Deleterious Effects Of Cigarette Smoking Research Articles

Indicaxanthin prevents eryptosis induced by cigarette smoke extract by interfering with active Fas-mediated signaling.

A physiological mechanism of programmed cell death called eryptosis occurs in aged or damaged red blood cells (RBCs). Dysregulated eryptosis contributes to abnormal microcirculation and prothrombotic risk. Cigarette smoke extract (CSE) induces a p38 MAPK-initiated, Fas-mediated eryptosis, activating the death-inducing signaling complex (DISC). Indicaxanthin (Ind) from cactus pear fruits, is a bioavailable dietary phytochemical in humans and it is able to incorporate into RBCs enhancing their defense against numerous stimuli. This in vitro work shows that Ind, at concentrations that mimic plasma concentrations after a fruit meal, protects erythrocytes from CSE-induced eryptosis. CSE from commercial cigarettes was prepared in aqueous solution using an impinger air sampler and nicotine content was determined. RBCs were treated with CSE for 3 h in the absence or presence of increasing concentrations of Ind (from 1 to 5 μM). Cytofluorimetric measurements indicated that Ind reduced CSE-induced phosphatidylserine externalization and ceramide formation in a concentration-dependent manner. Confocal microscopy visualization and coimmunoprecipitation experiments revealed that Ind prevented both CSE-triggered Fas aggregation and FasL/FADD/caspase 8 recruitment in the membrane, indicating inhibition of DISC assembly. Ind inhibited the phosphorylation of p38 MAPK, caspase-8/caspase-3 cleavage, and caspase-3 activity induced by CSE. Finally, Ind reduced CSE-induced ATP depletion and restored aminophospholipid translocase activity impaired by CSE treatment. In conclusion, Ind concentrations comparable to nutritionally relevant plasma concentrations, can prevent Fas-mediated RBC death signaling induced by CSE, which suggests that dietary intake of cactus pear fruits may limit the deleterious effects of cigarette smoking.

Therapeutic benefits of quercetin in traumatic brain injury model exposed to cigarette smoke

Scientific evidences reported the deleterious effect of cigarette smoking or passive smoking on brain health particularly cognitive functions, blood–brain barrier (BBB) permeability, up-regulation of inflammatory cascades, and depletion of the antioxidant system. These combined effects become more progressive in the events of stroke, traumatic brain injury (TBI), and many other neurodegenerative diseases. In the current study, we investigated the long-term administered therapeutic potential of quercetin in ameliorating the deleterious neurobiological consequences of chronic tobacco smoke exposure in TBI mice. After exposure to 21 days of cigarette smoke and treatment with 50 mg/kg of quercetin, C57BL/6 mice were challenged for the induction of TBI by the weight drop method. Subsequently, a battery of behavioral tests and immunohistochemical analyses revealed the beneficial effect of quercetin on the locomotive and cognitive function of TBI + smoked group mice (p < 0.05 vs control sham). Immunohistochemistry analysis (Nrf2, HO-1, NFkB, caspase 3) demonstrated a marked protection after 21 days of quercetin treatment in the chronic tobacco smoking group possibly by up-regulation of antioxidant pathways, and decreased apoptosis. In conclusion, our findings support the therapeutic effectiveness of quercetin in partly protecting the central neurological functions that become aberrantly impaired in combined habitual cigarette-smoking individuals impacted with TBI.

The Impacts of Cigarette Smoking on Nerves and Oral Health

This paper effects of cigarette smoking on nerves and oral health. Smoking adversely affects the trigeminal, lingual, and nasopalatine nerves, leading to taste and smell disturbances, xerostomia, and decreased somatosensory function. Additionally, cigarette smoke contains harmful chemicals such as carbon monoxide, tar, benzene, arsenic, and formaldehyde, which contribute to the development of chronic diseases such as lung cancer, COPD, stroke, and heart disease. Smoking also impedes oral health by negatively impacting wound healing and promoting bad breath, staining, and aging. The paper underscores the critical need for smoking cessation interventions and public education campaigns to raise awareness about the deleterious effects of cigarette smoking. Overall, prioritizing smoking cessation as part of a comprehensive approach to promoting healthy nerves and oral health is paramount. Keywords: Cigarette smoking, nerves, somatos, health effects, periodontal diseases, slow response, xerostomia.

Smoking Is Associated With Microbial Translocation in the Miami Adult Studies on HIV (MASH) Cohort

ObjectivesThe prevalence of cigarette smoking is 2 to 3 times greater among people living with HIV (PLWH) than in the HIV uninfected population. Smoking has also been associated with deleterious effects on the gut leading to potential microbial translocation. Thus, we sought to use CD14 (sCD14) as a surrogate marker of microbial translocation to determine if smoking was associated with changes in microbial translocation.MethodsA cross-sectional analysis was completed with participants from the Miami Adult Studies on HIV (MASH) cohort. Demographic characteristics and cigarette smoking status were self-reported. Levels of sCD14 were analyzed using ELISA kits in Dr. Sherman's laboratory. HIV serostatus and viral load (VL) were abstracted from medical records with the participants’ consent. Statistical analyses included descriptive statistics, T-test, linear regression for sCD14 levels, and logistic regression to calculate the odds of having an sCD14 level above the sample median (1064.3 ng/mL). All analyses were conducted on SPSS 26.ResultsA total of 470 participants were included in the analysis. The mean age was 53 ± 8 years, 42.8% were females and 64.5% were Black. PLWH accounted for 76.8% of participants and 85.1% had a suppressed VL (<50 copies/mL). Smokers had significantly higher mean sCD14 levels than non-smokers (1025.8 ± 429.0 vs. 1183.4 ± 465.7, respectively; P = 0.002). This relationship remained significant after adjusting for sex, age, BMI, and HIV status (β = 166.70, SE = 52.36, P = 0.002). Also, smoking tended to be associated with 1.6 times the odds of having high sCD14 levels, adjusted for BMI, age, sex, and HIV status (β = 1.6, 95% CI = 1.0–2.6, P = 0.051).ConclusionsCigarette smoking appears to contribute to immune activation regards of HIV status which may contribute to microbial translocation, regardless of HIV status. The findings provide further evidence of the deleterious effect of cigarette smoking on physiological functions, including gut health. Further research is needed to determine the long-term effects of smoking on immune activation and microbial translocation.Funding SourcesSupported by the National Institute on Drug Abuse.

The Aryl Hydrocarbon Receptor Suppresses Chronic Smoke-Induced Pulmonary Inflammation.

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor expressed in the lungs that is activated by numerous xenobiotic, endogenous and dietary ligands. Although historically the AhR is known for mediating the deleterious response to the environmental pollutant dioxin, emerging evidence supports a prominent role for the AhR in numerous biological process including inflammation. We have shown that the AhR suppresses pulmonary neutrophilia in response to acute cigarette smoke exposure. Whether the AhR can also prevent lung inflammation from chronic smoke exposure is not known but highly relevant, given that people smoke for decades. Using our preclinical smoke model, we report that exposure to chronic cigarette smoke for 8-weeks or 4 months significantly increased pulmonary inflammation, the response of which was greater in Ahr−/− mice. Notably, there was an increased number of multinucleated giant cells (MNGCs) in smoke-exposed Ahr−/− mice without a change in cytokine levels. These data support a protective role for the AhR against the deleterious effects of cigarette smoke, warranting continued investigation into its therapeutic potential for chronic lung diseases.

Brain Training Improves Cigarette Smoke Induced Dementia in Female C57 Black 6 Mice

Alzheimer’s disease is a chronic neurodegenerative disease among the elderly population. Various genetic, environmental and lifestyle factors have been associated with the etiology of Alzheimer’s disease. Cigarette smoke has been reported to be a major predisposing factor for Alzheimer’s disease and contributes to disease development. Conversely, studies have reported beneficial effects of brain training on the disease condition. The purpose of this study was to evaluate the effect of a brain training task in cigarette smoke induced dementia. Three groups of female C57 black 6 mice were used in the study with two of the groups subjected to cigarette smoke exposure. The third group was subjected to a novel object test immediately after the exposure. Brain training improved the cognitive domains of the smoke exposed mice. Brain training could also regain the neurotransmitter imbalances induced by cigarette smoke, importantly, decreased the glutamate levels in the hippocampus. Brain training also significantly decreased the hippocampal amyloid precursor protein expression levels by reducing the reactive oxygen species production. Additionally, the improved hippocampal neuronal count, post training supported the findings. The results indicated that brain training significantly decreased the deleterious effects of cigarette smoke in hippocampus tissue and improved dementia symptoms.

Inhibition of miR‐155 Attenuates Detrimental Vascular Effects of Tobacco Cigarette Smoking

BackgroundThe role of microRNAs dysregulation in tobacco cigarette smoking–induced vascular damage still needs to be clarified. We assessed the acute effects of tobacco cigarette smoking on endothelial cell‐related circulating microRNAs in healthy subjects. In addition, we investigated the potential role of microRNAs in smoking‐dependent endothelial cell damage.Methods and ResultsA panel of endothelial‐related microRNAs was quantified in healthy subjects before and after smoking 1 tobacco cigarette. Serum levels of miR‐155 were found to be significantly increased shortly after smoking. We also observed a progressive and significant miR‐155 accumulation in culture media of human endothelial cells after 30 minutes and up to 4 hours of cigarette smoke condensate treatment in vitro without evidence of cell death, indicating that miR‐155 can be released by endothelial cells in response to smoking stress. Cigarette smoke condensate appeared to enhance oxidative stress and impair cell survival, angiogenesis, and NO metabolism in human endothelial cells. Notably, these effects were abrogated by miR‐155 inhibition. We also observed that miR‐155 inhibition rescued the deleterious effects of cigarette smoke condensate on endothelial‐mediated vascular relaxation and oxidative stress in isolated mouse mesenteric arteries. Finally, we found that exogenous miR‐155 overexpression mimics the effects of smoking stress by inducing the upregulation of inflammatory markers, impairing angiogenesis and reducing cell survival. These deleterious effects were associated with downregulation of vascular endothelial growth factor and endothelial NO synthetase.ConclusionsOur results suggest that miR‐155 dysregulation may contribute to the deleterious vascular effects of tobacco smoking.

Peak expiratory flow rate among smokers and non-smokers working in Kathmandu Medical College

Background: Cigarette smoking has remained a popular habit since ages. Most people are well aware of the deleterious effects of cigarette smoking yet continue to give a blind eye which dete­riorates overall public health. The purpose of the present study was to assess Peak Expiratory Flow Rate among smoking and nonsmoking staffs who work in Kathmandu Medical College.&#x0D; Methods: In this comparative cross-sectional study Peak Expiratory Flow Rate was obtained using Mini Wright’s Peak Flow Meter of 108 smokers and 108 nonsmokers in the age group ranging from 25-45 years. Those who never smoked or who have quit smoking for the past 2 years were grouped as nonsmokers and the smokers with history of smoking at least five or more cigarettes per day for at least two years were included in the study for measuring their Peak Expiratory Flow Rate. Data was collected, compiled and analyzed by using Statistical Package of Social Science (SPSS) software version16. Student ‘t’ test was used for group comparison.&#x0D; Results: The Peak Expiratory Flow Rate value was significantly reduced in the smokers (p value&lt; 0.05). Mean Peak Expiratory Flow Rate was reduced with increasing age of the smokers. However, no significant difference was observed in Peak Expiratory Flow Rate with increase in the number of cigarettes smoked (p value&gt; 0.05).&#x0D; Conclusions: In the study Peak Expiratory Flow Rate among smokers (367.13 ± 74.182) was lower than nonsmokers (471.39±60.842), which was statistically significant proving that cigarette smok­ing reduced peak expiratory flow rate.

PEAK EXPIRATORY FLOW RATE AMONG SMOKERS AND NON-SMOKERS WORKING IN KATHMANDU MEDICAL COLLEGE

Background: Cigarette smoking has remained a popular habit since ages. Most people are well aware of the deleterious effects of cigarette smoking yet continue to give a blind eye which dete­riorates overall public health. The purpose of the present study was to assess Peak Expiratory Flow Rate among smoking and nonsmoking staffs who work in Kathmandu Medical College.&#x0D; Methods: In this comparative cross-sectional study Peak Expiratory Flow Rate was obtained using Mini Wright’s Peak Flow Meter of 108 smokers and 108 nonsmokers in the age group ranging from 25-45 years. Those who never smoked or who have quit smoking for the past 2 years were grouped as nonsmokers and the smokers with history of smoking at least five or more cigarettes per day for at least two years were included in the study for measuring their Peak Expiratory Flow Rate. Data was collected, compiled and analyzed by using Statistical Package of Social Science (SPSS) software version16. Student ‘t’ test was used for group comparison.&#x0D; Results: The Peak Expiratory Flow Rate value was significantly reduced in the smokers (p value&lt; 0.05). Mean Peak Expiratory Flow Rate was reduced with increasing age of the smokers. However, no significant difference was observed in Peak Expiratory Flow Rate with increase in the number of cigarettes smoked (p value&gt; 0.05).&#x0D; Conclusions: In the study Peak Expiratory Flow Rate among smokers (367.13 ± 74.182) was lower than nonsmokers (471.39±60.842), which was statistically significant proving that cigarette smok­ing reduced peak expiratory flow rate.

History of Cigarette Smoking and Heart Transplant Outcomes

Objective The deleterious effects of cigarette smoking (CS) have been well documented. Active cigarette use is a relative contraindication for heart transplantation (HT) with a recommendation that candidates be abstinent for at least 6 months prior to HT. Animal studies have shown that a history of CS is associated with increased risk of allograft rejection. Our study examines the association of CS history and HT outcomes. Methods Data were analyzed from HT recipients captured in the United Network for Organ Sharing (UNOS) transplant registry. Included in this study were adults who underwent HT from 1987 to 2018 and who had available smoking status data (N= 38,220). The cohort was categorized by smoking status (CS vs non-CS). Post-transplant outcomes of interest included survival, graft failure, treated hospitalizations and hospitalizations for infection. Baseline characteristics were compared between the two groups using chi-squared analysis. Unadjusted associations between CS and patient survival were determined using Kaplan-Meier estimations and confounding was addressed using multivariable Cox proportional hazards models. Results HT recipients with a history of CS were older (55 vs 50, p= Conclusions A history of CS was associated with increased risk for acute rejection, hospitalization for infection, graft failure, post-transplant malignancy and worse survival. A history of CS should be considered in post HT management.

Impact of smoking on stroke outcome after endovascular treatment

BackgroundRecent studies suggest a paradoxical association between smoking status and clinical outcome after intravenous thrombolysis (IVT). Little is known about relationship between smoking and stroke outcome after endovascular treatment (EVT).MethodsWe analyzed data of all stroke patients treated with EVT at the tertiary stroke centre of Berne between January 2005 and December 2015. Using uni- and multivariate modeling, we assessed whether smoking was independently associated with excellent clinical outcome (modified Rankin Scale (mRS) 0–1) and mortality at 3 months. In addition, we also measured the occurrence of symptomatic intracranial hemorrhage (sICH) and recanalization.ResultsOf 935 patients, 204 (21.8%) were smokers. They were younger (60.5 vs. 70.1 years of age, p<0.001), more often male (60.8% vs. 52.5%, p = 0.036), had less often from hypertension (56.4% vs. 69.6%, p<0.001) and were less often treated with antithrombotics (35.3% vs. 47.7%, p = 0.004) as compared to nonsmokers. In univariate analyses, smokers had higher rates of excellent clinical outcome (39.1% vs. 23.1%, p<0.001) and arterial recanalization (85.6% vs. 79.4%, p = 0.048), whereas mortality was lower (15.6% vs. 25%, p = 0.006) and frequency of sICH similar (4.4% vs. 4.1%, p = 0.86). After correcting for confounders, smoking still independently predicted excellent clinical outcome (OR 1.758, 95% CI 1.206–2.562; p<0.001).ConclusionSmoking in stroke patients may be a predictor of excellent clinical outcome after EVT. However, these data must not be misinterpreted as beneficial effect of smoking due to the observational study design. In view of deleterious effects of cigarette smoking on cardiovascular health, cessation of smoking should still be strongly recommended for stroke prevention.

The Effects Of Cigarette Smoking On The Serum Levels Of Some Antioxidants (Vitamin C And E ) Amongst Male Smokers In Levels In College Of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Anambra State

Smoking has been identified as one of the major risk factors in human diseases such as atherosclerosis and several cancers. This study investigated the effect of smoking on vitamin C and E levels in male cigarette smokers in College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Anambra State. A total of 100 subjects comprising of (50 smokers and controls) each were recruited for the study. A well structured questionnaire was used in obtaining the demographic and anthropometric data as well as dietary pattern of subjects. Thereafter, 5mls of blood sample was collected from subjects and used for the evaluation biochemical parameters. Biochemical parameters (vitamin C and E levels) were estimated using standard methods and results subjected to statistical analysis using student t-test and Pearson r correlation. The results show a significant decrease in the mean serum levels of Vitamins C (0.82±0.33 vs 1.49±0.25; p=0.000) and E (12.36±1.61 vs15.61±1.91; p=0.000) in smokers compared with non smokers respectively. More so, there was a significant positive correlation between BMI and serum level of Vitamin C (r=0.345; P=0.014) and E (r=0.187; P=0.024) in cigarette smokers. In conclusion, the study revealed the deleterious effects of cigarette smoking on serum levels of vitamins C and E in smokers. Hence, there is need for proper dietary management in patients.

Roflumilast reverses CFTR-mediated ion transport dysfunction in cigarette smoke-exposed mice

BackgroundDysfunction in cystic fibrosis transmembrane conductance regulator (CFTR) can be elicited by cigarette smoke and is observed in patients with chronic bronchitis. We have previously demonstrated in human airway epithelial cell monolayers that roflumilast, a clinically approved phosphodiesterase 4 inhibitor that reduces the risk of exacerbations in chronic obstructive pulmonary disease patients with chronic bronchitis and a history of exacerbations, activates CFTR-dependent chloride secretion via a cAMP-mediated pathway, partially restores the detrimental effects of cigarette smoke on CFTR-mediated ion transport, and increases CFTR-dependent gastrointestinal fluid secretion in isolated murine intestine segments. Based on these findings, we hypothesized that roflumilast could improve CFTR-mediated chloride transport and induce secretory diarrhea in mice exhibiting cigarette smoke-induced CFTR dysfunction.MethodsA/J mice expressing wild type CFTR (+/+) were exposed to cigarette smoke or air with or without roflumilast and the effect of treatment on CFTR-dependent chloride transport was quantified using nasal potential difference (NPD) measurements in vivo and short-circuit current (Isc) analysis of trachea ex vivo. Stool specimen were collected and the wet/dry ratio measured to assess the effect of roflumilast on secretory diarrhea.ResultsAcute roflumilast treatment increased CFTR-dependent chloride transport in both smoke- and air-exposed mice (smoke, −2.0 ± 0.4 mV, 131.3 ± 29.3 μA/cm2, P < 0.01 and air, 3.9 ± 0.8 mV, 147.7 ± 38.0 μA/cm2, P < 0.01 vs. vehicle −0.3 ± 0.7 mV, 10.4 ± 7.0 μA/cm2). Oral administration of roflumilast over five weeks completely reversed the deleterious effects of cigarette smoke on CFTR function in smoke-exposed animals, in which CFTR-dependent chloride transport was 64% that of air controls (roflumilast, −15.22 ± 2.7 mV vs. air, −14.45 ± 1.4 mV, P < 0.05). Smoke exposure increased the wet/dry ratio of stool specimen to a level beyond which roflumilast had little additional effect.ConclusionsRoflumilast effectively rescues CFTR-mediated chloride transport in vivo, further implicating CFTR activation as a mechanism through which roflumilast benefits patients with bronchitis.

Concise Review: The Deleterious Effects of Cigarette Smoking and Nicotine Usage and Mesenchymal Stem Cell Function and Implications for Cell-Based Therapies

Stem cell sources for cell‐based therapeutics are often screened for infectious agents and genetic diseases prior to implantation; however, there are other risk factors that are often overlooked, which may ultimately lead to less efficacious clinical outcomes. One such risk factor is exposure of mesenchymal stem cells (MSCs) to cigarette smoke or nicotine. Recent data have shown that exposure to cigarette smoke or nicotine leads to decreased regenerative potential, namely decreased proliferation, decreased migration, and decreased differentiation potential of exposed MSCs. This review provides a brief introduction into MSCs and their respective niches and a summary regarding the interactions of cigarettes and nicotine with MSCs populations. Specifically, the effects of cigarette smoke and nicotine on the regenerative potential of MSCs (i.e., proliferation, migration, and differentiation) will be covered with an emphasis on considerations for the development of future cell‐based clinical trials and therapies. stem cells translational medicine 2017;6:1815–1821

Nicotinic receptors in chronic kidney disease

Tobacco smoking remains the most important modifiable risk factor for improving overall morbidity and mortality. In addition to being a risk factor for cancer, cardiovascular and lung diseases, strong evidence from human and animal studies has demonstrated that cigarette smoking accelerates the progression of chronic kidney disease (CKD). Clinical studies have shown a strong association between cigarette smoking and worsening CKD in patients with diabetes mellitus, hypertension, polycystic kidney disease, and post kidney transplant. Nicotine, in addition to being responsible for the addictive properties of cigarette smoking, also has other important biological effects on a variety of organs and tissues. In humans, nicotine induces transitory increases in blood pressure accompanied by reductions in glomerular filtration rate and effective renal plasma flow. In animals, nicotine increases the severity of renal injury in subjects with diabetic nephropathy, CKD, and acute kidney injury (AKI). These effects of nicotine on the kidney are linked to increased generation of reactive oxygen species and activation of pro-fibrotic pathways. There are several nicotinic acetylcholine receptor (nAChR) subunits which are expressed in the normal kidney, and the specific blockade of α7-subunit ameliorates the effects of nicotine in animal models with CKD. In summary, the clinical and experimental evidence indicates that nicotine, via the activation of specific nAChRs, is partly responsible for the deleterious effects of cigarette smoking in the progression of CKD. Better understanding of these mechanisms may result in the development of novel strategies to ameliorate the effects of cigarette smoking in CKD.

Resveratrol protects SR-B1 levels in keratinocytes exposed to cigarette smoke

Cigarette smoking (CS) has been strongly linked to several health conditions including heart disease, lung cancer, and other respiratory and circulatory ailments. Deleterious effects of cigarette smoking on skin have also been well documented, but unlike effects on other organs, damage does not depend upon inhalation. The upper layer of the skin, the stratum corneum (rich in cholesterol fatty acids and ceramide), is very susceptible to damage induced by exposure to environmental stressors that can modify its lipid composition and thereby affect its function of protecting skin from dehydration. Scavenger receptor B1 (SR-B1) is involved in the uptake of cholesterol in several tissues including skin. We previously demonstrated that CS exposure induces formation of aldehyde (HNE) adducts that decrease SR-B1 expression. As topical resveratrol, a well-known polyphenolic stilbene, has been demonstrated to show benefits against skin disorders, we investigated its possible role as a protective agent against CS-induced reduction of SR-B1 expression in cutaneous tissue. In this study, we demonstrate that resveratrol at doses ranging from 0.5 to 10μM is not toxic and is able to increase SR-B1 protein levels in a dose-dependent manner in human keratinocytes. Moreover, when the cells that were pretreated with various doses of resveratrol were exposed to CS, the loss of SR-B1 was prevented in a dose-dependent manner. In addition, in keratinocytes, resveratrol was also able to prevent an increase in HNE–protein adducts induced by CS. In particular resveratrol was able to prevent HNE–SR-B1 adduct formation. Thus, resveratrol seems to be a natural compound that could provide skin with a defense against exogenous stressors by protecting the essential cholesterol receptor, SR-B1.

Protection of Cigarette Smoke‐Induced Lung Injury in Guinea Pigs by Inhalation of Aerosolic All‐Trans Retinoic Acid

Both mainstream (MS) and secondhand (SH) cigarette smoking are known to cause abnormality in lung function. We reported earlier that both MS and SH cigarette smoke exposure to guinea pigs caused lung injury associated with accumulation of retinol. The accumulation of retinol in lung was later found to be associated with a decrease in the levels of retinoic acid implying an abnormality in lung retinoid metabolism and signaling. The objective of the present study was to investigate whether inhalation of aerosolic all‐trans retinoic acid (ATRA) immediately smoke exposure can protect against lung damage. Four weeks old male guinea pig were exposed twice daily for 6 weeks to MS or SH smoke from 3 1R3F cigarettes. The sham control group (SC) received a treatment identical to smoke‐exposed groups but in the absence of cigarettes. Four animals from each group received either aerosolic ATRA (2.78mM) or vehicle twice for 20 min/day after smoke exposure. Morphological analysis of lungs showed deleterious alterations in the morphology of the lungs in both MS and SH groups. ATRA treatment showed significant protection against lung damage; however the protection was more evident in MS than SH groups. The mechanism by which ATRA aerosol protects lung against deleterious effects of cigarette smoke is under investigation. (Supported by NIH grant: 1R03HL095419–01A1).

Late Intervention with a Myeloperoxidase Inhibitor Stops Progression of Experimental Chronic Obstructive Pulmonary Disease

Inflammation and oxidative stress are linked to the deleterious effects of cigarette smoke in producing chronic obstructive pulmonary disease (COPD). Myeloperoxidase (MPO), a neutrophil and macrophage product, is important in bacterial killing, but also drives inflammatory reactions and tissue oxidation. To determine the role of MPO in COPD. We treated guinea pigs with a 2-thioxanthine MPO inhibitor, AZ1, in a 6-month cigarette smoke exposure model, with one group receiving compound from Smoking Day 1 and another group treated after 3 months of smoke exposure. At 6 months both treatments abolished smoke-induced increases in lavage inflammatory cells, largely ameliorated physiological changes, and prevented or stopped progression of morphologic emphysema and small airway remodeling. Cigarette smoke caused a marked increase in immunohistochemical staining for the myeloperoxidase-generated protein oxidation marker dityrosine, and this effect was considerably decreased with both treatment arms. Serum 8-isoprostane, another marker of oxidative stress, showed similar trends. Both treatments also prevented muscularization of the small intrapulmonary arteries, but only partially ameliorated smoke-induced pulmonary hypertension. Acutely, AZ1 prevented smoke-induced increases in expression of cytokine mediators and nuclear factor-κB binding. We conclude that an MPO inhibitor is able to stop progression of emphysema and small airway remodeling and to partially protect against pulmonary hypertension, even when treatment starts relatively late in the course of long-term smoke exposure, suggesting that inhibition of MPO may be a novel and useful therapeutic treatment for COPD. Protection appears to relate to inhibition of oxidative damage and down-regulation of the smoke-induced inflammatory response.

Effects of cigarette smoking on reproduction

BACKGROUND Cigarette smoking is associated with lower fecundity rates, adverse reproductive outcomes and a higher risk of IVF failures. Over the last few decades, prevalence of smoking among women of reproductive age has increased. This review focuses on current knowledge of the potential effects of smoke toxicants on all reproductive stages and the consequences of smoke exposure on reproductive functions. METHODS We conducted a systematic review of the scientific literature on the impact of cigarette smoking and smoke constituents on the different stages of reproductive function, including epidemiological, clinical and experimental studies. We attempted to create hypotheses and find explanations for the deleterious effects of cigarette smoke observed in experimental studies. RESULTS Cigarette smoke contains several thousand components (e.g. nicotine, polycyclic aromatic hydrocarbons and cadmium) with diverse effects. Each stage of reproductive function, folliculogenesis, steroidogenesis, embryo transport, endometrial receptivity, endometrial angiogenesis, uterine blood flow and uterine myometrium is a target for cigarette smoke components. The effects of cigarette smoke are dose-dependent and are influenced by the presence of other toxic substances and hormonal status. Individual sensitivity, dose, time and type of exposure also play a role in the impact of smoke constituents on human fertility. CONCLUSIONS All stages of reproductive functions are targets of cigarette smoke toxicants. Further studies are necessary to better understand the deleterious effects of cigarette smoke compounds on the reproductive system in order to improve health care, help to reduce cigarette smoking and provide a better knowledge of the molecular mechanisms involved in reproductive toxicology.

Cigarette smoking exacerbates nonalcoholic fatty liver disease in obese rats

The prevalence of cigarette smoking (CS) is increased among obese subjects, who are susceptible to develop nonalcoholic fatty liver disease (NAFLD). We investigated the hepatic effects of CS in control and obese rats. Control and obese Zucker rats were divided into smokers and nonsmokers (n = 12 per group). Smoker rats were exposed to 2 cigarettes/day, 5 days/week for 4 weeks. The effects of CS were assessed by biochemical analysis, hepatic histological examination, immunohistochemistry, and gene expression analysis. Phosphorylation of AKT and extracellular signal-regulated kinase (ERK) and quantification of carbonylated proteins were assessed by western blotting. As expected, obese rats showed hypercholesterolemia, insulin resistance, and histological features of NAFLD. Smoking did not modify the lipidic or glucidic serum profiles. Smoking increased alanine aminotransferase serum levels and the degree of liver injury in obese rats, whereas it only induced minor changes in control rats. Importantly, CS increased the histological severity of NAFLD in obese rats. We also explored the potential mechanisms involved in the deleterious effects of CS. Smoking increased the degree of oxidative stress and hepatocellular apoptosis in obese rats, but not in controls. Similarly, smoking increased the hepatic expression of tissue inhibitor of metalloproteinase-1 and procollagen-alpha2(I) in obese rats, but not in controls. Finally, smoking regulated ERK and AKT phosphorylation. The deleterious effects of CS were not observed after a short exposure (5 days). CS causes oxidative stress and worsens the severity of NAFLD in obese rats. Further studies should assess whether this finding also occurs in patients with obesity and NAFLD.