Journal article
The effect of an oral anti-oxidant, N-Acetyl-cysteine, on inflammatory and oxidative markers in pulmonary sarcoidosis
Respiratory medicine, Vol.112, pp.106-111
03/2016
DOI: 10.1016/j.rmed.2016.01.011
PMID: 26831541
Abstract
Oxidative stress (OS) has been shown to play a role in the pathogenesis of sarcoidosis and previous studies have shown that anti-oxidants can reduce markers of oxidative stress and inflammation in the peripheral blood of sarcoidosis subjects. We investigated the effect of N-Acetyl-Cysteine (NAC) on oxidative stress and inflammatory markers in the lungs of sarcoidosis patients.
We randomized 11 sarcoidosis subjects to active therapy and 3 to placebo for 8 weeks in a double blinded study. Bronchoscopy with bronchoalveolar lavage was performed pre and post therapy. Our primary endpoint was TNF-α production from stimulated and unstimulated BAL cells. Secondary outcomes included measures of oxidative stress (GSH, 8-OHdG) levels in the BAL. In-vitro studies were also performed to assess the effect of NAC on lipopolysaccharide stimulated BAL cell production of TNF-α.
Eight subjects in the active group and 2 in the placebo group completed the study protocol. Eight weeks of oral NAC did not have a significant impact on TNF-α levels from BAL cells in-vivo in spite of a 59% increase in BAL GSH levels. Our in vitro studies showed a significant decline in TNF-α production from LPS stimulated BAL cells treated with 5 and 10 mM of NAC.
Oral NAC increased GSH levels but failed to suppress in-vivo TNF-α production in contrast to effects in-vitro. Anti-oxidant therapy may still play a role in the management of sarcoidosis but therapy with better bioavailability or potency is needed to suppress the lung inflammatory response.
•N-Acetyl-cysteine (NAC) improves markers of oxidative stress in sarcoidosis.•The attenuation of lung oxidative stress by NAC is inadequate to suppress markers of lung inflammation in sarcoidosis.•The lack of improvement in lung inflammation by NAC is most likely due to poor NAC lung bioavailability.
Details
- Title: Subtitle
- The effect of an oral anti-oxidant, N-Acetyl-cysteine, on inflammatory and oxidative markers in pulmonary sarcoidosis
- Creators
- Nabeel Hamzeh - Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO, United StatesLi Li - Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO, United StatesBriana Barkes - Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO, United StatesJie Huang - National Jewish HealthBeth Canono - Department of Medicine, National Jewish Health, Denver, CO, United StatesMay Gillespie - Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO, United StatesLisa Maier - Division of Environmental and Occupational Health Sciences, National Jewish Health, Denver, CO, United StatesBrian Day - Department of Medicine, National Jewish Health, Denver, CO, United States
- Resource Type
- Journal article
- Publication Details
- Respiratory medicine, Vol.112, pp.106-111
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/j.rmed.2016.01.011
- PMID
- 26831541
- ISSN
- 0954-6111
- eISSN
- 1532-3064
- Language
- English
- Date published
- 03/2016
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Internal Medicine
- Record Identifier
- 9984094310502771
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