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1.
Multifaceted activity of N-acetyl-l-cysteine in chronic obstructive pulmonary disease.
Calzetta, L, Matera, MG, Rogliani, P, Cazzola, M
Expert review of respiratory medicine. 2018;(8):693-708
Abstract
N-acetyl-l-cysteine (NAC), a derivative of the naturally occurring amino acid l-cysteine, is a mucolytic agent that may also act as an antioxidant by providing cysteine intracellularly for increased production of glutathione. It is also used for the treatment of acetaminophen overdose. Areas covered: The recent international recommendations for the treatment of chronic obstructive pulmonary disease (COPD) report that NAC, because of its mucolytic activity, reduces acute exacerbation of COPD (AECOPD) with a modest improvement in health status. However, NAC is a pleiotropic drug with heterogeneous pharmacologic characteristics that certainly include mucolytic activity, but also has anti-infective properties and specific antioxidant and anti-inflammatory effects in the airways. Thus, the mechanisms leading to the protective role of this agent against AECOPD need to be adequately addressed. Expert commentary: The protective effect of NAC against AECOPD seems to be related not only to its well-documented mucolytic activity but also to activation of antioxidant pathways, inhibition of pro-oxidant and inflammatory pathways, and modulation of human bronchial tone. Thus, the dogma that NAC acts prevalently as a mucolytic agent is outdated, and the hypothesis that its anti-inflammatory effect is secondary to the antioxidant activity has been rejected.
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2.
Protection from Reperfusion Injury with Intracoronary N-Acetylcysteine in Patients with STEMI Undergoing Primary Percutaneous Coronary Intervention in a Cardiac Tertiary Center.
Nozari, Y, Eshraghi, A, Talasaz, AH, Bahremand, M, Salamzadeh, J, Salarifar, M, Pourhosseini, H, Jalali, A, Mortazavi, SH
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2018;(3):213-221
Abstract
BACKGROUND 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. OBJECTIVES Our objective was to investigate the impact of high-dose NAC on ischemia/reperfusion injury. METHODS 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 100 mg/kg bolus followed by intracoronary NAC 480 mg during PCI then intravenous NAC 10 mg/kg for 12 h) 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). RESULTS 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. CONCLUSIONS 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.
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3.
Chinese herbal medicines compared with N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis: Protocol for a systematic review.
Guo, J, Li, B, Li, W, Pan, Y, Wang, Z, Wu, Y, Wang, F
Medicine. 2018;(44):e13077
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Abstract
BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a major public health problem worldwide. There is no curative treatment for IPF except lung transplantation. Chinese herbal medicines (CHMs) are widely used in the treatment of IPF in China. However, their effectiveness and safety are still obscure and deserve further investigation. The aim of the study was to assess the efficacy and safety of CHMs in treating IPF compared with N-acetylcysteine (NAC). METHODS This review summarizes and meta-analyzes randomized controlled trials (RCTs) of CHMs for the treatment of IPF. RCTs compare either CHMs alone or in combination with NAC or conventional medicine treatment (CMT) vs NAC alone or in combination with CMT have been included. The following electronic databases have been searched: PubMed, Cochrane Library, Embase, CNKI, CBM, VIP, and WANFANG DATA. The methodologic quality of RCTs has been assessed using the Cochrane risk assessment tool. All trials included are analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.3, R-3.5.1 software, and GRADE pro GDT web solution are used for data synthesis and analysis. RESULTS This review evaluates the effects of CHMs on acute exacerbation, mortality, the quality of life, 6-minute walking test distance, lung function (total lung capacity, diffusing capacity of the lungs for carbon monoxide, and forced vital capacity), partial pressure of oxygen in blood (PaO2), and safety in patients with IPF. CONCLUSION This review provides clear evidence to assess the effectiveness and safety of CHMs for IPF.
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N-Acetylcysteine's Role in Sepsis and Potential Benefit in Patients With Microcirculatory Derangements.
Chertoff, J
Journal of intensive care medicine. 2018;(2):87-96
Abstract
OBJECTIVE To review the data surrounding the utility of N-acetylcysteine (NAC) in sepsis and identify areas needed for additional research. DATA SOURCES A review of articles describing the mechanisms of action and clinical use of NAC in sepsis. SUMMARY OF REVIEW Despite many advances in critical care medicine, still as many as 50% of patients with septic shock die. Treatments thus far have focused on resuscitation and restoration of macrocirculatory targets in the early phases of sepsis, with less focus on microcirculatory dysfunction. N-acetylcysteine, due to its anti-inflammatory and antioxidative properties, has been readily investigated in sepsis and has yielded largely incongruous and disappointing results. In addition to its known anti-inflammatory and antioxidative roles, one underappreciated property of NAC is its ability to vasodilate the microcirculation and improve locoregional blood flow. Some investigators have sought to capitalize on this mechanism with promising results, as evidenced by microcirculatory vasodilation, improvements in regional blood flow and oxygen delivery, and reductions in lactic acidosis, organ failure, and mortality. CONCLUSION In addition to its antioxidant and anti-inflammatory properties, N-acetylcysteine possesses vasodilatory properties that could benefit the microcirculation in sepsis. It is imperative that we investigate these properties to uncover NAC's full potential for benefit in sepsis.
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Mechanisms of acetaminophen-induced liver injury and its implications for therapeutic interventions.
Yan, M, Huo, Y, Yin, S, Hu, H
Redox biology. 2018;:274-283
Abstract
Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in many developed countries. Mitochondrial oxidative stress is considered to be the predominant cellular event in APAP-induced liver injury. Accordingly, N-acetyl cysteine, a known scavenger of reactive oxygen species (ROS), is recommended as an effective clinical antidote against APAP-induced acute liver injury (AILI) when it is given at an early phase; however, the narrow therapeutic window limits its use. Hence, the development of novel therapeutic approaches that can offer broadly protective effects against AILI is clearly needed. To this end, it is necessary to better understand the mechanisms of APAP hepatotoxicity. Up to now, in addition to mitochondrial oxidative stress, many other cellular processes, including phase I/phase II metabolism, endoplasmic reticulum stress, autophagy, sterile inflammation, microcirculatory dysfunction, and liver regeneration, have been identified to be involved in the pathogenesis of AILI, providing new targets for developing more effective therapeutic interventions against APAP-induced liver injury. In this review, we summarize intracellular and extracellular events involved in APAP hepatotoxicity, along with emphatic discussions on the possible therapeutic approaches targeting these different cellular events.
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Comparative efficacy of pharmacological interventions for contrast-induced nephropathy prevention after coronary angiography: a network meta-analysis from randomized trials.
Ma, WQ, Zhao, Y, Wang, Y, Han, XQ, Zhu, Y, Liu, NF
International urology and nephrology. 2018;(6):1085-1095
Abstract
BACKGROUND Contrast-induced nephropathy (CIN) is the major complication related to contrast media administration in patients after coronary angiography (CAG). However, inconsistent results have been published in the literature regarding the effects of pharmacological drugs on CIN prevention. We conducted a network meta-analysis to evaluate the relative efficacy of pharmacological interventions for the prevention of CIN. METHODS We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to July 2017. We included any randomized controlled trials of eleven pharmacological interventions that reported the prevention of CIN. RESULTS We identified 3850 records through database searches, of which 107 studies comprising 21,450 participants were finally identified. Compared with intravenous saline, intravenous saline plus pharmacological drugs including statin [relative risk (RR) 0.57; 95% credibility interval (CrI) 0.39 to 0.83], N-acetylcysteine (NAC) (RR 0.84; 95% CrI, 0.71 to 0.98), vitamin and its analogues (RR 0.66; 95% CrI 0.45 to 0.97), brain natriuretic peptide (BNP) and its analogues (RR 0.46; 95% CrI 0.30 to 0.70), prostaglandin analogues (RR 0.37; 95% CrI 0.18 to 0.76), NAC plus sodium bicarbonate (SB) (RR 0.60; 95% CrI 0.39 to 0.90), and statin plus NAC (RR 0.39; 95% CrI 0.21 to 0.70), have helped to reduce the incidence of CIN in patients after CAG. The top four ranked treatments were statin plus NAC, BNP and its analogues, statin, and vitamin and its analogues, respectively. NAC plus intravenous saline was associated with lower incidence of short-term all-cause mortality than intravenous saline alone (RR 0.62; 95% CI, 0.40 to 0.96; P = 0.03). However, no evidence indicated that any of the pharmacological drugs were associated with a reduced requirement for dialysis and major adverse cardiac and cerebrovascular events (MACCE). CONCLUSIONS Statin plus NAC plus intravenous saline seems to be the most effective treatment for the prevention of CIN in patients after CAG. NAC plus intravenous saline may have a protective role against short-term all-cause mortality. However, none of these drugs has effectively decreased the requirement for dialysis and MACCE.
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Assessment of Renal and Hepatic Tissue-Protective Effects of N-Acetylcysteine via Ammonia Metabolism: A Prospective Randomized Study.
Onk, D, Özçelik, F, Onk, OA, Günay, M, Akarsu Ayazoğlu, T, Ünver, E
Medical science monitor : international medical journal of experimental and clinical research. 2018;:1540-1546
Abstract
BACKGROUND The present study sought to assess the renal and liver protective effect of N-acetylcysteine through NH3 and urea metabolism in patients with chronic obstructive pulmonary disease who were scheduled for coronary artery bypass grafting surgery. MATERIAL AND METHODS Patients with chronic obstructive pulmonary disease (COPD) who were scheduled for coronary artery bypass grafting were divided into 2 groups so as to receive (Group 1, n=35) or not receive (Group 2, n=35) 900 mg/day of n-acetylcysteine for 7 days before the operation starting from their admission to the service by a pulmonologist with the purpose of treating COPD until the day of surgery. Both groups were subjected to the same anesthesia protocol. Blood samples were taken preoperatively, within the first 15th minute following cessation of the cardiopulmonary bypass, at postoperative 24th hour, and at postoperative 48th hour. Blood tests included ammonia (NH3), lactate, blood urea nitrogen, creatinine, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), troponin I (Tn I), and creatinine kinase-muscle brain (CKMB). RESULTS There was a significant difference between the groups' NH3 and lactate levels after cardiopulmonary bypass, postoperative 24th hour, and postoperative 48th hour (respectively, NH3: 39.0±8.8 vs. 55.4±19.6 and 40.1±8.4 vs. 53.2±20.2 mcg/dl, lactate: 1.7±0.9 vs. 2.1±1.2 and 1.2±0.5 vs. 1.8±1.4 mmol/L; p<0.01). Creatinine and BUN levels in Group 2 were found to be significantly higher at the postoperative 48th hour compared to the levels of Group 1 (P<0.05). CONCLUSIONS N-acetylcysteine pretreatment appears to improve renal and hepatic functions through regulation of ammonia and nitrogen metabolism and reduction of lactate in patients with chronic obstructive pulmonary disease who undergo coronary artery bypass grafting surgery. We found that N-acetylcysteine improved kidney and/or liver functions.
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N-acetylcysteine as add-on to antidepressant medication in therapy refractory major depressive disorder patients with increased inflammatory activity: study protocol of a double-blind randomized placebo-controlled trial.
Yang, C, Bosker, FJ, Li, J, Schoevers, RA
BMC psychiatry. 2018;(1):279
Abstract
BACKGROUND A subgroup of depressed patients with increased inflammatory activity was shown to be more susceptible to develop Treatment Resistant Depression (TRD). Earlier studies with anti-inflammatory drugs have shown benefits in the treatment of major depressive disorder (MDD), but the effects are expected to be higher in patients with increased inflammatory activity. Supplementation of N-acetylcysteine (NAC) to ongoing antidepressant therapy may positively influence outcome of depression treatment in these patients. Therefore, this study aims to investigate the efficacy of NAC supplementation in patients with insufficient response to standard antidepressant treatment, and to explore potential roles of inflammation and oxidative stress involved in the alleged pathophysiological processes of TRD. METHODS/DESIGN A double-blind randomized placebo-controlled study comparing NAC versus placebo as add-on medication to antidepressant treatment with 12-week treatment and 8-week follow up in patients with TRD and increased inflammatory activity. Apart from clinical efficacy defined as the change in Hamilton Depression Rating Scale (HAMD)-17 score, secondary outcomes include changes in pathophysiological mechanisms related to depression as well as changes in local brain activity (functional Magnetic Resonance Imaging, fMRI) and white matter integrity (Diffusion Tensor Imaging, DTI). Importantly, sole patients with CRP levels with values between 0.85 and 10 mg/L will be included. DISCUSSION This is the first clinical trial taking both TRD and increased inflammatory activity as inclusion criteria. This study will provide reliable evidence for the efficacy of NAC in patients with TRD displaying increased inflammatory activity. And this study also will help explore further the roles of inflammation and oxidative stress involved in the alleged pathophysiological processes of TRD. TRIAL REGISTRATION The trial protocol has been registered on "ClinicalTrials.gov"with protocol ID "NAC-2015-TJAH" and ClinicalTrials.gov ID " NCT02972398 ".
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Efficacy of N-Acetylcysteine in Preventing Acute Kidney Injury After Cardiac Surgery: A Meta-Analysis Study.
Mei, M, Zhao, HW, Pan, QG, Pu, YM, Tang, MZ, Shen, BB
Journal of investigative surgery : the official journal of the Academy of Surgical Research. 2018;(1):14-23
Abstract
PURPOSE To evaluate whether perioperative N-acetylcysteine (NAC) administration reduces the risk of cardiac surgery associated acute kidney injury (CSA-AKI). MATERIALS AND METHODS A systematic literature review (Medline, PubMed, Cochrane, Biomedical central, Google Scholar) identified 10 studies (1391 patients; 695 NAC and 696 placebo) that compared the efficacy and adverse effects of perioperative NAC administration for CSA-AKI prevention in adults undergoing elective cardiac surgery. Meta-analysis was performed using Comprehensive Meta-Analysis statistical software. RESULTS Patients in the NAC-treated and placebo groups had similar rate of CSA-AKI occurrence, change in creatinine levels, as well as the in-hospital mortality rate (RR = 0.841, 95% CI = 0.691 to 1.023, p = 0.083; pooled difference in means = -0.328, 95% CI = -0.712 to 0.056, p = 0.094; RR = 0.741, 95% CI = 0.388 to 1.418, p = 0.366, respectively). CONCLUSIONS Our study does not support perioperative NAC administration as a mean to reduce the risk of CSA-AKI.
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Acute kidney injury: Antioxidants do not PRESERVE kidney function after contrast exposure.
Solomon, R
Nature reviews. Nephrology. 2018;(3):148-149