Demiralay Rezan, Gürsan Nesrin, Erdem Havva
Department of Pulmonary Medicine, School of Medicine, Süleyman Demirel University, Isparta, Turkey.
J Cell Biochem. 2008 Aug 1;104(5):1740-6. doi: 10.1002/jcb.21739.
This study investigated the frequency of apoptosis in rat hippocampal neural cells after intraperitoneal nicotine injection, examining the roles of the inflammatory markers myeloperoxidase (MPO) and tumor necrosis factor alpha (TNF-alpha) in nicotine-induced brain damage and the protective effects of three known antioxidant agents, N-acetylcysteine (NAC), erdosteine, and vitamin E. Female Wistar rats were divided into seven groups, each composed of nine rats: 2 negative control groups, 2 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 intraperitoneally injected 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. Apoptosis level in hippocampal neural cells was determined by using TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick endlabeling) method. Staining of cytoplasmic TNF-alpha in hippocampal neural cells and hippocampus MPO activity were evaluated by immunohistochemistry. Nicotine administration had no effect on local TNF-alpha production, or hippocampal MPO activity. The treatments with erdosteine, NAC and vitamin E significantly reduced the rate of nicotine-induced hippocampal neural cell apoptosis. This findings suggest that erdosteine and NAC can be as effective as vitamin E in protecting against nicotine-induced hippocampal neural cell apoptosis.
本研究调查了腹腔注射尼古丁后大鼠海马神经细胞的凋亡频率，探讨了炎症标志物髓过氧化物酶（MPO）和肿瘤坏死因子α（TNF-α）在尼古丁诱导的脑损伤中的作用以及三种已知抗氧化剂N-乙酰半胱氨酸（NAC）、厄多司坦和维生素E的保护作用。雌性Wistar大鼠被分为七组，每组九只：2个阴性对照组、2个阳性对照组、1个厄多司坦治疗组（500 mg/kg）、1个NAC治疗组（500 mg/kg）和1个维生素E治疗组（500 mg/kg）。以0.6 mg/kg的剂量腹腔注射尼古丁，持续21天。注射尼古丁后，口服给予抗氧化剂；治疗持续至大鼠处死。采用TUNEL（末端脱氧核苷酸转移酶介导的dUTP缺口末端标记）法测定海马神经细胞的凋亡水平。通过免疫组织化学评估海马神经细胞中细胞质TNF-α的染色和海马MPO活性。给予尼古丁对局部TNF-α产生或海马MPO活性没有影响。厄多司坦、NAC和维生素E治疗显著降低了尼古丁诱导的海马神经细胞凋亡率。该研究结果表明，在预防尼古丁诱导的海马神经细胞凋亡方面，厄多司坦和NAC与维生素E同样有效。
