 (SIRT3)-mediated mitochondrial dysfunction and apoptosis.Materials and Methods: By constructing SIRT3 knockout mice and culturing kidney tubular epithelial cells (KTECs), we assessed the changes of renal function and detected the protein expression of adenine nucleotide translocator (ANT), cyclophilin (CypD) and voltage-dependent anion channel (VDAC) using western-blotting, and simultaneously detected toll-like receptor 4 (TLR4), inhibitor of kappa B kinase (IKKβ), inhibitor of Kappa Bα (IκBα), and p65 protein expression. We observed mitochondrial damage of KTECs using a transmission electron microscope and assessed apoptosis by TdT-mediated dUTP Nick-End Labeling and flow cytometry. Results: SIRT3 deficiency led to the deterioration of renal function, and caused a significant increase in inducible nitric oxide synthase production, a decrease in mitochondrial volume, up-regulation of TLR4, IκBα, IKKβ, and p65 proteins, and up-regulation of ANT, CypD and VDAC proteins. However, NAC significantly improved renal function and down-regulated the expression of TLR4, IκBα, IKKβ, and p65 proteins. Furthermore, SIRT3 deficiency led to a significant increase in KTEC apoptosis, while NAC up-regulated the expression of SIRT3 and inhibited apoptosis.Conclusion: NAC has a significant protective effect on SAKI by inhibiting SIRT3-mediated mitochondrial dysfunction and apoptosis of KTECs.

Background: N-acetyl cysteine (NAC) appears promising as a treatment in patients with substance use disorder (SUD) as it helps rebalance glutamate levels in the central nervous system (CNS). Basal concentrations of glutamate are indeed reduced in SUD patients but increased during craving. Materials and Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). We assessed whether NAC reduce craving rating as compared to a placebo in SUD patients. Secondary outcomes were withdrawal symptoms (WS), side effects (SE) and drop-outs. Estimates are presented as standardized mean differences (SMD) or risk ratio (RR) with 95% confidence interval (CI). Results: Eleven RCTs were included. NAC reduced craving rating (SMD -0.61 (-1.17, -0.06), p = 0.03, I2 = 85%), with no differences in the subgroup analysis according to the drug addiction (alcohol, cocaine, poly-drugs, amphetamine, nicotine) (p = 0.98). Among the secondary outcomes, for WS data showed no significant difference between groups (SMD -0.18 (-0.43, 0.08), p = 0.17); for SE no substantial difference was observed between the two treatment groups (RR = 1.06 (0.89-1.27), p = 0.52, I2 = 0%); for dropouts the results are in favor of the placebo but no statistically significant (RR 1.17 (0.85, 1.61), p = 0.34; I2 = 0%). Conclusion: NAC seem to reduce craving rating in SUD patients, but evidence is weak. More studies are needed to confirm this finding. [ABSTRACT FROM AUTHOR]

Background: Alcohol craving is related to problematic alcohol use; therefore, pharmacotherapies that modulate alcohol craving are of interest. N‐acetylcysteine, an over‐the‐counter antioxidant, is a candidate pharmacotherapy for adolescent alcohol use with the potential to impact craving. Cue‐reactivity paradigms using functional magnetic resonance imaging (fMRI) can identify neural regions implicated in craving and serve as a screening tool for novel pharmacotherapy options. Methods: This preliminary study examined the effect of N‐acetylcysteine on neural reactivity to alcohol cues and subjective craving among 31 non‐treatment‐seeking adolescents (17.6–19.9 years old, 55% female) who use alcohol heavily. In a randomized cross‐over design, participants completed three fMRI sessions: baseline and after a 10‐day course of N‐acetylcysteine (1200 mg twice daily) and matched placebo. The primary outcome was neural response to alcohol versus non‐alcohol beverage cues after N‐acetylcysteine versus placebo, with a secondary outcome of self‐reported subjective craving. Results: In the full sample (n = 31), there was no effect of N‐acetylcysteine versus placebo on neural alcohol reactivity (ps ≥ 0.49; ηp2s = 0.00–0.07) or self‐reported acute alcohol craving (p = 0.18, ηp2 = 0.06). However, N‐acetylcysteine did reduce self‐reported generalized alcohol craving (p = 0.03, ηp2 = 0.15). In a subsample of youth who met criteria for past‐year alcohol use disorder (n = 19), results remained unchanged. Conclusions: N‐acetylcysteine may not alter neural reactivity to alcohol cues or acute craving; however, it may reduce general subjective alcohol craving among adolescents who consume alcohol heavily. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) are the most common bacterial infections in children, occurring both in children with normal urinary tracts and in ones with urinary tract abnormalities. Children with UTIs can present relevant clinical symptoms and risk long-term consequences. Current recommended preventive measures include chemoprophylaxis and dietary supplements such as cranberry, probiotics and vitamins A and E. Although chemoprophylaxis still represents the gold standard, it raises concerns about antimicrobial resistance. N-acetylcysteine (NAC), a precursor of the antioxidant glutathione, has been proven both to inhibit biofilm formation and to destroy developed biofilms. In adults, NAC has been demonstrated to prevent UTIs and to improve the effect of antibiotics, but so far it has not been analyzed as an antimicrobial option for pediatric UTIs. In this work, we aim to discuss the current applications of NAC in adult urology and its future possible evolutions in pediatric urology. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the efficacy of N-acetylcysteine as an adjuvant therapy in chronic obstructive pulmonary disease (COPD) with pulmonary interstitial fibrosis (PIF), and its effect on inflammatory factors and serum vascular endothelial growth factor (VEGF) levels. Methods: A total of 94 patients with COPD-PIF from May 2020 to May 2022 in Wuhan Fourth Hospital, China were equally randomized into study and control groups. Control group was administered conventional treatment while the study group was given N-acetylcysteine in addition to conventional treatment. Therapeutic efficacy, forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC, blood gas, pulmonary fibrosis, and oxidative stress were evaluated. Changes in inflammatory factors, serum vascular endothelial growth factor (VEGF), and incidence of adverse drug reactions were compared. Results: The study group showed significantly higher efficacy, FEV1, FVC, FEV1/FVC compared to control group (p < 0.05). Also, study group showed significantly higher partial pressure of oxygen (PaO2), blood oxygen saturation, superoxide dismutase (SOD), and glutathione (GSH) levels after treatment compared to control group (p < 0.05). Platelet-derived growth factor (PDGF), transforming growth factor (TGF-ß), vascular cell adhesion molecule (VCAM), tumor necrosis factor (TNF), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) levels after treatment were significantly lower in the study group than in the control group (p < 0.05). Conclusion: N-acetylcysteine as an adjuvant therapy for COPD-IF is highly effective, improves lung function and oxidative stress, reduces airway inflammation, and VEGF, and attenuates the degree of hypoxia and pulmonary fibrosis with no serious adverse effects. A larger sample size, multicenter, randomized trials to validate these findings and evaluate the downstream regulatory mechanism of Nacetylcysteine in COPD-PIF. [ABSTRACT FROM AUTHOR]

In connection with the requirements of international and national organizations to comply with ethical principles for experiments using animals, alternative test systems are being sought and tested to replace animals in ecological, toxicological, and genotoxicological studies. One such alternative may be the nematode Caenorhabditis elegans, which has a biotransformation system of chemical compounds similar to the mammalian system. The genotoxicity of the pesticide paraquat and the antibacterial agent furacilin was studied on C. elegans by horizontal gel electrophoresis of total DNA in order to assess its integrity. It has been shown that paraquat in concentrations of 0.01 to 0.05 mol/L and furacilin in concentrations of 0.0001 and 0.00025 mol/L caused DNA breaks in nematode cells. The antioxidant N-acetylcysteine at a concentration of 0.01 mol/L reduced the genotoxicity of both compounds. [ABSTRACT FROM AUTHOR]

Oxidative stress results from an imbalance between the production and accumulation of reactive oxygen species (ROS), which can impede plant growth under various environmental stresses. While waterlogging is a well-known inducer of oxidative stress, the effects of oxidative stress on plant roots grown using the deep flow technique (DFT) hydroponic system remain poorly understood. In this study, we demonstrate that N-acetylcysteine (NAC) enhances the growth of lettuce seedlings transplanted into a DFT system. NAC application significantly improved both shoot and root growth, with the most pronounced effects observed at a concentration of 0.3 mM. Moreover, NAC mitigated the accumulation of hydrogen peroxide in roots following transplantation. It also reduced a temporary increase in lipid peroxidation and total phenolic content in both roots and shoots. These results suggest that NAC functions as an antioxidant, alleviating oxidative stress by scavenging hydrogen peroxide in the roots. Importantly, NAC's protective effects may extend to other hydroponically grown crops, offering broader potential for reducing oxidative stress across various cultivation systems. [ABSTRACT FROM AUTHOR]

Group B Coxsackieviruses (CVB) are one of the causative pathogens of myocarditis, which may progress to cardiomyopathy. The pathogenesis of CVB is not fully understood, and effective antiviral therapy is not available. N-acetylcysteine (NAC), the classic antioxidant, has been used in clinical practice for several decades to treat various medical conditions. In this study, the anti-CVB effect of NAC was investigated. We show that NAC dramatically suppressed viral replication and alleviated cardiac injury induced by CVB3. To further study the antiviral mechanism of NAC, RNA-sequencing was performed for CVB3-infected cells with NAC treatment. We found that eukaryotic elongation factor 1 alpha 1 (EEF1A1) is one of the most upregulated genes in CVB3-infected cells. However, EEF1A2, the highly homologous isoform of EEF1A1, remains unchanged. EEF1A1 expression was significantly suppressed by NAC treatment in CVB3-infected cells, while EEF1A2 was not affected. eEF1A1 knockdown significantly inhibited CVB3 replication, implicating that eEF1A1 facilitates viral replication. Importantly, we show that eEF1A1, which was not expressed in the myocardia of newborn mice, was significantly upregulated by CVB3 infection. NAC markedly downregulated the expression of eEF1A1 but not eEF1A2 in the myocardia of CVB3-infected mice. Furthermore, NAC accelerated eEF1A1 degradation by promoting autophagy in CVB3-infected cells. We show that p62, one of the critical adaptors of autophagic targets, interacts with eEF1A1 and was downregulated in CVB3-infected cells upon NAC treatment. Taken together, this study demonstrated that NAC shows a potent anti-CVB effect through the downregulation of eEF1A1. [ABSTRACT FROM AUTHOR]

Background: Many clinicians prescribe antifungal agents to treat canine otitis externa (OE). However, studies evaluating the antifungal effects of N‐acetylcysteine (NAC) and its combinations are limited. Hypothesis/objectives: The aim of this study was to evaluate the antifungal effects of NAC alone and in combination with other antifungal agents against Malassezia pachydermatis isolated from canine OE. Materials and methods: M. pachydermatis samples were collected from 13 dogs with OE. The final concentration of the inoculum suspensions of M. pachydermatis was 1–5 × 106 colony forming units/mL. The concentrations of the test compounds ketoconazole (KTZ), terbinafine (TER), nystatin (NYS) and NAC were 0.02–300 µg/mL, 0.04–80 µg/mL, 0.16–40 µg/mL and 1.25–20 mg/mL, respectively. The minimum inhibitory concentration (MIC) was measured to evaluate the susceptibility of the M. pachydermatis to KTZ, TER, NYS and NAC. The checkerboard testing method and fractional inhibitory concentration index were used to evaluate the effect of NAC in combination with KTZ, TER and NYS against M. pachydermatis. Results: The MIC90 values of M. pachydermatis were 4.6875–9.375 µg/mL, 1.25 µg/mL, 5–10 µg/mL and 10 mg/mL for KTZ, TER, NYS and NAC, respectively. The synergistic effects of KTZ, TER and NYS with NAC were identified in 0/13, 2/13 and 0/13 isolates, respectively. Conclusions and clinical relevance: NAC had an antifungal effect against M. pachydermatis but did not exert synergistic effects when used with KTZ, TER and NYS. Thus, the use of NAC alone as a topical solution could be considered an effective treatment option for canine OE involving M. pachydermatis. [ABSTRACT FROM AUTHOR]

Myocardial reperfusion injury (MRI) accounts for up to 50% of the final size in acute myocardial infarction and other conditions associated with ischemia‐reperfusion. Currently, there is still no therapy to prevent MRI, but it is well known that oxidative stress has a key role in its mechanism. We previously reduced MRI in rats through a combined antioxidant therapy (CAT) of ascorbic acid, N‐acetylcysteine, and deferoxamine. This study determines the safety and pharmacokinetics of CAT in a Phase I clinical trial. Healthy subjects (n = 18) were randomized 2:1 to CAT or placebo (NaCl 0.9% i.v.). Two different doses/infusion rates of CATs were tested in a single 90‐minute intravenous infusion. Blood samples were collected at specific times for 180 minutes to measure plasma drug concentrations (ascorbic acid, N‐acetylcysteine, and deferoxamine) and oxidative stress biomarkers. Adverse events were registered during infusion and followed for 30 days. Both CAT1 and CAT2 significantly increased the CAT drug concentrations compared to placebo (P <.05). Most of the pharmacokinetic parameters were similar between CAT1 and CAT2. In total, 6 adverse events were reported, all nonserious and observed in CAT1. The ferric‐reducing ability of plasma (an antioxidant biomarker) increased in both CAT groups compared to placebo (P <.001). The CAT is safe in humans and a potential treatment for patients with acute myocardial infarction undergoing reperfusion therapy. [ABSTRACT FROM AUTHOR]

N‐acetylcysteine (NAC) is regarded as an effective treatment of paracetamol overdoses. However, in cases of "massive" paracetamol overdoses, recent studies indicate that patients may not be sufficiently treated with the standard dose of NAC (300 mg/kg over 20–21 h). The subject is further complicated because "massive overdoses" and "high‐risk" are defined differently; some studies use the ingested amount (e.g., >40 g), and some studies use blood concentrations of paracetamol and transaminases. This narrative review investigates whether high‐dose NAC significantly decreases the risk of hepatotoxicity in patients with massive paracetamol overdoses. Three observational studies were analysed; one study with 373 patients found no significant difference (odds ratio [OR]: 1.27, 95% confidence interval [CI]: 0.49–3.29). One study with 79 patients found a significant difference (OR: 0.27, 95% CI: 0.08–0.94). The third study with 89 patients found a significant difference in hepatoxicity between the groups (p = 0.043). There are no solid evidence to support that treatment with high‐dose NAC significantly reduces the rate of hepatotoxicity in patients presenting with massive paracetamol overdoses. Differences in inclusion criteria in the included studies make the studies incomparable. This paper shows that standardized inclusion is needed to determine whether a high‐dose NAC regimen should be included in clinical practice. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ochratoxin A (OTA) is a type of mycotoxin commonly found in raw and processed foods. It is essential to be aware of this toxin, as it can harm your health if consumed in high quantities. OTA can induce toxic effects in various cell models. However, a more comprehensive understanding of the harmful effects of OTA on human astrocytes is required. This study evaluated OTA's neurotoxic effects on the Gibco® Human Astrocyte (GHA) cell line, its underlying mechanisms, and the antioxidant N‐acetylcysteine (NAC) ability to prevent them. OTA exposure within 5–30 μM has induced concentration‐dependent cytotoxicity. In the OTA‐treated cells, the levels of reactive oxygen species (ROS) were found to be significantly increased, while the glutathione (GSH) contents were found to decrease considerably. The western blotting of OTA‐treated cells has revealed increased Bax, cleaved caspase‐9/caspase‐3 protein levels, and increased Bax/Bcl‐2 ratio. In addition, exposure to OTA has resulted in the induction of antioxidant responses associated with the protein expressions of Nrf2, HO‐1, and NQO1. On the other hand, the pretreatment with NAC has partially alleviated the significant toxic effects of OTA. In conclusion, our findings suggest that oxidative stress and apoptosis are involved in the OTA‐induced cytotoxicity in GHA cells. NAC could act as a protective agent against OTA‐induced oxidative damage. Our findings suggest that oxidative stress and apoptosis are involved in the ochratoxin A (OTA)‐induced cytotoxicity in Gibco® Human Astrocyte (GHA) cells. N‐acetylcysteine (NAC) could act as a protective agent against OTA‐induced oxidative damage. This study has reported that NAC could alleviate the OTA‐induced cytotoxicity in GHA cells for the first time. It has also elucidated some of its mechanisms, providing a new perspective for treating OTA‐induced neurotoxicity. [ABSTRACT FROM AUTHOR]

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. Conclusion: In this study, we have established the effectiveness and safety of nebulized NAC over 12 weeks. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the influence of N-acetylcysteine (NAC) aerosol inhalation on serum inflammatory factors and immune function in children with upper airway cough syndrome (UACS). Methods: 118 children with UACS who were on admission at Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, China between September 2021 and February 2023, were enrolled in the study. They were assigned to control and study cohorts, with 59 patients per group. Control group received routine treatment (3 mL of normal saline via nebulized inhalation 2 times/day), while the study group received 3 mL of NAC aerosol inhalation via nebulized inhalation 2 times/day. Both groups were treated for 2 weeks. Thereafter, the two groups were compared with respect to total treatment effectiveness, cough symptom and Lund-Kennedy ratings, levels of inflammatory factors (interleukin-13 (IL-13), interleukin-27 (IL-27), C-reactive protein (CPR)) and concentrations of immune function indices (CD3 +, CD4 + and CD8 +) before and after treatment, and adverse reactions. Results: Treatment effectiveness (efficacy) was significantly higher (p < 0.05) in study cohort than in control cohort (89.83 vs 71.19 %). The 2 cohorts had significant reductions in scores on cough symptoms and Lund-Kennedy, with smaller values in study cohort. In both groups, the levels of IL-13 and CPR were decreased, while IL-27 level was increased. Levels of IL-13 and CPR in study group were significantly lower than those in control group, while IL-27 level was significantly higher than that in control group (p < 0.05). Conclusion: N-acetylcysteine aerosol inhalation enhances curative effect, relieves clinical symptoms, reduces inflammation, and improves immunity in UACS children, and shows good degree of safety. However, its long-term efficacy needs to be studied. [ABSTRACT FROM AUTHOR]

The research aims to determine the effect of high-dose administration of N-acetylcysteine by 5000 mg iv on kidney function in patients diagnosed with AKI based on creatinine serum, GFR, and urea. The research was a descriptive-analytic with retrospective cross- sectional. Further, the research employed medical data records. Differential analysis of kidney function with the laboratory results of urea, creatinine, and GFR parameters in AKI patients. It was performed on both the control and the testes groups, pre- and post- administration of a high-dose of N-acetylcysteine by 5000 mg iv. In addition, data were analyzed by bivariate with the paired t-test and independent t-test for differences between groups at p ≤ 0.05. There were 60 total samples, which were divided into 30 AKI patients, administered with N-acetylcysteine, and 30 patients, treated with N-acetylcysteine. The relationship analysis of pre-and post-administration of N-acetylcysteine in each group demonstrated significant differences in the tested group, such as the values of Creatinine Serum (p = 0.002) and GFR (p = 0.001). Meanwhile, the results of the differential test between the two groups show that there was a significant difference in the difference values of creatinine serum, such as (p=0.003), and the difference values of GFR, such as (p=0.014). These results depict that there was a significant difference in the improvement of kidney function between the group of patients, who were administered with N-acetylcysteine (the tested group), and the group of patients, who were not administered with N-acetylcysteine (the controlled group). It was seen from the values of SCr and GFR. However, the tested group provided a better-improving effect on kidney function than the controlled group. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Exogenous, well‐established antioxidant N‐acetylcysteine can reduce or prevent the deleterious effects of pesticides. In this study, utilizing a mouse model of daily single dose of N‐acetylcysteine administration, we investigated the impact of this adjuvant on the treatment with atropine and/or obidoxime as well as oxidative stress response in pyrimiphos‐methyl‐induced toxicity. We found that N‐acetylcysteine significantly reduces the oxidative stress generated by pyrimiphos‐methyl. The therapy consisting of atropine and/or obidoxime routinely used in organophosphorous insecticide poisonings, including pyrimiphos‐methyl, had no effect on the antioxidant properties of N‐acetylcysteine. Adjunctive treatment offered by N‐acetylcysteine fills therapeutic gap and may provide the full potential against pyrimiphos‐methyl‐induced toxicity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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-1β). 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. [ABSTRACT FROM AUTHOR]

Chemotherapy is an effective treatment for cancer, but it can cause cognitive disorders broadly referred to as “chemobrain.” One of the most commonly used chemotherapeutics, doxorubicin (DOX), has been associated with the potential for brain damage and cognitive dysfunction. N-acetylcysteine (NAC) has been identified as a potential brain protector with antiapoptotic, antioxidant, and anti-inflammatory effects. The objective of this study was to investigate the potential protective effect of NAC against DOX-induced brain damage. Female Wistar albino rats were randomly assigned to one of three groups: control, DOX, or NAC prophylaxis. Brain samples were collected for histopathological and immunohistochemical analyses, with a particular focus on regions that are crucial for cognition and memory. The DOX group exhibited significant histopathological changes, including neuronal shrinkage, degeneration, and necrosis in the striatum, hippocampal region, and cerebral cortex. Immunohistochemical analysis revealed the presence of neuroinflammation and neurodegeneration, with an increase in inducible nitric oxide synthetase (iNOS) immunopositivity. Administration of NAC effectively reduced iNOS immunopositivity, neuronal damage, degeneration, and necrosis in the prophylaxis group. Among the brain regions examined, the prophylaxis group demonstrated the most effective protection in the hippocampal region. Therefore, NAC has the potential to protect against or alleviate DOX-induced cognitive impairments. [ABSTRACT FROM AUTHOR]

Sunflower oil cake (SFC), a by-product of oil manufacturing, possesses a high protein content but is often disregarded due to its undesirable green color caused by phenolic compounds (PCs) during alkaline extraction. This study aimed at improving the color of extracted sunflower protein concentrate (SPC) without eliminating the PCs by employing two anti-greening additives, ascorbic acid (ASC) and N-acetylcysteine (NAC), at different concentrations (4, 8, and 12 mg/g meal) during extraction. Moreover, the effects of these additives on the chemical, structural, and functional properties of extracted proteins were assessed. The results showed that the SPC extracted without additives (control) and with 4 and 8 mg/g additives exhibited green color, while the most significant greening inhibition was attained with 12 mg/g of either ASC or NAC. All the extraction solutions resulted in SPC with comparable water solubility exceeding 90% and minor variations in the secondary structure, hydrophobicity, and thermal stability of the proteins. All extracted SPCs demonstrated substantial antioxidant activity, adding nutritional benefits to the protein concentrates. In conclusion, incorporating ASC and NAC during the alkaline extraction process proved to be an effective strategy for producing sunflower protein concentrate with improved color and acceptable functional properties. This approach offers the food industry an opportunity to reduce reliance on expensive protein sources, such as soy protein isolates, and paves the way for sustainable utilization of sunflower oil cake as a valuable and versatile protein ingredient in various food applications. [ABSTRACT FROM AUTHOR]