烟草生物碱尼古丁以其激活神经元烟碱乙酰胆碱受体而闻名。尼古丁以不同的方式消耗,例如通过常规吸烟,电子烟,鼻烟或尼古丁袋。鼻烟的使用与一些不良健康影响有关,如口腔粘膜的炎症反应和口腔癌。我们对暴露于尼古丁的THP-1人单核细胞进行了代谢组学分析。将细胞暴露于5mM生物碱长达4小时,和细胞提取物和培养基进行非目标液相色谱高分辨率质谱。原始数据处理揭示了17种尼古丁生物转化产物。其中,可替宁和去甲烟碱被确定为两种主要的细胞生物转化产物。多变量和单变量统计分析的应用导致了注释,达到一定的识别水平,细胞提取物中的12种化合物和培养基中的13种化合物因尼古丁暴露而改变。其中,四个被证实为甲硫腺苷,胞嘧啶,尿酸,和L-谷氨酸.甲硫腺苷水平在细胞和培养基中都受到影响,而胞嘧啶,尿酸,L-谷氨酸水平仅在培养基中受影响。先前已经在人类中证明了吸烟对涉及这些代谢物的途径的影响。大多数其他有区别的化合物,只是暂时或没有完全确定,氨基酸或氨基酸衍生物。总之,我们的初步数据表明,当通过鼻烟或尼古丁袋摄入尼古丁时,也可能会出现与吸烟有关的一些潜在不良反应。
The tobacco alkaloid nicotine is known for its activation of neuronal nicotinic acetylcholine receptors. Nicotine is consumed in different ways such as through conventional smoking, e-cigarettes, snuff or nicotine pouches. The use of snuff has been associated with several adverse health effects, such as inflammatory reactions of the oral mucosa and oral cavity cancer. We performed a metabolomic analysis of nicotine-exposed THP-1 human monocytes. Cells were exposed to 5 mM of the alkaloid for up to 4 h, and cell extracts and medium subjected to untargeted liquid chromatography high-resolution mass spectrometry. Raw data processing revealed 17 nicotine biotransformation products. Among these, cotinine and nornicotine were identified as the two major cellular biotransformation products. The application of multi- and univariate statistical analyses resulted in the annotation, up to a certain level of identification, of 12 compounds in the cell extracts and 13 compounds in the medium that were altered by nicotine exposure. Of these, four were verified as methylthioadenosine, cytosine, uric acid, and L-glutamate. Methylthioadenosine levels were affected in both cells and the medium, while cytosine, uric acid, and L-glutamate levels were affected in the medium only. The effects of smoking on the pathways involving these metabolites have been previously demonstrated in humans. Most of the other discriminating compounds, which were merely tentatively or not fully identified, were amino acids or amino acid derivatives. In conclusion, our preliminary data suggest that some of the potentially adverse effects related to smoking may also be expected when nicotine is consumed via snuff or nicotine pouches.