N-acetylcysteine Research Articles

Sirt7 protects against vascular calcification via modulation of reactive oxygen species and senescence of vascular smooth muscle cells

Vascular calcification is frequently seen in patients with chronic kidney disease (CKD), and significantly increases cardiovascular mortality and morbidity. Sirt7, a NAD+-dependent histone deacetylases, plays a crucial role in cardiovascular disease. However, the role of Sirt7 in vascular calcification remains largely unknown. Using in vitro and in vivo models of vascular calcification, this study showed that Sirt7 expression was significantly reduced in calcified arteries from mice administered with high dose of vitamin D3 (vD3). We found that knockdown or inhibition of Sirt7 promoted vascular smooth muscle cell (VSMC), aortic ring and vascular calcification in mice, whereas overexpression of Sirt7 had opposite effects. Intriguingly, this protective effect of Sirt7 on vascular calcification is dependent on its deacetylase activity. Unexpectedly, Sirt7 did not alter the osteogenic transition of VSMCs. However, our RNA-seq and subsequent studies demonstrated that knockdown of Sirt7 in VSMCs resulted in increased intracellular reactive oxygen species (ROS) accumulation, and induced an Nrf-2 mediated oxidative stress response. Treatment with the ROS inhibitor N-acetylcysteine (NAC) significantly attenuated the inhibitory effect of Sirt7 on VSMC calcification. Furthermore, we found that knockdown of Sirt7 delayed cell cycle progression and accelerated cellular senescence of VSMCs. Taken together, our results indicate that Sirt7 regulates vascular calcification at least in part through modulation of ROS and cellular senescence of VSMCs. Sirt7 may be a potential therapeutic target for vascular calcification.

N-Acetylcysteine Alleviates Necrotizing Enterocolitis by Depressing SESN2 Expression to Inhibit Ferroptosis in Intestinal Epithelial Cells.

Abstract-Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease in neonates, and effective strategies to prevent and treat NEC are still lacking. Studies have shown that N-acetylcysteine (NAC) has protective effects against NEC, however, the specific mechanism underlying its effects on intestinal functions remains unclear. Recently, NAC has been shown to suppress ferroptosis in many diseases, while it is unclear whether the beneficial effects of NAC on NEC are related to ferroptosis. In this study, we revealed that ferroptosis was significantly induced in intestinal samples from infants with NEC. NAC alleviated intestinal inflammation, barrier damage and ferroptosis in multifactorial NEC models in vivo and in vitro. Sestrin2 (SESN2) was identified as an important mediator of NAC-induced ferroptosis resistance in intestinal epithelial cells. Furthermore, SESN2 knockdown inhibited the inflammatory response, alleviated barrier damage and ferroptosis in intestinal epithelial cells and enhanced the protective effects of NAC to a certain extent. Conversely, cells overexpressing SESN2 showed the opposite changes. In summary, our study demonstrated that NAC attenuates NEC progression by decreasing SESN2 expression to inhibit ferroptosis in intestinal epithelial cells, suggesting that NAC might be an effective clinical treatment for NEC.

Microtubule depolymerization induces ferroptosis in neuroblastoma cells.

Estramustine (EM), a clinically successful hormone-refractory anti-prostate cancer drug, exhibited potent anti-proliferative activity, depolymerized microtubules, blocked cells at mitosis, and induced cell death in different cancer cells. Altered iron metabolism is a feature of cancer cells. Using EM, we examined the plausible relationship between microtubule depolymerization and induction of ferroptosis in human neuroblastoma (SH-SY5Y and IMR-32) cells. EM reduced glutathione (GSH) levels and induced reactive oxygen species (ROS) generation. The pre-treatment of neuroblastoma cells with ROS scavengers (N-acetyl cysteine and dithiothreitol) reduced the anti-proliferative effects of EM. EM treatment increased labile iron pool (LIP), depleted glutathione peroxidase 4 (GPX4) levels, and lipid peroxidation, hallmark features of ferroptosis, highlighting ferroptosis induction. Ferroptosis inhibitors (deferoxamine mesylate and liproxstatin-1) abrogated the cytotoxic effects of EM, further confirming ferroptosis induction. Vinblastine and nocodazole also increased LIP and induced lipid peroxidation in neuroblastoma cells. This study provides evidence for the coupling of microtubule integrity to ferroptosis. The results also suggest that microtubule-depolymerizing agents may be considered for developing pro-ferroptosis chemotherapeutics.

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.

Arsenite treatment induces Hsp90 aggregatesdistinct from conventional stress granules in fission yeast.

Various stress conditions, such as heat stress (HS) and oxidative stress, can cause biomolecular condensates represented by stress granules (SGs) via liquid-liquid phase separation. We have previously shown that Hsp90 forms aggregates in response to HS and that Hsp90 aggregates transiently co-localize with SGs as visualized by Pabp. Here, we showed that arsenite, one of the well-described SG-inducing stimuli, induces Hsp90 aggregates distinct from conventional SGs in fission yeast. Arsenite induced Hsp90 granules in a dose-dependent manner, and these granules were significantly diminished by the co-treatment with a ROS scavenger N-acetyl cysteine (NAC), indicating that ROS are required for the formation of Hsp90 granules upon arsenite stress. Notably, Hsp90 granules induced by arsenite do not overlap with conventional SGs as represented by eIF4G or Pabp, while HS-induced Hsp90 granules co-localize with SGs. Nrd1, an RNA-binding protein known as a HS-induced SG component, was recruited into Hsp90 aggregates but not to the conventional SGs upon arsenite stress. The non-phosphorylatable eIF2α mutants significantly delayed the Hsp90 granule formation upon arsenite treatment. Importantly, inhibition of Hsp90 by geldanamycin impaired the Hsp90 granule formation and reduced the arsenite tolerance. Collectively, arsenite stimulates two types of distinct aggregates, namely conventional SGs and a novel type of aggregates containing Hsp90 and Nrd1, wherein Hsp90 plays a role as a center for aggregation, and stress-specific compartmentalization of biomolecular condensates.

Thiol-Mediated Enhancement of Nε-Acetyllysine Formation in Lens Proteins.

Lysine acetylation (AcK) is a prominent post-translational modification in eye lens crystallins. We have observed that AcK formation is preferred in some lysine residues over others in crystallins. In this study, we have investigated the role of thiols in such AcK formation. Upon incubation with acetyl-CoA (AcCoA), αA-Crystallin, which contains two cysteine residues, showed significantly higher levels of AcK than αB-Crystallin, which lacks cysteine residues. Incubation with thiol-rich γS-Crystallin resulted in higher AcK formation in αB-Crystallin from AcCoA. External free thiol (glutathione and N-acetyl cysteine) increased the AcK content in AcCoA-incubated αB-Crystallin. Reductive alkylation of cysteine residues significantly decreased (p < 0.001) the AcCoA-mediated AcK formation in αA-Crystallin. Introduction of cysteine residues within ∼5 Å of lysine residues (K92C, E99C, and V169C) in αB-Crystallin followed by incubation with AcCoA resulted in a 3.5-, 1.3- and 1.3-fold increase in the AcK levels when compared to wild-type αB-Crystallin, respectively. Together, these results suggested that AcK formation in α-Crystallin is promoted by the proximal cysteine residues and protein-free thiols through an S → N acetyl transfer mechanism.

Lipopolysaccharide-Induced Lysosomal Cell Death Through Reactive Oxygen Species in Rat Liver Cell Clone 9.

In sepsis, bacterial components, particularly lipopolysaccharide (LPS), trigger organ injuries such as liver dysfunction. Although sepsis induces hepatocyte damage, the mechanisms underlying sepsis-related hepatic failure remain unclear. In this study, we demonstrated that the LPS-treated rat hepatocyte cell line Clone 9 not only induced reactive oxygen species (ROS) generation and apoptosis but also increased the expression of the autophagy marker proteins LC3-II and p62, and decreased the expression of intact Lamp2A, a lysosomal membrane protein. Additionally, LPS increased lysosomal membrane permeability and galectin-3 puncta formation, and promoted lysosomal alkalization in Clone 9 cells. Pharmacological inhibition of caspase-8 and cathepsin D (CTSD) suppressed the activation of caspase-3 and rescued the viability of LPS-treated Clone 9 cells. Furthermore, LPS induced CTSD release associated with lysosomal leakage and contributed to caspase-8 activation. Pretreatment with the antioxidant N-acetylcysteine (NAC) not only diminished ROS generation and increased the cell survival rate, but also decreased the expression of activated caspase-8 and caspase-3 and increased the protein level of Lamp2A in LPS-treated Clone 9 cells. These results demonstrate that LPS-induced ROS causes lysosomal membrane permeabilization and lysosomal cell death, which may play a crucial role in hepatic failure in sepsis. Our results may facilitate the development of new strategies for sepsis management.

A Combination of Cardamonin and Doxorubicin Selectively Affect Cell Viability of Melanoma Cells: An In Vitro Study.

Treatment of the most aggressive and deadliest form of skin cancer, the malignant melanoma, still has room for improvement. Its invasive nature and ability to rapidly metastasize and to develop resistance to standard treatment often result in a poor prognosis. While the highly effective standard chemotherapeutic agent doxorubicin (DOX) is widely used in a variety of cancers, systemic side effects still limit therapy. Especially, DOX-induced cardiotoxicity remains a big challenge. In contrast, the natural chalcone cardamonin (CD) has been shown to selectively kill tumor cells. Besides its anti-tumor activity, CD exhibits anti-oxidative, anti-inflammatory and anti-bacterial properties. In this study, we investigated the effect of the combinational treatment of DOX with CD on A375 melanoma cells compared to normal human dermal fibroblasts (NHDF) and rat cardiac myoblasts (H9C2 cells). DOX-induced cytotoxicity was unselective and affected all cell types, especially H9C2 cardiac myoblasts, demonstrating its cardiotoxic effect. In contrast, CD only decreased the cell viability of A375 melanoma cells, without harming normal (healthy) cells. The addition of CD selectively protected human dermal fibroblasts and rat cardiac myoblasts from DOX-induced cytotoxicity. While no apoptosis was induced by the combinational treatment in normal (healthy) cells, an apoptosis-mediated cytotoxicity was demonstrated in A375 melanoma cells. CD exhibited thiol reactivity as it was able to directly interact with N-acetylcysteine (NAC) in a cell-free assay and to induce heme oxygenase-1 (HO-1) in all cell types. And that took place in a reactive oxygen species (ROS)-independent manner. DOX decreased the mitochondrial membrane potential (Δψm) in all cell types, whereas CD selectively decreased mitochondrial respiration, affecting basal respiration, maximal respiration, spare respiratory capacity and ATP production in A375 melanoma cells, but not in healthy cardiac myoblasts. The DOX-induced cytotoxicity seen in melanoma cells was ROS-independent, whereas the cytotoxic effect of CD was associated with CD-induced ROS-formation and/or its thiol reactivity. This study highlights the beneficial properties of the addition of CD to DOX treatment, which might protect patients from DOX-induced cardiotoxicity. Future experiments with other tumor cell lines or a mouse model should substantiate this hypothesis.

Use of N-Acetylcysteine in Preterm Neonates with Enteral Feeding Intolerance and Intestinal Obstruction: A Case Series and Review of the Literature.

(1) Background: The use of N-acetylcysteine (NAC) to relieve meconium obstruction of prematurity in the first days of life has been reported, with NAC reducing the viscosity of luminal contents by cleaving the disulfide bonds of mucoproteins. However, its use in this population should be further explored since it has been associated with hypernatremia and transient increase in transaminases and bilirubin. (2) Methods: In this retrospective study, we included neonates admitted because of enteral feeding intolerance and intestinal obstruction from 2019 to 2021 who received NAC as a rescue therapy before explorative laparotomy. (3) Results: We summarized the clinical presentation of six preterm neonates with enteral feeding intolerance and intestinal obstruction who received NAC as a rescue therapy. Four infants (66.7%) gradually improved without the need for explorative laparotomy, whereas two infants (33.3%) underwent the creation of an ileostomy. No cases of hypernatremia or hepatic derangement associated with NAC therapy were observed. (4) Conclusions: We described the use of NAC treatment by nasogastric tube and/or rectal enemas in preterm infants with enteral feeding intolerance and intestinal obstruction after a multidisciplinary assessment, but the limited sample size did not allow us to obtain definitive conclusions and further research is needed in this field, given the limited evidence about NAC treatment in preterm infants.

N-acetylcysteine may improve endometrial receptivity by modulating endometrial stromal cells in goats

Abstract. Endometrial receptivity is essential for successful embryo implantation and pregnancy maintenance, and the achievement of normal physiological function of endometrial stromal cells (ESCs) is an important factor in the establishment of receptivity. N-acetylcysteine (NAC) was found to be beneficial as a small-molecule antioxidant for improving animal reproductive performance, but it is unclear whether NAC can improve receptivity by modulating ESCs in goats. In this study, we successfully isolated and cultured the ESCs of Qianbei Ma goats, used different concentrations of NAC to culture the ESCs of Qianbei Ma goats, and explored the effects of NAC on the biological functions of the ESCs of Qianbei Ma goats by using CCK-8, qRT-PCR, ELISA and flow cytometry. The results showed that 200 µmol L−1 NAC may promote the proliferation of ESCs in Qianbei Ma goats by increasing the expression of PCNA, Cyclin D2 (P&lt;0.01) and Cyclin E (P&lt;0.05) mRNAs. Meanwhile, 200 µmol L−1 NAC increased the cell viability (P&lt;0.01) and enhanced the superoxide dismutase (SOD) and glutathione reductase (GR) activities (P&lt;0.01) of ESCs in Qianbei Ma goats. In addition, 200 µmol L−1 NAC increased the mitochondrial membrane potential of ESCs (P&lt;0.01). Notably, 200 µmol L−1 NAC promoted the expression of the mRNA of the endometrial receptivity marker genes HOXA10, PTGS2, PGR (P&lt;0.01) and LIF (P&lt;0.05). Thus, our results suggest that NAC may benefit the establishment of endometrial receptivity in goats by regulating the proliferation, antioxidant properties, mitochondrial membrane potential and expression of endometrial receptivity marker genes in goat ESCs.

Real-time monitoring of cellular superoxide anion release in THP-1 cells using a catalytically amplified superoxide dismutase-based microbiosensor.

Reactive oxygen species (ROS) including the superoxide anion (O2•-) are typically studied in cell cultures using fluorescent dyes, which provide only discrete single-point measurements. These methods lack the capabilities for assessing O2•- kinetics and release in a quantitative manner over long monitoring times. Herein, we present the fabrication and application of an electrochemical biosensor that enables real-time continuous monitoring of O2•- release in cell cultures for extended periods (> 8h) using an O2•- specific microelectrode. To achieve the sensitivity and selectivity requirements for cellular sensing, we developed a biohybrid system consisting of superoxide dismutase (SOD) and Ti3C2Tx MXenes, deposited on a gold microwire electrode (AuME) as O2•- specific materials with catalytic amplification through the synergistic action of the enzyme and the biomimetic MXenes-based structure. The biosensor demonstrated a sensitivity of 18.35 nA/μM with a linear range from 147 to 930nM in a cell culture medium. To demonstrate its robustness and practicality, we applied the biosensor to monitor O2•- levels in human leukemia monocytic THP-1 cells upon stimulation with lipopolysaccharide (LPS). Using this strategy, we successfully monitored LPS-induced O2•- in THP-1 cells, as well as the quenching effect induced by the ROS scavenger N-acetyl-L-cysteine (NAC). The biosensor is generally useful for exploring the role of oxidative stress and longitudinally monitoring O2•- release in cell cultures, enabling studies of biochemical processes and associated oxidative stress mechanisms in cellular and other biological environments.

(E)-2-Benzylidenecyclanones: Part XIX. Reaction of (E)-2-(4'-X-Benzylidene)-1-tetralones with Cellular Thiols: Comparison of Thiol Reactivities of Open-Chain Chalcones and Their Six- and Seven-Membered Cyclic Analogs.

Non-enzyme-catalyzed thiol addition onto the α,β-unsaturated carbonyl system is associated with several biological effects. Kinetics and diastereoselectivity of non-enzyme catalyzed nucleophilic addition of reduced glutathione (GSH) and N-acetylcysteine (NAC) to the six-membered cyclic chalcone analogs 2a and 2b were investigated at different pH values (pH 3.2, 7.4 and 8.0). The selected compounds displayed in vitro cancer cell cytotoxicity (IC50) of different orders of magnitude. The chalcones intrinsically reacted with both thiols under all incubation conditions. The initial rates and compositions of the final mixtures depended both on the substitution and the pH. The stereochemical outcome of the reactions was evaluated using high-pressure liquid chromatography with UV detection (HPLC-UV). The structures of the formed thiol-conjugates and the retro-Michael products (Z)-2a and (Z)-2b were confirmed by high-pressure liquid chromatography-mass spectrometry (HPLC-MS). Frontier molecular orbitals and the Fukui function calculations were carried out to investigate their effects on the six-membered cyclic analogs. Data were compared with those obtained with the open-chain (1) and the seven-membered (3) analogs. The observed reactivities do not directly relate to the difference in in vitro cancer cell cytotoxicity of the compounds.

Anti-Inflammatory and Anti-Oxidant Properties of N-Acetylcysteine: A Fresh Perspective.

N-acetyl-L-cysteine (NAC) was initially introduced as a treatment for mucus reduction and widely used for chronic respiratory conditions associated with mucus overproduction. However, the mechanism of action for NAC extends beyond its mucolytic activity and is complex and multifaceted. Contrary to other mucoactive drugs, NAC has been found to exhibit antioxidant, anti-infective, and anti-inflammatory activity in pre-clinical and clinical reports. These properties have sparked interest in its potential for treating chronic lung diseases, including chronic obstructive pulmonary disease (COPD), bronchiectasis (BE), cystic fibrosis (CF), and idiopathic pulmonary fibrosis (IPF), which are associated with oxidative stress, increased levels of glutathione and inflammation. NAC's anti-inflammatory activity is noteworthy, and it is not solely secondary to its antioxidant capabilities. In ex vivo models of COPD exacerbation, the anti-inflammatory effects have been observed even at very low doses, especially with prolonged treatment. The mechanism involves the inhibition of the activation of NF-kB and neurokinin A production, resulting in a reduction in interleukin-6 production, a cytokine abundantly present in the sputum and breath condensate of patients with COPD and correlates with the number of exacerbations. The unique combination of mucolytic, antioxidant, anti-infective, and anti-inflammatory properties positions NAC as a safe, cost-effective, and efficacious therapy for a plethora of respiratory conditions.

Should high-dose N-acetylcysteine be given in cases of massive paracetamol overdoses: A narrative review.

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.

Mechanistic Investigation on the Antibacterial Activity of Biogenic Silver Nanoparticles Prepared Using Root Extract of Sarsaparilla and Demonstrated their In Vivo Efficacy in Zebrafish Model.

Antibiotic success rates are decreasing as drug-resistant bacteria become more prevalent, prompting the development of new therapeutic drugs. Herein, we demonstrated the antimicrobial activity of sarsaparilla root extract fabricated silver nanoparticles (sAgNPs). The UV-Visible spectra revealed that the surface Plasmon resonance maxima of sAgNPs were at 415nm. Transmission electron microscopy confirms that the particles are spherical with size of 12-35nm. The minimum inhibitory concentration (MIC) of sAgNPs against Escherichia coli, uropathogenic Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus was 62.5, 62.5, 62.5, 62.5, 125 and 125µM, respectively. At 1X MIC, sAgNPs induces excess reactive oxygen species (ROS) production and disturbs the bacteria membrane intergity, causing cytoplamic membrane depolarization. Interestingly, antibacterial activity of sAgNPs was considerably reduced in the presence of an antioxidant, N-acetyl cysteine, suggesting that ROS-induced membrane damage is a plausible cause of cell death. In contrast to many studies that only report the in vitro activity of NPs, we determined the in vivo antibacterial efficacy using the zebrafish model. It was found that sAgNPs protect fish from infection by inhibiting bacterial growth and eliminating them from the fish. In addition, the catalytic potential of sAgNPs for wastewater decontamination was demonstrated by degrading organic pollutants such as methyl orange, congo red, reactive black, and acid blue. The pollutants degraded in less than 10min, and the reaction follows pseudo-first-order kinetics. As a proof of concept, the catalytic potential of sAgNPs in degrading mixed dyes to satisfy industrial wastewater treatment needs was established. In summary, sAgNPs have the potential to act as nanocatalysts and nano-drugs, addressing key challenges in medical and environmental research.

REDD1 knockdown ameliorates endothelial cell senescence through repressing TXNIP-mediated oxidative stress

Endothelial cell senescence characterized by reactive oxygen species (ROS) accumulation and chronic inflammation is widely recognized as a key contributor to atherosclerosis (AS). Regulated in development and DNA damage response 1 (REDD1), a conserved stress-response protein that regulates ROS production, is involved in the pathogenesis of various age-related diseases. However, the role of REDD1 in endothelial cell senescence is still unclear. Here, we screened REDD1 as a differentially expressed senescence-related gene in the AS progression using bioinformatics methods, and validated the upregulation of REDD1 expression in AS plaques, senescent endothelial cells, and aging aorta by constructing AS mice, D-galactose (DG)-induced senescent endothelial cells and DG-induced accelerated aging mice, respectively. siRNA against REDD1 could improve DG-induced premature senescence of endothelial cells and inhibit ROS accumulation, similar to antioxidant N-Acetylcysteine (NAC) treatment. Meanwhile, NAC reduced the upregulation of REDD1 induced by DG, supporting the positive feedback loop between REDD1 and ROS contributes to endothelial cell senescence. Mechanistically, the regulatory effect of REDD1 on ROS might be related to the TXNIP-REDD1 interaction in DG-induced endothelial cell senescence. Collectively, experiments above provide evidence that REDD1 participates in endothelial cell senescence through repressing TXNIP-mediated oxidative stress, which may be involved in the progression of atherosclerosis.

Efficacy of N-acetylcysteine for treating dryness symptoms of Sjögren's disease: randomised placebo-controlled double-blind clinical study.

N-acetylcysteine (NAC) is used in Sjögren's disease (SjD) based on limited evidence. The aim of this study was to assess the efficacy of NAC for relieving dryness symptoms in SjD. In this placebo-controlled double-blind trial, 60 adult SjD females (with low disease activity) were randomised to receive NAC (1,200 mg/day orally) or placebo. At baseline (D0), 30 days (D30) and 90 days (D90), all participants underwent the following evaluations: EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), Ocular Surface Disease Index (OSDI), Xerostomia Inventory (XI), Leicester Cough Questionnaire (LCQ), unstimulated/stimulated salivary flow, Schirmer's test, and plasma levels of thiobarbituric acid reactive substances (TBARS), glutathione and NAC. At inclusion, both groups were balanced for age, ethnicity, disease duration, ESSPRI, OSDI, XI, Schirmer's test, salivary flow, ESSDAI and topical/systemic treatments (p>0.05). No significant differences were observed between NAC and placebo groups on D30 and D90 regarding ESSPRI, XI, OSDI, LCQ, Schirmer's test, stimulated salivary flow, ESSDAI and topical/systemic treatments (p>0.05). Unstimulated salivary flow was significantly higher in the placebo group on D90 (p=0.018). NAC blood concentrations were significantly higher in the NAC group on D30 (p=0.018) and D90 (p<0.001), however, no differences were found in TBARS and glutathione. Further analysis showed decrease≥1 in ESSPRI in the NAC compared with placebo group on D30 (p=0.045), a result not found on D90 (p=0.696). NAC is recommended as a rescue therapy for SjD. However, our well-designed study provides novel evidence demonstrating its inefficacy for improving dryness symptoms or reducing oxidative stress. gov-NCT04793646.

Ligand-Induced Red-Emitting Copper Nanoclusters for Selective Fluorescence Determination of Aluminum Ions.

Monitoring levels of excessive aluminum ions (Al3+) is crucial as it can harm the immune system, reduce enzyme activity, cause cell death, and damage environmental and biological systems. Developing a fast and efficient Al3+ ion determination method is the key to addressing this issue. In this work, red-emitting fluorescent copper nanoclusters (CuNCs) were synthesized using N-acetyl-l-cysteine (NAC) as a ligand and CuCl2·2H2O through a facile procedure. The NAC-CuNCs exhibited a large Stokes shift and displayed remarkable luminescence properties. A method for detecting Al3+ through a fluorescence probe was proposed. Its fluorescence mechanism was also explored. The probe showed rapid responsiveness (within 1 min) to Al3+ ion determination. The detection limit for Al3+ was found to be 19.7 nM, which is significantly lower than the WHO's value and most reports, with a linear range of 0-52.9 μM. The determination of Al3+ concentrations in actual water using the fluorescence probe yielded satisfactory outcomes. Moreover, the visual detection of Al3+ ions was also achieved through a smartphone, which can enhance its fast and practical detection.

N-acetyl Cysteine Overdose Induced Acute Toxicity and Hepatic Microvesicular Steatosis by Disrupting GSH and Interfering Lipid Metabolisms in Normal Mice.

N-acetyl cysteine (NAC) is a versatile drug used in various conditions, but the limitations and toxicities are not clear. The acute toxicity and toxicological mechanisms of an intraperitoneal injection of NAC in normal mice were deciphered. The LD50 for male and female BALB/cByJNarl mice were 800 mg/kg and 933 mg/kg. The toxicological mechanisms of 800 mg/kg NAC (N800) were investigated. The serum biomarkers of hepatic and renal indices dramatically increased, followed by hepatic microvesicular steatosis, renal tubular injury and necrosis, and splenic red pulp atrophy and loss. Thus, N800 resulted in mouse mortality mainly due to acute liver, kidney, and spleen damages. The safe dose (275 mg/kg) of NAC (N275) increased hepatic antioxidant capacity by increasing glutathione levels and catalase activity. N275 elevated the hepatic gene expressions of lipid transporter, lipid synthesis, β-oxidation, and ketogenesis, suggesting a balance between lipid production and consumption, and finally, increased ATP production. In contrast, N800 increased hepatic oxidative stress by decreasing glutathione levels through suppressing Gclc, and reducing catalase activity. N800 decreased the hepatic gene expressions of lipid transporter, lipid synthesis, and interferred β-oxidation, leading to lipid accumulation and increasing Cyp2E1 expression, and finally, decreased ATP production. Therefore, NAC doses are limited for normal individuals, especially via intraperitoneal injection or similar means.

Preliminary evidence for therapeutic impact of intravesical glucosamine on protamine sulfate and potassium chloride-induced bladder overactivity in rat model.

To investigate the protective effect of intravesical glucosamine in treating overactive bladder (OAB). Ninety-two female Sprague-Dawley (SD) rats were divided into 4 groups i.e. protamine sulfate (PS), N-acetylcysteine (NAC), and glucosamine-treated PS (GPS), and normal saline control (NC) were used. We induced hyperactivity in rats via intravesical infusion of PS and potassium chloride (KCl), whereas the NC group underwent a sustained intravesical saline infusion for 1h. N-acetylcysteine (NAC), a potential antioxidant as well as anti-inflammatory agent was employed as positive control. Cystometrography (CMG) was then conducted to determine urodynamic parameters, i.e., leak point pressure (LPP, n = 48) and inter-contractile interval, the duration between two voids (ICI, n = 32). LPP was significantly elevated in the GPS group (mean ± SD: 110.9 ± 6.2 mmHg) compared to the NC (81.0 ± 32.5 mmHg), PS (40.3 ± 10.9 mmHg), and NAC group (70.3 ± 19.4 mmHg). The cystometrogram data also reveals a prolonged ICI in the GPS group (241.3 ± 40.2s) compared to the NC group (216.0 ± 41.7s), PS group (128.8 ± 23.6s), and NAC group (193.8 ± 28.3s). This preliminary study implies the ameliorative impact of GPS treatment on OAB in terms of improved urodynamic parameters, including LPP and ICI.