title: The effects of erdosteine, N-acetylcysteine, and vitamin E on nicotine-induced apoptosis of pulmonary cells.
abstract: 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.
authors.affiliation: Department of Pulmonary Medicine, School of Medicine, Süleyman Demirel University, Isparta, Turkey. rezan@sdu.edu.tr
authors.forename: Rezan
authors.initials: R
authors.lastname: Demiralay
authors.forename: Nesrin
authors.initials: N
authors.lastname: Gürsan
authors.forename: Havva
authors.initials: H
authors.lastname: Erdem
mesh_terms: 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*
chemical_list: 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