Chang Yu-Chao, Huang Fu-Mei, Tai Kuo-Wei, Yang Li-Chiu, Chou Ming-Yung
Department of Periodontics, College of Oral Medicine, Chung Shan Medical University Hospital, 110, Sec. 1, Chien-Kuo N. Road., Taichung, Taiwan.
J Periodontal Res. 2002 Aug;37(4):279-85. doi: 10.1034/j.1600-0765.2002.01612.x.
The use of tobacco products significantly contributes to the progression of periodontal disease and poor response to healing following periodontal therapy. The purpose of this study was to determine the effects of nicotine, a major component of cigarette smoking, on human periodontal ligament fibroblast (PDLF) growth, proliferation, and protein synthesis to elucidate its role in periodontal destruction associated with its use. Human PDLFs were derived from three healthy individuals undergoing extraction for orthodontic reasons. At a concentration higher than 2.5 mM, nicotine was found to be cytotoxic to human PDLFs (P < 0.05). Nicotine also significantly inhibited cell proliferation and decreased protein synthesis in a dose-dependent manner. At concentrations of 50 and 200 microM, nicotine suppressed the growth of PDLFs by 48% and 86% (P < 0.05), respectively. A 10-mM concentration level of nicotine significantly inhibited the protein synthesis to only 44% of these in the untreated control (P < 0.05). Furthermore, the effects of antioxidants (superoxide dismutase (SOD); catalase and 2-oxothiazolidine-4-carboxylic acid (OTZ) and buthionine sulfoximine (BSO) were added to search for the possible mechanism of action, as well as a method for the prevention, of cigarette smoking-associated periodontal diseases. The addition of OTZ, a precursor of cysteine that metabolically promotes GSH synthesis, acted as a protective effect on the nicotine-induced cytotoxicity. However, SOD and catalase did not decrease the nicotine-induced cytotoxicity. In contrast, the addition of BSO, a cellular GSH synthesis inhibitor, enhanced the nicotine-induced cytotoxicity. These results indicate that thiol depletion could be the mechanism for nicotine cytotoxicity. The levels of nicotine tested inhibited cell growth, proliferation, and protein synthesis on human PDLFs. This suggests that nicotine itself might augment the destruction of periodontium associated with cigarette smoking. In addition, these inhibitory effects were associated with intracellular thiol levels. Factors that induce glutathione synthesis of human PDLF may be used for further chemoprevention of cigarette smoking-related periodontal diseases.
烟草制品的使用显著促进了牙周疾病的进展以及牙周治疗后愈合反应不佳。本研究的目的是确定香烟烟雾的主要成分尼古丁对人牙周膜成纤维细胞（PDLF）生长、增殖和蛋白质合成的影响，以阐明其在与吸烟相关的牙周破坏中的作用。人PDLF来自三名因正畸原因接受拔牙的健康个体。当浓度高于2.5 mM时，发现尼古丁对人PDLF具有细胞毒性（P < 0.05）。尼古丁还以剂量依赖性方式显著抑制细胞增殖并降低蛋白质合成。在50和200 microM浓度下，尼古丁分别抑制PDLF生长48%和86%（P < 0.05）。10 mM浓度水平的尼古丁显著抑制蛋白质合成，仅为未处理对照的44%（P < 0.05）。此外，添加抗氧化剂（超氧化物歧化酶（SOD）、过氧化氢酶以及2-氧代噻唑烷-4-羧酸（OTZ）和丁硫氨酸亚砜胺（BSO））以寻找可能的作用机制以及预防与吸烟相关的牙周疾病的方法。添加OTZ（一种代谢促进谷胱甘肽合成的半胱氨酸前体）对尼古丁诱导的细胞毒性具有保护作用。然而，SOD和过氧化氢酶并未降低尼古丁诱导的细胞毒性。相反，添加细胞内谷胱甘肽合成抑制剂BSO增强了尼古丁诱导的细胞毒性。这些结果表明，硫醇耗竭可能是尼古丁细胞毒性的机制。所测试的尼古丁水平抑制了人PDLF的细胞生长、增殖和蛋白质合成。这表明尼古丁本身可能加剧与吸烟相关的牙周组织破坏。此外，这些抑制作用与细胞内硫醇水平有关。诱导人PDLF谷胱甘肽合成的因素可能用于进一步化学预防与吸烟相关 的牙周疾病。
