Effect of inhaled N-acetylcysteine on hydrogen peroxide exhalation in healthy subjects

Szkudlarek, Urszula; Zdziechowski, Adam; Witkowski, Konrad; Kasielski, Marek; Luczyńska, Maria; Luczynski, Rafal; Sarniak, Agata; Nowak, Dariusz

doi:10.1016/j.pupt.2004.01.007

Cited by 32 publications

(27 citation statements)

References 29 publications

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“…According to that report (12), this concentration can be reached in patients with severe respiratory disorders treated with high doses of NAC. Moreover, it has been proposed that the concentration of active NAC in the lower airways after its administration via nebulization of a single dose of 300 mg may be as high as 29 mM (21). Therefore, 10 mM is a realistic concentration of NAC to be tested.…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, a large effect on imipenem activity can be observed at concentrations of NAC as low as 0.8 mg/ml (equivalent to 5 mM), which are in the range of concentrations attainable in plasma after intravenous administration (23) or in lungs after its administration via nebulization (21). However, the mean plasma concentration of NAC after oral administration is far below the concentration of NAC necessary to affect imipenem activity (24), even in patients with end-stage renal disease (25).…”

Section: Fig 2 Antagonistic Effect Of Nac On Imipenem Activity Diffementioning

confidence: 99%

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N-Acetylcysteine Selectively Antagonizes the Activity of Imipenem in Pseudomonas aeruginosa by an OprD-Mediated Mechanism

Rodríguez-Beltrán

Cabot²,

Valencia

et al. 2015

Antimicrob Agents Chemother

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The modulating effect of N-acetylcysteine (NAC) on the activity of different antibiotics has been studied in Pseudomonas aeruginosa. Our results demonstrate that, in contrast to previous reports, only the activity of imipenem is clearly affected by NAC. MIC and checkerboard determinations indicate that the NAC-based modulation of imipenem activity is dependent mainly on OprD. SDS-PAGE of outer membrane proteins (OMPs) after NAC treatments demonstrates that NAC does not modify the expression of OprD, suggesting that NAC competitively inhibits the uptake of imipenem through OprD. Similar effects on imipenem activity were obtained with P. aeruginosa clinical isolates. Our results indicate that imipenem-susceptible P. aeruginosa strains become resistant upon simultaneous treatment with NAC and imipenem. Moreover, the generality of the observed effects of NAC on antibiotic activity was assessed with two additional bacterial species, Escherichia coli and Acinetobacter baumannii. Caution should be taken during treatments, as the activity of imipenem may be modified by physiologically attainable concentrations of NAC, particularly during intravenous and nebulized regimes.A lthough its benefit has been questioned (1), N-acetylcysteine (NAC) is being used for the treatment of numerous disorders, including paracetamol intoxication, doxorubicin cardiotoxicity, ischemia-reperfusion cardiac injury, acute respiratory distress syndrome, bronchitis, chemotherapy-induced toxicity, HIV/ AIDS, heavy metal toxicity, and psychiatric disorders (2). This compound is also sold as a dietary supplement, with claims of antioxidant and liver-protecting effects. The antioxidant activity of NAC has been attributed to its reactivity with ·OH, ·NO2, CO 3 · Ϫ , and thiyl radicals, to its capacity for repair of oxidized key cellular molecules, and to its activity as a precursor for glutathione biosynthesis (2). Because of this mucolytic capacity, it has also been used to facilitate the processing of sputum specimens in bacteriology laboratories (3). The ability of NAC to reduce biofilms, alone or in combination with antimicrobials, has been addressed in several bacterial species (4-6). Furthermore, NAC has been proposed as a treatment in Helicobacter pylori infections (7). NAC utility in reducing sputum viscosity in patients with cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) (8), likely due to its ability to break disulfide bonds, has also been claimed, although its mechanism of action is not well understood.As a result of an imbalance between the production of reactive oxygen species (ROS) caused by inflammation and their inactivation by the impaired antioxidant systems, CF patients with chronic Pseudomonas aeruginosa lung infection have increased oxidative stress. Therefore, antioxidant interventions, including the use of NAC, have been proposed to reduce the extent of oxidative lesions and the rate of lung deterioration (for a review, see reference 9). However, although controversial results on the improvement of lung f...

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Section: Resultsmentioning

confidence: 99%

Section: Fig 2 Antagonistic Effect Of Nac On Imipenem Activity Diffementioning

confidence: 99%

N-Acetylcysteine Selectively Antagonizes the Activity of Imipenem in Pseudomonas aeruginosa by an OprD-Mediated Mechanism

Rodríguez-Beltrán

Cabot²,

Valencia

et al. 2015

Antimicrob Agents Chemother

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“…Inhaled deionised water or 0.9% NaCl does not affect EBC H 2 O 2 concentrations. However, nebulised N-acetylcysteine almost completely abolishes EBC H 2 O 2 levels 30 min after administration, although this rises almost two-fold above baseline 2.5 h later [ 95 ]. A transient increase in EBC H 2 O 2 following nebulised N-acetylcysteine has been demonstrated in patients with stable COPD [ 96 ], despite a decrease with long-term treatment [ 97 ].…”

Section: Medicationmentioning

confidence: 97%

Exhaled breath condensate: a comprehensive update

Ahmadzai

Huang²,

Hettiarachchi³

et al. 2013

Clinical Chemistry and Laboratory Medicine

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Since the late 1990s, a surge in interest in the analysis of exhaled breath condensate (EBC) resulted in the American Thoracic Society and European Respiratory Society (ATS/ERS) organising a Task Force in 2001 to develop guidelines on EBC collection and measurement of biomarkers. This Task Force published their guidelines in 2005 based on literature and expert opinions at that time, and multiple shortcomings and knowledge deficits were also identified. The clinical application of EBC collection and its biomarkers are currently still limited by several of these knowledge gaps, hence further guidelines for standardisation are required to ensure external validity. Using related articles produced since the publication of the ATS/ERS Task Force report, this paper attempts to provide a comprehensive update to the original guideline and review the methodological shortcomings identified. This review can hopefully serve as a yardstick for future studies involving this emerging clinical tool.

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“…In this study, we used 10 and 50 mM NAC concentrations, which represented the concentration tested in previous studies and a 5-fold higher concentration, respectively. The latter concentration was used since it was suggested that concentrations of active NAC as high as 29 mM can be achieved after a single topical administration of 10% NAC (13), and even higher concentrations could be achieved by multiple-dosing regimens, by using 20% NAC for nebulization, or by following direct instillation.…”

Section: Textmentioning

confidence: 99%

Effect of High N -Acetylcysteine Concentrations on Antibiotic Activity against a Large Collection of Respiratory Pathogens

Landini

Maggio

Sergio

et al. 2016

Antimicrob Agents Chemother

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The effect of high N-acetylcysteine (NAC) concentrations (10 and 50 mM) on antibiotic activity against 40 strains of respiratory pathogens was investigated. NAC compromised the activity of carbapenems (of mostly imipenem and, to lesser extents, meropenem and ertapenem) in a dose-dependent fashion. We demonstrated chemical instability of carbapenems in the presence of NAC. With other antibiotics, 10 mM NAC had no major effects, while 50 mM NAC sporadically decreased (ceftriaxone and aminoglycosides) or increased (penicillins) antibiotic activity.

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Effect of inhaled N-acetylcysteine on hydrogen peroxide exhalation in healthy subjects

Cited by 32 publications

References 29 publications

N-Acetylcysteine Selectively Antagonizes the Activity of Imipenem in Pseudomonas aeruginosa by an OprD-Mediated Mechanism

N-Acetylcysteine Selectively Antagonizes the Activity of Imipenem in Pseudomonas aeruginosa by an OprD-Mediated Mechanism

Exhaled breath condensate: a comprehensive update

Effect of High N -Acetylcysteine Concentrations on Antibiotic Activity against a Large Collection of Respiratory Pathogens

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