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Comparison of monoamine oxidase inhibition by cigarettes and modified risk tobacco products
The adverse effects of cigarette smoking are well documented, and the two main strategies for reducing smoking prevalence are prevention of smoking initiation and promotion of smoking cessation. More recently, a third and complementary avenue, tobacco harm reduction has emerged, which is aimed to re...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872813/ https://www.ncbi.nlm.nih.gov/pubmed/31768332 http://dx.doi.org/10.1016/j.toxrep.2019.11.008 |
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author | van der Toorn, Marco Koshibu, Kyoko Schlage, Walter K. Majeed, Shoaib Pospisil, Pavel Hoeng, Julia Peitsch, Manuel C. |
author_facet | van der Toorn, Marco Koshibu, Kyoko Schlage, Walter K. Majeed, Shoaib Pospisil, Pavel Hoeng, Julia Peitsch, Manuel C. |
author_sort | van der Toorn, Marco |
collection | PubMed |
description | The adverse effects of cigarette smoking are well documented, and the two main strategies for reducing smoking prevalence are prevention of smoking initiation and promotion of smoking cessation. More recently, a third and complementary avenue, tobacco harm reduction has emerged, which is aimed to reduce the burden of smoking-related diseases. This has been enabled by the development of novel products such as electronic cigarettes (e-cigarettes) and heated tobacco products, designed to deliver nicotine with significantly reduced levels of the toxicants that are emitted by cigarettes. Several potential modified risk tobacco products (pMRTP) have been reported to emit significantly less toxicants than cigarettes and significantly reduce toxicant exposure in smokers who switch completely to such products. These are two prerequisites for pMRTPs to reduce harm and the risk of smoking-related disease. However, concerns remain regarding the addictive nature of these products. Smoking addiction is a complex phenomenon involving multiple pharmacological and non-pharmacological factors. Although the main pharmacological substance associated with smoking addiction is nicotine, accumulating evidence suggests that nicotine mostly acts as a primary reinforcer and that other factors are involved in establishing smoking addiction. Inhibition of monoamine oxidases (MAO)—mammalian flavoenzymes with a central role in neurotransmitter metabolism—has also been suggested to be involved in this process. Therefore, we aimed to comparatively investigate the ability of several types of pMRTPs and cigarette smoke (3R4F) to inhibit MAO activity. The results showed that the heated tobacco product Tobacco Heating System (THS) 2.2 and the MESH 1.1 e-cigarette possessed no MAO inhibitory activity while 3R4F significantly inhibits the levels of MAO activity (3R4F MAO-A and B; > 2 μM nicotine). Snus products have similar inhibition profiles as 3R4F but for larger nicotine concentrations (snus MAO-A; ∼68-fold, snus MAO-B; ∼23-fold higher compared to 3R4F). These observations were confirmed by analytical datasets of potential MAO inhibitors emitted by these products. In conclusion, we have demonstrated that specific pMRTPs, namely THS 2.2 and MESH 1.1, have a significantly lower MAO-inhibitory activity than 3R4F. These findings provide a basis for further investigation of the role of MAO inhibitors in cigarette addiction as well as the implications of the findings for abuse liability of pMRTPs in comparison with cigarettes. |
format | Online Article Text |
id | pubmed-6872813 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-68728132019-11-25 Comparison of monoamine oxidase inhibition by cigarettes and modified risk tobacco products van der Toorn, Marco Koshibu, Kyoko Schlage, Walter K. Majeed, Shoaib Pospisil, Pavel Hoeng, Julia Peitsch, Manuel C. Toxicol Rep Article The adverse effects of cigarette smoking are well documented, and the two main strategies for reducing smoking prevalence are prevention of smoking initiation and promotion of smoking cessation. More recently, a third and complementary avenue, tobacco harm reduction has emerged, which is aimed to reduce the burden of smoking-related diseases. This has been enabled by the development of novel products such as electronic cigarettes (e-cigarettes) and heated tobacco products, designed to deliver nicotine with significantly reduced levels of the toxicants that are emitted by cigarettes. Several potential modified risk tobacco products (pMRTP) have been reported to emit significantly less toxicants than cigarettes and significantly reduce toxicant exposure in smokers who switch completely to such products. These are two prerequisites for pMRTPs to reduce harm and the risk of smoking-related disease. However, concerns remain regarding the addictive nature of these products. Smoking addiction is a complex phenomenon involving multiple pharmacological and non-pharmacological factors. Although the main pharmacological substance associated with smoking addiction is nicotine, accumulating evidence suggests that nicotine mostly acts as a primary reinforcer and that other factors are involved in establishing smoking addiction. Inhibition of monoamine oxidases (MAO)—mammalian flavoenzymes with a central role in neurotransmitter metabolism—has also been suggested to be involved in this process. Therefore, we aimed to comparatively investigate the ability of several types of pMRTPs and cigarette smoke (3R4F) to inhibit MAO activity. The results showed that the heated tobacco product Tobacco Heating System (THS) 2.2 and the MESH 1.1 e-cigarette possessed no MAO inhibitory activity while 3R4F significantly inhibits the levels of MAO activity (3R4F MAO-A and B; > 2 μM nicotine). Snus products have similar inhibition profiles as 3R4F but for larger nicotine concentrations (snus MAO-A; ∼68-fold, snus MAO-B; ∼23-fold higher compared to 3R4F). These observations were confirmed by analytical datasets of potential MAO inhibitors emitted by these products. In conclusion, we have demonstrated that specific pMRTPs, namely THS 2.2 and MESH 1.1, have a significantly lower MAO-inhibitory activity than 3R4F. These findings provide a basis for further investigation of the role of MAO inhibitors in cigarette addiction as well as the implications of the findings for abuse liability of pMRTPs in comparison with cigarettes. Elsevier 2019-11-13 /pmc/articles/PMC6872813/ /pubmed/31768332 http://dx.doi.org/10.1016/j.toxrep.2019.11.008 Text en © 2019 The Authors. Published by Elsevier B.V. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article van der Toorn, Marco Koshibu, Kyoko Schlage, Walter K. Majeed, Shoaib Pospisil, Pavel Hoeng, Julia Peitsch, Manuel C. Comparison of monoamine oxidase inhibition by cigarettes and modified risk tobacco products |
title | Comparison of monoamine oxidase inhibition by cigarettes and modified risk tobacco products |
title_full | Comparison of monoamine oxidase inhibition by cigarettes and modified risk tobacco products |
title_fullStr | Comparison of monoamine oxidase inhibition by cigarettes and modified risk tobacco products |
title_full_unstemmed | Comparison of monoamine oxidase inhibition by cigarettes and modified risk tobacco products |
title_short | Comparison of monoamine oxidase inhibition by cigarettes and modified risk tobacco products |
title_sort | comparison of monoamine oxidase inhibition by cigarettes and modified risk tobacco products |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6872813/ https://www.ncbi.nlm.nih.gov/pubmed/31768332 http://dx.doi.org/10.1016/j.toxrep.2019.11.008 |
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