Administration Of N-acetylcysteine Research Articles

Efficacy of N-acetylcysteine in reducing the risk of postoperative atrial fibrillation in cardiothoracic surgery: a systematic review and meta-analysis of randomized controlled trials.

New-onset postoperative atrial fibrillation (POAF) is a common complication following cardiac surgeries. N-acetylcysteine (NAC) showed a significant reduction in the incidence of POAF. This review aimed to systematically summarize and Meta-analyze data from previously published Randomized Controlled Trials (RCTs). Electronic databases: PubMed, Cochrane, Embase, Scopus, and Web of Science were searched. Data was extracted and the quality of the included studies was assessed. A random-effects DerSimonian Laird model was employed for meta-analysis. Fifteen RCTs were included in this study (NAC, N.=940; control, N.=935). In the NAC group, 16.38% developed POAF compared with 23.53% in the control group. NAC supplementation was associated with a decreased incidence of POAF in patients undergoing cardiothoracic surgery (RR 0.69; 95% CI 0.52, 0.91; P=0.008). Meta-regression of randomized trial data showed that the incidence of POAF was not related to the NAC dose (P=0.439). A subgroup analysis in terms of the time of NAC administration revealed that preoperative and postoperative NAC administration was the only subgroup that demonstrated a statistically significant difference (RR 0.48, 95% CI 0.32, 0.71; P=0.0003) compared with placebo and showed no heterogeneity. Atrial fibrillation is a significant postoperative complication, particularly in cardiothoracic surgery. This study highlights the need for further research on optimal NAC dosing and timing, with evidence suggesting that preoperative and postoperative NAC administration may significantly decrease postoperative atrial fibrillation in cardiothoracic surgery patients, although limitations and variability in study designs need to be considered.

Alternative use of the cough drug - N-acetylcysteine in psychiatry: a review of recent clinical trials

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.

N-acetyl cysteine (NAC) administration induces behavioral abnormalities in mice experiencing proteotoxic cardiac disease

Background: The co-occurrence of cardiac and neurological complications is becoming increasingly common among individuals diagnosed with either of these disorders. Hypothesis: We tested the hypothesis that elevating glutathione (GSH) levels through N-acetyl cysteine (NAC), a precursor for GSH synthesis, leads to behavioral abnormalities in a mouse model with proteotoxic heart disease. Approach: We used a transgenic mouse model expressing a cardiac-specific human mutant R120G-αB-crystallin (hR120GCryAB-TG), which develops progressive heart failure due to proteotoxicity. Our investigation aimed to understand the effects of NAC on brain redox and behavior in this model. Results: Administering NAC for a period of 12 weeks, we observed an increase in glutathione levels and its redox state (GSH/GSSG) in both heart (1.0 vs. 3.0 Fold in NTG vs. TG; p>0.001) and brain (1.0 vs. 4.0 Fold in NTG vs. TG; p>0.01) tissues. Interestingly, this increase was associated with exacerbated cardiac dysfunction and abnormal behavior. The administration of NAC worsened both structural and functional defects in the hearts of the transgenic (TG) mice, indicating that enhancing antioxidant defense mechanisms could trigger proteotoxic insults through reductive stress (RS). Additionally, the brain of TG mice exhibited enhanced reductive capacity (p>0.01), accompanied by significant alterations in the levels of Tau and α-Synuclein proteins, when compared to non-transgenic (NTG) mice. While NTG mice, with or without NAC treatment, displayed normal behavior, TG mice treated with NAC developed severe behavioral abnormalities, including cognitive impairment (p>0.01). Conclusions: These findings suggest that increased GSH levels (i.e. RS) in progressive heart failure could cause behavioral issues. Thus, further research into the underlying redox mechanisms in other organs, including the brain, is necessary to better understand the use of antioxidant supplements for heart failure treatment. This study will aid in developing personalized therapeutic strategies. National Institute of Health - NHLBI R01 (R01-2RHL118067; Namakkal-Soorappan) American Heart Assocaition (20POST35200085; Sunny). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

H2S prevents the disruption of the blood-brain barrier in rats with prenatal hyperhomocysteinemia

Elevation of the homocysteine concentration in the plasma called hyperhomocysteinemia (hHCY) during pregnancy causes a number of pre- and postnatal developmental disorders. The aim of our study was to analyze the effects of H2S donors –NaHS and N-acetylcysteine (NAC) on blood-brain barrier (BBB) permeability in rats with prenatal hHCY. In rats with mild hHCY BBB permeability assessed by Evans Blue extravasation in brain increased markedly throughout life. Administration of NaHS or NAC during pregnancy attenuated hHCY-associated damage and increased endogenous concentrations of sulfides in brain tissues. Acute application of dl-homocysteine thiolactone induced BBB leakage, which was prevented by the NMDA receptor antagonist MK-801 or H2S donors. Rats with hHCY demonstrated high levels of NO metabolite – nitrites and proinflammatory cytokines (IL-1β, TNF-α, IL-6) in brain. Lactate dehydrogenase (LDH) activity in the serum was higher in rats with hHCY. Mitochondrial complex-I activity was lower in brain of hHCY rats. NaHS treatment during pregnancy restored levels of proinflammatory cytokines, nitrites and activity of the respiratory chain complex in brain as well as the LDH activity in serum. Our data suggest that H2S has neuroprotective effects against prenatal hHCY-associated BBB disturbance providing a potential strategy for the prevention of developmental impairments in newborns.

Two versus Three Infusion Regimens of N-Acetylcysteine for Acetaminophen Overdose.

Acetaminophen overdose is a common clinical condition, often leading to liver toxicity. Current treatments involve the three-infusion N-Acetylcysteine (NAC) regimen (FDA-labeled), which may be complex, time-consuming, and need to be changed. An alternative uses two infusions instead, which offers possible advantages regarding simplicity and administration errors. This study sought to compare the respective efficacies and safety outcomes when treating acute acetaminophen overdose among children and adolescents. At Montreal Children's Hospital, a retrospective study was conducted comparing pre-2003 FDA-labelled three-infusion NAC therapy with a two-infusion regimen. Information was collected regarding patient demographics, NAC administration details, errors, rates of hepatotoxicity, and adverse reactions, and the statistical test Chi-square test was employed to obtain the results. A total of 126 patients met the inclusion criteria. Of these patients, 65 received a two-infusion regimen, and 61 patients received the FDA-labeled regimen. The two-infusion group experienced significantly fewer administration errors (4 errors vs. 23 errors; p < 0.001), while the rates of hepatotoxicity between them were similar. There were no instances of liver transplantation or mortality due to either regimen. Adverse reactions occurred equally frequently between both regimens with no discernible difference-the meantime to administer NAC was 9 h for the two-infusion regimen and 8.5 h for FDA-labeled regimen groups, respectively. Three cases of hepatitis were successfully treated with timely NAC therapy, and no liver transplantation or mortality occurred. Adverse reactions, including anaphylactoid reactions, were observed in both groups but were resolved when temporarily stopped and restarted at a slower infusion rate. The two-infusion NAC regimen proved similar efficacy at protecting liver damage and improving patient outcomes compared to its FDA-labeled three-stage counterpart, with significantly fewer administration errors for this version of NAC treatment, suggesting potential advantages in terms of safety and simplicity. Future research should investigate larger cohorts and more variables to validate these results further and optimize the management of acetaminophen overdose cases; further investigation should focus on dosing strategies, personalized approaches, and long-term patient care in this context.

The Use and Potential Benefits of N-Acetylcysteine in Non-Acetaminophen Acute Liver Failure: An Etiology-Based Review.

Acute liver failure represents a life-threatening organ dysfunction with high mortality rates and an urgent need for liver transplantation. The etiology of the disease varies widely depending on various socio-economic factors and is represented mainly by paracetamol overdose and other drug-induced forms of liver dysfunction in the developed world and by viral hepatitis and mushroom poisoning in less developed countries. Current medical care constitutes either specific antidotes or supportive measures to ensure spontaneous recovery. Although it has been proven to have beneficial effects in paracetamol-induced liver failure, N-acetylcysteine is widely used for all forms of acute liver failure. Despite this, few well-designed studies have been conducted on the assessment of the potential benefits, dose regimens, or route of administration of N-acetylcysteine in non-acetaminophen liver failure. This review aims to summarize the current evidence behind the use of this drug in different forms of liver failure.

Effects of N-Acetylcysteine Supplementation on Semen Analysis, Hormonal Profile and Spontaneous Pregnancy Rate in Idiopathic Infertile Men: Before and After Clinical Trial

Objective: To compare sperm quality and quantity, hormonal profiles and spontaneous pregnancy rates before and after administering a 3 months course of N-Acetylcysteine (NAC) Material and Methods: This prospective clinical trial was conducted at the Infertility Unit of the Obstetrics and Gynecology Department at Bhumibol Adulyadej Hospital, Thailand. The study period was from June 1, 2023 to September 30, 2023. Subjects were idiopathic infertile males aged between 20 and 50 years old. All subjects received 600 mg of NAC orally per day. Semen analysis (SA) and male hormonal profiles (MHP; testosterone, LH, FSH and prolactin) were performed before and three months after NAC administration. Demographic, clinical characters and laboratory change were recorded. Results: The 92 participants were recruited. The mean age of couples was 34.5 years old. The average duration of infertility was 3.6 years. Increase of semen volume (2.1 vs 2.4 ml, p &lt; 0.001), semen concentration (30.5 vs 43.1 x 106/mL, p &lt; 0.001), total motility (59.57 vs 72.38 %, p &lt; 0.001), progressive motility (59 vs 69.8 %, p &lt; 0.001), normozoospermia (60 vs 83 %, p &lt; 0.001), testosterone (452.8 vs 479.0 ng/dL, p = 0.038), LH (4.6 vs 5.3 mIU/mL, p = 0.004) and FSH (4.4 vs 4.6 mIU/mL, p = 0.009) were observed after three months of NAC administration. No changes in sperm morphology and prolactin level. One-third (27/92) of each participant’s spouse conceived spontaneously. Conclusion: NAC potentially enhances male hormonal profiles, sperm quality and quantity with an impressive spontaneous pregnancy rate.

A Comparison of the Protective Effect of Pyridoxine and N-Acetylcysteine in Paracetamol Induced Hepatotoxicity in Rats

Paracetamol is a common over the counter drug. Paracetamol-induced hepatotoxicity results in over 300,000 hospitalizations each year and accounts for up to 42% of all cases of acute liver failure. N-acetylcysteine (NAC) is a potential antidote to manage paracetamol toxicity. Objective: To investigate the effects of pyridoxine, alone and in combination with NAC in repairing paracetamol-induced liver damage in male Wister rats. Methods: A single oral dose of paracetamol (650 mg/kg) was administered to Wistar rats to induce hepatotoxicity. The hepato-protective effects of NAC at a dose 300 mg/kg, and pyridoxine (200 mg/kg) were evaluated using standard liver function tests and histopathological along with serum glutathione levels. Results: The administration of pyridoxine and NAC resulted in a significant decrease in AST, ALT, and total bilirubin levels and the reversal of histopathological changes. Conversely, administering NAC and pyridoxine in combination yielded significant changes except for the glutathione level. Conclusions: The study concluded that pyridoxine may be used as a potential hepatoprotective drug in paracetamol-induced hepatotoxicity. In combination with NAC, it showed protective effects in paracetamol-induced hepatoxicity.

Analysis of High-Dose N-Acetylcysteine Administration of Kidney Function F Patients Diagnosed with Acute Kidney Injury For The Period January – December 2021 at RSPON Jakarta

In the last decades, the incidence of Acute Kidney Injury (AKI) has been increasing and resulting in prolonged adverse effects. The success of AKI therapy has not been maximally achieved, considering that AKI management is currently still conducted based on the arising causes and symptoms. The AKI management requires to be increasingly developed due to the serious effects of AKI. Thus, supportive therapy is needed to increase the cure rate for AKI. One of the treatment options is high-dose administration of N-acetylcysteine antioxidant therapy of 5000 mg. 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).

N-acetyl cysteine augments adipose tissue-derived stem cell efficacy on inflammatory markers and regulatory T cell system balance in an allergic asthma model

Background Allergic asthma is a destructive inflammatory process in the respiratory system. The anti-inflammatory and antioxidant effects of N-acetylcysteine (NAC) have been reported in patients with obstructive pulmonary disease. On the other hand, several studies have shown the modulatory effects of mesenchymal stem cells on the immune system and inflammatory responses. Accordingly, the purpose of the current study was to evaluate the effect of administration of adipose tissue-derived stem cells (ADSCs) plus NAC on regulatory T cell system balance in an allergic asthma model. Methods Eighty Sprague– Dawley rats were randomly divided into the following groups: Control, Plasmalite, Allergic asthma, Allergic asthma + ADSCs, NAC, Allergic asthma + NAC, Allergic asthma + ADSCs + NAC and Allergic asthma + Prednisolone. at the end of the experiment, arterial blood gas analysis, inflammatory cell counts in bronchoalveolar lavage fluid (BALF), inflammatory cytokine concentration, total IgE and specific OVA-IgE levels, gene expression levels of CD4+-T cell subsets, pulmonary indicators, edema, and lung histopathology were evaluated in all groups. Results Administration of NAC plus ADSCs demonstrated a significant decrease in total WBC and eosinophil counts, which was in line with remarkable decrease in IL-17 and TNF-α concentrations and increases in IL-10 level compared with other treated groups. NAC plus ADSC treatment showed significant increases in Treg gene expression, although Th17 and Th2 expression significantly decreased compared with that in prednisolone- treated rats. Conclusion The results of the present study documented that the administration of ADSCs plus NAC has an inhibitory effect on the inflammation caused by allergic asthma in a rat model. The improvement of inflammatory indexes was significantly higher than that with prednisolone treatment.

The Role of Twice-Daily N-acetylcysteine (NAC) 2400 mg in Smoking Cessation: A Randomized, Placebo-Controlled Trial in Indonesia.

Tobacco smoking remains a health concern, especially in developing countries. Nicotine is significantly linked to many cancers and even second-hand exposure. Hence, smoking can increase the risk of lung and heart disease.This makes quitting smoking important and challenging. Success tends to rise by achieving abstinence with assisted pharmacology. These treatments aim to reduce symptoms of nicotine withdrawal. This is a preclinical trial on glutamate modulator in N-acetylcysteine (NAC) as a new potential treatment for smoking cessation.It is based on the administration of NAC related to elevated levels of dopamine in the central nervous system to accomplish successful smoking cessation. This study evaluated the efficacy and tolerability of NAC for smoking cessation. The primary outcome was abstinence rate and the secondary outcomes of the study were to assess carbon monoxide exhalation value (COexh), the withdrawal symptoms, craving score, safety, and tolerability associated with the administration of NAC. This is a randomized clinical trial. Eligible smokers were treated with NAC 2400 mg twice daily (BID) or placebo to obtain a potential effective abstinence rate.Subjects recruited from the smoking cessation clinic were screened for eligibility and wererandomized to either the NAC or placebo group. The trial consisted of a four-week treatment phase and participants were evaluated each week with a brief counseling. Intention to treat data analysis was performed from 2018 to 2019. Smoking cessation status was verified by measuring the amount of carbon monoxide exhaled and by documenting their smoking habits.Adverse events (AEs) have also been observed on each visit. A total of 90male smokers with a mean (SD) age of 38.7 (11) years were randomized into two groups to receive NAC (n=45) and placebo (n=45). The primary outcome revealed that the abstinence rate was significantly higher for the NACgroup than the placebo group (37.7% vs 6.6%; p=0.02). These findings were supported by data comparison between the NAC group and placebo group of COexh (ppm)(9.59±7.4 vs 13,4±6.1; p=0.04) and cigarette consumption/week (10 vs 46; p <0.001), which were statistically significant. Comparison of withdrawal with the Minnesota Nicotine Withdrawal Score between theNACgroup and the placebo group showed lower values (8 (1-31) vs 11 (0-43); p=0.178), respectively, even though not statistically significant. Compared to the placebo group, the craving score (6 (2-29) vs 12 (6-31); p=0.04) in the NAC group was significantly lower. The most common adverse event was mild gastrointestinal effects (28.9%) and arthralgia (2.2%). No serious adverse events were detected. Despite a small sample size, the data demonstrate the potential benefits of NAC that may help elevate abstinence rates and promote successful smoking cessation pharmacotherapy. Comprehensive treatment combining pharmacologic therapy and counseling increases smoking cessation success rates. It is essential to conduct a randomized multicenter study with a large population to support a sustained abstinence rate using NAC.

Oxidative stress-mediated activation of FTO exacerbates impairment of the epithelial barrier by up-regulating IKBKB via N6-methyladenosine-dependent mRNA stability in asthmatic mice exposed to PM2.5

In order to comprehend the underlying mechanisms contributing to the development and exacerbation of asthma resulting from exposure to fine particulate matter (PM2.5), we established an asthmatic model in fat mass and obesity-associated gene knockdown mice subjected to PM2.5 exposure. Histological analyses using hematoxylin-eosin (HE) and Periodic Acid-Schiff (PAS) staining revealed that the down-regulation of the fat mass and obesity-associated gene (Fto) expression significantly ameliorated the pathophysiological alterations observed in asthmatic mice exposed to PM2.5. Furthermore, the down-regulation of Fto gene expression effectively attenuated damage to the airway epithelial barrier. Additionally, employing in vivo and in vitro models, we elucidated that PM2.5 modulated FTO expression by inducing oxidative stress. Asthmatic mice exposed to PM2.5 exhibited elevated Fto expression, which correlated with increased levels of reactive oxygen species. Similarly, when cells were exposed to PM2.5, FTO expression was up-regulated in a ROS-dependent manner. Notably, the administration of N-acetyl cysteine successfully reversed the PM2.5-induced elevation in FTO expression. Concurrently, we performed transcriptome-wide Methylated RNA immunoprecipitation Sequencing (MeRIP-seq) analysis subsequent to PM2.5 exposure. Through the implementation of Gene Set Enrichment Analysis and m6A-IP-qPCR, we successfully identified inhibitor of nuclear factor kappa B kinase subunit beta (IKBKB) as a target gene regulated by FTO. Interestingly, exposure to PM2.5 led to increased expression of IKBKB, while m6A modification on IKBKB mRNA was reduced. Furthermore, our investigation revealed that PM2.5 also regulated IKBKB through oxidative stress. Significantly, the down-regulation of IKBKB effectively mitigated epithelial barrier damage in cells exposed to PM2.5 by modulating nuclear factor-kappa B (NF-κB) signaling. Importantly, we discovered that decreased m6A modification on IKBKB mRNA facilitated by FTO enhanced its stability, consequently resulting in up-regulation of IKBKB expression. Collectively, our findings propose a novel role for FTO in the regulation of IKBKB through m6A-dependent mRNA stability in the context of PM2.5-induced oxidative stress. Therefore, it is conceivable that the utilization of antioxidants or inhibition of FTO could represent potential therapeutic strategies for the management of asthma exacerbated by PM2.5 exposure.

Administration of N-acetylcysteine Attenuates Post-Myocardial Infarction Remodeling

Administration of N-acetylcysteine Attenuates Post-Myocardial Infarction Remodeling

Modulatory role of N-acetyl-cysteine on gastric mucosal lesions and some biochemical changes in Wistar rats subjected to cold restraint stress

Background: Gastric ulcer affects many people worldwide and it is caused by many factors such as stress, medications, particularly non- steroidal anti-inflammatory drugs, infections caused by Helicobacter pylori and Cytomegalovirus. Exposure to Cold restraint stress (CRS) has been established to cause oxidative stress leading to cellular death. Nacetyl-cysteine (NAC) is an antioxidant that protects the lipid bio-membrane against oxidative stress. This study investigated the effect NAC on gastric mucosal lesion and some biochemical changes in Wistar rats subjected to CRS.&#x0D; Methodology: Sixteen (16) adult male rats were divided into four (4) groups; Group I (Control): Distilled water/Kg Group II: Distilled water + CRS 3½ hrs (Ulcer group), Group III: NAC 500 mg/kg orally + CRS 3½ hrs Group IV: Ranitidine 50 mg/ kg + CRS 3½ hrs. All treatment lasted for 7 days while exposure to CRS was for 3½ hours on 7th day. Three hours after exposure of rats to CRS, rats of all groups were euthanized under diazepam and ketamine anesthesia. The stomach and blood samples were collected for physical and biochemical analysis. Data were analysed using ANOVA and p &lt; 0.05 was considered significant.&#x0D; Results: The P index of NAC in CRS induced ulcer was found to be 66.7 %. A significant increase (P = 0.001) in body weight was observed in CRS + Ranitidine group, when compared to the control. A significant (P = 0.001) increase was observed in the INOS concentration in NAC + CRS, Ranitidine + CRS, when compared to the control.&#x0D; Conclusion: We surmise that acute administration of NAC significantly increased body weight of rats subjected to CRS. The high preventive index of N-acetyl cysteine on CRS induced ulcer was as the result of the antioxidant properties of NAC which might have contributed to its’ gastro protection against gastric mucosal lesions.

The potential use of N-acetylcysteine in respiratory conditions

Currently, despite the accumulated experience with the use of N-acetylcysteine (NAC) in scientific and real clinical practice, there are a number of questions about its potential and the future prospects for its use.The aim of this work was to summarize new data on the use of NAC in patients with various conditions, based on publications in domestic and foreign medical journals.Results. The article presents an overview of publications in domestic and foreign medical journals devoted to the use of N-acetylcysteine (NAC) in pulmonology practice. The experience with the use of NAC in chronic bronchitis (CB), chronic obstructive pulmonary disease (COPD), bronchial asthma, community-acquired pneumonia, idiopathic pulmonary fibrosis, postinfectious bronchiectasis, and acute respiratory distress syndrome associated with COVID-19 (COronaVIrus Disease 2019) is summarized. The aspects of dose-dependent clinical effects and long-term administration of NAC in CB and COPD are analyzed. In addition, there are controversial and contradictory data on the possibility of prescribing NAC for idiopathic pulmonary fibrosis.Conclusion. NAC is a drug with a broad spectrum of action. Due to its antioxidant and anti-inflammatory properties, minor side effects compared to other anti-inflammatory drugs even at high doses, and low price, NAC can be prescribed for many respiratory diseases. Although it has been used for more than half a century, interest in both its practical application and clinical research has not waned to this day.

Comparative Analysis of Outcomes in Acute Organophosphate Poisoning With and Without N-acetyl Cysteine Intervention.

Organophosphorus poisoning (OPP) stands as a significant health concern in numerous regions, especially in developing nations. Despite the rising complexities and case fatalities associated with exposure, the treatment approach has remained unchanged for many years. Based on clinical insights, certain pharmacologic agents have demonstrated utility in enhancing outcomes and reducing complications arising from this type of exposure. The objective of this study is to compare the outcome of N-acetyl cysteine in the treatment of acute organophosphate poisoning cases. In terms of a) its impact on the requirement of atropine, b) Length of hospital stay, and mortality. The study was conducted in the intensive care unit (ICU) of the General Hospital Lahore. Thirty patients with a history and clinical presentation indicative of acute organophosphorus poisoning were randomly divided into two groups in a 1:1 ratio. The treatment group received parenteral administration of atropine, pralidoxime, and N-acetylcysteine (NAC) as an adjuvant, and the control group received standard treatment for acute organophosphate (OP) toxicity. Throughout the study duration, 30 patients suffering acute organophosphate (OP) toxicity (14 men, 16 women) were examined, with an age mean of (25.83±11.59) years. In the interventional group, only four patients required ICU admission, but in the control group, eight patients were admitted to ICU. The correlation result between the dose of atropine and length of hospital stays was not statistically significant between both study groups (<0.005). Plasma Cholinesterase (PChE) level (KU L-1) and total dose of Pralidoxime (g) were statistically significant in the length of hospital stay. The data was not normally distributed, so the non-parametric tests were applied. The Wilcoxon ranked test showed significant improvement in both the controlled and interventional groups because the p-value was (<0.005). Intergroup comparison analyzed by using the Mann-Whitney U test showed a significant reduction in the severity and other associated symptoms in the interventional group because the p-value was (0.001). The outcome demonstrated that the NAC group had a decreased demand for atropine rather than Pralidoxime. In the NAC group, the length of hospital stay and mortality was decreased. The administration of NAC to the present study procedure for acute organophosphate (OP) poisoning is suggested.

Morphofunctional characteristics of the pancreas after N-acetylcysteine administration in an acute postradiation pancreatitis model

BACKGROUND: The development of effective nondrug and drug-based methods for protecting humans and animals from the effects of ionizing radiation remains important. A morphofunctional assessment of changes in the pancreatic parenchyma is required to determine the degree of radiosensitization of acinar cells and islet cells outside the tumor and during electron treatment of cancer of nearby organs, such as the colon and stomach.&#x0D; AIM: Morphofunctional assessment of the pancreas after N-acetylcysteine administration in a model of acute radiation-induced pancreatitis.&#x0D; MATERIALS AND METHODS: Wistar rats (Rattus Wistar; n=40) were divided into three experimental groups: control group I (n=10); II (n=10) — fractional irradiation with electrons in a total dose of 25 Gy; III (n=10) — administration of N-acetylcysteine before electron irradiation; and IV (n=10) — administration of N-acetylcysteine. A week after the last fraction, animals from all groups were removed from the experiment.&#x0D; RESULTS: A week after electron irradiation, a disruption in histoarchitecture was found in group II due to signs of acute postradiation pancreatitis. Increases in glucose, amylase, and malondialdehyde levels were associated with decreases in insulin and superoxide dismutase levels. In group III, the depth and range of damage to the pancreas were less evident with N-acetylcysteine administration.&#x0D; CONCLUSIONS: After a week of local irradiation with electrons at a total irradiation dose of 25 Gy, the histoarchitecture of the pancreas is disrupted, resulting in acute postradiation pancreatitis. N-acetylcysteine reduces the depth and range of radiation-induced damage while increasing the effectiveness of antioxidant protection.

The Cardioprotective Effect of Nacetylcysteine on Doxorubicin Induced Cardiotoxicity in Heart Tissue of Rats.

Doxorubicin (DOX) is a chemotherapeutic agent and is widely used in cancer treatment. There are some studies suggesting oxidative stress-induced toxic changes in the liver due to DOX administration. The aim of this study was to reveal the oxidative damage of DOX in liver tissue at molecular level and to evaluate the protective effect of N-acetylcysteine (NAC) against DOX oxidative damage. Twenty four rats weighing 150-200 g were randomly divided into four equal groups; group I : control, group 2: received a single dose of DOX, group 3: received NAC for 28 days and group 4: received a single dose of DOX, followed by NAC for 28 days. At the end of the experiment, heart tissues were taken from all animals. Malondialdehyde (MDA), Total Antioxidant Capacity (TAC), Total Oxidant Capacity (TOC) levels were determined in these samples by spectrophotometric methods. It was determined that TOC level increased, TAC levels decreased in the group given DOX compared to the control group. In addition, TAC levels increased in the DOX+NAC group (p0.05). It was concluded that DOX administration increased oxidative stress and NAC administration could prevent it. NAC caused modulatory effects on oxidative stress and antioxidant redox system in DOX-induced heart toxicity in the rat.

Inhibition of NRF2 enhances the acute myeloid leukemia cell death induced by venetoclax via the ferroptosis pathway

Venetoclax, an inhibitor that selectively targets B cell lymphoma-2 (BCL-2) that has been approved for treating adult acute myeloid leukemia (AML) in combination with hypomethylating agents. However, its short duration of response and emergence of resistance are significant issues. In this study, we found that the sensitivity of AML cells to venetoclax was considerably enhanced by ML385, an inhibitor of the ferroptosis factor nuclear transcription factor erythroid 2-related factor 2 (NRF2). Using AML samples, we verified that NRF2 and its target gene ferritin heavy chain 1 (FTH1) were highly expressed in patients with AML and correlated with poor prognosis. Downregulation of NRF2 could inhibit FTH1 expression and significantly enhance the venetoclax-induced labile iron pool and lipid peroxidation. By contrast, NRF2 overexpression or administration of the reactive oxygen species inhibitor N-acetylcysteine and vitamin E could effectively suppress the anti-AML effects of ML385+venetoclax. Furthermore, the ferroptosis inducer erastin increased the anti-AML effects of venetoclax. Our study demonstrated that NRF2 inhibition could enhance the AML cell death induced by venetoclax via the ferroptosis pathway. Thus, the combination of ML385 with venetoclax may offer a favorable strategy for AML treatment.

N-acetylcysteine attenuates accumbal core neuronal activity in response to morphine in the reinstatement of morphine CPP in morphine extinguished rats

Numerous studies have suggested that N-acetylcysteine (NAC), has the potential to suppress drug craving in people with substance use disorder and reduce drug-seeking behaviors in animals. The nucleus accumbens (NAc) plays a crucial role in the brain's reward system, with the nucleus accumbens core (NAcore) specifically implicated in compulsive drug seeking and relapse. In this study, we aimed to explore the impact of subchronic NAC administration during the extinction period and acute NAC administration on the electrical activity of NAcore neurons in response to a priming dose of morphine in rats subjected to extinction from morphine-induced place preference (CPP).We conducted single-unit recordings in anesthetized rats on the reinstatement day, following the establishment of morphine-induced conditioned place preference (7 mg/kg, s.c., 3 days), and subsequent drug-free extinction. In the subchronically NAC-treated groups, rats received daily injections of either NAC (50 mg/kg; i.p.) or saline during the extinction period. On the reinstatement day, we recorded the spontaneous activity of NAcore neurons for 15 min, administered a priming dose of morphine, and continued recording for an additional 45 min. While morphine excited most recorded neurons in saline-treated rats, it failed to alter firing rates in NAC-treated rats that had received NAC during the extinction period. For acutely NAC-treated animals, we recorded the baseline activity of NAcore neurons for 10 min before administering a single injection of either NAC (50 mg/kg; i.p.) or saline in rats with no treatment during the extinction. Following 30 min of recording and a priming dose of morphine (1 mg/kg, s.c.), the recording continued for an additional 30 min. The firing activity of NAcore neurons did not show significant changes after morphine or NAC injection. In conclusion, our findings emphasize that daily NAC administration during the extinction period significantly attenuates the morphine-induced increase in firing rates of NAcore neurons during the reinstatement of morphine CPP. However, acute NAC injection does not produce the same effect. These results suggest that modulating glutamate transmission through daily NAC during extinction may effectively inhibit the morphine place preference following the excitatory effects of morphine on NAcore neurons.