A Systematic Review of Analytical Methods for the Separation of Nicotine Enantiomers and Evaluation of Nicotine Sources

Salam, Sally; Moussa, Fatima El-Hajj; El-Hage, Rachel; El‐Hellani, Ahmad; Saliba, Najat A.

doi:10.1021/acs.chemrestox.2c00310

Cited by 6 publications

(4 citation statements)

References 40 publications

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“…Nicotine is a naturally occurring alkaloid extracted from tobacco leaves that exists in two isomers: (R)-(+)-nicotine and (S)-(−)-nicotine [ 3 , 4 ]. Traditionally tobacco products have utilized nicotine extracted from tobacco leaves which contains predominantly S-nicotine [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Tobacco-derived and tobacco-free nicotine cause differential inflammatory cell influx and MMP-9 in mouse lung

Lamb,

Kaur,

Rahman

2024

Respir Res

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Background Electronic nicotine delivery systems (ENDS) or electronic cigarettes (e-cigarettes) aerosolize an e-liquid composed of propylene glycol (PG) and vegetable glycerin (VG) as humectants, flavoring chemicals, and nicotine. Nicotine naturally occurs in two isomers R- and S-nicotine, with tobacco-derived nicotine (TDN) composed of S-nicotine, and tobacco-free/synthetic nicotine (TFN) composed of a racemic mixture of R- and S-nicotine. Currently, there is limited knowledge of the potential differences in the toxicity of TFN versus TDN. We hypothesized that exposure of TFN and TDN salts to C57BL/6J mice would result in a differential response in lung inflammation and protease/ antiprotease imbalance. Methods Five-week-old male and female C57BL/6J mice were exposed to air, PG/VG, PG/VG with TFN salts (TFN), or PG/VG with TDN salts (TDN) by nose-only exposure. Lung inflammatory cell counts, cytokine/chemokine levels, and matrix metalloproteinase (MMP) protein abundance and activity levels were determined by flow cytometry, ELISA, immunoblotting, and gel zymography, respectively. Results Exposure to the humectants (PG/VG) alone increased cytokine levels- IL-6, KC, and MCP-1 in the BALF and KC levels in lung homogenate of exposed mice. While no change was observed in the cytokine levels in lung homogenate of TDN aerosol exposed mice, exposure to TFN aerosols resulted in an increase in KC levels in the lungs of these mice compared to air controls. Interestingly, exposure to TDN aerosols increased MMP-9 protein abundance in the lungs of female mice, while exposure to TFN aerosol showed no change. The metabolism of nicotine or the clearance of cotinine for TFN exposure may differ from that for TDN. Conclusion Exposure to humectants, PG/VG alone, induces an inflammatory response in C57BL/6J mice. TFN and TDN salts show distinct changes in inflammatory responses and lung proteases on acute exposures. These data suggest variable toxicological profiles of the two forms of nicotine in vivo. Future work is thus warranted to delineate the harmful effects of synthetic/natural nicotine with humectants to determine the potential toxicological risks for users.

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Section: Introductionmentioning

confidence: 99%

Tobacco-derived and tobacco-free nicotine cause differential inflammatory cell influx and MMP-9 in mouse lung

Lamb,

Kaur,

Rahman

2024

Respir Res

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“…The most abundant natural form is (−)-nicotine, which constitutes about 99% of the nicotine content in raw tobacco, with (+)-nicotine making up the remaining 1%. 15 (−)-Nicotine functions as a natural ligand for nicotinic acetylcholine receptors (nAChRs). However, our previous study revealed that (−)-nicotine modulates LPSinduced inflammation through TLR4/MD2 rather than nAChRs, with MD2 acting specifically as its target.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Nicotine is the predominant psychoactive substance in tobacco, with a feature of a chiral carbon at the 2′-position of the pyrrolidine ring. The most abundant natural form is (−)-nicotine, which constitutes about 99% of the nicotine content in raw tobacco, with (+)-nicotine making up the remaining 1% . (−)-Nicotine functions as a natural ligand for nicotinic acetylcholine receptors (nAChRs).…”

Section: Introductionmentioning

confidence: 99%

Nicotine Enantioselectively Targets Myeloid Differentiation Protein 2 and Inhibits the Toll-like Receptor 4 Signaling

Jiang,

Zhang,

Wang

et al. 2024

J. Chem. Inf. Model.

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“…Nicotine is a naturally occurring alkaloid extracted from tobacco leaves that exists in two isomers: (R)-(+)nicotine and (S)-(-)-nicotine [3,4]. Traditionally tobacco products have utilized nicotine extracted from tobacco leaves which contains predominantly S-nicotine [5,6].…”

Section: Introductionmentioning

confidence: 99%

Tobacco-Derived and Tobacco-Free Nicotine cause differential inflammatory cell influx and MMP9 in mouse lung

Lamb,

Kaur,

Rahman

2023

Preprint

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Electronic nicotine delivery systems (ENDS) or electronic cigarettes (e-cigarettes) have propylene glycol (PG) and vegetable glycerin (VG) as humectants, flavoring chemicals, and nicotine. Nicotine naturally occurs in two isomers R- and S-nicotine, with both tobacco-derived nicotine (TDN) composed of S-nicotine and synthetic nicotine (TFN) composed of a racemic mixture of R- and S-nicotine. Currently there is limited knowledge of the potential differences in the toxicity of TFN vs TDN. We hypothesized that exposure of TFN salts to C57BL/6J mice will result in a differential response in inflammation and lung protease and antiprotease imbalance compared to TDN salts exposed mice. We studied the toxicological impact of these isomers by exposing mice to air, PG/VG, PG/VG with TFN salts, or PG/VG with TDN salts by nose-only exposure and measured the cytokine levels in BALF and lung homogenate along with MMP protein abundance in the lungs of exposed mice. Exposure to the humectants, PG/VG, used in e-cigarettes alone was able to increase cytokine levels- IL-6, KC, and MCP-1 in BALF and KC levels in lung homogenate. Further, it showed differential responses on exposure to PG/VG with TDN salts and PG/VG with TFN salts since PG/VG with TDN salts did not alter the cytokine levels in lung homogenate while PG/VG with TFN salts resulted in an increase in KC levels. PG/VG with TDN salts increased the levels of MMP9 protein abundance in female exposed mice, while PG/VG with TFN salts did not alter MMP9 levels in female mice. The metabolism of nicotine or the clearance of cotinine from TFN may differ from the metabolism of nicotine or the clearance of cotinine from TDN. Thus exposure of humectants alone to induce an inflammatory response while PG/VG with TFN salts and PG/VG with TDN salts may differentially alter inflammatory responses and lung proteases in acute exposures. These data suggest the harmful effects of synthetic/natural nicotine and PG/VG and potential toxicological risk for users.

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A Systematic Review of Analytical Methods for the Separation of Nicotine Enantiomers and Evaluation of Nicotine Sources

Cited by 6 publications

References 40 publications

Tobacco-derived and tobacco-free nicotine cause differential inflammatory cell influx and MMP-9 in mouse lung

Tobacco-derived and tobacco-free nicotine cause differential inflammatory cell influx and MMP-9 in mouse lung

Nicotine Enantioselectively Targets Myeloid Differentiation Protein 2 and Inhibits the Toll-like Receptor 4 Signaling

Tobacco-Derived and Tobacco-Free Nicotine cause differential inflammatory cell influx and MMP9 in mouse lung

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