Systemic Toxicity of Smokeless Tobacco Products in Mice

Malovichko, Marina V; Zeller, Iris; Krivokhizhina, Tatiana; Xie, Zhengzhi; Lorkiewicz, Pawel; Agarwal, Abhinav; Wickramasinghe, Nalinie S.; Sithu, Srinivas D; Shah, Jasmit; O’Toole, Timothy E.; Shesh, N.; Bhatnagar, Aruni; Conklin, Daniel J.; Srivastava, Sanjay

doi:10.1093/ntr/ntx230

Cited by 26 publications

(29 citation statements)

References 46 publications

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“…42 Beyond that, TNFα expression increases in mice fed with nicotine containing drinking water with a concentration of 100 μg/mL as well as in mice exposed to Copenhagen snuff, a smokeless tobacco product inhaled into the nasal cavity. 43 TNFα can promote VC in vitro. 44 Another effect of nicotine at concentrations resembling that of smokers on EC and VSMC of mice is the induction of vascular cell adhesion protein 1 (VCAM-1) expression in vitro.…”

Section: Study Design Application Results Referencesmentioning

confidence: 98%

“…Nicotine can bind to the nAChR α‐7 subunit on macrophages and monocytes and thus increase the TNFα expression in nicotine‐fed mice . Beyond that, TNFα expression increases in mice fed with nicotine containing drinking water with a concentration of 100 μg/mL as well as in mice exposed to Copenhagen snuff, a smokeless tobacco product inhaled into the nasal cavity . TNFα can promote VC in vitro …”

Section: Effects Of Nicotine On Vascular Calcificationmentioning

confidence: 99%

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In times of tobacco‐free nicotine consumption: The influence of nicotine on vascular calcification

Babic

Schuchardt

Tölle

et al. 2019

Eur J Clin Investigation

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Background Smoking remains the most important avoidable cause of global mortality. Even though the number of cigarette smokers declines in first world countries, the uses of alternative nicotine delivery products increase and may even surpass the sells of cigarettes. In this light, the explicit role of nicotine in the development of cardiovascular diseases should be elucidated. Objectives This narrative review attempts to connect current literature about possible effects of nicotine on the environment of the vasculature to the pathogenesis of vascular calcification, focusing on the tunica media of the vessel wall. Methods For this review, papers found on Pubmed and Medline until December 2018 by searching for the keywords nicotine, vascular calcification, oxidative stress, osteoblastic transdifferentiation and matrix degradation were considered. Results Nicotine creates an environment that probably facilitates and maybe even induces osteogenic transdifferentiation of VSMC by inflammation, endothelial dysfunction and reactive oxygen species. This process is believed to be a key event in calcification of the tunica media of the vessel wall. Furthermore, nicotine could lead to the formation of nucleation sites for hydroxyapatite by facilitating matrix vesicles and extracellular matrix degradation. Conclusions There is a growing body of evidence implicating that nicotine alone could impair vascular function and lead to vascular calcification. Further research is necessary to elucidate the explicit influence of nicotine on arteriosclerosis.

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Section: Study Design Application Results Referencesmentioning

confidence: 98%

Section: Effects Of Nicotine On Vascular Calcificationmentioning

confidence: 99%

In times of tobacco‐free nicotine consumption: The influence of nicotine on vascular calcification

Babic

Schuchardt

Tölle

et al. 2019

Eur J Clin Investigation

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“…Also, the association of serum TNFα with ST use has been previously addressed only in some in-vitro and animal studies. 11 , 12 …”

Section: Discussionmentioning

confidence: 99%

Evaluation of systemic inflammatory and thrombotic markers of cardiovascular risk among young Indian oral tobacco users

Zutshi

Gupta

et al. 2020

Indian Heart Journal

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Background While the pro-inflammatory and pro-coagulant effects of cigarette smoking have been well described, the effect of smokeless tobacco (ST) on inflammatory and coagulation markers is still not clear. The study aimed to evaluate impact of smokeless tobacco use on systemic markers of inflammation [(TLC), neutrophil-lymphocyte ratio (NLR) (ESR), interleukin (IL) IL-1β, IL-6 and tumor necrosis factor alpha (TNFα)] and hypercoagulable state [fibrinogen and d-dimer] leading to increased cardiovascular risk in ST users as compared to non-users. Methods 150 healthy young adults using oral tobacco products for at least 1 year were included in the case group and 50 age-matched non-consumers as controls. Subjects with any known chronic illness or comorbidity were excluded from the study. Blood samples were tested for TLC, NLR, ESR, IL-1β, IL-6, TNFα, fibrinogen and d-dimer. Statistical analysis was done using SPSS 17.0 software. Results The baseline clinical and cardio-metabolic characteristics were comparable between the two groups. ST users had significantly elevated serum IL-6 [59.29 ± 124.69 pg/mL (n = 149) vs 8.21 ± 27.27 pg/mL (n = 47), p-value = 0.005], TNFα [77.18 ± 236.10 pg/mL (n = 149) vs 8.32 ± 9.36 pg/mL (n = 47), p-value = 0.041], fibrinogen [310.53 ± 129.05 mg/dL (n = 143) vs 282.82 ± 65.23 mg/dL (n = 42), p-value = 0.045] and d-dimer [0.28 ± 0.42 mg/L (n = 144) vs 0.17 ± 0.09 mg/L (n = 45), p-value = 0.043] levels as compared to non-users. Serum TLC, NLR, ESR and IL-1β remained unchanged in ST users and were similar to that of controls. Conclusions Chronic use of ST is associated with systemic inflammation and coagulation, which may increase the risk of athero-thrombotic cardiovascular events among ST users.

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“…Metabolites of unsaturated aldehydes and tobacco alkaloids in urine were analyzed using a slightly modified UPLC-MS/MS method described previously (Malovichko et al 2017). Briefly, urine (25 µL) was diluted with solvent A (15 mM ammonium acetate, pH 6.8) spiked with IS and then applied on a UPLC-MS/MS instrument (ACQUITY UPLC coupled with a Quattro Premier XE triple quadrupole MS (Waters Inc, MA).…”

Section: Methodsmentioning

confidence: 99%

Electronic cigarette-generated aldehydes: The contribution of e-liquid components to their formation and the use of urinary aldehyde metabolites as biomarkers of exposure

Conklin

Ogunwale

Chen

et al. 2018

Aerosol Science and Technology

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Electronic cigarettes (e-cigarette) have emerged as a popular electronic nicotine delivery system (ENDS) in the last decade. Despite the absence of combustion products and toxins such as carbon monoxide (CO) and tobacco-specific nitrosamines (TSNA), carbonyls including short-chain, toxic aldehydes have been detected in e-cigarette-derived aerosols up to levels found in tobacco smoke. Given the health concerns regarding exposures to toxic aldehydes, understanding both aldehyde generation in e-cigarette and e-cigarette exposure is critical. Thus, we measured aldehydes generated in aerosols derived from propylene glycol (PG):vegetable glycerin (VG) mixtures and from commercial e-liquids with flavorants using a state-of-the-art carbonyl trap and mass spectrometry. To track e-cigarette exposure in mice, we measured urinary metabolites of 4 aldehydes using ULPC-MS/MS or GC-MS. Aldehyde levels, regardless of abundance (saturated: formaldehyde, acetaldehyde >> unsaturated: acrolein, crotonaldehyde), were dependent on the PG:VG ratio and the presence of flavorants. The metabolites of 3 aldehydes - formate, acetate and 3-hydroxypropyl mercapturic acid (3-HPMA; acrolein metabolite) -- were increased in urine after e-cigarette aerosol and mainstream cigarette smoke (MCS) exposures, but the crotonaldehyde metabolite (3-hydroxy-1-methylpropylmercapturic acid, HPMMA) was increased only after MCS exposure. Interestingly, exposure to menthol-flavored e-cigarette aerosol increased the levels of urinary 3-HPMA and sum of nicotine exposure (nicotine, cotinine, trans-3’-hydroxycotinine) relative to exposure to a Classic Tobacco-flavored e-cigarette aerosol. Comparing these findings with aerosols of other ENDS and by measuring aldehyde-derived metabolites in human urine following exposure to e-cigarette aerosols will further our understanding of the relationship between ENDS use, aldehyde exposure and health risk.

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Systemic Toxicity of Smokeless Tobacco Products in Mice

Cited by 26 publications

References 46 publications

In times of tobacco‐free nicotine consumption: The influence of nicotine on vascular calcification

In times of tobacco‐free nicotine consumption: The influence of nicotine on vascular calcification

Evaluation of systemic inflammatory and thrombotic markers of cardiovascular risk among young Indian oral tobacco users

Electronic cigarette-generated aldehydes: The contribution of e-liquid components to their formation and the use of urinary aldehyde metabolites as biomarkers of exposure

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