Menthol attenuates respiratory irritation and elevates blood cotinine in cigarette smoke exposed mice.
Menthol attenuates respiratory irritation and elevates blood cotinine in cigarette smoke exposed mice.
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DOI：
10.1371/journal.pone.0117128
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Morris JB
中科院分区：
文献类型：
--
作者：
Ha MA;Smith GJ;Cichocki JA;Fan L;Liu YS;Caceres AI;Jordt SE;Morris JB
在香烟中添加薄荷醇可能与吸烟的开始增加有关。这种关联的潜在机制尚不清楚。可能是由于其对冷感觉外周感觉神经元的作用，已知Menglutamine抑制由呼吸刺激物引起的刺激感。然而，目前尚不清楚薄荷醇是否在最初暴露于香烟期间调节香烟烟雾刺激性和尼古丁吸收，从而促进吸烟开始。在C57 Bl/6 J小鼠模型中使用体积描记法，我们检查了添加到香烟中的薄荷醇异构体L-薄荷醇对主要烟雾刺激物（丙烯醛和环己酮）和肯塔基州参考2 R4香烟的烟雾的呼吸感觉刺激反应的影响。我们还研究了暴露于香烟烟雾后，L-薄荷醇对尼古丁代谢物可替宁血液水平的影响。L-薄荷醇抑制丙烯醛的刺激反应，表观IC释放量为4ppm。即使在丙烯醛水平远高于产生最大响应所需的水平时也观察到抑制。香烟烟雾，在暴露水平为10毫克/立方米或更高，引起小鼠立即和显着的感官刺激反应。即使在烟雾浓度高达300 mg/m³时，L-薄荷醇也能显著抑制这种反应。通过用瞬时受体电位Melastatin 8（TRPM 8）（神经元冷/薄荷醇受体）的选择性抑制剂治疗来消除由L-薄荷醇引起的反刺激。在香烟烟雾中加入薄荷醇导致血浆可替宁水平比暴露于烟雾而不添加薄荷醇的小鼠中观察到的水平增加约1.5倍。这些发现证明，L-薄荷醇通过TRPM 8是呼吸道刺激反应的强抑制剂，即使在高度有害的暴露于香烟烟雾或烟雾刺激物期间，也是如此，并增加血液可替宁。因此，L-薄荷醇作为卷烟添加剂可能促进吸烟和尼古丁成瘾。
Addition of menthol to cigarettes may be associated with increased initiation of smoking. The potential mechanisms underlying this association are not known. Menthol, likely due to its effects on cold-sensing peripheral sensory neurons, is known to inhibit the sensation of irritation elicited by respiratory irritants. However, it remains unclear whether menthol modulates cigarette smoke irritancy and nicotine absorption during initial exposures to cigarettes, thereby facilitating smoking initiation. Using plethysmography in a C57Bl/6J mouse model, we examined the effects of L-menthol, the menthol isomer added to cigarettes, on the respiratory sensory irritation response to primary smoke irritants (acrolein and cyclohexanone) and smoke of Kentucky reference 2R4 cigarettes. We also studied L-menthol’s effect on blood levels of the nicotine metabolite, cotinine, immediately after exposure to cigarette smoke. L-menthol suppressed the irritation response to acrolein with an apparent IC₅₀ of 4 ppm. Suppression was observed even at acrolein levels well above those necessary to produce a maximal response. Cigarette smoke, at exposure levels of 10 mg/m³ or higher, caused an immediate and marked sensory irritation response in mice. This response was significantly suppressed by L-menthol even at smoke concentrations as high as 300 mg/m³. Counterirritation by L-menthol was abolished by treatment with a selective inhibitor of Transient Receptor Potential Melastatin 8 (TRPM8), the neuronal cold/menthol receptor. Inclusion of menthol in the cigarette smoke resulted in roughly a 1.5-fold increase in plasma cotinine levels over those observed in mice exposed to smoke without added menthol. These findings document that, L-menthol, through TRPM8, is a strong suppressor of respiratory irritation responses, even during highly noxious exposures to cigarette smoke or smoke irritants, and increases blood cotinine. Therefore, L-menthol, as a cigarette additive, may promote smoking initiation and nicotine addiction.
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影响因子：
7.4
作者：
Liu B;Fan L;Balakrishna S;Sui A;Morris JB;Jordt SE
通讯作者：
Jordt SE
影响因子：
3.3
作者：
Gavva NR;Davis C;Lehto SG;Rao S;Wang W;Zhu DX
通讯作者：
Zhu DX
DOI：
10.1016/0015-6264(81)90513-7
发表时间：
1981-01-01
期刊：
FOOD AND COSMETICS TOXICOLOGY
影响因子：
--
作者：
ALARIE, Y
通讯作者：
ALARIE, Y
DOI：
10.3109/10408447309082020
发表时间：
1973-11-01
期刊：
CRC critical reviews in toxicology
影响因子：
--
作者：
Alarie, Y
通讯作者：
Alarie, Y
DOI：
10.1513/pats.201001-004sm
发表时间：
2010-07-01
期刊：
Proceedings of the American Thoracic Society
影响因子：
--
作者：
Bessac, Bret F;Jordt, Sven-Eric
通讯作者：
Jordt, Sven-Eric