N-Acetylcysteine protects human bronchi by modulating the release of neurokinin A in an ex vivo model of COPD exacerbation.
Biomed Pharmacother
; 103: 1-8, 2018 Jul.
Article
in En
| MEDLINE
| ID: mdl-29635121
ABSTRACT
AIMS:
N-Acetylcysteine (NAC) reduces the risk of exacerbation of chronic obstructive pulmonary disease (COPD). Although NAC also has anti-inflammatory activity, the detailed mechanism leading to its protective role remains to be elucidated. We tested the impact of NAC against the effects of lipopolysaccharide (LPS) in an ex vivo model of COPD exacerbation, and investigated the role of neurokinin A (NKA) in this context. MAINMETHODS:
Isolated airways from COPD patients were incubated overnight with LPS (100â¯ng/ml). NAC was tested at concentrations resembling the plasma levels elicited by oral administration of NAC at 200â¯mg/day (very low dose), 600â¯mg/day (low dose) and 1.200â¯mg/day (high dose). KEYFINDINGS:
NAC at high concentrations normalized the peroxidase activity, H2O2, malondialdehyde (MDA), nitric oxide, glutathione (GSH), total antioxidant capacity (TAC), and interleukin 6 (IL-6) (overall change 34.32%⯱â¯4.22%, Pâ¯<â¯0.05 vs. LPS-treated). NAC at low concentrations modulated peroxidase activity, H2O2, MDA, GSH, TAC, and IL-6 (overall change 34.88%⯱â¯7.39%, Pâ¯<â¯0.05 vs. LPS-treated). NAC at very-low concentrations was effective on peroxidase activity, H2O2, GSH, and IL-6 (overall change 35.05⯱â¯7.71%, Pâ¯<â¯0.05 vs. LPS-treated). Binary logistic regression analysis indicated that the modulatory effect of NAC on NKA levels was associated with a reduction of pro-oxidant factors and IL-6, and selectively blocking the NK2 receptor abolished such an association.SIGNIFICANCE:
This study demonstrates that, along with its well-known antioxidant activity, the protective effect of NAC against the detrimental effect of LPS is due to the modulation of NKA and IL-6 levels.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Acetylcysteine
/
Bronchi
/
Neurokinin A
/
Disease Progression
/
Protective Agents
/
Pulmonary Disease, Chronic Obstructive
/
Models, Biological
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
Biomed Pharmacother
Year:
2018
Document type:
Article