Effects of goniopora toxin on nicotine-induced responses in the adrenergic nerve terminals

Ikushima, Shinobu; Muramatsu, Ikunobu; Ashida, Kouzou; Fujiwara, Motohatsu

doi:10.1016/s0021-5198(19)53791-x

Cited by 2 publications

(4 citation statements)

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“…Although TFN has only recently begun to be used in tobacco products, TFN has been around for many years. However, unlike TDN, the health effects of TFN salts are relatively unknown [ 5 , 16 , 17 , 22 ]. This study attempted to understand the potential toxicological differences between TDN and TFN salts.…”

Section: Discussionmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

“…Current data has indicated that R-nicotine is a less potent agonist of nicotinic acetylcholine receptors and can bind and inhibit acetylcholinesterase. Further, R-nicotine and R-cotinine have a faster clearance than S-nicotine or S-cotinine [ 5 , 16 , 17 ].…”

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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“…Although TFN has only recently begun to be used in tobacco products, TFN has been around for many years. However, unlike TDN, the health effects of TFN salts are relatively unknown [5,7,17,18]. This study attempted to understand the potential toxicological differences between tobacco-derived nicotine (TDN) and synthetic nicotine (TFN).…”

Section: Discussionmentioning

confidence: 99%

“…Further, R-nicotine and R-cotinine has been found to have a faster clearance than S-nicotine or S-cotinine [5,17,18].…”

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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Effects of goniopora toxin on nicotine-induced responses in the adrenergic nerve terminals

Cited by 2 publications

References 0 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

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

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