Nicotine Research Articles (Page 1)

Introduction: Diabetes Mellitus (DM) and smoking, nicotine exposure, are prominent risk factors for cardiovascular diseases (CVD). The interaction of these factors can potentiate vascular damage, while physical training (PT) is recommended for CVD prevention. Objective: To evaluate the effects of moderate PT on hemodynamic parameters, oxidative stress profile and cardiorenal risk markers in DM animals exposed to nicotine. Method: Wistar male rats weighing between 250-350 g were divided into groups: Citrate (CT): healthy control animals receiving citrate buffer; Nicotine (NIC): animals exposed to nicotine (0.6 mg/kg, intraperitoneally, 28 days; Type 1 Diabetes (DM): animals receiving streptozotocin (60 mg/kg, i.v., caudal vein, single dose); DM+NIC: DM animals exposed to nicotine (as described); DM+NIC+PT: DM + NIC animals submitted to moderate intensity PT, (swimming; 3 times a week, once a day, 50 minutes). Renal function, redox profile and body and renal hemodynamics were evaluated. Hemodynamic parameters (mean arterial pressure - MAP, renal vascular resistance - RVR, renal blood flow - RBF), redox profile (thiols, lipid and urinary peroxidation), and renal function/cardiorenal risk markers (serum creatinine, inulin clearance, microalbuminuria) were assessed. Results: DM and NIC groups showed increased MAP and RVR, with reduced RBF. Exacerbated alterations in these parameters were observde in the DM+NIC group. PT significantly attenuated these adverse hemodynamic changes (DM+NIC+PT vs. DM+NIC). Increased oxidative stress (reduced thiols, increased lipid/urinary peroxidation) was observed in the DM, NIC, and especially DM+NIC groups. PT improved the redox balance in the trained groups (DM+NIC+PT vs. DM+NIC). Microalbuminuria, a cardiorenal risk marker, increased in the DM, NIC, and DM+NIC groups but was significantly attenuated by PT in the DM+NIC+PT group. Conclusion: Moderate physical training demonstrated significant cardioprotective effects in this experimental model, mitigating adverse hemodynamic changes, oxidative stress, and cardiorenal risk, assessed by microalbuminuria, induced by the combination of diabetes and nicotine exposure.

Moringa oleifera leaves aqueous extract mitigates nicotine-induced reproductive toxicity in male rats.

Evaluation of Emerging Contaminants and Biochemical Parameters in the Blood Plasma of Wild American Alligators (Alligator mississippiensis).

ObjectiveCigarette smoking accelerates kidney disease progression. Emerging evidence suggests that dapagliflozin (DAPA) exerts protective effects against various kidney injuries. This study aimed to investigate the effects of DAPA on nicotine (NIC)-induced apoptosis in human kidney proximal tubular epithelial (HK-2) cells.MethodsHK-2 cells were treated with NIC, DAPA or selective mitogen-activated protein kinase (MAPK) inhibitors (SP600125 and SB203580). Cell viability, apoptotic cell death and reactive oxygen species (ROS), namely intracellular ROS and MitoSOX, were assessed using a CCK-8 assay and flow cytometry. The concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were determined by enzyme-linked immunosorbent assay. Protein expression levels related to mitochondrial function, endoplasmic reticulum (ER) stress and the MAPK signalling pathway were analysed by immunoblotting.ResultsDapagliflozin and MAPK inhibitors significantly attenuated NIC-induced apoptosis and improved HK-2 cell viability, as evidenced by increased Bcl-2 expression and decreased Bax and Caspase-3 expression. Apoptosis attenuation was closely associated with the suppression of p-ASK1/p-JNK/p-p38 MAPKs and p-MEK3/p-MEK4 activation. Dapagliflozin and MAPK attenuations regulate the expression of oxidant and antioxidant proteins, reducing intracellular ROS and MitoSOX overproduction and thereby alleviating mitochondrial dysfunction and ER stress. Both agents also significantly reduced pro-inflammatory cytokine levels, including TNF-α and IL-1β.ConclusionsThese findings suggest that DAPA protects HK-2 cells from NIC-induced apoptosis by modulating the ASK1/p38/JNK MAPK signalling pathway, reducing oxidative stress and alleviating inflammation.

ABSTRACT During the tobacco crop sorting process, workers come in contact with various substances found in dried leaves, including tobacco-specific nitrosamines: N’-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and nicotine (NIC). The objective of this study was to assess the cytotoxic and genotoxic effects initiated by exposure to aqueous extract of dry tobacco leaves (TLE) and by compounds NNN, NNK, and NIC, both alone and in combination, using the human hepatocarcinoma cell line (HepG2) as a model. The relationship of exposure with mechanisms of oxidative damage was also assessed. To determine cytotoxicity, the MTT assay was employed, and to assess genotoxicity, the alkaline comet assay and its modified version with the enzyme FPG were utilized, along with the measurement of telomere length. Further systems biology tools were employed to generate the protein network for the combination of NIC, NNN, and NNK. No marked cytotoxicity was observed through the MTT assay. Genotoxicity was detected at the highest concentrations of TLE (1.25 and 5 mg/ml), for NIC, NNN, NNK, and in combinations of these samples. The modified comet assay with formamidopyrimidine DNA glycosylase (FPG) enzyme found that genotoxicity was related to oxidative damage. No significant difference in telomere length was observed. Through in silico analysis, data demonstrated that the predominant proteins associated with the combined agents NNN, NNK, and NIC exhibited connections with signaling pathways related to oxidative damage mechanisms and carcinogenic processes.

Cigarette smoke exposure induces oxidative stress and neuroinflammation, contributing to nicotine dependence and withdrawal-related anxiety. Rhoifolin (ROF), a naturally occurring flavonoid glycoside, possesses notable oxidative stress and inflammation reducing properties. This study investigated the potential ameliorative effects of ROF against cigarette smoke-induced neuroinflammation, oxidative damage, and withdrawal-induced anxiety-like behavior in rats. Rats were allocated into four treatment groups: a control group subjected only to ambient air; a nicotine (NIC) group exposed to cigarette smoke five days a week for seven weeks; a NIC/ROF group similarly exposed to smoke, but also treated with 20mg/kg ROF daily for the last three weeks; and a ROF-only group treated with ROF while subjected to room air. Cigarette smoke exposure evoked anxiety during withdrawal periods, elevated levels of proinflammatory cytokines IL-1β and TNF-α, and a markedly reduced levels of key antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase. ROF treatment significantly reversed these effects, reducing anxiety, lowering inflammatory markers, and restoring antioxidant enzyme activity to near-normal levels. Molecular modeling simulations showed a potential binding interaction for ROF at an allosteric pocket in each of the antioxidant enzyme structures, providing a potential mechanism by which ROF might act as an activator of these enzymes, thereby promoting antioxidant activity. Our findings suggest that ROF exhibits anxiolytic effects related to cigarette smoke exposure, likely mediated by its ameliorative role against inflammation and oxidative stress, supporting its potential role in improving behavioral outcomes of cigarette smoke withdrawal.

Electrochemical sensor based on tadpole-shaped Au nanostructures supported on TiO2: Enhanced detection of nicotine in electronic cigarettes and clinical samples.

To elucidate the principal interaction of nicotine (NIC) with the binding pocket of nicotinic acetylcholine receptor (nAChR), a simplified model complex comprising of N'-methyl-indolyl-2-propanamide (MIPA) and NIC was studied using infrared spectroscopy and theoretical calculations. MIPA serves as a surrogate for the tryptophan 156 residue of the α-subunit of nAChR, which was previously identified to stabilize NIC binding in a model binding pocket. The MIPA-NIC interaction stabilizes the bioactive N-methylpyrrolidinium protomer of NIC (Pyrro-H+, 60% population) that stimulates nAChR over the inactive pyridinium protomer (Pyri-H+, 40% population) via the interaction of Trp with the indole side chain of MIPA. The observed selectivity of NIC's pyrrolidine protonation site in its complex with MIPA originates from its stabilization via cooperative interactions between the amide and indole functional groups. This work illustrates the importance of fundamental interactions at the molecular level in describing biological activity between an agonist and the binding pocket of the nAChR.

Brazilian grocery stores and local markets commonly sell handmade cigarettes made from cornhusk and treated tobacco. This artisanal cigarette, once regionally traditional, has become the second most consumed form of cigarettes in the country. Tobacco products contain nicotine (NIC), a substance known for its high addiction potential and association with cardiovascular diseases. This study proposes an electrochemical synthesis method for a reduced graphene oxide/silver‐copper‐hexacyanoferrate (rGO/AgCuHCF) composite to optimize conditions for sensitive electrochemical NIC detection. The optimized material was prepared using a 3:1 Ag:Cu ratio in an initial cyclic voltammetry (CV) step, followed by a ferricyanide solution with pH = 7.0, achieving a sensitivity of 13.0 nA L mol‐1 through a 2² factorial design experiments. Microscopic analysis showed uniform PBA particles distributed over the wrinkled carbon support, while spectroscopic techniques confirmed bimetallic PBA structural features distinct from monometallic variants. Batch injection analysis‐assisted amperometry using the rGO/AgCuHCF modified electrode demonstrated a linear current response for NIC in the range of 5.0 to 2000.0 μmol L‐1, yielding a superior sensitivity of 32.9 nA L mol‐1 and a low detection limit of 0.9 μmol L‐1. This sensor proved viable and reliable for detecting NIC in industrial and artisanal cigarettes tobacco samples.

Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited. In this study, we demonstrate that NIC increases the abundance and proliferative activity of murine intestinal stem cells (ISCs) in vivo and ex vivo. Moreover, NIC induces Yes-associated protein (YAP) /Transcriptional coactivator with PDZ-binding motif (TAZ) and Notch signaling in ISCs via α7-nicotinic acetylcholine receptor (nAchR) and protein kinase C (PKC) activation; this effect was not detected in Paneth cells. The inhibition of Notch signaling by dibenzazepine (DBZ) nullified the effects of NIC on ISCs. NIC enhances in vivo tumor formation from ISCs after loss of the tumor suppressor gene Apc, DBZ inhibited NIC-induced tumor growth. Hence, this study identifies a NIC-triggered pathway regulating the stemness and tumorigenicity of ISCs and suggests the use of DBZ as a potential therapeutic strategy for treating intestinal tumors.

Cigarette smoking is a well-known risk factor inducing the development and progression of various diseases. Nicotine (NIC) is the major constituent of cigarette smoke. However, knowledge of the mechanism underlying the NIC-regulated stem cell functions is limited. In this study, we demonstrate that NIC increases the abundance and proliferative activity of murine intestinal stem cells (ISCs) in vivo and ex vivo. Moreover, NIC induces Yes-associated protein (YAP) /Transcriptional coactivator with PDZ-binding motif (TAZ) and Notch signaling in ISCs via α7-nicotinic acetylcholine receptor (nAchR) and protein kinase C (PKC) activation; this effect was not detected in Paneth cells. The inhibition of Notch signaling by dibenzazepine (DBZ) nullified the effects of NIC on ISCs. NIC enhances in vivo tumor formation from ISCs after loss of the tumor suppressor gene Apc, DBZ inhibited NIC-induced tumor growth. Hence, this study identifies a NIC-triggered pathway regulating the stemness and tumorigenicity of ISCs and suggests the use of DBZ as a potential therapeutic strategy for treating intestinal tumors.

This study investigates the metabolic disruptions caused by nicotine (NIC) exposure, with a particular focus on amino acid and lipid metabolism, and evaluates resveratrol (RSV) as a potential protective agent. Mice were divided into four groups: control (CON), NIC-exposed, NIC + RSV-treated, and RSV-only. NIC exposure resulted in significant weight loss, elevated glucose levels, altered lipid profiles, and organ damage, particularly in the liver and kidneys. Increased inflammation was evidenced by elevated levels of IL-6 and CRP. In contrast, RSV treatment mitigated these effects by improving lipid profiles, glycemic indices, and reducing inflammatory markers. Histopathological analysis confirmed reduced tissue damage in the NIC + RSV group compared to the NIC-alone group. Metabolomics analysis using LC-MS/MS revealed significant dysregulation in lipid, amino acid, and nucleotide metabolism in NIC-exposed mice. Fold-change analysis identified altered metabolites, including sphingomyelin 36:1;02 (p < 0.001), valine (p < 0.001), triacylglycerol 4:0-18:1 (p < 0.001), and ceramide 32:1;02 (p < 0.001). Amino acids such as arginine, phenylalanine, glutamic acid, tyrosine, and lysine, as well as NIC metabolites like nornicotine and cotinine, were identified, underscoring molecular fragmentation analysis findings. RSV treatment partially restored metabolic balance, highlighting its role as a metabolic modulator. This study underscores the therapeutic potential of RSV in alleviating NIC-induced metabolic dysfunctions by restoring lipid homeostasis and reducing inflammation. Additionally, it emphasizes the importance of RSV in addressing NIC-related metabolic impairments and the need for noninvasive biomarkers for early disease detection.

Caffeine (CAF) and nicotine (NIC) are emerging contaminants and are among the most consumed substances in the world, making it crucial to monitor these contaminants. In this work, an alternative electrolyte, 2-hydroxyethylammonium acetate (2HEAA) was used for the development of an electroanalytical method for determination and quantification of CAF and NIC, simultaneously, using differential pulse voltammetry (DPV). The system with the 2HEAA electrolyte was characterized by cyclic voltammetry and electrochemical impedance spectroscopy, and the DPV parameters were optimized for the best conditions. The method was validated from a calibration curve obtained which showed limit of detection (LOD) of 0.82 and 6.26 μmol L-1 and limit of quantification (LOQ) of 2.73 and 20.8 μmol L-1 for CAF and NIC, respectively. In the precision analyses, values lower than 10% of relative standard deviation were obtained. In the presence of concomitant inorganic and organic species, the system proved to be selective in the determination of analytes. The method was used to determine the analytes in fortified samples (river water, synthetic urine and commercial milk), obtaining recoveries between 87.25 and 111.40%. The 2HEAA demonstrated high efficiency as an alternative electrolyte with good signal-to-noise ratio, increased analytical sensitivity of the method, in addition to presenting low cost and fast electrolyte preparation.

6-hydroxy-L-nicotine (6HLN) is a nicotine (NIC) derivative with proven therapeutic potential in neurodegenerative disorders. Here, the impact of 6HLN on cell growth, migratory behavior, and inflammatory status of three different cancer cell lines (A549, MCF7, and U87) and two normal cell lines (16HBE14o and MCF10A) was investigated. In silico analyses were conducted to evaluate the binding affinity of 6HLN to nicotinic receptors (nAChRs) containing α9 and α5 subunits. The obtained in silico data revealed that 6HLN might act on the cholinergic system. Interestingly, the in vitro data showed the compound has cancer-stimulatory effects in U87 glioblastoma cells and cancer-inhibitory effects in MCF7 breast cancer cells. In A549 lung cancer cells, no changes were detected upon 6HLN administration. More importantly, 6HLN appears not to be deleterious for normal cells, with the viability of 16HBE14o pulmonary cells and MCF10A mammary cells remaining unchanged.

Introduction: Electronic cigarettes (e-cig) have been promoted as nicotine (NIC) delivery systems without the adverse effects of tobacco cigarettes; however, the increasing popularity of EC has prompted concerns about their potential cardiovascular (CV) toxicity. As e-cig are relatively new products, their long-term CV effects over the lifetime of the user remain unclear. We developed a mouse model of chronic e-cig exposure that mimics human NIC exposure levels to simulate long-term human use. Objective: To characterize the effects of long-term e-cig exposure on the structure, contractile function and electrophysiological function of the heart with exposures for &gt;50% of life-span. Methods: C57/BL6 male mice were exposed to either air (25 mice) or aerosol from e-cig liquid containing 24 mg/ml NIC (25 mice) for 3 hours/day, 5 days/week, over 64 weeks. Blood pressure (BP) was measured by tail-cuff. Echocardiography was performed to assess the structure and function of the left ventricle (LV) and right ventricle (RV). High-resolution 3D visualization of LV and RV was also performed by cardiac CINE-MRI. Cardiac rate and electrophysiology was measured by electrocardiography (ECG). Results: Compared to the air control group, e-cig exposure for 64 weeks led to major changes in heart structure and function (Table 1). Marked elevations in systolic BP (SBP), diastolic BP (DBP), and mean BP (MBP) of 49%, 66%, and 63%, respectively, were observed. Echocardiography revealed concentric LV hypertrophy (LVH) with increases in both LV and RV end-diastolic and end-systolic wall thicknesses. LV mass was 43% increased. Marked RV hypertrophy (RVH) was also observed. The presence of LVH and RVH was confirmed on cardiac MRI. ECG exhibited 6% slower heart rate with e-cig exposure along with 23% prolonged PR interval and 91% increase in P wave duration. QT interval was 20% prolonged indicative of delayed ventricular depolarization and repolarization. Conclusions: Long term e-cig exposure caused hypertension with LV and RV hypertrophy with alterations in atrial and ventricular conduction seen. Thus, long-term e-cig use may predispose to hypertrophic heart disease and cardiac conduction abnormalities.

Gas sensors are used for monitoring hazardous gases and vapors. With the emergence of S-terminated MXene synthesis, herein, we explore the sensing ability of Ti3C2S2 toward N-containing gases, including NH3, NO, NO2, trimethylamine (TMA), and nicotine (NT), using first-principles calculations and a statistical thermodynamic model. We find that Ti3C2S2 exhibits high selectivity to TMA, NO, and NT with moderate adsorption energies of -0.610, -0.490, and -0.476 eV, respectively, minimizing environmental noise from ambient gases. The electronic structure of Ti3C2S2 subtly alters upon adsorption of TMA, NO, and NT, facilitating detectable signals in the sensing device. However, the adsorption of NO2 and NH3 is less pronounced due to weak physisorption (<0.3 eV). Employing engineering strategies including biaxial strain and an external electric field greatly enhances the selectivity and sensitivity of NO2 (NH3) detection by boosting adsorption strength up to -0.351 eV with ε = 5% (-0.370 eV with |E⃗| = 0.6 V/ Å). In addition, the moderate adsorption energies of the gases result in a suitable recovery time in the range of milliseconds, leading to high reusability of the sensing device. The estimated adsorption densities suggest potential coverage of these N-containing molecules even at low concentrations and room temperature. Computational analysis of the sensing capability of Ti3C2S2 using the nonequilibrium Green's function method indicates that it is a promising gas-sensing material. In addition, mechanical modifications, electric field adjustments, and gate voltage alterations could be used to obtain effective sensing materials for N-containing gas detection.

The availability of well-established analytical methods is crucial to cope with the fast-ongoing research for the development of new drug delivery formulations. In this work, a rapid highly green chromatographic method was developed for the simultaneous determination of nicotine (NIC) and caffeine (CAF) to be applied for an in-vitro release study from a newly prepared quick mist mouth spray co-formula (QMS), as a complementary synergistic fast-onset relief of cravings during smoking cessation. The chromatographic resolution was accomplished on a cyano column using isocratically delivered (1.0 mL/ min) glycerol: orthophosphoric acid (OPA) (0.2 M) adjusted to pH 3.0 using 0.05 M triethylamine (5:95, v/v) and UV detection at 260 nm. Well resolved peaks of NIC and CAF were eluted at 2.1 and 3.9 min (Rs = 5.64), with linear responses between 0.1 and 20.0 µg/mL and 0.2–40.0 µg/mL, and detection limits of 0.03 and 0.07 µg/mL for NIC and CAF, respectively. The developed method showed good analytical performance (accuracy, precision, robustness, and selectivity) as well as superiority in practicality and ecological profile compared to reported methods applying GAPI, analytical eco-scale, AGREE, BAGI, and whiteness metric tool. The developed method was successfully applied for NIC and CAF determination in their pharmaceutical preparations, and artificial saliva with no significant differences from reported method results (F-test and t-test). Moreover, an in-vitro release study of NIC and CAF from QMS was performed employing the developed method that revealed diffusion-controlled release, compared to mixed diffusion/ polymer chain relaxation for marketed single component formulation, showing the superiority of QMS in reducing drug level fluctuations of NIC and CAF and improving their bioavailability.Graphical

Biotransformation of carbamazepine and nicotine in juvenile American alligator (Alligator mississippiensis) in vitro hepatic S9 vs. in situ perfused liver

The tobacco epidemic signifies a major public health threat. Nicotine (NIC), a major active constituent in tobacco, impedes male fertility and semen quality. This work is implemented to explore the potential of selenium nanoparticles (SeNPs) and the newly fabricated SeNPs @vitamin C (SeNPs@VITC) nanocomposite in mitigating testicular toxicity induced by NIC. The six groups of 48 adult Wistar rats were designed as follows: the control group injected intraperitoneally with normal saline, the SeNPs group treated orally with 2mg/kg of SeNPs, the SeNPs@VITC nanocomposite group treated orally with 2mg/kg of SeNPs@VITC nanocomposite, the NIC group injected intraperitoneally with 1.25mL/kg of NIC, the NIC+ SeNPs group received SeNPs plus NIC, and the NIC+ SeNPs@VITC nanocomposite group received SeNPs@VITC nanocomposite plus NIC. Treatments were administered over a 28-day period. NIC treatment significantly caused poor sperm quality, decreased serum testosterone, increased follicle-stimulating hormone (FSH), luteinizing hormone (LH) concentrations, reduced hemoglobin levels, leukocytosis, disrupted testicular oxidant/antioxidant balance, and disorganized testicular structure. The construction of the novel SeNPs@VITC nanocomposite, compared to NIC plus SeNPs alone, demonstrated a more potent ameliorative effect on NIC-induced reproductive toxicity in adult rats. The SeNPs@VITC nanocomposite significantly increased sperm count, reduced the percentage of sperm head abnormalities, lowered both serum FSH and LH concentrations, and improved the hemoglobin response. Both SeNPs and SeNPs@VITC nanocomposite alleviated the testicular toxicity induced by NIC, but the SeNPs@VITC nanocomposite exhibited superior efficacy. The SeNPs@VITC nanocomposite could be employed to advance enhanced therapeutic strategies for addressing male infertility.

Nicotine inhalation and metabolism triggers AOX-mediated superoxide generation with oxidative lung injury