<i>N</i>-Acetylcysteine mucolysis in the management of chronic obstructive pulmonary disease

Sadowska, Anna

doi:10.1177/1753465812437563

Cited by 82 publications

(66 citation statements)

References 48 publications

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“…Acetyl-cysteine is a derivative of cysteine in which an acetyl group is attached to nitrogen. Due to its disulfide reducing activity, NAC is used as a mucolytic agent to promote expectoration [2]. NAC is commonly prescribed as an adjunct therapy in patients with a wide range of respiratory diseases characterized by formation of thick mucus, such as cystic fibrosis [2–4].…”

Section: Introductionmentioning

confidence: 99%

“…Due to its disulfide reducing activity, NAC is used as a mucolytic agent to promote expectoration [2]. NAC is commonly prescribed as an adjunct therapy in patients with a wide range of respiratory diseases characterized by formation of thick mucus, such as cystic fibrosis [2–4]. At high doses, NAC results in significantly improved small airway function and decreased exacerbation frequency in patients with stable chronic obstructive pulmonary disease (COPD) [3, 4].…”

Section: Introductionmentioning

confidence: 99%

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N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions

et al. 2016

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Background Mycobacterium tuberculosis infection is thought to induce oxidative stress. N-acetyl-cysteine (NAC) is widely used in patients with chronic pulmonary diseases including tuberculosis due to its mucolytic and anti-oxidant activities. Here, we tested whether NAC exerts a direct antibiotic activity against mycobacteria.MethodsOxidative stress status in plasma was compared between pulmonary TB (PTB) patients and those with latent M. tuberculosis infection (LTBI) or healthy uninfected individuals. Lipid peroxidation, DNA oxidation and cell death, as well as accumulation of reactive oxygen species (ROS) were measured in cultures of primary human monocyte-derived macrophages infected with M. tuberculosis and treated or not with NAC. M. tuberculosis, M. avium and M. bovis BCG cultures were also exposed to different doses of NAC with or without medium pH adjustment to control for acidity. The anti-mycobacterial effect of NAC was assessed in M. tuberculosis infected human THP-1 cells and bone marrow-derived macrophages from mice lacking a fully functional NADPH oxidase system. The capacity of NAC to control M. tuberculosis infection was further tested in vivo in a mouse (C57BL/6) model.ResultsPTB patients exhibited elevated levels of oxidation products and a reduction of anti-oxidants compared with LTBI cases or uninfected controls. NAC treatment in M. tuberculosis-infected human macrophages resulted in a decrease of oxidative stress and cell death evoked by mycobacteria. Importantly, we observed a dose-dependent reduction in metabolic activity and in vitro growth of NAC treated M. tuberculosis, M. avium and M. bovis BCG. Furthermore, anti-mycobacterial activity in infected macrophages was shown to be independent of the effects of NAC on the host NADPH oxidase system in vitro. Short-term NAC treatment of M. tuberculosis infected mice in vivo resulted in a significant reduction of mycobacterial loads in the lungs.ConclusionsNAC exhibits potent anti-mycobacterial effects and may limit M. tuberculosis infection and disease both through suppression of the host oxidative response and through direct antimicrobial activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-016-0872-7) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions

et al. 2016

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“…However, whether propofol can effectively attenuate ALI induced by liver transplantation remains unclear. Thus, in the current study, a rat OALT model was used to explore the protective effects of propofol on ALI induced by liver transplantation compared with positive controls, including: NAC [a non-specific antioxidant (14)] and AP [a specific NADPH oxidase inhibitor (15)]. The mechanisms of the protective effect of propofol were analyzed, and suggested to be associated with the reduction in oxidative stress and inflammatory reaction mediated by the inhibition of NADPH oxidase.…”

Section: Introductionmentioning

confidence: 99%

Propofol alleviates acute lung injury following orthotopic autologous liver transplantation in rats via inhibition of the NADPH oxidase pathway

Luo

Zhu

Yuan

et al. 2014

Molecular Medicine Reports

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Abstract. Acute lung injury (ALI) induced by liver transplantation is detrimental to patient survival, and therapeutic strategies remain limited. Thus, the protective effects of propofol, a commonly used anesthetic with antioxidative and anti-inflammatory properties, were investigated in the present study on ALI induced by orthotopic autologous liver transplantation (OALT). The protective mechanism of propofol was determined to be associated with the inhibition of NADPH oxidase, by comparing its effects with the positive controls apocynin (AP; an NADPH oxidase inhibitor) and N-acegysteine (NAC; a scavenger of reactive oxygen species). The results demonstrated that two proteins (p47phox and gp91phox) of the NADPH oxidase system presented increased expression in rats with ALI induced by OALT, thus leading to increased activation of the oxidative stress and inflammatory reactions. Preconditioning with NAC or AP eliminated this increase, suggesting that antioxidative treatment, particularly with inhibitors of NADPH oxidase, is a promising protective strategy against ALI induced by OALT. Propofol preconditioning at a high (100 mg/kg) or low (50 mg/kg) dose promoted similar protective effects, with the high-dose propofol producing a more marked effect than the low dose. The results suggested that propofol may protect against ALI induced by OALT, the mechanism of which may involve a reduced oxidative stress and inflammatory reaction mediated by NADPH oxidase inhibition.

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“…However, NAC could not rescue growth inhibition caused by c-CuNPs. While NAC can function as an antioxidant when it is imported into cells, NAC is the precursor to glutathione, which is more potent at reducing ROS 35 . Therefore, while the pattern of c-CuNP sensitivity approximately mirrored soluble Cu sensitivity, the difference in NAC rescue suggests differences in Cu delivery, and likely, cellular internalization, between cells exposed to soluble Cu and c-CuNPs.…”

Section: Resultsmentioning

confidence: 99%

Proteomic and genetic analysis of the response of S. cerevisiae to soluble copper leads to improvement of the antimicrobial function of cellulosic copper nanoparticles

et al. 2017

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Copper (Cu) was used in antiquity to prevent waterborne and food diseases because, as a broad-spectrum antimicrobial agent, it generates reactive oxygen species, ROS. New technologies incorporating Cu into low-cost biodegradable nanomaterials built on cellulose, known as cellulosic cupric nanoparticles or c-CuNPs, present novel approaches to deliver Cu in a controlled manner to control microbial growth. We challenged strains of Saccharomyces cerevisiae to soluble Cu and c-CuNPs to evaluate the potential of c-CuNPs as antifungal agents. Cells exposed to c-CuNPs demonstrated greater sensitivity to Cu than cells exposed to soluble Cu, although Cu-resistant strains were more tolerant than Cu-sensitive strains of c-CuNP exposure. At the same level of growth inhibition, 157 μM c-CuNP led to the same internal Cu levels as did 400 CuSO4, offering evidence for alternative mechanisms of toxicity, perhaps through β-arrestin dependent endocytosis, which was supported by flow cytometry and fluorescence microscopy of c-CuNPs distributed both on the cell surface and within the cytoplasm. Genes responsible for genetic variation to copper were mapped to the ZRT2 and the CUP1 loci. Through proteomic analyses, we found that the expression of other zinc (Zn) transporters increased in Cu-tolerant yeast compared to Cu-sensitive strains. Further, the addition of Zn at low levels increased the potency of c-CuNP to inhibit even the most Cu-tolerant yeast. Through unbiased systems biological approaches, we identified Zn as a critical component of yeast response to Cu and the addition of Zn increased potency of the c-CuNPs.

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N-Acetylcysteine mucolysis in the management of chronic obstructive pulmonary disease

Cited by 82 publications

References 48 publications

N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions

N-acetyl-cysteine exhibits potent anti-mycobacterial activity in addition to its known anti-oxidative functions

Propofol alleviates acute lung injury following orthotopic autologous liver transplantation in rats via inhibition of the NADPH oxidase pathway

Proteomic and genetic analysis of the response of S. cerevisiae to soluble copper leads to improvement of the antimicrobial function of cellulosic copper nanoparticles

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