N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Oxidative stress is considered to be part of the pathogenic mechanism for community-acquired pneumonia (CAP) and is closely linked to inflammation. Attenuation of oxidative stress would be expected to reduce pulmonary damage. Antioxidants have been found to be effective in alleviating lung injury and protecting against damage of other organs.

The aim of the study was to compare the effect of adding N-acetylcysteine (NAC) to conventional treatment versus conventional treatment on oxidative stress, inflammatory factors, and radiological changes in CAP patients.

Eligible CAP patients at Weihai Municipal Hospital were stratified and randomly assigned to either NAC group or non-NAC group between August 2016 and March 2017. The NAC group received conventional treatment for pneumonia and NAC (1200 mg/d). Thenon-NAC group received conventional therapy. malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (TAOC), tumor necrosis factor-α (TNF-α), and computed tomography (CT) images were evaluated at baseline and after treatment. The primary endpoint indicators were the changes in oxidative stress parameters (MDA, TAOC, SOD) and TNF-α after treatment in the NAC group compared with those in the non-NAC group. The secondary endpoint indicator was any difference in CT scores after treatment in the NAC group compared with the non-NAC group.

Baseline levels of MDA, TAOC, SOD, and TNF-α were similar between the 2 groups before treatment. Plasma levels of MDA and TNF-α decreased more ( P < .05 MDA:p 0.004, TNF-α:p <0.001) in the NAC group than the non-NAC group, and there was a reliable increase in TAOC content (p 0.005). There was no significant difference in increased plasma SOD activity between the groups (p 0.368), and the NAC group did not show a greater improvement from CT scores. No NAC-related adverse effects were observed.

Addition of NAC therapy for CAP patients reduced MDA and TNF-α and increased TAOC. Treatment with NAC may help to reduce oxidative and inflammatory damage in pneumonia patients.

Related collections

Most cited references 34

Record: found
Abstract: found
Article: not found

Oxidative stress and regulation of glutathione in lung inflammation.

W MacNee, Irfan Rahman (2000)

Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance, a major cause of cell damage. The development of an oxidant/antioxidant imbalance in lung inflammation may activate redox-sensitive transcription factors such as nuclear factor-KB, and activator protein-1 (AP-1), which regulate the genes for pro-inflammatory mediators and protective antioxidant genes. Glutathione (GSH), a ubiquitous tripeptide thiol, is a vital intra- and extracellular protective antioxidant against oxidative/nitrosative stresses, which plays a key role in the control of pro-inflammatory processes in the lungs. Recent findings have suggested that GSH is important in immune modulation, remodelling of the extracellular matrix, apoptosis and mitochondrial respiration. The rate-limiting enzyme in GSH synthesis is gamma-glutamylcysteine synthetase (gamma-GCS). The human gamma-GCS heavy and light subunits are regulated by AP-1 and antioxidant response elements and are modulated by oxidants, phenolic antioxidants, growth factors, and inflammatory and anti-inflammatory agents in lung cells. Alterations in alveolar and lung GSH metabolism are widely recognized as a central feature of many inflammatory lung diseases such as idiopathic pulmonary fibrosis, acute respiratory distress syndrome, cystic fibrosis and asthma. The imbalance and/or genetic variation in antioxidant gamma-GCS and pro-inflammatory versus antioxidant genes in response to oxidative stress and inflammation in some individuals may render them more susceptible to lung inflammation. Knowledge of the mechanisms of GSH regulation and balance between the release and expression of pro- and anti-inflammatory mediators could lead to the development of novel therapies based on the pharmacological manipulation of the production as well as gene transfer of this important antioxidant in lung inflammation and injury. This review describes the redox control and involvement of nuclear factor-kappaB and activator protein-1 in the regulation of cellular glutathione and gamma-glutamylcysteine synthetase under conditions of oxidative stress and inflammation, the role of glutathione in oxidant-mediated susceptibility/tolerance, gamma-glutamylcysteine synthetase genetic susceptibility and the potential therapeutic role of glutathione and its precursors in protecting against lung oxidant stress, inflammation and injury.

0 comments Cited 84 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types.

Vicki Stone, Simon H J Brown, Ken Donaldson … (2002)

PM10 contains an ultrafine component, which is generally derived from combustion processes. This ultrafine fraction may be a factor in the increases in exacerbations of respiratory disease and deaths from cardiorespiratory causes associated with transient increases in levels of PM10. By using four different ultrafine particles (carbon black, cobalt, nickel, and titanium dioxide), we set out to determine the attributes of the ultrafine particle (surface area, chemical composition, particle number, or surface reactivity) that contribute most to its toxicity and proinflammatory effects both in vivo and in vitro. Instillation of 125 micro g ultrafine carbon black (UFCB) and ultrafine cobalt (UFCo) particles induced a significant influx of neutrophils at both 4 and 18 h postinstillation. Accompanying the influx of neutrophils was an increase in macrophage inflammatory protein-2 (MIP-2) (at 4 h) and an increase in gamma-glutamyl transpeptidase (at 18 h) in bronchoalveolar lavage fluid (BAL). Ultrafine nickel (UFNi) did not induce a significant increase in neutrophil influx until 18 h postinstillation. The increase in neutrophils induced by UFNi at this timepoint was comparable to that induced by UFCo and UFCB. UFTi did not induce a significant increase in neutrophils following instillation into the rat lung. The levels of MIP-2 observed at 4 h and neutrophil influx at 18 h induced by the particle samples were consistent with the pattern of surface free radical generation (as measured by the plasmid scission assay) whereby UFCo, UFCB, and UFNi all cause significant increases in inflammatory markers, as well as inducing a significant depletion of supercoiled plasmid DNA, indicative of hydroxyl radical generation. A role for free radicals and reactive oxygen species (ROS) in mediating ultrafine inflammation is further strengthened by the ability of the antioxidants N-acetylcysteine (NAC) and glutathione monoethyl ester (GSHme) to block the particle induced release of tumour necrosis factor-alpha (TNF-alpha) from alveolar macrophages in vitro. The ultrafine particles in PM10 may cause adverse effects via oxidative stress, and this could have implications for susceptible individuals. Susceptible individuals, such as those with COPD or asthma, already exhibit preexisting oxidative stress and hence are in a primed state for further oxidative stress induced by occupational or environmental particles.

0 comments Cited 60 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

N-acetyl-L-cysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with respiratory syncytial virus (RSV).

Manuel Mata, Julio Cortijo, Concepción Gimeno … (2011)

64% of chronic obstructive pulmonary disease (COPD) exacerbations are caused by respiratory infections including influenza (strains A and B) and respiratory syncytial virus (RSV). They affect the airway epithelium increasing inflammatory and apoptosis events through mechanisms involving ROS generation, and induce the release of mucins from epithelial cells that are involved in the deterioration of the patient's health during the course of the disease. The antioxidant NAC has proved useful in the management of COPD reducing symptoms, exacerbations and accelerated lung function decline. It has been shown to inhibit influenza virus replication and to diminish the release of inflammatory and apoptotic mediators during virus infection. The main objective of this study is to analyze the effects of NAC in modulating MUC5AC over-expression and release in an in vitro infection model of alveolar type II A549 cells infected with influenza (strains A and B) and RSV. We have also analyzed virus replication and different pro-inflammatory responses. Our results indicate a significant induction of MUC5AC, IL8, IL6 and TNF-alpha that is strongly inhibited by NAC at the expression and at the release level. It also decreased the intracellular H(2)O(2) concentration and restored the intracellular total thiol contents. Mechanisms of NAC included inhibition of NF-κB translocation to the cellular nucleus and phosphorylation of MAPK p38. NAC also inhibited replication of the three viruses under study. This work supports the use of antioxidants in order to ameliorate the inflammatory effects of different viral infections during COPD exacerbations. Copyright © 2011 Elsevier Inc. All rights reserved.

0 comments Cited 54 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Medicine (Baltimore)

Journal ID (iso-abbrev): Medicine (Baltimore)

Journal ID (publisher-id): MEDI

Title: Medicine

Publisher: Wolters Kluwer Health

ISSN (Print): 0025-7974

ISSN (Electronic): 1536-5964

Publication date Collection: November 2018

Publication date (Electronic): 09 November 2018

Volume: 97

Issue: 45

Electronic Location Identifier: e13087

Affiliations

[a ]Department of Respiratory and Critical Care Medicine, Shandong Provincial Hospital Affiliated to Shandong University

[b ]Department of Respiratory, Weihai Municipal Hospital, Weihai

[c ]Shandong Medical Imaging Research Institute Affiliated to Shandong University, Jinan, Shandong, China.

Author notes

[∗ ]Correspondence: Tao Wang, Shandong Medical Imaging Research Institute Affiliated to Shandong University, 324 Jingwu Weiqi Road, Jinan, Shandong 250021, China (e-mail: 1142555214@ 123456qq.com)

Article

Publisher ID: MD-D-18-01903 Accession ID: 13087

DOI: 10.1097/MD.0000000000013087

PMC ID: 6250560

PubMed ID: 30407312

SO-VID: be8a2fbb-7833-4d8a-b7f0-70b22aac8d55

License:

This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0

History

Date received : 15 March 2018

Date accepted : 11 October 2018

Custom metadata

OPEN-ACCESS TRUE

Keywords: n-acetylcysteine,oxidative stress,pneumonia

Data availability:

Keywords: n-acetylcysteine, oxidative stress, pneumonia

Comments

Comment on this article

scite_

Cited by 41

See all cited by

Most referenced authors 634

See all reference authors

- Version 1

N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia : A randomized controlled trial

Read this article at

Abstract

Related collections

Stress signalling in stem cells

Most cited references 34

Oxidative stress and regulation of glutathione in lung inflammation.

The role of free radicals in the toxic and inflammatory effects of four different ultrafine particle types.

N-acetyl-L-cysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with respiratory syncytial virus (RSV).

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Custom metadata

Comments

Comment on this article

Similar content 206

Cited by 41

Most referenced authors 634