Effects Of Nicotine Research Articles

Vesicular glutamate transporter 2 expression in the ventral tegmental area of outbred male rats following exposure to nicotine and alcohol

BackgroundInitiation of use/co-use of nicotine and alcohol, commonly occurring in an episodic manner during adolescence, can imprint vulnerability to the developing brain and lead to addiction. The ventral tegmental area (VTA) is a key heterogeneous region of the mesocorticolimbic circuit involved in the binge-drinking and intoxication step of the addiction circuit. Higher human post-mortem VTA expression of vesicular glutamate transporter 2 (VGLUT2), a marker of the glutamatergic phenotype also expressed in dopaminergic [Tyrosine Hydroxylase (Th)-positive] neurons, has been associated with chronic nicotine use and co-use with alcohol. MethodsThe present study aimed to map and characterize the Vglut2- and Th-expressing neurons in the VTA of adolescent male rats exposed or not to prolonged (six-weeks) episodic (three consecutive days/week) nicotine and/or alcohol administration. Nicotine (0.35 mg/kg free base) was injected subcutaneously, whereas alcohol (2 g/kg 20%) was administrated via gavage. Vglut2 and Th mRNA was assessed in the anterior and posterior VTA by use of in situ hybridization. ResultsThe profile of neurons varied with substance-exposure among VTA subregions. Th-only expressing neurons were more abundant in the posterior VTA of the group exposed to nicotine-only, compared to controls. The same neurons were, on the contrary, less present in the anterior VTA of animals exposed to alcohol-only, who also displayed a higher number of Vglut2-expressing neurons in the lateral anterior VTA. ConclusionsVTA Vglut2- and Th-only neurons seem differentially involved in the effects of adolescent episodic nicotine and alcohol exposure in the anterior and posterior VTA.

Early-onset smoking theory of compulsivity development: a neurocognitive model for the development of compulsive tobacco smoking.

According to the literature, individuals who start tobacco smoking during adolescence are at greater risk of developing severe tobacco addiction and heavier smoking behavior in comparison with individuals who uptake tobacco smoking during subsequent developmental stages. As suggested by animal models, this may be related to the unique neuroadaptive and neurotoxic effects of nicotine on adolescents' fronto-striatal brain regions modulating cognitive control and impulsivity. Previous research has proposed that these neuroadaptive and neurotoxic effects may cause a heightened reward-oriented impulsive behavior that may foster smoking relapses during quit attempts. However, developments in the field of addiction neuroscience have proposed drug addiction to represent a type of compulsive behavior characterized by the persistent use of a particular drug despite evident adverse consequences. One brain region that has received increased attention in recent years and that has been proposed to play a central role in modulating such compulsive drug-seeking and using behavior is the insular cortex. Lesion studies have shown that structural damages in the insular cortex may disrupt smoking behavior, while neuroimaging studies reported lower gray matter volume in the anterior insular cortex of chronic smokers compared with non-smokers, in addition to correlations between gray matter volume in the anterior insular cortex and measures of compulsive cigarette smoking. Based on the findings of our recent study reporting on early-onset smokers (mean age at regular smoking initiation = 13.2 years) displaying lower gray matter and white matter volume in the anterior insular cortex compared to late-onset smokers (mean age at regular smoking initiation = 18.0 years), we propose that the anterior insular cortex may play a central role in mediating the association between smoking uptake during adolescence and smoking heaviness/tobacco addiction during adulthood.

Liver tryptophan 2,3-dioxygenase: a determinant of anxiety-like behaviour - studies with chronic nicotine administration in rats.

Deletion of the tryptophan 2,3-dioxygenase ( TDO2 ) gene induces an anxiolytic-like behaviour in mice and TDO inhibition by allopurinol elicits an antidepressant-like effect in rats exposed to restraint stress. Chronic nicotine administration inhibits TDO activity, enhances brain serotonin synthesis and exerts anxiolytic- and antidepressant-like effects in rodent models. There is a strong association between anxiety, depression and tobacco use, which is stronger in women than in men. The present study aimed to examine the relationship between behavioural measures of anxiety and depression with liver TDO activity, brain tryptophan concentration and serotonin synthesis in rats treated chronically with nicotine. Behavioural measures included the elevated plus maze (EPM), open field (OFT) and forced swim (FST) tests. Biochemical measures included TDO activity, serum corticosterone and brain Trp, 5-HT and 5-HIAA concentrations. Anxiolytic-like and antidepressant-like effects of chronic nicotine were confirmed in association with TDO inhibition and elevation of brain Trp and 5-HT. Sex differences in behaviour were independent of the biochemical changes. At baseline, female rats performed better than males in OFT and FST. Nicotine was less anxiolytic in females in the open arm test. Nicotine treatment did not elicit different responses between sexes in the FST. Our findings support the notion that liver TDO activity exhibits a strong association with behavioural measures of anxiety and depression in experimental models, but provide little evidence for sex differences in behavioural response to nicotine. The TDO-anxiety link may be underpinned by kynurenine metabolites as well as serotonin.

The Influence of Nicotine on Trophoblast-Derived Exosomes in a Mouse Model of Pathogenic Preeclampsia.

Preeclampsia (PE) is a serious complication of pregnancy with a pathogenesis that is not fully understood, though it involves the impaired invasion of extravillous trophoblasts (EVTs) into the decidual layer during implantation. Because the risk of PE is actually decreased by cigarette smoking, we considered the possibility that nicotine, a critical component of tobacco smoke, might protect against PE by modifying the content of exosomes from EVTs. We investigated the effects of nicotine on our PE model mouse and evaluated blood pressure. Next, exosomes were extracted from nicotine-treated extravillous trophoblasts (HTR-8/SVneo), and the peptide samples were evaluated by DIA (Data Independent Acquisition) proteomic analysis following nano LC-MS/MS. Hub proteins were identified using bioinformatic analysis. We found that nicotine significantly reduced blood pressure in a PE mouse model. Furthermore, we identified many proteins whose abundance in exosomes was modified by nicotine treatment of EVTs, and we used bioinformatic annotation and network analysis to select five key hub proteins with potential roles in the pathogenesis or prevention of PE. EVT-derived exosomes might influence the pathogenesis of PE because the cargo delivered by exosomes can signal to and modify the receiving cells and their environment.

Smoking prevalence among adults in households with children: parental survey

The effects of tobacco smoke and nicotine on the health of adults and children remain one of the most burning problem in our days. In 2019 the prevalence of active smoking in Ukraine reached 42.0 among men and 14.4% among women. The negative effects of second-hand tobacco smoke exposure are most significant in children under 5 years of life, especially in families with smoking mothers. The goal of the study was to assess the current smoking prevalence in families with children, including the use of modern electronic nicotine delivery devices. A self-reported survey of 414 families living in Odessa and Odessa region (Ukraine) was conducted. All questionnaires were divided into two groups depending on the presence of tobacco smoke exposure. To asses the factor's relevance the odds ratio (OR) and its 95% confidence interval (CI) were used. The prevalence of smoking in families was associated with the age of the father up to 30 years (16.13 [95% CI 11.54–22.09]%; OR 2.73 [1.42–5.25]), mother’s and father’s low education lever (OR 2.73 [1.42–5.25] and 2.70 [1.64–4.44]), as well as with the residence of the family in the city (OR 4.30). The prevalence of smoking exposure was not associated with the income level or number of household members. The prevalence of smoking in women before pregnancy was more than 20%, and during pregnancy – 10%. After delivery women smoked in 23.91 (95% CI 20.06-28.25)% of cases. Proportion of families where smoked someone other than the mother reached 42.75 (95% CI 38.08–47.56)%. Other family members smoking negatively affected mothers’ tobacco consumption, both before and after childbirth. After pregnancy, women used both smoked tobacco and noncombustible forms of nicotine (51.52 vs 48.48%) with the same frequency. Other family members consumed smoking tobacco more often than e-cigarettes. All smokers who used electronic nicotine delivery devices more likely smoked at home (OR 5.33 [95% CI 0.53–54.04]).

Pulmonary thromboembolism following organophosphate intoxication: a case report

Various symptoms manifest after organophosphate intoxication due to muscarinic, nicotinic, and central nervous system effects. Complications are common, and morbidity occurs due to respiratory center depression, cardiovascular complications, aspiration pneumonia, general weakness, and neurological symptoms. Some studies have reported a statistically significant association between organophosphate intoxication and deep vein thrombosis. However, cases of pulmonary thromboembolism (PTE) resulting from organophosphate poisoning are very rare. A 45-year-old male patient was transferred to our hospital after ingesting an unknown amount of an insecticide and receiving 6 L of gastric lavage at a local hospital. Other than nausea, no symptoms (e.g., dyspnea) were present, but a hemodynamic test showed an elevated lactic acid level, and metabolic acidosis worsened over time. Accordingly, we conducted initial treatment including continuous renal replacement therapy. After 7 hours, the poisoning analysis result was confirmed, and lambda-cyhalothrin and chlorpyrifos (0.441 µg/mL and 0.401 µg/mL, respectively) were detected. We introduced pralidoxime. Although no increase in pseudocholinesterase was found during hospitalization, continuous renal replacement therapy and pralidoxime were discontinued because the patient did not show symptoms of intermediate syndrome, including dyspnea and altered consciousness. The patient complained of abdominal pain on hospital day 8. Abdominal computed tomography was performed to evaluate the possibility of a corrosive injury to the stomach or esophagus, and we confirmed PTE. The D-dimer level was 1.96 mg/L (normal range, 0–0.55 mg/dL). A radiologic examination showed a PTE in the main pulmonary artery leading to the segmental pulmonary artery. After heparinization, the patient was discharged after being prescribed a vitamin K-independent oral anticoagulant. Through this case, we would like to emphasize the need for a thorough evaluation of clinical symptoms because atypical symptoms can occur after poisoning with organophosphate pesticides.

Nicotine promotes Mycobacterium tuberculosis H37Rv growth and overexpression of virulence genes.

Tobacco consumption increases the susceptibility to develop infectious diseases such as tuberculosis (TB). Nicotine (Nc) is the main component of cigarette smoke with immunomodulatory properties, however, its effect on Mycobacterium tuberculosis (Mtb) has been scarcely investigated. The present study evaluated the effect of nicotine on the growth of Mtb and on the induction of virulence-related genes. Mycobacteria were exposed to different concentrations of nicotine then Mtb growth was evaluated. Subsequently, the expression of the virulence-related genes lysX, pirG, fad26, fbpa, ompa, hbhA, esxA, esxB, hspx, katG, lpqh, and caeA was evaluated by RT-qPCR. The effect of nicotine on intracellular Mtb was also evaluated. The results showed that nicotine promotes the growth of Mtb both extracellularly and intracellularly and increases the expression of genes related to virulence. In summary, nicotine promotes the growth of Mtb and the expression of virulence-related genes that could be correlated with the increased the risk of smokers developing TB.

Astrocytic α4-containing nAChR signaling in the hippocampus governs the formation of temporal association memory

Everyday episodic memories involve linking together related events that are temporally separated. However, the mechanisms of forming this temporal association have remained unclear. Here, using astrocyte-specific manipulations, we show that potentiating astrocyte Ca2+ signaling in the hippocampal cornu ammonis 1 (CA1) enhances the strength of such temporal association, in parallel with long-term potentiation (LTP) enhancement of temporoammonic pathway to CA1, whereas attenuation of astrocyte Ca2+ signaling has the opposite effect. Moreover, we identify that these effects are mediated by astrocytic α4 subunit-containing nicotinic acetylcholine receptors (α4-nAChRs) via mechanisms involving NMDAR co-agonist supply. Finally, astrocytic α4-nAChRs underlie the cognitive enhancer nicotine's physiological effects. Together, these findings highlight the importance of astrocyte Ca2+ signaling in cognitive behavior and reveal a mechanism in governing the temporal association of episodic memory formation that operates through α4-nAChRs on hippocampal astrocytes.

Nicotine reduces social dominance and neutralizes experience-dependent effects during social conflicts in zebrafish (Danio rerio)

Nicotine, a psychoactive pollutant, binds to nicotinic acetylcholine receptors and disrupts the cholinergic modulation and reward systems of the brain, leading to attention deficit, memory loss, and addiction. However, whether nicotine affects social behaviors remains unknown. We assessed the effects of nicotine on the fighting behavior of zebrafish. Adult zebrafish treated with 5 μM nicotine were used in dyadic fighting tests with size-matched control siblings. The results indicate that nicotine treatment not only significantly reduced the likelihood of winning but also impaired the winner–loser effects (winner and loser fish did not show higher winning and losing tendencies in the second fight, respectively, after treatment.) Nicotine led to a considerable increase in c-fos-positive signals in the interpeduncular nucleus (IPN) of the brain, indicating that nicotine induces neural activity in the habenula (Hb)–IPN circuit. We used transgenic fish in which the Hb–IPN circuit was silenced to verify whether nicotine impaired the winner–loser effect through the Hb–IPN pathway. Nicotine-treated fish in which the medial part of the dorsal Hb was silenced did not have a higher winning rate, and nicotine-treated fish in which the lateral part of the dorsal Hb was silenced did not have a higher loss rate. This finding suggests that nicotine impairs the winner–loser effect by modulating the Hb–IPN circuit. Therefore, in these zebrafish, nicotine exposure impaired social dominance and neutralized experience-dependent effects in social conflicts, and it may thereby disturb the social hierarchy and population stability of such fish.

Association of the rs3864283 Polymorphism Located in the HINT1 Gene with Cigarette Use and Personality Traits.

Nicotine is the major reinforcing component of tobacco and it is believed that the pharmacological effects of nicotine motivate the initiation and maintenance of a smoking habit. HINT1 appears to play a role in the modulation of the effects of drug abuse. Hence, the aim of this study was the analysis of the association between the rs3864283 polymorphism of the HINT1 gene and cigarette use; the analysis of personality traits assessed by the means of the NEO-FFI Inventory; the analysis of anxiety measured by the STAI questionnaire; and the analysis of the interactions between the rs3864283 and both personality traits and anxiety. The study group consisted of 522 volunteers. Of these, 371 were cigarette users and 151 were never-smokers. The genomic DNA was isolated from venous blood using standard procedures. The results of both inventories, i.e., NEO-FFI and STAI., were reported as the sten scores. Genotyping was conducted with the real-time PCR method. Statistically significant differences were found in the frequency of rs3864283 genotypes and alleles in the tested sample of Cigarette Users when compared to the control group. The Cigarette Users compared to the control group obtained higher scores in the assessment of NEO-FFI extraversion scale, and significantly lower results were obtained for the NEO-FFI openness scale, the agreeableness scale, and the conscientiousness scale. There was a statistically significant effect of rs3864283 genotype interaction and Cigarette Use or not using (control group) on the extraversion scale. There was also a statistically significant effect of Cigarette Users or the control group on the extraversion scale score. The results obtained in the presented study indicated a significant association between the HINT1 rs3864283 variant and smoking status. Moreover, this is the first study incorporating genetic association of above-mentioned polymorphic site with interaction analysis of personality traits and anxiety. Overall, the results of this study suggest that HINT1 is an important genetic component associated with nicotine usage mechanisms.

Salvia officinalis L. Methanolic Extract Reduces Lead and Nicotine-Induced Sperm Quality Degeneration in Male Rats.

The current study is aimed at evaluating the potential health benefits of Salvia officinalis L. (sage)methanol extract on lead and nicotine hydrogen tartrate-induced sperm quality degeneration in male rats and also identifying some of the non-polar volatile bioactive compounds that might be attributed to the bioactivity of S. officinalis extract using gas chromatography-mass spectrometry (GC-MS). In the study, fifty-four mature male albino rats of about 220 - 250 g [were divided randomly and equally into 9 groups (n=6)]. Sperm quality degeneration was induced through the oral administration of 1.5 g/L of lead acetate in drinking water or peritoneal injection of 0.50 mg/kg (animal weight) nicotine hydrogen tartrate for sixty days. Two doses (200 & 400 mg/kg b.w.) of S. officinalis L. were used. Twelve major compounds were identified. Lead and nicotine toxicity had a great effect on the rats' sperm quality causing a significant (p<0.05) decrease in the quantity of sperm and sperm motility as well as an upsurge in the abnormalities of the sperm and a reduction in the length & diameter of seminiferous tubules and size & weight of sexual organs.The administration of S. officinalis L. methanol extract ameliorates the adversative effects of lead and nicotine.

Sex steroid hormone levels associated with dopamine D2/3 receptor availability in people who smoke cigarettes.

Sex differences exist in tobacco smoking. Women have greater difficulty quitting smoking than men. Tobacco smoking is driven by the reinforcing effects of nicotine, the primary addictive component in cigarettes. Nicotine binds to nicotinic acetylcholine receptors, facilitating dopamine release in striatal and cortical brain regions. Dysregulated dopamine D2/3 receptor signaling in the dorsolateral prefrontal cortex (dlPFC) is associated with cognitive deficits such as impairments in attention, learning, and inhibitory control that impede quit attempts. Sex steroid hormones, such as estradiol and progesterone, influence drug-taking behaviors, through dopaminergic actions, suggesting that their influence may explain sex differences in tobacco smoking. The goal of this study was to relate dlPFC dopamine metrics to sex steroid hormone levels in people who smoke and healthy controls. Twenty-four (12 women) people who smoke cigarettes and 25 sex- and age-matched controls participated in two same-day [11C]FLB457 positron emission tomography scans, one before and one after amphetamine administration. D2R availability (BPND) at baseline and after amphetamine administration was calculated. On the same day, plasma samples were collected for the analysis of sex steroid hormone levels: estradiol, progesterone, and free testosterone. Women who smoke had trending lower levels of estradiol than their sex-matched counterparts. Men who smoke had higher levels of estradiol and trending higher levels of free testosterone than their sex-matched counterparts. Among women only, lower estradiol levels were significantly associated with lower pre-amphetamine dlPFC BPND. This study demonstrated that lower estradiol levels are associated with lower dlPFC D2R availability in women which may underlie difficulty resisting smoking.

N-acetylcysteine for smoking cessation among dual users of tobacco and cannabis: Protocol and rationale for a randomized controlled trial

BackgroundTobacco and cannabis co-use is a growing public health problem. The synergistic effects of cannabis and nicotine on neurobiological systems that mediate reward and shared environmental cues reinforcing use may make tobacco smoking cessation more difficult. N-acetylcysteine (NAC), an FDA-approved medication and over-the-counter supplement, has shown promise in animal studies and randomized controlled trials (RCTs) in reducing tobacco and cannabis craving and use. NAC's potential efficacy in treating addiction may be attributable to its central nervous system effects in reducing excessive glutamatergic activity, oxidative stress, and inflammation. To date, no RCT has examined NAC for smoking cessation among dual users of tobacco and cannabis. MethodIn a double-blind, placebo-controlled RCT, we will examine NAC for smoking cessation among dual users of tobacco and cannabis. Sixty adult cigarette-cannabis co-users are randomized to receive NAC 3600 mg per day or placebo over 8 weeks. Participants in both groups receive 8 weekly cognitive behavioral therapy sessions addressing smoking cessation and cannabis reduction. Outcomes are assessed at Weeks 0, 4, 8, and 12. Primary aims are to determine NAC's efficacy in decreasing cigarette craving, nicotine dependence, and use; and cannabis craving and use. Exploratory aims include examination of changes in neurocognition with NAC and their potential mediational effects on cigarette and cannabis use outcomes. ConclusionResults will inform smoking cessation treatment among dual users of tobacco and cannabis.ClinicalTrials.gov Identifier: NCT04627922.

Effects of Nicotine on the Progression and Metastasis of HumanOvarian Cancer cells by Exacerbating EMT

Does nicotine, a main constituent of toxicants in Cigarette Smoke, relate to EMT and contribute to the progression ofovarian cancer? Treat SK-OV3 xenograft mice with increasing nicotine and measure TGF-β in blood by ELISA assayand tumor cell metastasis by confocal microscopy, looking for cancer cells in the liver, bone, brain, stomach, ovary andthen measure xenograft tumor size by weight. A positive control is benzene treatment, and the negative control is PBS.The results will reveal the effects of nicotine on ovarian cancer cell proliferation, which will improve our understandingof the harm environmental toxicants can do to human health. At the same time, the physiological processes that lead tocarcinogenesis will also provide prevention awareness and treatment ideas for ovarian cancer caused by smoking.

Effects of smoking on controlled hypotension with nitroglycerin during ear-nose-throat surgery.

In this study, the aim was to research the effects of smoking habits on controlled hypotension administered with nitroglycerin during ear-nose-throat surgery. This study administered controlled hypotension with nitroglycerin and total intravenous anesthesia to a total of 80 patients undergoing septoplasty operations. The patients were divided into two groups of 40 non-smokers (Group 1) and 40 smokers (Group 2). Intravenous propofol infusion was used for anesthesia maintenance. Nitroglycerin with 0.25-1 μg/kg/min dose was titrated to provide controlled hypotension. During this process, the hemodynamic parameters of patients, total propofol and nitroglycerin amounts used, operation duration, and duration of controlled hypotension were recorded at the end of the operation. At the end of the operation, the surgeon assessed the lack of blood in the surgical field with Fromme Scale. Fromme scale values were significantly higher in Group 2 compared to Group 1. The MAP values at 10, 20, 30 min, and end of operation were lower, while 10- and 20-min heart rate values were higher in Group 2 compared to Group 1. Nitroglycerin, chosen for controlled hypotension to reduce hemorrhage in the surgical field during nasal surgery, was shown to cause more pronounced hypotension and reflex tachycardia due to endothelial dysfunction linked to nicotine in patients who smoke. Despite lower pressure values in the smoking group, the negative effects of nicotine on platelet functions combined with similar effects of nitroglycerin to increase bleeding amounts.

Functional α7 nicotinic receptors in human airway smooth muscle increase intracellular calcium concentration and contractility in asthmatics.

Although nicotinic acetylcholine receptors (nAChRs) are commonly associated with neurons in the brain and periphery, recent data indicate that they are also expressed in non-neuronal tissues. We recently found the alpha7 (α7nAChR) subunit is highly expressed in human airway smooth muscle (hASM) with substantial increase in asthmatics, but their functionality remains unknown. We investigated the location and functional role of α7nAChRs in hASM cells from normal versus mild-moderate asthmatic patients. Immunostaining and protein analyses showed α7nAChR in the plasma membrane including in asthmatics. In asthmatic hASM, patch-clamp recordings revealed significantly higher functional homomeric α7nAChR channels. Real-time fluorescence imaging showed nicotine, via α7nAChR, increases intracellular Ca2+ ([Ca2+]i) independent of ACh effects, particularly in asthmatic hASM, while cellular traction force microscopy showed nicotine-induced contractility including in asthmatics. These results indicate functional homomeric and heteromeric nAChRs that are increased in asthmatic hASM, with pharmacology that likely differ owing to different subunit interfaces that form the orthosteric sites. nAChRs may represent a novel target in alleviating airway hyperresponsiveness in asthma.NEW & NOTEWORTHY Cigarette smoking and vaping exacerbate asthma. Understanding the mechanisms of nicotine effects in asthmatic airways is important. This study demonstrates that functional alpha7 nicotinic acetylcholine receptors (α7nAChRs) are expressed in human airway smooth muscle, including from asthmatics, and enhance intracellular calcium and contractility. Although a7nAChRs are associated with neuronal pathways, α7nAChR in smooth muscle suggests inhaled nicotine (e.g., vaping) can directly influence airway contractility. Targeting α7nAChR may represent a novel approach to alleviating airway hyperresponsiveness in asthma.

Association between cadmium and lead in active and passive cigarette smokers with bone mass: a retrospective study

Objective: Cigarette smoking harms all body systems, and its effects are primarily related to nicotine. However, the heavy metal content (mainly lead and cadmium) could add to nicotine's hazardous effects. Thus, the current study aimed to investigate the effect of cigarette smoking content of cadmium and lead on bone mineral density. Subjects and Methods: A retrospective analysis of data from active, passive, and non-smokers (every 70 subjects) was analyzed for patient demographics, laboratory investigation, serum cotinine (as a confirmatory marker of smoking, bone mineral density (BMD), blood and urinary levels of cadmium and lead). Results: Hemoglobin concentrations and red blood cell count were significantly reduced, while erythrocyte sedimentation rate and liver enzymes were significantly increased in active and passive smokers than non-smokers. Serum cadmium, lead, and cotinine were raised considerably in passive and active than non-smokers (0.47±0.05, 21.94±3.99, 5.35±0.90 in active, 0.32±0.09, 18.91±3.30, and 4.35±0.89 in passive, versus 0.09±0.06, 9.84±2.63, and 1.28±0.21 in the control group, successively). Bone mineral density was reduced in active and passive than non-smokers at the radial shaft, femoral neck, and spine. Cotinine was significantly and proportionately correlated with serum cadmium and lead and inversely correlated with bone mineral density. Furthermore, cadmium and lead were inversely correlated with BMD. Conclusion: Cigarettesmoke was associated with higher concentrations of cadmium, and lead may directly and indirectly share in the harmful effects of smoking on BMD. Keywords: Bone Mineral Density, Cotinine, Toxic Heavy Metals, Smoking

Current tobacco use and SARS-CoV-2 infection in two Norwegian population-based cohorts

BackgroundClear evidence of an increased risk for SARS-CoV-2 infection among smokers has not been established. We aimed to investigate associations between cigarette smoking or use of snus (snuff) and other nicotine-containing products and a positive SARS-CoV-2 test, taking test behavior into account.MethodsCurrent tobacco use and testing behavior during the pandemic were recorded by adult participants from the Norwegian Mother, Father and Child Cohort Study and The Norwegian Influenza Pregnancy Cohort. SARS-CoV-2 infection status was obtained from The Norwegian Surveillance System for Communicable Diseases (MSIS) in May 2021 (n = 78,860) and antibody measurements (n = 5581). We used logistic regression models stratified by gender and adjusted for age, education, region, number of household members, and work situation.ResultsSnus use was more common among men (26%) than women (9%) and more prevalent than cigarette smoking. We found no clear associations between cigarette smoking or snus and a COVID-19 diagnosis among men. Associations among women were conflicting, indicating that cigarette smoke was negatively associated with a diagnosis (OR 0.51, 95% CI 0.35, 0.75), while no association was found for snus use (OR 1.07, 95% CI 0.86, 1.34). Compared with non-users of tobacco, both cigarette smokers and snus users had increased odds of being tested for SARS-CoV-2.ConclusionsCigarette smoking, but not snus use, was negatively associated with SARS-CoV-2 infection in women. The lack of an association between snus use and SARS-CoV-2 infection in this population with prevalent snus use does not support the hypothesis of a protective effect of nicotine.

Nicotine activates HIF-1α and regulates acid extruders through the nicotinic acetylcholine receptor to promote the Warburg effect in non-small cell lung cancer cells

Cigarette smoking is the greatest risk factor for lung cancer, accounting for approximately 90% of all lung cancer-related deaths. Moreover, nicotine is associated with lung cancer onset and progression. Hypoxia-inducible factor 1α (HIF-1α) is involved in the metabolic reprogramming of cancer cells and accelerates cancer progression via regulation of pH and acid–base homeostasis. Previous studies have reported that nicotine upregulates HIF-1α expression. Therefore, we hypothesized that nicotine-mediated activation of HIF-1α regulates metabolic reprogramming and pH homeostasis in non-small cell lung cancer A549 cells and could potentially play a role in the progression of lung cancer. We examined the effects of nicotine on metabolic reprogramming and intracellular pH (pHi) homeostasis, which are critical for cancer progression. A549 cells were exposed to nicotine in the absence and presence of the nicotinic acetylcholine receptor antagonist, mecamylamine (MEC). We then analyzed glycolytic stress and the activity and expression of acid-extruder proteins, including the Na+–H+ exchanger 1 (NHE1) and monocarboxylate cotransporters 1 & 4 (MCT1 and MCT4, respectively). Nicotine promoted the Warburg effect, which is associated with accelerated migration of A549 cells through the activation of nicotinic acetylcholine receptors. Furthermore, nicotine upregulated the activities and expression of acid-extruder proteins, namely NHE1 and MCT4, and facilitated glycolysis. To the best of our knowledge, this is the first study to demonstrate that nicotine plays a pivotal regulatory role in metabolic reprogramming as well as regulation of pHi homeostasis in A549 cells via activation of nicotinic acetylcholine receptors and can therefore aggravate lung cancer progression.

Long-term Stimulation of α7 Nicotinic Acetylcholine Receptor Rescues Hemorrhagic Neuron Loss via Apoptosis of M1 Microglia.

We previously revealed that long-term treatment with nicotine suppresses microglial activation, resulting in a protective effect against thrombin-induced shrinkage of the striatal tissue in organotypic slice cultures. Here, the effect of nicotine on impaired M1 and protective M2 microglial polarization was investigated using the BV-2 microglial cell line in the presence or absence of thrombin. Following nicotine treatment, α7 nicotinic acetylcholine receptor expression transiently increased and then gradually decreased until 14 days. Treatment with nicotine for 14 days slightly polarized M0 microglia to M2b and d subtypes. Co-exposure of thrombin and low concentration of interferon-γ recruited inducible NO synthase (iNOS)- and interleukin-1β-double-positive M1 microglia in a thrombin-concentration-dependent manner. Treatment with nicotine for 14 days significantly decreased the thrombin-induced increase of iNOS mRNA levels and conversely showed a tendency to increase arginase1 mRNA levels. Moreover, treatment with nicotine for 14 days suppressed thrombin-induced phosphorylation of p38 MAPK through the α7 receptor. Repeated intraperitoneal administration of α7 agonist PNU-282987 for 14 days selectively evoked the apoptosis of iNOS-positive M1 microglia at the perihematomal area and showed a neuroprotective effect in an in vivo intracerebral hemorrhage model. These findings revealed that long-term stimulation of α7 receptor causes suppression of thrombin-induced activation of p38 MAPK followed by apoptosis in neuropathic M1 microglia.