The effects of erdosteine, N-acetylcysteine, and vitamin E on nicotine-induced apoptosis of pulmonary cells.
This study was conducted to investigate the frequency of apoptosis in the pulmonary epithelial cells of rats after intratraperitoneal nicotine injection, in order to examine the role of inflammatory markers [myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-alpha)] in nicotine-induced lung damage, and to determine the protective effects of three known antioxidant agents [N-acetylcysteine (NAC), erdosteine, and vitamin E] on the lung toxicity of nicotine in the lungs. Female Wistar rats were divided into seven groups, each composed of nine rats: two negative control groups, two positive control groups, one erdosteine-treated group (500 mg/kg), one NAC-treated group (500 mg/kg), and one vitamin E-treated group (500 mg/kg). Nicotine was injected intraperitoneally at a dosage of 0.6 mg/kg for 21 days. Following nicotine injection, the antioxidants were administered orally, treatment was continued until the rats were killed. Lung tissue samples were stained with hematoxylin-eosin (H&E) for histopathological assessments. The apoptosis level in the lung bronchiolar and alveolar epithelium was determined by using the terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) method. Cytoplasmic TNF-alpha in the bronchiolar and alveolar epithelial cells and the lung MPO activity were evaluated immunohistochemically. The protective effect of vitamin E on lung histology was stronger than that of erdosteine or NAC. Treatment with erdosteine, NAC, and vitamin E significantly reduced the rate of nicotine-induced pulmonary epithelial cell apoptosis, and there were no significant differences in apoptosis among the three antioxidants groups. Erdosteine, NAC, and vitamin E significantly reduced the increases in TNF-alpha staining and lung MPO activity. The effects of erdosteine on the increases in the local TNF-alpha level and lung MPO activity were weaker than that of NAC or vitamin E. This findings suggest that erdosteine and NAC can be as effective as vitamin E in protecting against nicotine-induced pulmonary cell apoptosis.
Demiralay
Rezan
R
Department of Pulmonary Medicine, School of Medicine, Süleyman Demirel University, Isparta, Turkey. rezan@sdu.edu.tr
Gürsan
Nesrin
N
Erdem
Havva
H
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D004847:Epithelial Cells / Q000187:drug effects; D005100:Expectorants / Q000494:pharmacology*; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D009538:Nicotine / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D018733:Nicotinic Antagonists; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013864:Thioglycolates / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D005100:Expectorants; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D013864:Thioglycolates; D013876:Thiophenes; D014409:Tumor Necrosis Factor-alpha; D014810:Vitamin E; D009538:Nicotine; C048498:erdosteine; D009195:Peroxidase; D000111:Acetylcysteine