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.