Administration Of N-acetylcysteine Research Articles

Oxidative Stress-mediated Loss of Hippocampal Parvalbumin Interneurons Contributes to Memory Precision Decline After Acute Sleep Deprivation.

Sleep is pivotal to memory consolidation, and sleep deprivation (SD) after learning can impede this process, leading to memory disorders. In the present study, we aimed to explore the effects of acute sleep deprivation (ASD) on memory disorders and the underlying mechanisms. ASD model was induced by subjecting the mice to 6h of SD following fear conditioning training. Different cohorts were used for behavioral, biochemical, and electrophysiological tests. Here, we showed that memory precision decline was induced by ASD, concomitant with a notable elevation in oxidative stress within PV interneurons, loss of PV, and disturbed neuronal oscillation in the CA1 region. Notably, chemogenetic activation of PV interneurons effectively ameliorated abnormal gamma oscillation and memory precision decline observed in ASD mice. Meanwhile, chemogenetic inhibition of PV interneurons successfully mimicked the abnormal brain oscillations and memory precision decline observed in ASD mice. Additionally, prior administration of the antioxidant medication N-acetylcysteine effectively reversed memory precision decline and mitigated PV loss and abnormal oscillation triggered by ASD. Collectively, our findings indicated that ASD increased oxidative stress in PV interneurons, thereby disrupting neural oscillation in the CA1 and ultimately leading to memory precision decline.

The effects of antioxidant administration in the early stages of radiation-induced tumorigenesis.

ApcMin/+ mouse was a model mouse for human familial adenomatous polyposis, and irradiation at an early age increases tumors in the small and large intestine. To study the effects of antioxidant administration on tumor incidence after continuous whole-body exposure to gamma rays, ApcMin/+ mice were exposed to a medium-dose-rate, 200mGy/d, from postnatal Day 0 to 21 of age or a high-dose-rate of 0.65Gy/min (total dose 4.2Gy) on postnatal Day 7. The dams and pups were supplied with the N-acetylcysteine (NAC) in drinking water (7g/L), from gestation Day 15 until weaning (21days-old). A significant increase in the number of intestinal tumors were observed in ApcMin/+ mice irradiated with high dose-rate gamma rays as compared with the non-irradiated controls, but there was no significant difference in tumor counts between the non-irradiated controls and the medium-dose rate irradiation groups. NAC administration did not have any significant effect at least at this dose. These results suggest that the supplementation of anti-oxidant at the early stage of tumorigenesis does not suppress the formation of irradiation-induced small intestinal tumors.

ASSESSMENT OF THE INFLAMMATORY RESPONSE IN THE PANCREAS AFTER ADMINISTRATION OF N-ACETYL CYSTEINE IN A MODEL OF POST-RADIATION PANCREATITIS

Introduction. Ionizing radiation can lead to radiation damage to healthy pancreatic tissue, with the development of signs of post-radiation pancreatitis. Electron irradiation potentially has the most “sparing” effect on healthy tissue, but data on this are sparse. The search for means to protect healthy tissues from the effects of ionizing radiation remains relevant. Thus, the use of agents with antioxidant properties (N-acetylcysteine) can potentially slow down the development of post-radiation pancreatitis. The aim of the study: assessment of the inflammatory response in the pancreas after administration of N-acetylcysteine in a radiation-induced pancreatitis model. Methods. Wistar rats (n=120) were divided into four groups: I (n=30) – control; II (n=30) – irradiation with electrons in a total irradiation dose of 25 Gy; III (n=30) – pre-irradiation administration of N-acetylcysteine before electron irradiation; IV (n=30) – administration of N-acetylcysteine. Animals were removed from the experiment on the 7th, 30th and 90th days. A morphological assessment of pancreatic fragments and an immunohistochemical study with antibodies to pro- (IL-1, IL-6) and anti-inflammatory (IL-10) cytokines, markers of T-lymphocytes (CD3) and macrophages (CD68) were carried out. Results. At all stages of the experiment, high levels of expression of pro- and anti-inflammatory cytokines were observed in the electron irradiation group with a slight increase in the number of CD3+ T-lymphocytes and CD68+ macrophages. In the group of pre-radiation administration of N-acetylcysteine, increased levels of immunolabeling were also found when conducting reactions with antibodies to pro- and anti-inflammatory cytokines, however, by the third month of the experiment, practically no CD3+ and CD68+ immunocompetent cells were noted in this group. Conclusion. Pancreatic local electron irradiation at a total dose of 25 Gy in the early stages leads to the development of a stromal-vascular inflammatory reaction with a capillary-parenchymal block with practically no cellular inflammatory infiltration. At the same time, pre-radiation administration of N-acetylcysteine partially prevents the development of post-radiation pancreatitis.

The impact of N-acetylcysteine on hypoxia-induced testicular apoptosis in male rats: TUNEL and IHC findings

The present study aimed to evaluate the impact of N-acetylcysteine (NAC) on testicular hypoxia caused by varicocele, focusing specifically on the regulation of genes related to apoptosis and oxidative stress in the testes of mature Wistar rats.Thirty-two rats were divided into four groups: Control (Sham), hypoxia, testicular hypoxia treated with NAC (Hypoxia + NAC), and healthy animals treated with NAC. After the 8-week treatment period, testicular histopathology and the levels of oxidative stress markers—superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA)—in serum were examined. The expression of Bax and Bcl-2 mRNA was analyzed using immunocytochemistry and RT-qPCR assays, while the apoptosis rate was determined using the TUNEL method.Histopathological evaluations showed that parameters such as Johnsen's score, epithelium width, and seminiferous tubule diameter indicated significant improvement in the Hypoxia + NAC group compared to the Hypoxia group. NAC administration resulted in elevated serum levels of GPx and SOD, accompanied by a reduction in MDA levels (p < 0.003). Furthermore, the study revealed that NAC decreased Bax expression and enhanced Bcl-2 gene and protein expression compared to the varicocele group (p < 0.05). Additionally, NAC administration significantly decreased the rate of apoptosis in germ cells (p < 0.05).These findings suggest that NAC administration can mitigate testicular damage induced by hypoxia from varicocele in rats, primarily due to its antioxidant properties.

Ameliorative Effects of N-Acetyl Cysteine and Zinc Sulfate on Reproductive Dysfunction Induced by Short-Term Crude Oil Exposure in Male Wistar Rats

Background: Crude oil contamination by accidental or voluntary ingestion is prevalent in the Niger Delta region of Nigeria. One of the possible impacts of crude oil contamination is reproductive toxicity leading to infertility. The present study evaluated the potential protective effects of N-Acetyl Cysteine (NAC) and Zinc Sulfate (ZnSO4) in mitigating reproductive dysfunction caused by short-term Bonny Light Crude oil (BLCO) exposure in male Wistar rats. Materials and Methods: Fifty (50) male Wistar (180 – 200g) were used for the study. They were divided into ten (10) groups of five (5) animals each. Groups I and II served as the control and negative control and received distilled water and BLCO (600mg/kg) respectively while groups III to X served as the experimental groups and received NAC (100 and 200mg/kg) and ZnSO4 (0.5mg/kg and 1mg/kg) orally for three (3) weeks. Animals were euthanized, and blood and semen were collected for biochemical and seminal analysis. Results: The results of this current study show that BLCO exposure caused a disruption in reproductive functions in rats by decreasing reproductive hormones and semen quality parameters in Wistar rats. NAC and ZnSO4 administration significantly improved semen quality parameters by improving sperm count, sperm motility and morphology in experimental rats. Conclusion: Evidence from the present study suggests that NAC and ZnSO4 protected the testes, preventing reproductive alterations linked to BLCO exposure.

The Administration of N-Acetyl Cysteine has Dramatically Suppressed the Ox-LDL Level in High Fat Diet Mice: A Novel Approaches to Prevent Atherosclerosis using Antioxidant

The Administration of N-Acetyl Cysteine has Dramatically Suppressed the Ox-LDL Level in High Fat Diet Mice: A Novel Approaches to Prevent Atherosclerosis using Antioxidant

Brain mitochondrial damage attenuation by quercetin and N-acetyl cysteine: peripheral and central antiemetic effects.

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 60mg/kg, orally, respectively). QU and NAC (with doses of 50, 100, 200mg/kg), and their combination were administered, along with a standard therapy (metoclopramide; MET 2mg/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.

Use of N-acetyl-cysteine in the Perioperative Period of Liver Transplantation: A Scoping Review

Objective: To !nd evidence on the use of N-acetyl-cysteine (NAC) in the perioperative period of liver transplantation, since NAC, as it is the acetylated precursor of L-cysteine and reduced glutathione, contributes to the hepatic supply of glutathione, helping the liver to recover from ischemia and reperfusion injury. Methodology: "is is a scoping review of the PubMed, VHL and Web of Science databases. "e descriptors “Liver transplantation”, “N-acetyl-cysteine” and “Reperfusion Ischemia” were used, with the Boolean operator “AND”, and articles relevant to the topic were selected. Initially, 60 articles were selected, all published in the last 24 years, in Portuguese and/or English. After analysis, eight articles corresponded to the proposed objective. Results:"e groups that received NAC during TxF showed post-reperfusion hypotension, lower intraoperative pH values, higher plasma concentrations of IL-4 and a signi!cant increase in IL-10 levels !ve minutes before reperfusion. Inhibition of α-glutathione S-transferase (α-GST) was also observed after reperfusion, unlike the control group, which showed a signi!cant increase in this enzyme. Furthermore, sVCAM-1 and sICAM-1 levels were signi!cantly lower in the NAC group 24 hours after reperfusion compared with the placebo group. "e maximum AST value during the !rst 72 postoperative hours was similar in both groups, although the peak ALT was lower in the NAC group than in the placebo group. In grafts that received NAC in the perfusion solution, survival rates at 3 and 12 months were 93% and 90%, respectively, and in the control group were 82% and 70%, respectively. "e incidence of postoperative complications was 23% in the NAC group and 51% in the control group. "e incidence of EPD was lower for the NAC group, which was 15% versus 32% in the control group. Regarding the administration of NAC during the intraoperative TxF, the one-year patient survival rate was 78.4% in the NAC group compared to 80.9% in the placebo group. Conclusion: Intraoperative administration of NAC during the anhepatic phase was associated with a protective effect against reperfusion injury, however in other studies limitations were observed in protection against liver injury, in biomarkers of oxidative stress, in in$ammation and in the functioning of liver enzymes.

N-acetyl-cysteine in Intensive Care Unit Patients with Acute Respiratory Distress Syndrome due to COVID-19: A Retrospective Cohort Study.

We assessed the potential association between N-acetyl-cysteine (NAC) and clinical outcomes in critically ill subjects with COVID-19-related ARDS. We included subjects with confirmed COVID-19 who were admitted to our ICU between March 1, 2020, and January 31, 2021, due to ARDS and necessitating invasive mechanical ventilation (IMV). Subjects who received standard of care (SOC) were compared with subjects who additionally received NAC 600 mg bid orally. A total of 243 subjects were included in this study. The results indicate significantly improved survival rates in the NAC plus SOC group, both in the unadjusted analysis and after adjusting for confounding factors such as ARDS severity (HR 0.48, 95% CI 0.32-0.70). We found that oral administration of NAC was associated with reduced mortality in critically ill patients with COVID-19 related ARDS.

Neuroprotective role of n-acetylcysteine (NAC): countering doxorubicin neurotoxicity via TH, Nurr1, and iNOS expression

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.

Adjunctive N-Acetylcysteine and Lung Function in Pulmonary Tuberculosis

BackgroundTuberculosis remains a global health concern, and half of cured patients have permanent lung injury. N-acetylcysteine (NAC) has shown beneficial antimicrobial, antioxidant, and immunomodulatory effects in preclinical tuberculosis models. We examined its effects on tuberculosis treatment outcomes.MethodsThis prospective, randomized, controlled trial nested within the TB SEQUEL cohort study enrolled 140 adults with moderate or far-advanced tuberculosis. Participants were randomly assigned 1:1 to standard therapy with or without 1200 mg of oral NAC twice daily for days 1 to 112. Clinical evaluations, sputum culture, and spirometry were performed at specified intervals through day 168, after which participants returned to the TB SEQUEL cohort. The primary outcome was culture conversion. Secondary outcomes included whole-blood glutathione levels and lung function.ResultsParticipants were predominantly young, male, and human immunodeficiency virus 1–negative and had heavy sputum Mycobacterium tuberculosis (MTB) infection burdens. NAC increased glutathione levels (NAC × day interaction, 8.48; 95% confidence interval [CI], 1.93 to 15.02) but did not increase stable culture conversion (hazard ratio, 0.84; 95% CI, 0.59 to 1.20; P=0.33). NAC treatment was associated with improved recovery of lung function (NAC × month, 0.49 [95% CI, 0.02 to 0.95] and 0.42 [95% CI, −0.06 to 0.91] for forced vital capacity and forced expiratory volume in the first second, respectively, as percentages of predicted values). The effects of NAC on lung function were greatest in participants with severe baseline lung impairment and appeared to persist beyond the period of NAC administration. Rates of serious or grade 3 to 4 nonserious adverse events did not differ between the groups.ConclusionsDespite increasing whole-blood glutathione levels, NAC did not affect eradication of MTB infection in adults with pulmonary tuberculosis that was moderate to far advanced. Secondary outcomes of lung function showed changes that merit further investigation. (Funded by TB SEQUEL grant 01KA1613 of the German Ministry for Education and Research, the Health Africa Project, and the German Center for Infection Research; ClinicalTrials.gov number, NCT03702738.)

Systematic review and meta-analysis of the effect of N-acetylcysteine on outcomes after liver resection.

N-Acetylcysteine (NAC) is a recognized antioxidative agent that facilitates the conjugation of toxic metabolites. In recent years, NAC has been routinely used to limit ischaemia-reperfusion injury in liver transplantation. There remains, however, contradictory evidence on its effectiveness in liver resection. This meta-analysis examines the effectiveness of NAC in improving outcomes following hepatectomy. A comprehensive search of the MEDLINE, EMBASE, and Cochrane databases was performed to identify relevant randomized controlled trials (RCTs) published since database inception until November 2023. The outcomes of Day 1 biochemical markers (lactate, ALT, bilirubin, and INR), length of stay, transfusion rates, and morbidity were extracted. Quantitative pooling of data was based on a random-effects model. The study protocol was registered on PROSPERO (Registration no: CRD42023442429). Five RCTs reporting on 388 patients undergoing hepatectomy were included in the analysis. There were no significant differences in patient demographics between groups. Post-operative lactate was lower in patients receiving NAC (WMD -0.61, 95% CI -1.19 to -0.04, I2 = 67%). There were, however, no differences in the post-operative INR (WMD -0.04, 95% CI -0.19 to 0.12, I2 = 96%) and ALT (WMD -94.94, 95% CI -228.46 to 40.38; I2 = 67%). More importantly, there were no statistically significant differences in length of stay, transfusion rates, and morbidity between the two groups. The administration of NAC in liver resection did not alter important biochemical parameters suggesting any real effectiveness in reducing hepatic dysfunction. There were no improvements in the clinical outcomes of length of stay, transfusion rates, and overall morbidity.

Chronic N-acetyl cysteine treatment does not improve respiratory system performance in the mdx mouse model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is characterised by respiratory muscle injury, inflammation, fibrosis and weakness, ultimately culminating in respiratory failure. The dystrophin-deficient mouse model of DMD (mdx) shows evidence of respiratory muscle remodelling and dysfunction contributing to impaired respiratory system performance. The antioxidant N-acetylcysteine (NAC) has been shown to exert anti-inflammatory and anti-fibrotic effects leading to improved respiratory muscle performance in a range of animal models of muscle dysfunction, including mdx mice, following short-term administration (2weeks). We sought to build on previous work by exploring the effects of chronic NAC administration (3months) on respiratory system performance in mdx mice. One-month-old male mdx mice were randomised to receive normal drinking water (n=30) or 1% NAC in the drinking water (n=30) for 3months. At 4months of age, we assessed breathing in conscious mice by plethysmography followed by ex vivo assessment of diaphragm force-generating capacity. Additionally, diaphragm histology was performed. In separate studies, in anaesthetised mice, respiratory electromyogram (EMG) activity and inspiratory pressure across a range of behaviours were determined, including assessment of peak inspiratory pressure-generating capacity. NAC treatment did not affect force-generating capacity of the mdx diaphragm. Collagen content and immune cell infiltration were unchanged in mdx + NAC compared with mdx diaphragms. Additionally, there was no significant effect of NAC on breathing, ventilatory responsiveness, inspiratory EMG activity or inspiratory pressure across the range of behaviours from basal conditions to peak system performance. We conclude that chronic NAC treatment has no apparent beneficial effects on respiratory system performance in the mdx mouse model of DMD suggesting limited potential of NAC treatment alone for human DMD.

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.

Perioperative N-acetylcysteine: evidence and indications.

Nonopioid analgesics serve to improve analgesia and limit side effects and risks of perioperative opioids. N-acetylcysteine (NAC), the primary treatment of acetaminophen toxicity, may have perioperative indications, including analgesia. NAC impacts glutathione synthesis, oxidant scavenging, glutamate receptor modulationand neuroinflammation. Potential perioperative benefits include arrhythmia prevention after cardiac surgery, decreased contrast-induced nephropathy, improved post-transplant liver functionand superior pulmonary outcomes with general anesthesia. NAC may improve perioperative analgesia, with some studies displaying a reduction in postoperative opioid use. NAC is generally well tolerated with an established safety profile. NAC administration may predispose to gastrointestinal effects, while parenteral administration may carry a risk of anaphylactoid reactions, including bronchospasm. Larger randomized trials may clarify the impact of NAC on perioperative analgesic outcomes.

Evaluation of the Effectiveness of Adjunctive N-Acetylcysteine Nebulizer in Critically Ill Patients with COVID-19: A Pre-post Study

Abstract Background: The uncontrolled inflammatory immune response associated with SARS-CoV-2 can lead to cytokine storm and acute respiratory distress syndrome. N-Acetylcysteine (NAC) nebulizer therapy is being considered as a potential treatment option in coronavirus disease 2019 (COVID-19) patients due to its mucolytic, antioxidant, anti-inflammatory, and antiviral properties. However, the use of NAC in critically ill COVID-19 patients has not been extensively studied. Therefore, a study was conducted to evaluate the effectiveness of adjunctive NAC on respiratory function in critically ill patients with COVID-19. Materials and Methods: A pre-post retrospective study included critically ill patients with COVID-19 admitted to the intensive care units and received NAC nebulizers between March 2020 and July 2021. The primary outcome was to assess the PaO2/FiO2 (P/F) ratio differences before and after NAC administration. Other outcomes were considered secondary, such as the positive end-expiratory pressure (PEEP), tidal volume, and invasive mechanical ventilation (MV) status. A paired t test or Wilcoxon signed-rank test was used based on the data distribution. A P value of &lt;0.05 was considered statistically significant. Results: The results revealed that a total of 1081 critically ill patients with COVID-19 were screened during the study period, and only 44 were included. Most of the patients were male (75%) with a median age of 58 years (range = 48.5–76.5 years). Before NAC initiation, the median P/F ratio was 136.55 (with a range of 92.15–207.3), whereas 24 h post-initiation, it increased significantly to a median of 159.7 (with a range of 109.6–270.2; P = 0.02). In contrast, no statistically significant differences were observed in PEEP, tidal volume, and invasive MV status before and after NAC initiation. Conclusion: This study concludes that adjunctive NAC therapy in critically ill patients with COVID-19 was associated with improved P/F ratio 24 h:24-h post-initiation. This improvement occurred without significant differences observed in PEEP, tidal volume, and invasive MV status. However, it is essential to conduct randomized control trials to validate these findings and determine their clinical significance.

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

In recent years, the increase in environmental pollutants has been one of the most important factors threatening human and environmental health. Arsenic, a naturally occurring element found in soil, water, and air, easily enters the human body and leads to many metabolic disorders. In this study, we focused on the possible protective effects of N-acetylcysteine (NAC) against sodium arsenite (As)-induced toxic effects on embryonic fibroblast cells. The effects of As and NAC treatment on cells were evaluated, including cytotoxicity, oxidative stress, and apoptosis. Embryonic fibroblast cells were exposed to As (ranging from 0.01μM to 10μM) and NAC (at a concentration of 2mM) for 24h. 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.

CHARACTERISTICS OF ENDOCRINE COMPONENT OF PANCREAS AFTER ADMINISTRATION OF N-ACETYLCYSTEINE IN THE MODEL OF ACUTE RADIATION-INDUCED PANCREATITIS

Studies of radiation-induced pancreatic lesions after irradiation with charged particles (electrons, protons) are rare. The effectiveness of certain antioxidants to reduce pancreatic radiation-induced damage is proved. However, the mechanisms of radiation-induced pancreatic damage have not been fully disclosed, and studies of its endocrine component after electron irradiation are rare. The aim of the paper is to assess insulin and glucagon expression in pancreatic islets after administration of N-acetylcysteine in the model of acute post-radiation pancreatitis. Materials and Methods. Wistar rats (Rattus Wistar; n=60) were divided into four experimental groups: Group 1 (n=10) – control; Group 2 (n=20) – fractional local electron irradiation; Group 3 (n=20) – N-acetylcysteine before electron irradiation; Group 4 (n=10) – N-acetylcysteine. All animals were removed from the experiment a week after the last fraction. Pancreatic fragments were prepared for morphological and immunohistochemical (with insulin and glucagon antibodies) studies. Analysis of variance was used for comparison. Statistical analysis of the obtained data was performed according to the Kruskal–Wallis test and a Bonferroni-corrected Mann-Whitney U test. Results. In an immunohistochemical study, a week after electron irradiation (total radiation dosage – 25 Gy), decreased expression levels of insulin (2 points) and glucagon (1 point) were observed compared with the control group. In the group of pre-irradiation administration of N-acetylcysteine, a week after electron irradiation, the number of immunopositive insulocytes (2–3 points) and glucagonocytes (2 points) was close to control values. Conclusion. Seven-day local irradiation with electrons (total radiation dosage – 25 Gy) leads to a decrease in the endocrine activity of insulocytes and glucagonocytes, which is partially preserved after pre-irradiation administration of N-acetylcysteine, indicating its protective effect.

N-acetylcysteine as a potentially safe adjuvant in the treatment of neurotoxicity due to pirimiphos-methyl poisoning.

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.

Mitigative Effects of l-Arginine and N-Acetyl Cysteine against Cisplatin-Induced Testicular Dysfunction and Toxicity through the Regulation of Antioxidant, Anti-inflammatory, and Antiapoptotic Markers: Role of miR-155 and miR-34c Expression.

Testicular dysfunction is a common adverse effect of cisplatin (CIS) administration as a chemotherapeutic drug. The current study has outlined the role of micro-RNAs (miR-155 and 34c) in CIS-induced testicular dysfunction and evaluated the protective effect of N-acetyl cysteine (NAC) and/or l-arginine (LA). Seven groups of Albino rats were used for this study. The control (C) group received physiological saline; the CIS group was injected CIS (7 mg/kg IP, once) on day 21 of the experiment; the NAC group was administered NAC (150 mg/kg intragastric, for 28 days); and the LA group was injected LA (50 mg/kg IP, for 28 days). NAC+CIS, LA+CIS, and NAC+LA+CIS groups received the above regime. CIS significantly reduced serum testosterone, LH, and FSH concentrations with decline of testicular enzyme activities. CIS caused significant elevation in testicular oxidative-stress biomarkers, inflammation-associated cytokines, and apoptosis markers, along with overexpression of miR-155 and low miR-34c expression. Additionally, marked testicular degenerative changes were observed in the examined histological section; a significant decrease in the expression of PCNA with significant increase in expressions of F4/80 and BAX was confirmed. The administration of NAC or LA upregulated testicular functions and improved histopathological and immunohistochemical changes as well as miRNA expression compared with the CIS-administered group. Rats receiving both NAC and LA showed a more significant ameliorative effect compared with groups receiving NAC or LA alone. In conclusion, NAC or LA showed an ameliorative effect against CIS-induced testicular toxicity and dysfunction through the regulation of antioxidant, anti-inflammatory, and antiapoptotic markers and via modulating miR-155 and miR-34c expression.