Toxic Effects Of Cigarette Smoke Research Articles

Cigarette smoke is associated with up-regulation of inducible NOS and COX-2 protein expression and activity in granulosa cells of women undergoing in vitro fertilization

Cigarette smoke exposure represents a well-established ovotoxic exogenous stress, but the molecular mechanisms underlying of this effect are still unclear. Cigarette smoke upregulates inflammatory genes in the female reproductive organs, therefore an abnormal inflammation response may contribute to the impairment of female fertility. In this study we investigated for the first time the effect of cigarette smoke exposure on NOS and COX expression and activity and on their transcription factors (CREB and NF-kB) in human GCs and on the release of NO and PGE2 in the FF in smoking and non-smoking patients undergoing IVF treatment. In addition, correlation analysis between AMH serum levels, an index of ovarian reserve, and smoking exposure or iNOS and COX-2 protein expression levels were performed using a Pearson correlation method. Cigarette smoke exposure resulted in a significant increase of iNOS and COX-2 protein expression together with an increase of iNOS activity and PGE2 levels. pNF-kB and pCREB protein expression were upregulated in the GCs of smokers compared to non-smokers. The habit of smoking was negatively correlated with serum AMH levels, and positively correlated with iNOS and COX-2 protein expression levels. The data presented in the current study revealed a novel molecular mechanism underlying the toxic effects of cigarette smoke on fertility. Additional pathways mediating the effects of cigarette smoke exposure in human GCs cannot be excluded and should be investigated in future studies.

A simple sampling method for quantification of hazardous volatile organic compounds in mainstream cigarette smoke: Method development and prestudy validation

Cigarette smoke can be fatal to human health, as it contains a plethora of hazardous compounds such as volatile organic compounds (VOCs). To assess the toxic effects of cigarette smoke, both qualitative and quantitative information about the VOCs in cigarette smoke are essential. However, sampling and analysis of cigarette smoke are not simple tasks and require complicated validation procedures. Here, we develop and verify a simple sampling method for the quantification of VOCs in mainstream cigarette smoke using three steps: direct collection of the mainstream cigarette smoke sample by gas-tight syringe, injection of the sample into a bag sampler for dilution, and extraction of VOCs into an adsorption-tube sampler for quantitation by thermal desorption-gas chromatography-mass spectrometry. This method has been employed successfully to quantify seven target VOCs (isoprene, methyl ethyl ketone, benzene, acrylonitrile, toluene, m-xylene, and styrene) in cigarette smoke from 3R4F reference cigarettes. The quantities of these major five VOCs (isoprene, methyl ethyl ketone, benzene, acrylonitrile, and toluene: average of 459 ± 646 ng mL−1), when measured from 3R4F samples based on our method, were comparable to or moderately higher than those measured based on the established standard methods (e.g., Health Canada Intense (462 ± 557 ng mL−1) and International Standardization Organization (356 ± 438 ng mL−1)). As such, we succeeded in reliably collecting and quantifying VOCs in cigarette smoke using a simple sampling method proposed in this research. The proposed method is thus recommended as an alternative to complicated and costly representative methods based on international guidelines.

Saliva and Lung Microbiome Associations with Electronic Cigarette Use and Smoking.

The microbiome affects cancer and other disease risk. The effects of e-cig usage on the lung microbiome are essentially unknown. Given the importance of lung microbiome dysbiosis populated by oral species which have been observed to drive lung cancer progression, it is important to study effects of e-cig use on microbiome.

Copper Tannic Acid Coordination Nanosheet: A Potent Nanozyme for Scavenging ROS from Cigarette Smoke.

The global tobacco epidemic is still a devastating threat to public health. Toxic reactive oxygen species (ROS) in the cigarette smoke cannot be efficiently eliminated by currently available cigarette filters. The resultant oxidative stress causes severe lung injury and further diseases. To tackle this challenge, herein, a novel copper tannic acid coordination (CuTA) nanozyme is reported as a highly active and thermostable ROS scavenger. The CuTA nanozyme exhibits intrinsic superoxide dismutase-like activity, catalase-like activity, and hydroxyl radical elimination capacity. These synergistic antioxidant abilities make the CuTA nanozyme a promising candidate for the improvement of commercial cigarette filters. Mouse model results show that commercial cigarettes loaded with CuTA nanozyme efficiently scavenge ROS in the cigarette smoke, reduce oxidative stress-induced lung inflammation, and minimize the resultant acute lung injury. The developed CuTA nanozyme offers an efficient ROS scavenger with multiple antioxidant ability and opens up new opportunities for the modification of cigarette filters to reduce the toxic effects of cigarette smoke.

A Reliable Preclinical Model to Study the Impact of Cigarette Smoke in Development and Disease.

The World Health Organization has estimated that, worldwide, cigarette smoking has caused more than 100 million deaths in the last century, a number that is expected to increase in the future. Understanding cigarette smoke toxicity is key for research and development of proper public health policies. The current challenge is to establish a reliable preclinical model to evaluate the effects of cigarette smoke. In this work, we describe a simple method that allows for quantifying the toxic effects of cigarette smoke using zebrafish. Here, viability of larvae and adult fish, as well as the effects of cigarette smoke extracts on vascular development and tissue regeneration, can be easily assayed. © 2019 by John Wiley & Sons, Inc.

Toxic Effects of Cigarette Smoke and Alcohol on Conceptuses of Exposed Wistar Rats

Toxic Effects of Cigarette Smoke and Alcohol on Conceptuses of Exposed Wistar Rats

Salivary Antioxidant Power of Passive Smokers

Introduction: Cigarette smoke has been proven to be injurious to both oral cavity and internal body environment. Passive smokers could also suffer from smoke. Saliva, the first biological fluid which encounters cigarette smoke, contains antioxidant defense system to reduce the toxic effects of cigarette smoke. Objectives: The aim was investigating salivary antioxidants of passive smokers as compared to non-smokers. Method: Un-stimulated whole saliva samples, obtained from passive smokers and non-smokers, were centrifuged and stored at -70°C. The antioxidant power was then measure using various methods. Results: No statistically significant difference in antioxidant capacity, total phenol, and radical scavenging activity of saliva between studied groups was found. However, concentration of uric acid, the important antioxidant of saliva, was decreased dramatically in passive smokers. Conclusions: It was suggested that measurement of antioxidants in salivary fluid could be a useful noninvasive method to investigate abnormalities related to oral cavity and gastrointestinal tract.

Resistance to cigarette smoke is increased in periodontal ligament cells by attachment to collagen and fibronectin.

The toxic effects of cigarette smoke often presents in smokers as increased incidence and severity of periodontal disease. These patients demonstrate symptomatic inflammation, increased probing depth, and tooth loss likely attributable to the direct effects of cigarette smoke on periodontal ligament (PDL) fibroblasts. The goal of this in vitro study is to investigate the direct effects of smoking on PDL fibroblasts, focusing on cell-extracellular matrix (ECM) interactions and cell survival. PDL cells were plated for various times on tissue culture plastic, PDL-derived ECMs, collagen Type I, or fibronectin. Cells were exposed to various concentrations of cigarette smoke extract (CSE) at different times during the cell attachment process. Subsequently, cell survival was quantified using calcein-acetoxymethyl ester compound and a fluorescent plate reader. After exposure to CSE, PDL cell survival increased with increased cell attachment time to plastic. These observations were independent of soluble factors present in PDL cell-conditioned media. PDL-derived ECMs and collagen Type I-pretreated plates promoted increased cell survival after 1 day of cell attachment. Fibronectin-pretreated plates demonstrated increased cell survival after 3 days of cell attachment. Cell-ECM interactions increase survival of PDL cells exposed to CSE. It is suggested that the increased survival is attributable to PDL cells altering their ECM, potentially by depositing collagen and fibronectin. This may imply that cells embedded in an ECM would be more resistant to the toxic effects of cigarette smoke, leading to increased cell death near the exposed edges of a wound.

The role of lipotoxicity in smoke cardiomyopathy.

Background/AimsExperimental and clinical studies have shown the direct toxic effects of cigarette smoke (CS) on the myocardium, independent of vascular effects. However, the underlying mechanisms are not well known.MethodsWistar rats were allocated to control (C) and cigarette smoke (CS) groups. CS rats were exposed to cigarette smoke for 2 months.ResultsAfter that morphometric, functional and biochemical parameters were measured. The echocardiographic study showed enlargement of the left atria, increase in the left ventricular systolic volume and reduced systolic function. Within the cardiac metabolism, exposure to CS decreased beta hydroxy acyl coenzyme A dehydrogenases and citrate synthases and increased lactate dehydrogenases. Peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) were expressed similarly in both groups. CS increased serum lipids and myocardial triacylglycerols (TGs). These data suggest that impairment in fatty acid oxidation and the accumulation of cardiac lipids characterize lipotoxicity. CS group exhibited increased oxidative stress and decreased antioxidant defense. Finally, the myocyte cross-sectional area and active Caspase 3 were increased in the CS group.ConclusionThe cardiac remodeling that was observed in the CS exposure model may be explained by abnormalities in energy metabolism, including lipotoxicity and oxidative stress.

Hemodynamic assessment of patients with pulmonary hypertension due to lung disease and/or hypoxia

PURPOSE: Current guidelines classify PH due to lung disease and/or hypoxia (group 3) as pre-capillary PH (mean pulmonary artery pressure (mPAP) ≥25mmHg and mean pulmonary capillary wedge pressure (mPCWP) ≤15mmHg). In the setting of lung disease, multiple mechanisms of disease play a role apart from classical pulmonary arteriopathy, hypoxia, hypercapnia, mechanical stress of hyperinflated lungs, emphysematous and fibrotic changes, inflammation and toxic effects of cigarette smoke. We hypothesized that a significant proportion of patients with PH due to lung diseases carries a post-capillary component. METHODS: A large database (n=3107) of right and left heart catheterizations was interrogated. RESULTS: Of 291 patients with PH due to lung disease, 96 patients had normal hemodynamics (“Non-PH” mPAP 15mmHg). Multivariate analysis identified stable ischemic heart disease as an independent predictor of survival (p=0.014). CONCLUSION: The data demonstrate that a significant proportion of patients with PH due to lung disease suffers from post-capillary pulmonary hypertension.

Efficacy of Vitamin E against Cigarette Smoke Induced Alterations in Pulmonary Tissue, Serum Enzymes and Lipid Profile in Albino Rats

The present study was designed to evaluate the protective role of vitamin E(50mg/kg bwt) against adverse effects of cigarette smoke (60 and 120 days) on lung tissue , serum enzyme activity and lipid profile in male albino rats. Reduction in the histopathological changes like emphysema, pulmonary edema, debris, capillary permeability and thick epithelium have been seen after supplementation of vitamin E in comparison to cigarette smoke exposed rats. Decrease in serum enzyme activity viz. SGPT (P 0.05) and SALP (P 0.05), serum triglycerides (P 0.05) and VLDL (P 0.05) have also reported after pre-exposure supplementation of vitamin E in comparison to cigarette smoke exposed rats. Vitamin E is able to mitigate the toxic effects of cigarette smoke on albino rats.

Genetic variants in carcinogen-metabolizing enzymes, cigarette smoking and pancreatic cancer risk

Individual susceptibility to the toxic effects of cigarette smoke may be modified by inherited variability in carcinogen metabolism. The purpose of the present study was to investigate pancreatic cancer risk associated with cigarette smoking and 33 variants within carcinogen metabolism genes and examine whether these variants modify the association between smoking and pancreatic cancer. A population-based study was conducted with 455 pancreatic cancer cases and 893 controls. Epidemiological and smoking data were collected from questionnaires and variants were genotyped by mass spectrometry. Age- and sex-adjusted odds ratio (ASOR) and multivariate-adjusted odds ratio (MVOR) estimates were obtained using multivariate logistic regression, and interactions between each variant and smoking were investigated. Current smoker status [MVOR = 2.29, 95% confidence interval (95% CI): 1.62, 3.22], 10-27 pack-years (MVOR = 1.57, 95% CI: 1.13, 2.18), >27 pack-years (MVOR = 1.77, 95% CI: 1.27, 2.46) and longer durations of smoking (19-32 years: MVOR = 1.46, 95% CI: 1.05, 2.05; >32 years: MVOR = 1.78, 95% CI: 1.30, 2.45) were associated with increased pancreatic cancer risk. CYP1B1-4390-GG (ASOR = 0.36, 95% CI: 0.15, 0.86) and Uridine 5'-diphospho glucuronosyltransferase 1 family, polypeptide A7-622-CT (ASOR = 0.77, 95% CI: 0.60, 0.99) were associated with reduced risk. N-acetyltransferase 1-640-GT/GG (ASOR = 1.75, 95% CI: 1.00, 3.05), GSTM1 (rs737497)-GG (ASOR = 1.41, 95% CI: 1.02, 1.95), GSTM1 gene deletion (ASOR = 4.89, 95% CI: 3.52, 6.79) and glutathione S-transferase theta-1 gene deletion (ASOR = 4.41, 95% CI: 2.67, 7.29) were associated with increased risk. Significant interactions were observed between pack-years and EPHX1-415 (P = 0.04) and smoking status and N-acetyltransferase 2-857 (P = 0.03). Variants of carcinogen metabolism genes are independently associated with pancreatic cancer risk and may modify the risk posed by smoking.

Pulmonary Hypertension in COPD: Pathophysiology and Therapeutic Targets

The incidence of mild to moderate pulmonary hypertension (PH) is highly prevalent, reaching to 50% in advanced chronic obstructive pulmonary disease (COPD). However, a subpopulation (1-4% in most studies) with grim prognosis despite moderate airflow limitation, present with "out-of-proportion" severe PH, is arbitrarily defined by a mean PH ≥ 40 mmHg, at rest. The sequence of changes that lead to PH in COPD begins at early disease stages by the impairment of endothelial function, which is associated with impaired release of endothelium-derived vasodilating (nitric oxide, prostacyclin) and vasoconstrictive agents (endothelin-1) and imbalance among them. PH in COPD is caused by vasoconstriction and remodelling of pulmonary arteries, which is characterized by the intimal proliferation of poorly differentiated smooth muscle cells and the deposition of elastic and collagen fibres. Hypoxia, inflammation and toxic effects of cigarette smoke, independently or additively interacting, are confirmed factors leading to PH. To date, long-term supplemental oxygen remains the primary treatment in COPD patients with PH. The administration of new vasodilators (prostanoids, endothelin-1 receptor antagonists and phosphodiesterase-5 inhibitors) dedicated to idiopathic pulmonary arterial hypertension in the disproportionate subgroup of patients with "out-of-proportion" PH may be considered in the setting of clinical trials. The use of these drugs in COPD patients with PH < 40 mmHg may worsen gas exchange, and to date, has no proven benefit. Future treatments must target more directly pathogenetic mechanisms. Therefore, novel agents have been proposed and are under active investigation, including 5-HT receptor antagonists, Rho-kinase inhibitors, statins and stem cell therapy.

Increased Rho-kinase expression and activity and pulmonary endothelial dysfunction in smokers with normal lung function

Endothelial dysfunction is one of the main consequences of the toxic effects of cigarette smoke on the vascular system. Increasing evidence suggests that the small G-protein RhoA and its downstream effectors, the Rho-kinases (ROCKs), are involved in systemic endothelial dysfunction induced by cigarette smoke. This study aimed to evaluate the role of the RhoA/ROCKs pathway in pulmonary artery endothelial function in current smokers with normal lung function. Lung tissues were obtained from nonsmokers and smokers who underwent lobectomy for lung carcinoma. Arterial relaxation in response to acetylcholine (ACh) was assessed in isolated pulmonary arterial rings. Protein expressions and activities of endothelial nitric oxide synthase (eNOS), ROCKs and the myosin phosphatase subunit 1 (MYPT-1) were sought. Relaxation in response to ACh was significantly lower in smokers as compared with nonsmokers (n = 8 in each group), consistent with reduced eNOS activity in the former compared with the latter. eNOS protein expression remained, however, the same in both groups. Expression of ROCKs, guanosine triphosphate-RhoA and phosphorylated MYPT-1 were significantly increased in smokers compared with controls. Pulmonary endothelial dysfunction is present in smokers whose lung function has not yet been impaired. Reduced activity of eNOS accounts at least in part for this endothelial dysfunction. Increased expression and activity of ROCKs accounts for another part through direct or indirect inhibition of the Rho-A/ROCKs pathway on nitric oxide synthesis and sustained pulmonary vasoconstriction through inhibition of myosin phosphatase.

Cigarette smoke causes follicle loss in mice ovaries at concentrations representative of human exposure

Cigarette smoke is a documented reproductive toxicant associated with infertility and ovarian failure. However, the underlying mechanism(s) regulating the toxic effects of cigarette smoke are unknown. Therefore, we tested the hypothesis that mainstream cigarette smoke and a cigarette smoke constituent, benzo[a]pyrene (BaP), induce apoptosis in ovarian follicles. Mice were exposed to mainstream cigarette smoke and the ovaries were analysed for follicle loss and markers of apoptosis (TUNEL, Caspase 3, Caspase 8, Bax, Bcl-2, Fas and FasL). Isolated ovaries from female pups were cultured in media containing increasing concentrations of BaP (1-10 000 ng ml(-1)), and markers of apoptosis were quantified. Cigarette smoke exposure induced a significant reduction in the number of primordial follicles, but not growing or antral follicles compared with controls. Mainstream cigarette smoke exposure had no effect on any marker of apoptosis measured. Exposure of ovaries to BaP in vitro resulted in an increase in the pro-survival marker Bcl-2, but no change in apoptosis. Our data suggest that cigarette smoke-induced follicle loss is not mediated via BaP-induced apoptosis.

Quantification of benzo[a]pyrene and other PAHs in the serum and follicular fluid of smokers versus non-smokers

Cigarette smoking is a well-established reproductive hazard that has been linked with decreased fertility in both smokers and those exposed to second hand smoke. The chemical components responsible for the reproductive toxic effects of cigarette smoke are unknown. Moreover, exposure of reproductive tissues to the chemical constituents of cigarette smoke is largely unknown. Therefore, we measured the levels of benzo[a]pyrene (B[a]P), and other polycyclic aromatic hydrocarbons (PAH) present in cigarette smoke, in the serum and follicular fluid of women exposed to mainstream ( n = 19) and side stream smoke ( n = 7) compared to non-smokers ( n = 10). Women exposed to mainstream smoke had significantly higher levels of B[a]P (1.32 ± 0.68 ng/ml) in their follicular fluid compared to side stream exposed (0.05 ± 0.01 ng/ml) or their non-smoking (0.03 ± 0.01 ng/ml) counterparts. More importantly we found significantly higher ( p < 0.001) levels of B[a]P in the follicular fluid of women who did not conceive (1.79 ± 0.03 ng/ml) compared to those that achieved a pregnancy (0.08 ± 0.03 ng/ml). Other PAHs known to be present in cigarette smoke were also detectable in both serum and follicular fluid of study subjects studied but with lower frequency compared to B[a]P and no differences in serum or follicular fluid levels between the groups could be demonstrated. The important finding that B[a]P reaches the follicular fluid and the fact that it is found at much higher levels in women who smoke provides further evidence that of the many toxicants present in cigarette smoke, B[a]P may be a key compound that is central to the documented adverse effects of cigarette smoke on follicular development and subsequent fertility.

Sodium pertechnetate (Na99mTcO4) biodistribution in mice exposed to cigarette smoke

BackgroundThe biological effects of cigarette smoke are not fully known. To improve our understanding of the action of various chemical agents, we investigated the biodistribution of sodium pertechnetate (Na99mTcO4) in mice exposed to cigarette smoke.MethodsFifteen BALB/c male mice were exposed to the smoke of nine whole commercial cigarettes per day, 3 times/day, for up to 10 days to whole body exposure in a chamber. A control group of 5 BALB/c male mice was sham-smoked. One day later, the exposed and control groups of mice received (7.4 MBq/0.3 ml) of Na99mTcO4 before being killed at 30 min. Bones, brain, heart, intestine, kidney, liver, lungs, muscle, pancreas, spleen, stomach, testis and thyroid were weighed and these organs and blood radioactivity recorded with a gamma counter. The percentage per gram of tissue of injected dose (%ID/g) was determined for each organ.ResultsCigarette smoke significantly decreased (p < 0.05) the %ID/g in red blood cells, bone, kidney, lung, spleen, stomach, testis and thyroid of the exposed mice.ConclusionThe toxic effects of cigarette smoke reduced the Na99mTcO4 biodistribution.

Effect of cigarette smoke extract on the polymorphonuclear leukocytes chemiluminescence: influence of a filter containing glutathione

Cigarette smoking is known to be a risk factor for several chronic and neoplastic diseases. Many compounds formed by cigarette burning, ranging from particulate materials to water solutes and gaseous extracts, are considered to be noxious agents, and many biochemical and molecular mechanisms have been proposed for the toxic effects of cigarette smoke. The oral cavity and the upper respiratory tract represent the first contact areas for smoke compounds; even a single cigarette can produce marked effects on some components of the oral cavity, either chemical compounds, such as glutathione and enzymes, or cellular elements, such as polymorphonuclear leukocytes. Several studies suggest a protective role of glutathione against the noxious effects of tobacco smoke; the sulphydril groups of glutathione, in fact, could react with some smoke products, such as unsaturated aldehydes, leading to the formation of harmless intermediate compounds and simultaneously preventing the inactivation of metabolically essential molecules, such as some enzymes. In this paper we analyse the effect of a filter containing glutathione on the respiratory burst of polymorphonuclear leukocytes exposed to aqueous extract of cigarette smoke, measuring their chemiluminescence activity. The results of this paper indicate that the GSH-containing filter has a likely protective effect against the inhibition of cigarette smoke extract on polymorphonuclear leukocyte activity.

Chronic obstructive pulmonary disease in women: exploring gender differences.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality throughout the world. This major public health threat is ranked twelfth as a worldwide burden of disease and is projected to rank fifth by the year 2020 as a cause of lost quantity and quality of life. The impact of this disease in women is significantly understudied but the evidence that does exist reveals potentially substantial gender differences in the susceptibility to, severity of, and response to management of COPD. The best known risk factor for the development of COPD is tobacco smoking. While smoking rates in women have largely stabilized in developed countries, the rates are continuing to climb in developing countries. While it is not clear whether women are more susceptible to the toxic effects of cigarette smoke than men, it is known that the incidence and prevalence of COPD will continue to climb as more women smoke. Other known risk factors for the development of COPD include air pollution, infections, occupational exposures, and genetic factors. Air pollution, particularly fine particulate indoor air pollution from biomass fuels disproportionately affects women. Infections such as human immunodeficiency virus (HIV) and tuberculosis (TB) disproportionately affect vulnerable populations such as poor women and occupational exposures to various dusts and toxins are often gender specific. Genetic factors are still being explored but there seems a preponderance of women who are affected by early-onset and non-smoking related COPD. Women with COPD also seem to be underdiagnosed by physicians and may have different responses to medical treatment, smoking cessation interventions, and pulmonary rehabilitation programs. Chronic obstructive pulmonary disease in women is an understudied subject but is gaining attention as a significant public health threat. In developed countries, efforts at preventing the initiation of tobacco smoking and targeting smoking cessation programs in women are needed. In developing countries, efforts to promote cleaner fuels, improved stoves, better home ventilation, reduce toxic dust and fume exposures, combat infectious diseases such as TB and HIV, and improve nutrition are all ways in which the lung health of women can be improved.

Nicotine and the fertilization story: smoking versus endogenous function

Objective: There is debate concerning the toxic effects of cigarette smoke on human reproduction. Contradictory results have been reported from studies focused on human IVF rates and sperm motility. We have investigated the in vitro impact of nicotine and/or cotinine (major metabolite) on sperm/egg binding (Hemizona Assay; HZA), modifications of the sperm acrosomal cap and hyperactivated (HA) motility patterns, three required functions. Since human sperm have a nicotinic (cholinergic) receptor, very low concentrations of nicotine (NIC) and/or cotinine (COT) may also mimic the physiological effects of endogenous cholinergic agonists.