A prototypic modified risk tobacco product exhibits reduced effects on chemotaxis and transendothelial migration of monocytes compared with a reference cigarette

Toorn, Marco van der; Frentzel, Stefan; Goedertier, Didier; Peitsch, Manuel C.; Hoeng, Julia; León, Héctor De

doi:10.1016/j.fct.2015.03.026

Cited by 17 publications

(12 citation statements)

References 46 publications

(55 reference statements)

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“…11 are in line with the data from our previous report, indicating that pretreatment of monocytes with an extract generated from a combustible cigarette product triggers a more potent cytotoxic and inflammatory response than extract from a carbon-heated tobacco product (van der Toorn et al, 2015).…”

Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 91%

“…We demonstrated that the extract from heated tobacco is less cytotoxic and inflammatory, and exerts a lower effect on monocyte chemotaxis and transendothelial migration (TEM) than that from combustible tobacco (van der Toorn et al, 2015). In the present study, we confirmed that heating rather than combusting tobacco results in a smaller effect on endothelial functions and the migratory behavior of monocytes using a new candidate modified risk tobacco product (MRTP) (FDA, 2012).…”

supporting

confidence: 93%

“…In this study, we tested a new candidate MRTP, THS2.2, the principle of which is similar to an earlier prototype MRTP described in our previous study (van der Toorn et al, 2015). To monitor batch consistency of the extracts and compare selective chemical compositions, the concentration of nicotine and eight different carbonyls were determined in 3R4F and THS2.2 extracts.…”

Section: Chemical Analyses Of 3r4f and Ths22 Extractsmentioning

confidence: 99%

“…were determined by liquid chromatography-electrospray ionization tandem mass spectrometry according to the method described by van der Toorn et al (2015). Nicotine concentration was analyzed using an AT1100 liquid chromatography system including a binary pump and a column oven (Agilent Technologies, Waldbronn, Germany) connected to an HTC Pal autosampler (CTC Analytics, Zwingen, Switzerland).…”

Section: Selective Chemical Analysis Of 3r4f and Ths22 Extractsmentioning

confidence: 99%

“…In the present study, we confirmed that heating rather than combusting tobacco results in a smaller effect on endothelial functions and the migratory behavior of monocytes using a new candidate modified risk tobacco product (MRTP) (FDA, 2012). Compared with the prototype MRTP described in the earlier publication (van der Toorn et al, 2015), which uses a pressed carbon heat source, the tobacco heating system (THS)2.2 used in the present is a different innovation to heat rather than burn tobacco.…”

mentioning

confidence: 97%

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Aerosol from a candidate modified risk tobacco product has reduced effects on chemotaxis and transendothelial migration compared to combustion of conventional cigarettes

Toorn

Frentzel

León

et al. 2015

Food and Chemical Toxicology

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Reduction of harmful constituents by heating rather than combusting tobacco is a promising new approach to reduce harmful effects associated with cigarette smoking. We investigated the effect from a new candidate modified risk tobacco product, the tobacco heating system (THS) 2.2, on the migratory behavior of monocytes in comparison with combustible 3R4F reference cigarettes. The monocytic cell line (THP-1) and human coronary arterial endothelial cells (HCAECs) were used to analyze chemotaxis and transendothelial migration (TEM). To assess the influence of aerosol extract from THS2.2 and smoke extract from 3R4F on toxicity and inflammation, flow cytometry and ELISA assays were performed. The results show that treatment of THP-1 cells with extract from 3R4F or THS2.2 induced concentration-dependent increases in cytotoxicity and inflammation. The inhibitory effects of THS2.2 extract for chemotaxis and TEM were ∼18 times less effective compared to 3R4F extract. Furthermore, extract from 3R4F or THS2.2 induced concentration-dependent decreases in the integrity of HCAEC monolayer. For all examined endpoints, the extract from 3R4F showed more than one order of magnitude stronger effects than that from THS2.2 extract. These data indicate the potential of a heat not burn tobacco product to reduce the risk for cardiovascular disease compared to combustible cigarettes.

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Section: A C C E P T E D Accepted Manuscriptsupporting

confidence: 91%

supporting

confidence: 93%

Section: Chemical Analyses Of 3r4f and Ths22 Extractsmentioning

confidence: 99%

Section: Selective Chemical Analysis Of 3r4f and Ths22 Extractsmentioning

confidence: 99%

mentioning

confidence: 97%

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Aerosol from a candidate modified risk tobacco product has reduced effects on chemotaxis and transendothelial migration compared to combustion of conventional cigarettes

Toorn

Frentzel

León

et al. 2015

Food and Chemical Toxicology

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Developmental toxicity of e‐cigarette aerosols

Greene

Pisano

2019

Birth Defects Research

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Maternal smoking during pregnancy represents a major public health concern increasing the risk for low birth weight, congenital anomalies, preterm birth, fetal mortality, and morbidity. In an effort to diminish adverse developmental effects of exposure to cigarette smoking, pregnant women, and women of reproductive age, are increasingly turning to electronic nicotine delivery systems (ENDS), such as e‐cigarettes, as an alternative. Given that health risks associated with ENDS use during pregnancy are largely unknown, there is an acute need to determine risks vs. benefits of e‐cigarette use by pregnant women. While the most recent Surgeon General's Report on the “Health Consequences of Smoking” states that “the evidence is sufficient to infer that nicotine adversely affects maternal and fetal health during pregnancy, contributing to multiple adverse outcomes,” it remains unclear whether use of ENDS represents a “safer alternative” to tobacco smoking during pregnancy. This is due, in part, to the lack of sufficient and conclusive evidence concerning whether or not maternal e‐cigarette use adversely affects embryonic/fetal development. While several recent developmental studies have challenged the safety of nicotine inhalation via ENDS, the true risks of smoking e‐cigarettes during the first trimester of pregnancy—the period of organogenesis—are largely unknown. Moreover, evidence is emerging that even nicotine‐free e‐cigarette aerosols may harm the developing conceptus, suggesting that components of e‐cigarette liquid, including flavorings, may be developmentally toxicity. Focused human epidemiological analyses, and carefully designed animal studies are critically needed to address the question of the safety of ENDS use during pregnancy.

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Systems toxicology study reveals reduced impact of heated tobacco product aerosol extract relative to cigarette smoke on premature aging and exacerbation effects in aged aortic cells in vitro

et al. 2021

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Aging and smoking are major risk factors for cardiovascular diseases (CVD). Our in vitro study compared, in the context of aging, the effects of the aerosol of Tobacco Heating System 2.2 (THS; an electrically heated tobacco product) and 3R4F reference cigarette smoke (CS) on processes that contribute to vascular pathomechanisms leading to CVD. Young and old human aortic smooth muscle cells (HAoSMC) were exposed to various concentrations of aqueous extracts (AE) from 3R4F CS [0.014–0.22 puffs/mL] or THS aerosol [0.11–1.76 puffs/mL] for 24 h. Key markers were measured by high-content imaging, transcriptomics profiling and multianalyte profiling. In our study, in vitro aging increased senescence, DNA damage, and inflammation and decreased proliferation in the HAoSMCs. At higher concentrations of 3R4F AE, young HAoSMCs behaved similarly to aged cells, while old HAoSMCs showed additional DNA damage and apoptosis effects. At 3R4F AE concentrations with the maximum effect, the THS AE showed no significant effect in young or old HAoSMCs. It required an approximately ten-fold higher concentration of THS AE to induce effects similar to those observed with 3R4F. These effects were independent of nicotine, which did not show a significant effect on HAoSMCs at any tested concentration. Our results show that 3R4F AE accelerates aging in young HAoSMCs and exacerbates the aging effect in old HAoSMCs in vitro, consistent with CS-related contributions to the risk of CVD. Relative to 3R4F AE, the THS AE showed a significantly reduced impact on HAoSMCs, suggesting its lower risk for vascular SMC-associated pathomechanisms leading to CVD.

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A prototypic modified risk tobacco product exhibits reduced effects on chemotaxis and transendothelial migration of monocytes compared with a reference cigarette

Cited by 17 publications

References 46 publications

Aerosol from a candidate modified risk tobacco product has reduced effects on chemotaxis and transendothelial migration compared to combustion of conventional cigarettes

Aerosol from a candidate modified risk tobacco product has reduced effects on chemotaxis and transendothelial migration compared to combustion of conventional cigarettes

Developmental toxicity of e‐cigarette aerosols

Systems toxicology study reveals reduced impact of heated tobacco product aerosol extract relative to cigarette smoke on premature aging and exacerbation effects in aged aortic cells in vitro

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