Oral N-acetylcysteine attenuates pulmonary emphysema and alveolar septal cell apoptosis in smoking-induced COPD in rats.

Abstract

BACKGROUND AND OBJECTIVE:

The role of apoptosis in lung destruction in emphysema/COPD is increasingly being recognized. The relationship between anti-oxidants and alveolar septal cell apoptosis in COPD lungs remains to be elucidated. The aim of this study was to investigate the effects of the anti-oxidant, N-acetylcysteine (NAC), on the development of emphysema and alveolar septal cell apoptosis in smoking-induced COPD in rats.

METHODS:

Sprague-Dawley rats (n = 48) were randomly assigned to normal, COPD, sham and NAC groups. The effects of treatment were assessed by measuring the levels of vascular endothelial growth factor (VEGF) in BAL fluid by ELISA, VEGF and VEGF receptor-2 (VEGFR2) protein expression by western blotting, and the apoptotic index (AI) of alveolar septal cells by terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) assay. Histopathological evaluations (mean linear intercept (MLI), destructive index (DI)) and lung function measurements were performed.

RESULTS:

FEV(0.3)/FVC and PEF were lower in the COPD group than in the normal group. MLI and DI were lower in the NAC-treated group than in the COPD or sham-treated groups. As confirmed by western blotting, the levels of VEGF in BAL fluid were higher in the NAC-treated group than in the COPD group. VEGFR2 protein expression was higher in the NAC-treated group than in the COPD group. The AI was significantly lower in the NAC-treated group than in the COPD group. There was an inverse correlation between levels of VEGF in BAL fluid and the AI of alveolar septal cells.

CONCLUSIONS:

NAC attenuates lung damage, pulmonary emphysema and alveolar septal cell apoptosis by partly reversing the decrease in VEGF secretion and VEGFR2 protein expression in smoking-induced COPD in rats.

• Authors: Shan Cai, Ping Chen, Cheng Zhang, Jian-Bo Chen, Jie Wu
• Journal: Respirology (Carlton, Vic.) (Respirology) Vol. 14 Issue 3 Pg. 354-9 (Apr 2009) ISSN: 1440-1843 [Electronic] Australia
• PMID: 19341424 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antioxidants
• Vascular Endothelial Growth Factor A
• Acetylcysteine

Topics

• Acetylcysteine (administration & dosage, pharmacology, therapeutic use)
• Administration, Oral
• Animals
• Antioxidants (administration & dosage, pharmacology, therapeutic use)
• Apoptosis (drug effects)
• Bronchoalveolar Lavage Fluid
• Disease Models, Animal
• Male
• Pulmonary Alveoli (drug effects, pathology, physiopathology)
• Pulmonary Disease, Chronic Obstructive (drug therapy, pathology, physiopathology)
• Pulmonary Emphysema (drug therapy, pathology, physiopathology)
• Rats
• Rats, Sprague-Dawley
• Smoking (adverse effects)
• Vascular Endothelial Growth Factor A (metabolism)