Nicotine Content Research Articles

Comparison of the toxicological potential of two JUUL ENDS products to reference cigarette 3R4F and filtered air in a 90-day nose-only inhalation toxicity study.

Electronic nicotine delivery systems (ENDS) are generally recognized as less harmful alternatives for those who would otherwise continue to smoke cigarettes. The potential toxicity of aerosols generated from JUUL Device and Virginia Tobacco (VT3) or Menthol (ME3) JUULpods at 3.0% nicotine concentration was assessed in rats exposed at target aerosol concentrations of 1400μg/L for up to 6h/day on a 5 day/week basis for at least 90 days (general accordance with OECD 413). 3R4F reference cigarette smoke (250μg/L) and Filtered Air were used as comparators. JUUL ENDS product aerosol exposures at >5x the 3R4F cigarette smoke level resulted in greater plasma nicotine and cotinine levels (up to 2x). Notable cigarette smoke related effects included pronounced body weight reductions in male rats, pulmonary inflammation evidenced by elevated lactate dehydrogenase, pro-inflammatory cytokines and neutrophils in bronchoalveolar lavage fluid, increased heart and lung weights, and minimal to marked respiratory tract histopathology. In contrast, ENDS aerosol exposed animals had minimal body weight changes, no measurable inflammatory changes and minimal to mild laryngeal squamous metaplasia. Despite the higher exposure levels, VT3 and ME3 did not result in significant toxicity or appreciable respiratory histopathology relative to 3R4F cigarette smoke following 90 days administration.

Preliminary study on the E-liquid and aerosol on the neurobehavior of C. elegans

E-cigarettes, also known as electronic nicotine delivery systems (ENDS), are mainly used among adolescents and young adults. Similar to traditional cigarettes, different concentrations of nicotine are also added to E-cigarette's liquid (E-liquid), but due to the supplementation of chemicals such as propylene glycol (PG), vegetable glycerin (VG) and flavors, it is difficult to determine the risk after using E-cigarettes. And given to the specificity of the aerosol particle composition and atomization process of E-cigarettes, it is necessary to assess the neurotoxic effects of long-term E-cigarettes use. In this study, two commercial nicotine-containing (5%) and nicotine-free E-liquids were diluted to investigate the neurobehavioral changes and addictive tendencies of developing C. elegans after sub-chronic exposure to E-liquid. The results showed that sub-chronic exposure of E-liquid could lead to impaired growth and development of nematodes, abnormal general neuromotor behavior and advanced learning and memory behavior, and nicotine-containing E-liquid could also lead to increased addiction tendency of nematodes. Although the damage effect of nicotine free E-liquid is smaller than that of the nicotine-containing group, its toxic effect cannot be ignored. Further analysis of the neurotoxicity mechanism found that redox imbalance-mediated mitochondrial stress and aging may be important causes of E-liquid-induced biological damage. The biosafety of e-cigarette aerosols was also included in the assessment. The study found that the heated atomization process did not alter the E-liquid components, and E-cigarette aerosols still have the effect of interfering with the growth and development of nematodes and neurobehavior, and its addictive nature is also of concern. This study can provide new ideas for future studies on the neurotoxic effects and safety assessment of the E-cigarettes, and provide theoretical reference for the study on the injury mechanism of E-cigarettes.

Including E-Cigarettes in the FDA Rule Limiting Nicotine

This Viewpoint discusses why the US Food and Drug Administration (FDA) should include e-cigarettes in its proposed cap of the nicotine concentration in combustible cigarettes to address the public health problem of vaping among adolescents.

Examining Quitting Experiences on Quit Vaping Subreddits From 2015 to 2021: Content Analysis.

Despite the prevalence of vaping nicotine, most nicotine cessation research remains focused on smoking cigarettes. However, the lived experience of quitting smoking is different from quitting vaping. As a result, research examining the unique experiences of those quitting vaping can better inform quitting resources and cessation programs specific to e-cigarette use. Examining Reddit forums (ie, subreddits) dedicated to the topics of quitting vaping nicotine can provide insight into the discussion around experiences on quitting vaping. Prior literature examining limited discussions around quitting vaping on Reddit has identified the sharing of barriers and facilitators for quitting, but more research is needed to investigate the content comprehensively across all subreddits. The objective of this study is to examine content across quit vaping subreddits since their inception to better understand quitting vaping within the context of the expanding nicotine market. All posts from January 2015 to October 2021 were scraped from all quit vaping subreddits: r/QuittingJuul, r/QuitVaping, r/quit_vaping, and r/stopvaping (N=7110). Rolling weekly average post volume was calculated. A codebook informed by a latent Dirichlet allocation topic model was developed to characterize themes in a subsample of 695 randomly selected posts. Frequencies and percentages of posts containing each coded theme were assessed along with the number of upvotes and comments. Post volume increased across all subreddits over time, spiking from August - September of 2019 when vaping lung injury emerged. Just over 52% of posts discussed seeking social support and 16.83% discussed providing social support. Posts providing support received the most positive engagements (i.e. upvotes) of all coded categories. Posts also discussed physical and psychological symptoms of withdrawal (30.65% and 18.85%, respectively), strategies for quitting including: quitting cold turkey (38.33%), using alternative nicotine products (17%), and tapering down nicotine content (10.50%). Most posts shared a personal narrative (92.37%) and some discussed quit motivation (28.20%) and relapse (14.99%). This work identifies a desire for peer-to-peer support for quitting vaping, which reinforces existing literature and highlights characteristics of quitting vaping specific to a changing nicotine product environment. Given that posts providing social support were the most upvoted, this suggests that subreddit contributors are seeking support from their peers when discussing quitting vaping. Additionally, this analysis shows the sharing of barriers and facilitators for quitting, supporting findings from prior exploration of quit vaping subreddits. Finally, quitting vaping in an ever-growing nicotine market has led to the evolution of vaping-specific quit methods such as tapering down nicotine content. These findings have direct implications for quit vaping product implementation and development.

Development of Electrochemical Sensor Using Iron (III) Phthalocyanine/Gold Nanoparticle/Graphene Hybrid Film for Highly Selective Determination of Nicotine in Human Salivary Samples.

Nicotine is the one of the major addictive substances; the overdose of nicotine (NIC) consumption causes increasing heart rate, blood pressure, stroke, lung cancer, and respiratory illnesses. In this study, we have developed a precise and sensitive electrochemical sensor for nicotine detection in saliva samples. It was built on a glassy carbon electrode (GCE) modified with graphene (Gr), iron (III) phthalocyanine-4,4',4″,4'''-tetrasulfonic acid (Fe(III)Pc), and gold nanoparticles (AuNPs/Fe(III)Pc/Gr/GCE). The AuNPs/Fe(III)Pc/Gr nanocomposite was prepared and characterized by using FE-SEM, EDX, and E-mapping techniques to confirm the composite formation as well as the even distribution of elements. Furthermore, the newly prepared AuNPs/Fe(III)Pc/Gr/GCE-nanocomposite-based sensor was used to detect the nicotine in phosphate-buffered solution (0.1 M PBS, pH 7.4). The AuNPs/Fe(III)Pc/Gr/GCE-based sensor offered a linear response against NIC from 0.5 to 27 µM with a limit of detection (LOD) of 17 nM using the amperometry (i-t curve) technique. This electrochemical sensor demonstrated astounding selectivity and sensitivity during NIC detection in the presence of common interfering molecules in 0.1 M PBS. Moreover, the effect of pH on NIC electro-oxidation was studied, which indicated that PBS with pH 7.4 was the best medium for NIC determination. Finally, the AuNPs/Fe(III)Pc/Gr/GCE sensor was used to accurately determine NIC concentration in human saliva samples, and the recovery percentages were also calculated.

Effects of reduced nicotine content cigarette advertising with warning labels and social media features on product perceptions among young adults.

This study sought to understand reactions to very low nicotine (VLN) cigarette advertising compared with conventional cigarette advertising with consideration of warning labels and social media context. The online experimental study recruited young adult cigarette smokers and nonsmokers (N = 1,608). Participants completed a discrete choice task with a 2 × 2 × 3 mixed design: brand, (VLN, Marlboro), context (Ad only, Ad on social media), and warning (Text-only, Well-known risk pictorial, or Lesser-known risk pictorial). Participants made choices about attention, appeal, harm, buying, and quitting intentions. Social media context increased attention and appeal. A well-known risk pictorial warning outperformed a text-only warning. Smokers had increased odds of quit intentions for VLN ads, yet nonsmokers had increased intentions to buy cigarettes on social media with a text-only warning. Results indicate differences in how young adults react to cigarette ads on social media, especially with the warnings they portray.

Reactions to Messages About a Nicotine Reduction Policy: A Focus Group Study Among People Who Use Little Cigars and Cigarillos.

The U.S. Food and Drug Administration (FDA) has proposed rulemaking to reduce the nicotine content in cigarettes and other combusted tobacco products to non-addictive levels. This qualitative study documents reactions to messages communicating this policy among people who use little cigars and cigarillos (LCCs). We conducted eight focus groups with participants from four populations with the highest prevalence of cigar use (African American males and females, white males and females). Participants described their reactions to eight messages about the policy: Three messages about the equal risk of LCCs with regular and low nicotine levels; three quit efficacy messages about low nicotine LCCs being easier to quit; one "compensation" message to correct misperceptions about the policy causing people to smoke more to get desired nicotine; and one message about using alternative nicotine sources (eg, e-cigarettes). Participants perceived risk messages as the most motivating to quit, whereas efficacy messages made some participants feel that the policy would cause former users of LCCs to relapse. Many participants expressed favorable responses to the compensation message. The message about using alternative nicotine sources sparked intense responses, with many participants expressing outrage and mistrust of the message. Participants' beliefs that they were not addicted to LCCs dampened their perceptions of the effectiveness of the policy. Perceptions of the addictiveness and relative harms of LCCS influenced responses to policy messages. The FDA should consider using different messages to communicate with people who use LCCs because they perceive LCCs as different from cigarettes. This is the first study to document affective and cognitive responses to the FDA's reduced nicotine policy among people who use LCCs. The false belief that cigar products are less harmful than cigarettes may be influencing people's lack of support for the reduced nicotine policy and difficulty in understanding its potential positive impact. To maximize the public health benefit of the reduced nicotine policy, the FDA should include LCC products in the policy; however, it is crucial that they use educational messaging to clarify misperceptions regarding nicotine and harm as it applies to LCCs.

Assessment of Nicotine Degradation in Cigarette Smoke under Different Storage Conditions (Light and Duration)

Nicotine, the primary component of cigarette smoke, is not only addictive but also indirectly contributes to lung diseases by increasing heart rate and blood pressure upon inhalation. Therefore, managing nicotine content in cigarette smoke necessitates accurate quantitative analysis. Nicotine from cigarette smoke is collected using a Cambridge filter, subjected to solvent extraction, and analyzed using instrumental techniques. However, since nicotine is susceptible to light-induced oxidation, losses may occur during pretreatment, reducing result reliability. This study assesses nicotine loss under various lighting conditions and storage durations. Nicotine collected in Cambridge filters is exposed to dark, visible radiation, and UV radiation (254 nm) for different time intervals (0–48 h), and the nicotine content is analyzed and compared. In dark conditions, a 1.6% decline in nicotine concentration occurs after 48 h. With visible radiation, a 9% reduction is observed, while under UV exposure, the concentration decreases by 16.9%. The UV radiation-associated decrease in nicotine concentration is −0.335% h−1, exhibiting strong linearity ( R 2 = 0.9465 ). Consequently, significant nicotine loss in Cambridge filter-collected samples is influenced by storage duration and lighting conditions. This study’s findings can enhance the accuracy of nicotine quantification in cigarette smoke, thereby improving the understanding of nicotine’s harmful effects in cigarette smoke.

A core-molecule-shell Au@PATP@Ag nanorod for nicotine detection based on surface-enhanced Raman scattering technology

Nicotine is an addictive substance often found in tobacco and cigarette smoke and excessive exposure to it can cause various diseases. Herein, core-molecule-shell gold/4-aminothiophenol/silver nanorods (Au@PATP@Ag NRs) were prepared for quantitative detection of nicotine by using surface-enhanced Raman scattering (SERS) technology. The obtained Au@PATP@Ag NRs showed an outstanding SERS effect due to the plasticity of their morphology and the bimetallic synergistic effect between the excellent stability of Au and the highly enhanced effect of Ag. The Au@PATP@Ag NRs substrate exhibited an extremely high enhancement factor (EF) of 2.17 × 107. In addition, in-situ synthesized PATP was used as an internal standard to correct signal fluctuation and improve the reliability of quantitative nicotine detection. A wide linear dynamic range from 10−8 to 10−3 M was obtained and an ultra-low limit of detection (LOD) was about 3.12 × 10−9 M, which was superior to most of previously reported methods. This work has also been used for determining nicotine content in cigarettes and simulated environmental tobacco smoke by using a portable device. These results indicated that the developed SERS method had many potential applications in the quantitative determination of nicotine in real tobacco samples.

Bigger, stronger and cheaper: growth in e-cigarette market driven by disposable devices with more e-liquid, higher nicotine concentration and declining prices

ObjectiveGiven the evolving changes in the disposable e-cigarette market, we explore patterns of sales in the USA by e-liquid volume capacity, nicotine strength and real sales-weighted average prices by both...

The Impact of High or Low Doses of Nicotine in a Mouse Model of Vapor Self-Administration.

A wide variety of nicotine concentrations and formulations are available to users of electronic nicotine delivery systems (ENDS). This is increasingly true when considering the many flavors available with ENDS products. To date, there have been few preclinical investigations into the impact of nicotine doses, with and without flavors, on vaping-related behaviors. This present study evaluated how nicotine concentrations relevant to tank-based and pod-based ENDS, with and without flavors, impact reinforcement-related behavior in a mouse model. Adult male and female C57/BL6J mice were used in vapor-inhalation self-administration assays. Mice were assigned e-liquids containing 6 mg/mL or 60 mg/mL nicotine. Additional mice were assigned these nicotine doses with green apple or menthol flavorants. Mice were trained on fixed-ratio 1 for 10, 2-hour sessions, then five sessions at FR3, three progressive ratio sessions, and two FR3 sessions. We observed male mice exhibited higher reinforcement-related behavior to menthol-flavored 6 mg/mL nicotine when compared to female mice. Males were only observed to have a menthol-induced enhancement of self-administration at 6 mg/mL nicotine and not 60 mg/mL nicotine. However, female mice exhibited significant menthol-induced increases in reinforcement-related behaviors with 60 mg/mL nicotine. These data provide evidence that males and females exhibit different dose sensitivities to nicotine. These sex-dependent differences in nicotine sensitivity also indicate that flavor-induced enhancement in nicotine intake is dependent on the different doses for each sex. There has been much discussion recently regarding the impact of flavors on vaping-related behavior. Our current study may support prior investigations that suggest flavors enhance the palatability of nicotine-containing products. However, this current study provides evidence that males and females exhibit different sensitivities to nicotine.

Controllable Synthesis of Carboxymethyl Cellulose and Its Application in Tobacco Sheets

Carboxymethyl cellulose (CMC) with different degree of substitution (DS) was prepared by controlling feed ratio and times of alkalization and etherification. CMC with different molecular weight was prepared by degradation of hydrochloric acid solution. Orthogonal experiments were designed to study the effects of addition amount, molecular weight and DS of CMC on the tensile strength of tobacco sheets. The effects of CMC on the thermal properties and aerosol release of tobacco sheets were also studied. The results showed that the addition amount and the molecular weight of CMC had obvious effect on the tensile strength of tobacco sheets. The DS of CMC had no significant effect on the tensile strength of tobacco sheets. The addition of CMC improved the thermal stability of tobacco sheets to a certain extent, and had certain influence on the content of nicotine in aerosol.

Evaluation of the Effects of e-Cigarette Aerosol Extracts and Tobacco Cigarette Smoke Extracts on RAW264.7 Cells.

With the advancement of society, electronic cigarettes (e-cigarettes) have gained popularity among a growing number of individuals. While numerous toxicological studies have suggested that e-cigarettes are a safer alternative to traditional cigarettes, there is also a body of literature presenting contrasting findings. This in vitro study aimed to compare the effects of e-cigarettes and tobacco cigarettes (t-cigarettes) on RAW264.7 cells by using four e-cigarette aerosol extracts (ECA) and cigarette smoking extracts (CS) containing different nicotine concentrations. The results revealed that low concentration of nicotine in CS as well as in ECA with grape, watermelon, and cola flavors could promote cell viability. Conversely, high nicotine concentration in CS and ECA with four flavors decreased cell viability. Furthermore, our study demonstrated that CS significantly reduced the phagocytic capability of RAW264.7 cells and increased the levels of inflammatory cytokines (IL-6, TNF-α, and IL-1β) and reactive oxygen species (ROS) compared to ECA. Overall, our findings indicate all four e-cigarettes induced less cytotoxicity to RAW264.7 cells and might be safer than t-cigarettes.

Cigarette smoking exposure disrupts the regenerative potential of dental pulp stem cells.

Smoking is known to alter the regenerative and immunomodulatory properties of many types of mesenchymal stem cells (MSCs). This study investigates the impact of cigarette smoke exposure on the regenerative potential of dental pulp stem cells (DPSCs). DPSCs were treated with various doses of cigarette smoke condensate (CSC) or nicotine. Cell proliferation and survival were evaluated by a water-soluble tetrazolium salt (WST-1) and a survival assay. DPSC migration, cytokine expression, mutagenesis, and the signaling pathway were also measured during CSC and nicotine treatment. Low concentrations of CSC and nicotine did not impair cell proliferation, but higher concentrations reduced cell proliferation. CSC and nicotine could impede DPSC survival and migration in a dose-dependent manner. In addition, the cytokine secretion expression profile was altered with CSC or nicotine treatments. In particular, secretion of IL-6, TNF-α, and IL-10 significantly increased, while TGF-β1 levels showed different patterns after exposure to CSC or nicotine, as shown by ELISA and quantitative PCR. Nicotine treatment increased AKT (also known as protein kinase B) and extracellular signal-regulated kinase (ERK) phosphorylation. Finally, CSC induced higher levels of mutagenicity than nicotine, as shown by the Ames test. These findings suggest that cigarette smoke exposure alters the regenerative abilities of DPSCs in various ways. Future studies are warranted to further characterize the underlying molecular mechanisms of smoking-mediated damage to DPSCs, which will guide the personalized stem cell treatment plan for smoking patients.

Effects of the multi-stress-resistant strain Zygosaccharomyces parabailii MC-5K3 bioaugmentation on microbial communities and metabolomics in tobacco waste extract.

Industrial tobacco waste was mainly treated via a reconstituted tobacco process using the paper-making method, which involves aqueous concentrated tobacco waste extract (cTWE) fermentation (aging). The fermentation was done to improve the quality of reconstituted tobacco. However, cTWE is a multi-stress environment that is characterized by low pH (about 4), as well as high sugar (above 150g/L) and nicotine (above 15g/L) content. In this study, a specific selection strategy was used to successfully isolate multi-stress-resistant bacterial or fungal strains, that exhibited positive effects on cTWE fermentation, thereby improving the quality of final products. A potential strain Zygosaccharomyces parabailii MC-5K3 was used for the bioaugmentation of cTWE fermentation and it significantly influenced the microbial diversity of the fermented cTWE. Zygosaccharomyces was observed to be the only dominant fungal genus instead of some pathogenic bacterial genera, with an abundance of over 95% after four days, and still more than 80% after a week. Meanwhile, metabolomics profiling showed significant concentration decrease with regard to some flavor-improving relative metabolites, such as 3-hydroxybenzoic acid (log2FC = -5.25) and sorbitol (log2FC = -5.54). This finding is extrapolated to be the key influence factor on the quality of the fermented cTWE. The correlation analysis also showed that the alterations in microbial diversity in the fermented cTWE led to some important differential metabolite changes, which finally improved various properties of tobacco products.

Individual differences in response to alcohol and nicotine in zebrafish: Gene expression and behavior.

Alcohol and nicotine are psychoactive substances responsible for serious health consequences. Although the biological mechanisms of alcohol and nicotine have been studied extensively, individual differences in the response to these drugs have received little attention. Here we evaluated gene expression and behavior of bold and shy individuals after acute exposure to alcohol and nicotine. For this, zebrafish were classified as bold and shy individuals based on emergence tests, and then fish were exposed to 0.00, 0.10, and 0.50% alcohol or 0.00, 1.00, and 5.00 mg/L nicotine and their anxiety-like and locomotor behavior was observed. After behavioral assessment, brain mRNA expression (ache, bdnf, gaba1, gad1b, th1, and tph1) was evaluated. Locomotion patterns differed between profiles depending on alcohol and nicotine concentration. Anxiety increased in shy fish and decreased in bold fish after exposure to both drugs. Alcohol exposure induced an increase in tph1 mRNA expression in bold fish, while bdnf mRNA expression was increased in shy fish. Nicotine increased ache, bdnf, and tph1 mRNA levels in both profiles, but at higher levels in bold fish. Based on our research, we found that alcohol induces anxiogenic effects in both bold and shy zebrafish. Additionally, shy individuals exposed to a low concentration of nicotine exhibited stronger anxiety-like responses than their bold counterparts. These findings further support the validity of using zebrafish as a dependable tool for studying the effects of drugs and uncovering the underlying mechanisms associated with individual variations.

Determination of nicotine and cotinine in human hair using online solid phase extraction coupled with liquid chromatography-tandem mass spectrometry and their relation to hair cortisol and cortisone

Tobacco smoking is one of the critical public health threats all over the world. Since nicotine and its metabolite cotinine have been routinely used as the biomarkers to estimate the exposure to tobacco smoking, hair nicotine and cotinine analyses can provide of a retrospective index of nicotine and cotinine integrated over extended periods of several months prior to hair sampling to estimate the long-term exposure to tobacco smoking. Since the relationship between tobacco smoking and hypothalamic-pituitary-adrenal (HPA) axis is implicated in both stress response and nicotine addiction, better understanding of the association between hair nicotine, cotinine levels and hair cortisol, cortisone levels is an important prerequisite toward more adequate use of this method in future research. We here presented an online solid phase extraction (SPE) coupled with liquid chromatography- tandem mass spectrometry (LC-MS/MS) method for quantification of long-term integrated nicotine and cotinine in human hair. This method was applied to the analysis of hair nicotine and cotinine in 40 participants of smokers and nonsmokers (mean ± SD age: 46.25 ± 11.92 years; 40 % male) and the investigation of their association with hair cortisol and cortisone. Methanol together with glass tube was used for hair nicotine and cotinine extraction during the incubation time of 18-h. The limits of quantification were 1 pg/mg for nicotine as well as 0.1 pg/mg for cotinine. The inter- and intra-day coefficients of variation were below 15 %. The method recovery ranged between 90 % and 104 %. Group-level analyses revealed that smokers exhibited higher hair nicotine and cotinine levels compared to nonsmokers. Hair nicotine and cotinine levels showed significant positive associations with hair cortisol and cortisone levels in smokers (nicotine and cortisol: Spearman's ρ = 0.619, p = 0.005; cotinine and cortisol: Spearman's ρ = 0.468, p = 0.043; nicotine and cortisone: Spearman's ρ = 0.773, p = 0.000; cotinine and cortisone: Spearman's ρ = 0.531, p = 0.016), but not in nonsmokers. The presented online SPE LC-MS/MS method provides a simply and highly specific analytical strategy for the detection of nicotine and cotinine concentrations in human hair for the retrospective assessment of cumulative long-term nicotine and cotinine exposure. Furthermore, hair nicotine, cotinine levels correlate with hair cortisol, cortisone levels in smokers other than nonsmokers.

Effects of Modified Tobacco Risk Products with Claims and Nicotine Features on Perceptions among Racial and Ethnic Groups.

Research suggests consumers may misunderstand modified risk tobacco product (MRTP) claims. We examined the effects of nicotine content across four tobacco products with and without MRTP claims among a racially and ethnically diverse sample of adults who do and do not smoke. Adults (n = 1484) aged 21-65 completed an online experiment using a 2 × 2 × 4 mixed factorial design to examine the effects of tobacco product (Classic White Snus, IQOS, JUUL e-cigarette, and VLN cigarette) and nicotine content (high vs. low) stratified by MRTP claim (present vs. absent) across four outcomes: (1) likely to try (2) serious disease if used regularly, (3) least addictive, and (4) ease of quitting smoking. Not including an MRTP claim resulted in an increased likelihood of trying a product, decreased concern of serious disease, lower perceived addictiveness, and increased ease of quitting smoking. Participants selected low nicotine IQOS without a claim as the least likely to cause serious disease. Low nicotine JUUL, without a claim, was selected as least addictive and most likely to facilitate quitting. Intentions to try were highest for low nicotine JUUL. Participants selected low-nicotine products as less addictive than high nicotine products. Regulatory efforts should consider how MRTP claims interact with different product characteristics. Subtle differences exist across outcomes between racial and ethnic groups, which indicates that further research is warranted.

ATR-FTIR spectroscopy combined with chemometrics for quantification of total nicotine in Algerian smokeless tobacco products

Chemma, an oral moist snuff widespread used in Algeria, is prepared from grounded tobacco and inorganic salts or other plant materials. In addition to its adverse health issues, Chemma contains unknown amounts of nicotine and other harmful constituents. Twenty seven samples of commercial products and tobacco leaves varieties were characterized in the aim to quantitatively determine total nicotine by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy coupled with two regression methods (univariate and multivariate). For this purpose, a highly specific-to-analyte extraction method was applied on calibration and test sets of standards for a wide concentration range. The optimal analytical models were evaluated by selecting the appropriate spectral measurement, spectral pre-processing strategies and critical figures of merit estimated according to the latest approaches. Then, the predictive ability of the method was demonstrated with the elliptical joint confidence region test and with comparing to results in literature.The linear baseline correction and the extended multiplicative scatter correction pre-processing of the combined reduced spectral regions 1333–1299 and 740–690 cm−1 followed by partial least squares regression (PLSR) offered the best analytical outcomes. Using this latter, total nicotine content in the manufactured smokeless tobacco (ST) products have been found ranging from 3.9 to 12.6 mg/g of dry weight; while in the ST leaves, it was between 5.9 and 45.0 mg/g, dry weight basis. The developed method, besides to the high predictive performance, provides advanced statistical tests that can qualitatively assess the target analyte in real sample spectra, allowing more reliable result.With the increasing number of new products containing complex agents and adulterants, the aforementioned method can be successfully adapted to routine analyses for rapid quality control of nicotine in ST and cigarettes.

Chronic Inhalation of Pod-based e-cigarette Aerosols on Inflammatory Biomarkers in the Central Nervous and Peripheral Systems

Electronic cigarettes (e-cigs) use has been dramatically increased recently, especially among youths. In this study, we evaluated the effect of one- and three-months continuous exposure to e-cig vapor (JUUL pods), containing high nicotine concentration, on the expression of glutamate receptors and transporters and mainly the associated neuroinflammatory markers in drug reward brain regions such as nucleus accumbens (NAc) core (NAc-core), NAc shell (NAc-shell) and hippocampus (HIP) in female C57BL/6 mice. We revealed that three months’ exposure to mint or mango flavored-JUUL (containing 5% nicotine, 59 mg/ml) induced upregulation in metabotropic glutamate receptor 1 (mGluR1) and postsynaptic density protein 95 (phosphorylated and total PSD95) expression, and downregulation of mGluR5 and glutamate transporter 1 (GLT-1) in the NAc-shell. Three months’ exposure to JUUL induced upregulation of mGluR5 and GLT-1 expression in the HIPP. We further revealed that mice exposed to JUUL Mango and JUUL Mint for one month had significantly increased TNF-α expression in the NAc-core and NAc-shell, with elevation in IL-1β as well. NAc-shell also showed significantly increased levels of IL-6 and HMGB-1 for both flavors. There were significantly increased levels of TNF-α in the NAc-core and NAc-shell for both Mint- and Mango-exposed JUUL mice for three months. NAc-shell also showed significantly increased levels of IL-1β, IL-6, HMGB-1, and RAGE after three months of JULL exposure, while the hippocampus showed significantly decreased levels of HMGB-1 for both flavors. These findings demonstrated that exposure to e-cig vapor containing high nicotine concentrations induced differential effects on glutamatergic system as well as induction of proinflammatory markers in the brain.