Antioxidant Properties Of N-acetylcysteine Research Articles

Antioxidative effects of N-acetylcysteine in patients with β-thalassemia: A quick review on clinical trials.

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

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.

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.

High-dose N-acetylcysteine therapy in the treatment of pneumonia

The article presents modern data on the use of N-acetylcysteine in the treatment of infectious diseases of the respiratory tract in the practice of a physician. Its antioxidant, mucolytic, anti-inflammatory, pulmoprotective and antitoxic properties are described. The emphasis is placed on the antioxidant properties of N-acetylcysteine, which are expressed when used in high doses of 1200 mg/day or more. There is a review of the literature on the use of high doses of N-acetylcysteine in the treatment of pneumonia, cystic fibrosis, COPD, ARDS. The effect of N-acetylcysteine on individual risk factors for prolonged pneumonia is analyzed. Given the epidemiological situation around the world, the antioxidant properties of N-acetylcysteine in the treatment of pneumonia, including complicated COVID-19, are relevant and require further study.

Protection from Reperfusion Injury with Intracoronary N-Acetylcysteine in Patients with STEMI Undergoing Primary Percutaneous Coronary Intervention in a Cardiac Tertiary Center

Evidence suggests that oxidative stress plays a principal role in myocardial damage following ischemia/reperfusion events. Recent studies have shown that the antioxidant properties of N-acetylcysteine (NAC) may have cardioprotective effects in high doses, but-to the best of our knowledge-few studies have assessed this. Our objective was to investigate the impact of high-dose NAC on ischemia/reperfusion injury. We conducted a randomized double-blind placebo-controlled trial in which 100 consecutive patients with ST-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) were randomly assigned to the case group (high-dose NAC 100mg/kg bolus followed by intracoronary NAC 480mg during PCI then intravenous NAC 10mg/kg for 12h) or the control group (5% dextrose). We measured differences in peak creatine kinase-myocardial band (CK-MB) concentration, highly sensitive troponin T (hs-TnT), thrombolysis in myocardial infarction (TIMI) flow, myocardial blush grade (MBG), and corrected thrombolysis in myocardial infarction frame count (cTFC). The peak CK-MB level was comparable between the two groups (P=0.327), but patients receiving high-dose NAC demonstrated a significantly larger reduction in hs-TnT (P=0.02). In total, 94% of the NAC group achieved TIMI flow grade 3 versus 80% of the control group (P=0.03). No significant differences were observed between the two groups in terms of changes in the cTFC and MBG. In this study, NAC improved myocardial reperfusion markers and coronary blood flow, as revealed by differences in peak hs-TnT and TIMI flow grade 3 levels, respectively. Further studies with large samples are warranted to elucidate the role of NAC in this population. ClinicalTrials.gov identifier: NCT01741207, and the Iranian Registry of Clinical Trials (IRCT; http://irct.ir ) registration number: IRCT201301048698N8.

Effect of N‐acetylcysteine on cardiac injury and oxidative stress after abdominal aortic aneurysm repair: A randomized controlled trial

Several studies have reported that the antioxidant properties of N-acetylcysteine (NAC) can provide cardiac protection through scavenging of free radicals. The present study was aimed to assess the efficacy of NAC for cardiac protection in patients undergoing elective abdominal aortic aneurysm (AAA) repair. Fifty adult patients undergoing (AAA) repair were randomly allocated to receive NAC infusion (n = 25) or placebo infusion (n = 25). NAC infusion in group I (NAC group) was started at a rate of 0.3 mg/kg/min intravenously during surgery then decreased to a rate of 0.2 mg/kg/min for 24 h post-operatively. Group II (placebo group) received an equivalent rate of placebo infusion. The following parameters: myocardial-specific protein troponin-I, creatine phosphokinase-MB (CPK-MB), plasma pro-inflammatory cytokines [tumour necrosis factor-α (TNF-α) and interleukin (IL)-1β], were assessed at the following time points: preoperatively and at 1 h, 12 h, 24 h, 48 h, and 96 h after surgery. Furthermore, serum malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured preoperatively as a baseline, during aortic clamping, 30 min after declamping, at the end of surgery, 2 h after surgery, 12 h after surgery, and 24 h after surgery. NAC infusion patients had significantly lower post-operative concentrations of myocardial-specific protein [cTnI, CPK-MB] and pro-inflammatory cytokines [TNF-α, IL-1β]. In addition, MDA level was less and TAC was higher in patients who received NAC infusion. NAC infusion provided cardiac protection through scavenging of oxygen free radicals.

Influence of N-acetylcysteine against dimethylnitrosamine induced hepatotoxicity in rats

This study evaluates the hepatoprotective and antioxidant properties of N-acetylcysteine (NAC) on dimethylnitrosamine (DMN) induced hepatotoxicity in male Wistar albino rats. A single intraperitoneal dose of DMN (5 mg/kg b.w.) caused a significant increase in the levels of the serum marker enzymes (aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), glutamyl transpeptidase (γ-GT)) and a subsequent decrease in AST, ALT, ALP and increase in LDH and γ-GT in the liver tissue indicating hepatocellular damage. Elevation in the status of lipid peroxidation, fall in the activities of the enzymic (superoxide dismutase, catalase) and non-enzymic antioxidants (vitamin C, vitamin E) in the liver tissue further confirms oxidative stress and hepatocellular damage induced on DMN administration. Oral administration of NAC (50 mg/kg b.w.) for 7 days significantly prevented the above alterations in the status of the marker enzymes of hepatotoxicity and antioxidant parameters and restored them towards normalcy, which was further substantiated by the histopathological studies of the liver tissue. These results suggest that NAC offers hepatoprotection by ameliorating DMN-induced oxidative stress and hepatotoxicity and this protective effect was attributed to its antioxidant and free radical scavenging properties.

N-Acetylcysteine–Enhanced Contrast Provides Cardiorenal Protection

We sought to evaluate the cardiac and renal effects of an N-acetylcysteine (NAC)-enhanced intracoronary radiographic contrast agent. Recent studies suggest that high-dose NAC provides better protection from contrast-induced nephropathy, and the antioxidant properties of NAC may also provide cardiac protection. The use of angiographic contrast agents as a drug delivery vehicle for cardiorenal protection effects has not been investigated. In a pig model of prolonged cardiac ischemia-reperfusion, NAC-enhanced contrast medium was tested and compared with iopamidol contrast only. Myocardium and renal function were assessed after 24 h. There was no significant difference in the area-at-risk for myocardial infarction (MI) between contrast only and NAC-enhanced contrast medium. In contrast, MI size was about 40% smaller in NAC-enhanced contrast medium-treated animals. These findings were associated with a significant difference in MI morphology. MIs in the NAC-enhanced contrast medium group had a mottled appearance, whereas in the contrast only group they were homogeneous and had a discrete border zone. These differences could explain a higher incidence of periprocedural ventricular arrhythmias in the NAC-enhanced contrast medium group. Histopathological analysis of the myocardium revealed a reduction in programmed cell death by NAC-enhanced contrast medium that may explain the increase in ischemia tolerance. Last, NAC-enhanced contrast medium administration blunted the rise in serum creatinine levels by about 60% and protected from renotubular apotosis. NAC-enhanced contrast medium reduces MI size and protects renal function in a pig model of ischemia and reperfusion.

Overexpression of manganese superoxide dismutase by N-acetylcysteine in hyperoxic lung injury

Exposure of animals to hyperoxia causes lung injury, characterized by diffuse alveolar damage and exudation of plasma into the alveolar space. Reactive oxygen species (ROS) play an important role in the development of hyperoxic lung injury. Mitochondrial oxidative phosphorylation is one of the major sources of ROS. N-acetylcysteine (NAC) is a precursor of glutathione (GSH), which functions as an antioxidant by reducing hydrogen peroxide to water and alcohols. NAC has been shown to diminish lung injury in a large variety of animal models. We elucidated the mechanism underlying the protective effects of NAC in hyperoxia-induced lung injury. Male BALB/c mice were exposed to 98% oxygen for 72 h. The mice inhaled NAC or saline twice a day from 72 h before oxygen exposure to the end of experiment. Inhaled NAC increased the GSH level in lung homogenate. NAC also attenuated cellular infiltrations in both bronchoalveolar lavage fluid (BALF) and lung tissue. The total protein level in BALF and the level of 8-isoprostane, a marker of lipid peroxidation, in lung homogenate were decreased by inhalation of NAC. Inhaled NAC induced the overexpression of Mn superoxide dismutase (MnSOD) mRNA and protein, but did not alter the expressions of other antioxidant enzymes, including CuZnSOD, extracellular SOD, and glutathione peroxydase 1. These findings suggest that the antioxidant properties of NAC in hyperoxic lung injury involve a decrease in mitochondrial ROS in association with the induction of MnSOD, in addition to its role as a precursor of GSH.

Magnesium Supplementation Combined with N-Acetylcysteine Protects against Postischemic Acute Renal Failure

Magnesium is a potent vasodilator whose effects have not been evaluated in renal ischemia. The antioxidant properties of N-acetylcysteine (NAC) partially protect animals from ischemic/reperfusion injury. This study was designed to evaluate magnesium supplementation, alone or combined with NAC, on ischemic acute renal failure. Rats were maintained on normal diets, supplemented or not with MgCl(2).6H(2)O (1% in drinking water) for 23 d, and some rats received NAC (440 mg/kg body wt) on days 20 to 23. On day 21, ischemia was induced by clamping both renal arteries for 30 min. Five groups were studied: Normal, ischemia, ischemia+magnesium, ischemia+NAC, and ischemia+magnesium+NAC. GFR (inulin clearance), renal blood flow (RBF), FEH(2)O, and FENa were determined. Serum magnesium was decreased in ischemia-only rats. Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. However, NAC completely restored the tubular damage induced by ischemia/reperfusion. Semiquantitative immunoblotting showed that NAC prevented the decreased expression of Na-K-2Cl co-transporter and aquaporin 2 after renal ischemia/reperfusion. Untreated rats with acute renal failure demonstrated markedly decreased endothelial nitric oxide synthase expression. Significantly, treatment with NAC, magnesium, or both completely inhibited downregulation of endothelial nitric oxide synthase. The tubular necrosis scores were lower in rats that were treated with NAC alone or with the magnesium-NAC combination. Magnesium prevented postischemia GFR and RBF decreases but did not protect against tubular damage. The NAC protected tubules from ischemia, decreased infiltrating macrophages/lymphocytes, and had a mild protective effect on GFR. In ischemic/reperfusion injury, renal function benefits more from the magnesium-NAC combination than from magnesium alone.

Antioxidant properties of N-acetylcysteine: their relevance in relation to chronic obstructive pulmonary disease.

Oxidative stress has been implicated in the pathogenesis and progression of chronic obstructive pulmonary disease. Both reactive oxidant species from inhaled cigarette smoke and those endogenously formed by inflammatory cells constitute an increased intrapulmonary oxidant burden. Structural changes to essential components of the lung are caused by oxidative stress, contributing to irreversible damage of both parenchyma and airway walls. In addition, oxidative stress results in alterations in the local immune response, increasing the risk of infections and exacerbations, which, in turn, may accelerate lung function decline. The antioxidant N-acetylcysteine, a glutathione precursor, has been applied in these patients in order to reduce symptoms, exacerbations and the accelerated lung function decline. This article reviews the presently available experimental and clinical data on the antioxidative effects of N-acetylcysteine in chronic obstructive pulmonary disease.

N-acetylcysteine does not protect against type II cell injury after prolonged exposure to hyperoxia in rats.

Although the antioxidant properties of N-acetylcysteine (NAC) in vitro are widely accepted, the efficacy of NAC in the prevention of O2 toxicity in vivo is poorly documented. The aim of our study was to investigate the presumed protective effect of NAC on hyperoxic lung injury, focusing on gamma-glutamyltransferase (gamma-GT) activity and glutathione (GSH) levels in lung tissue, epithelial lining fluid (ELF), and isolated rat type II cells immediately after their isolation and 48 h later when kept in culture in normoxia. Thirty-four male Wistar rats were divided in three groups (n = 10-14) and were exposed to air or to 60 or 85% O2 for 7 days. One-half of the rats in each group received 200 mg/kg NAC intraperitoneally one time per day from 3 days before exposure until the end of the experiment, and the other one-half received the vehicle. In the 85% O2-exposed animals, NAC led to more respiratory distress and weight loss. NAC did not prevent the rise in bronchoalveolar lavage lactate dehydrogenase and alkaline phosphatase, but it did prevent the rise in calculated ELF volume. NAC decreased GSH levels (1.4-fold) and gamma-GT activity (1.8-fold) in the air-exposed type II cells. In the 60% O2-exposed group, no effects of NAC were seen (except for a decrease in gamma-GT mRNA expression), but, in the 85% O2-exposed group, NAC gave rise to higher GSH (2.6-fold) and higher gamma-GT activity (2.9-fold) in the ELF and lower GSH (6.9-fold) and higher gamma-GT activity (3.6-fold) in the type II cells. Even in culture, GSH levels remained 1.5-fold lower than in the cells from the air-exposed animals and 2-fold lower than in the cells from the 85% O2-exposed animals. There was increased DNA damage (as assessed by thymidine incorporation) and apoptosis after hyperoxia, especially after 60% O2, and this effect was amplified after NAC treatment. Although protective at the endothelial side, NAC treatment led to adverse effects at the epithelial side, despite, or probably because of, restoration of the ELF GSH levels in the presence of high O2 levels. Because NAC is rapidly metabolized to cysteine, it is plausible that the effects of NAC are manifested through the toxic effects of cysteine.

Chemopreventive properties and mechanisms of N-Acetylcysteine. The experimental background.

The thiol N-acetylcysteine (NAC), now under clinical trial for cancer chemoprevention both in Europe (project Euroscan) and in the US (National Cancer Institute), has been shown during the past decade to exert protective effects in a variety of experimental test systems. NAC inhibited spontaneous mutagenicity and that induced by a number of chemical compounds and complex mixtures. Moreover, NAC significantly decreased the incidence of neoplastic and preneoplastic lesions induced by several chemical carcinogens in rodents (mice, rats, hamsters), e.g., in lung, trachea, colon, liver, mammary gland, Zymbal gland, bladder and skin. Our studies provided evidence that multiple mechanisms contribute to NAC antimutagenicity and anticarcinogenicity. They include extracellular mechanisms, such as detoxification of reactive compounds due to the nucleophilic and antioxidant properties of NAC, inhibition of nitrosation products, and enhancement of thiol concentration in intestinal bacteria; trapping and enhanced detoxification of carcinogens in long-lived non-target cells, such as erythrocytes and bronchoalveolar lavage cells; mechanisms working in the cytoplasm of target cells, such as replenishment of GSH stores, modulation of metabolism of mutagens/carcinogens, blocking of electrophiles, and scavenging of reactive oxygen species; and nuclear effects, such as inhibition of DNA adduction by metabolites of carcinogens, inhibition of "spontaneous" mutations, attenuation of carcinogen-induced DNA damage, and protection of nuclear enzymes, such as poly(ADP-ribose) polymerase.(ABSTRACT TRUNCATED AT 250 WORDS)