Yildiz D, Ercal N, Armstrong D W
Department of Chemistry, University of Missouri-Rolla, 65409-0010, USA.
Toxicology. 1998 Sep 15;130(2-3):155-65. doi: 10.1016/s0300-483x(98)00105-x.
Nicotine affects a variety of cellular processes ranging from induction of gene expression to secretion of hormones and modulation of enzymatic activities. The objective of this study was to characterize the toxicity of nicotine enantiomers as well as their ability to induce oxidative stress in an in vitro model using Chinese hamster ovary (CHO) cells. Colony formation assay has demonstrated that (-)-nicotine is the more toxic of the enantiomers. At 6 mM concentrations, (-)-nicotine was found to be approximately 28- and 19-fold more potent than (+)-, and (+/-)-nicotine (racemic), respectively. Results also indicated that the toxicity of (+/-)-nicotine is higher than that of (+)-nicotine. (-)-Nicotine at a 10 mM concentration substantially decreased glutathione (GSH) levels (46% decrease). In addition, a 3-fold increase in malondialdehyde (MDA) level was evident in cells after exposure to 10 mM (-)-nicotine. Increased lactate dehydrogenase (LDH) activities in the media demonstrated that cellular membrane integrity was disturbed in nicotine treated cells. In the presence of superoxide dismutase (SOD) and catalase (CAT), the LDH activities returned to control value in 24 h with all concentrations of (-)-, (+)-, and (+/-)-nicotine. The decreases in LDH activities in the presence of the radical scavenging enzymes SOD and CAT suggest that membrane damage may be due to free radical generation.
尼古丁会影响多种细胞过程，从基因表达的诱导到激素分泌以及酶活性的调节。本研究的目的是在使用中国仓鼠卵巢（CHO）细胞的体外模型中，表征尼古丁对映体的毒性及其诱导氧化应激的能力。集落形成试验表明，（-）-尼古丁是对映体中毒性更强的。在6 mM浓度下，发现（-）-尼古丁的效力分别比（+）-尼古丁和（±）-尼古丁（外消旋体）高约28倍和19倍。结果还表明，（±）-尼古丁的毒性高于（+）-尼古丁。10 mM浓度的（-）-尼古丁可显著降低谷胱甘肽（GSH）水平（降低46%）。此外，暴露于10 mM（-）-尼古丁后，细胞中的丙二醛（MDA）水平明显增加了3倍。培养基中乳酸脱氢酶（LDH）活性的增加表明，尼古丁处理的细胞中细胞膜完整性受到了干扰。在超氧化物歧化酶（SOD）和过氧化氢酶（CAT）存在的情况下，所有浓度的（-）-、（+）-和（±）-尼古丁处理后，LDH活性在24小时内恢复到对照值。自由基清除酶SOD和CAT存在时LDH活性的降低表明，膜损伤可能是由于自由基的产生。
