Functional, Cellular, and Molecular Remodeling of the Heart under Influence of Oxidative Cigarette Tobacco Smoke.
Ontology highlight
ABSTRACT:
SUBMITTER: Kaplan A
PROVIDER: S-EPMC5541812 | biostudies-other | 2017
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Cigarette smoke (CS) induces oxidative stress, which disables macrophage function. In this study, we examined whether Resolvin E1 (RvE1), a pro-resolving mediator known to enhance macrophage functions, attenuates the damage of macrophages by CS extract (CSE) induced oxidative stress. RvE1 blocked p47phox translocation to plasma membrane induced by CSE in a macrophage cell line, RAW264.7 cells, resulting in suppression of superoxide production. Furthermore, pretreatment of RAW264.7 cells with RvE1 restored the phagocytic activity and reduced cell death induced by treatment of CSE. These results suggest that RvE1 plays important roles in preserving macrophage function under CS-induced oxidative stress.
| S-EPMC3678121 | biostudies-literature
Project description:ObjectiveCigarette smoke exposure (CSE) is a risk factor for cerebral aneurysm (CA) formation, but the molecular mechanisms are unclear. Although CSE is known to contribute to excess reactive oxygen species generation, the role of oxidative stress on vascular smooth muscle cell (VSMC) phenotypic modulation and pathogenesis of CAs is unknown. The goal of this study was to investigate whether CSE activates a NOX (NADPH oxidase)-dependent pathway leading to VSMC phenotypic modulation and CA formation and rupture.Approach and resultsIn cultured cerebral VSMCs, CSE increased expression of NOX1 and reactive oxygen species which preceded upregulation of proinflammatory/matrix remodeling genes (MCP-1, MMPs [matrix metalloproteinase], TNF-α, IL-1β, NF-κB, KLF4 [Kruppel-like factor 4]) and downregulation of contractile genes (SM-α-actin [smooth muscle α actin], SM-22α [smooth muscle 22α], SM-MHC [smooth muscle myosin heavy chain]) and myocardin. Inhibition of reactive oxygen species production and knockdown of NOX1 with siRNA or antisense decreased CSE-induced upregulation of NOX1 and inflammatory genes and downregulation of VSMC contractile genes and myocardin. p47phox-/- NOX knockout mice, or pretreatment with the NOX inhibitor, apocynin, significantly decreased CA formation and rupture compared with controls. NOX1 protein and mRNA expression were similar in p47phox-/- mice and those pretreated with apocynin but were elevated in unruptured and ruptured CAs. CSE increased CA formation and rupture, which was diminished with apocynin pretreatment. Similarly, NOX1 protein and mRNA and reactive oxygen species were elevated by CSE, and in unruptured and ruptured CAs.ConclusionsCSE initiates oxidative stress-induced phenotypic modulation of VSMCs and CA formation and rupture. These molecular changes implicate oxidative stress in the pathogenesis of CAs and may provide a potential target for future therapeutic strategies.
| S-EPMC5823774 | biostudies-literature
Project description:Cigarette smoke is a major exogenous source of free radicals, and the resulting oxidative stress is one of the major causes of smoking-caused diseases. Yet, many of the factors that impact free radical delivery from cigarettes remain unclear. In this study, we machine-smoked cigarettes and measured the levels of gas- and particulate-phase radicals by electron paramagnetic resonance (EPR) spectroscopy using standardized smoking regimens (International Organization of Standardization (ISO) and Canadian Intense (CI)), puffing parameters, and tobacco blends. Radical delivery per cigarette was significantly greater in both gas (4-fold) and particulate (6-fold) phases when cigarettes were smoked under the CI protocol compared to the ISO protocol. Total puff volume per cigarette was the major factor with radical production being proportional to total volume, regardless of whether volume differences were achieved by changes in individual puff volume or puff frequency. Changing puff shape (bell vs sharp vs square) or puff duration (1-5 s), without changing volume, had no effect on radical yields. Tobacco variety did have a significant impact on free radical production, with gas-phase radicals highest in reconstituted > burley > oriental > bright tobacco and particulate-phase radicals highest in burley > bright > oriental > reconstituted tobacco. Our findings show that modifiable cigarette design features and measurable user smoking behaviors are key factors determining free radical exposure in smokers.
| S-EPMC6471496 | biostudies-literature
Project description:Cigarette smoke inhalation exposes the respiratory system to thousands of potentially toxic substances and causes chronic obstructive pulmonary disease (COPD). COPD is characterized by cycles of inflammation and infection with a dysregulated immune response contributing to disease progression. While smoking cessation can slow the damage in COPD, lung immunity remains impaired. Alveolar macrophages (AMΦ) are innate immune cells strategically poised at the interface between lungs, respiratory pathogens, and environmental toxins including cigarette smoke. We studied the effects of cigarette smoke on model THP-1 and peripheral blood monocyte derived macrophages, and discovered a marked inhibition of bacterial phagocytosis which was replicated in primary human AMΦ. Cigarette smoke decreased AMΦ cystic fibrosis transmembrane conductance regulator (CFTR) expression, previously shown to be integral to phagocytosis. In contrast to cystic fibrosis macrophages, smoke-exposed THP-1 and AMΦ failed to augment phagocytosis in the presence of CFTR modulators. Cigarette smoke also inhibited THP-1 and AMΦ mitochondrial respiration while inducing glycolysis and reactive oxygen species. These effects were mitigated by the free radical scavenger N-acetylcysteine, which also reverted phagocytosis to baseline levels. Collectively these results implicate metabolic dysfunction as a key factor in the toxicity of cigarette smoke to AMΦ, and illuminate avenues of potential intervention.
| S-EPMC6610132 | biostudies-literature
Project description:Smoke from conventional cigarettes (C-cigarettes) contains various reactive oxygen species and toxic chemicals, which potentially cause oxidative damage not only to airways but also to the whole body, leading eventually to diseases, including emphysema, advanced atherosclerosis, and cancer. Many heat-not-burn tobacco products (HTPs) have been commercialized recently in Japan to maintain the smoking population by advertising that HTPs are less toxic. However, there were few studies reported from neutral organizations whether HTPs are indeed less damaging. To evaluate the potential capacity of HTPs to induce oxidative stress, we here compared two different HTPs with two types of C-cigarettes, using human fibroblast IMR90SV cells and 5% aqueous extracts in 10-ml phosphate-buffered saline (50-ml smoke/10 s). HTPs exhibited significantly lower oxidative toxicity in comparison to C-cigarettes. Whereas C-cigarettes induced ferroptosis in fibroblasts, the effects of HTPs were significantly reduced by measuring the levels of peroxides, pro-inflammatory cytokine expression, autophagy, catalytic Fe(II) and 8-hydroxy-2'-deoxyguanosine. Notably, major portions of C-cigarettes-induced pathogenic responses were inhibited by catalase. However, HTPs still induced p62 autophagy-adaptor at 5%-dilution and caused lethal effects to fibroblasts with undiluted solution. In conclusion, HTPs smoke per se can be toxic despite less toxicity in comparison to C-cigarettes, which warrants further investigation.
| S-EPMC9309084 | biostudies-literature
Project description:BackgroundCigarette smoking constitutes a major lifestyle risk factor for osteoporosis and hip fracture. It is reported to impair the outcome of many clinical procedures, such as wound infection treatment and fracture healing. Importantly, although several studies have already demonstrated the negative correlation between cigarette consume and impaired bone homeostasis, there is still a poor understanding of how does smoking affect bone health, due to the lack of an adequately designed animal model. Our goal was to determine that cigarette smoke exposure impairs the dynamic bone remodeling process through induction of bone resorption and inhibition of bone formation.MethodsWe developed cigarette smoke exposure protocols exposing mice to environmental smoking for 10 days or 3 months to determine acute and chronic smoke exposure effects. We used these models, to demonstrate the effect of smoking exposure on the cellular and molecular changes of bone remodeling and correlate these early alterations with subsequent bone structure changes measured by microCT and pQCT. We examined the bone phenotype alterations in vivo and ex vivo in the acute and chronic smoke exposure mice by measuring bone mineral density and bone histomorphometry. Further, we measured osteoclast and osteoblast differentiation gene expression levels in each group. The function changes of osteoclast or osteoblast were evaluated.ResultsSmoke exposure caused a significant imbalance between bone resorption and bone formation. A 10-day exposure to cigarette smoke sufficiently and effectively induced osteoclast activity, leading to the inhibition of osteoblast differentiation, although it did not immediately alter bone structure as demonstrated in mice exposed to smoke for 3 months. Cigarette smoke exposure also induced DNA-binding activity of nuclear factor kappaB (NFκB) in osteoclasts, which subsequently gave rise to changes in bone remodeling-related gene expression.ConclusionsOur findings suggest that smoke exposure induces RANKL activation-mediated by NFκB, which could be a "smoke sensor" for bone remodeling.
| S-EPMC8061040 | biostudies-literature
Project description:Background: As e-cigarette popularity has increased, there is growing evidence to suggest that while they are highly likely to be considerably less harmful than cigarettes, their use is not free of risk to the user. There is therefore an ongoing need to characterise the chemical composition of e-cigarette aerosols, as a starting point in characterising risks associated with their use. This study examined the chemical complexity of aerosols generated by an e-cigarette containing one unflavored and three flavored e-liquids. A combination of targeted and untargeted chemical analysis approaches was used to examine the number of compounds comprising the aerosol. Contributions of e-liquid flavors to aerosol complexity were investigated, and the sources of other aerosol constituents sought. Emissions of 98 aerosol toxicants were quantified and compared to those in smoke from a reference tobacco cigarette generated under two different smoking regimes. Results: Combined untargeted and targeted aerosol analyses identified between 94 and 139 compounds in the flavored aerosols, compared with an estimated 72-79 in the unflavored aerosol. This is significantly less complex (by 1-2 orders of magnitude) than the reported composition of cigarette smoke. Combining both types of analysis identified 5-12 compounds over and above those found by untargeted analysis alone. Gravimetrically, 89-99% of the e-cigarette aerosol composition was composed of glycerol, propylene glycol, water and nicotine, and around 3% comprised other, more minor, constituents. Comparable data for the Ky3R4F reference tobacco cigarette pointed to 58-76% of cigarette smoke "tar" being composed of minor constituents. Levels of the targeted toxicants in the e-cigarette aerosols were significantly lower than those in cigarette smoke, with 68.5->99% reductions under ISO 3308 puffing conditions and 88.4->99% reductions under ISO 20778 (intense) conditions; reductions against the WHO TobReg 9 priority list were around 99%. Conclusion: These analyses showed that the e-cigarette aerosols contain fewer compounds and at significantly lower concentrations than cigarette smoke. The chemical diversity of an e-cigarette aerosol is strongly impacted by the choice of e-liquid ingredients.
| S-EPMC8514950 | biostudies-literature
Project description:The strong epidemiological association between cigarette smoke (CS) exposure and respiratory tract infections is conventionally attributed to immunosuppressive and irritant effects of CS on human cells. Since pathogenic bacteria such as Staphylococcus aureus are members of the normal microbiota and reside in close proximity to human nasopharyngeal cells, we hypothesized that bioactive components of CS might affect these organisms and potentiate their virulence. Using Staphylococcus aureus as a model organism, we observed that the presence of CS increased both biofilm formation and host cell adherence. Analysis of putative molecular pathways revealed that CS exposure decreased expression of the quorum-sensing agr system, which is involved in biofilm dispersal, and increased transcription of biofilm inducers such as sarA and rbf. CS contains bioactive compounds, including free radicals and reactive oxygen species, and we observed transcriptional induction of bacterial oxidoreductases, including superoxide dismutase, following exposure. Moreover, pretreatment of CS with an antioxidant abrogated CS-mediated enhancement of biofilms. Exposure of bacteria to hydrogen peroxide alone increased biofilm formation. These observations are consistent with the hypothesis that CS induces staphylococcal biofilm formation in an oxidant-dependent manner. CS treatment induced transcription of fnbA (encoding fibronectin binding protein A), leading to increased binding of CS-treated staphylococci to immobilized fibronectin and increased adherence to human cells. These observations indicate that the bioactive effects of CS may extend to the resident microbiota of the nasopharynx, with implications for the pathogenesis of respiratory infection in CS-exposed humans.
| S-EPMC3486061 | biostudies-literature
Project description:The respiratory system is continuously exposed to variety of biological and chemical irritants that contain reactive oxygen species, and these are well known to cause oxidative stress responses in lung epithelial cells. There is a clinical need to identify biomarkers of oxidative stress which could potentially support early indicators of disease and health management. To identify volatile biomarkers of oxidative stress, we analyzed the headspace above human bronchial epithelial cell cultures (HBE1) before and after hydrogen peroxide (H2O2) and cigarette smoke extract (CSE) exposure. Using stir bar and headspace sorptive extraction-gas chromatography-mass spectrometry, we searched for volatile organic compounds (VOC) of these oxidative measures. In the H2O2 cell peroxidation experiments, four different H2O2 concentrations (0.1, 0.5, 10, 50 mM) were applied to the HBE1 cells, and VOCs were collected every 12 h over the time course of 48 h. In the CSE cell peroxidation experiments, four different smoke extract concentrations (0%, 10%, 30%, 60%) were applied to the cells, and VOCs were collected every 12 h over the time course of 48 h. We used partial-least squares (PLS) analysis to identify putative compounds from the mass spectrometry results that highly correlated with the known applied oxidative stress. We observed chemical emissions from the cells that related to both the intensity of the oxidative stress and followed distinct time courses. Additionally, some of these chemicals are aldehydes, which are thought to be non-invasive indicators of oxidative stress in exhaled human breath. Together, these results illustrate a powerful in situ cell culture model of oxidative stress that can be used to explore the putative biological genesis of exhaled breath biomarkers that are often observed in human clinical studies.
| S-EPMC9798928 | biostudies-literature
Project description:ImportanceWith the prevalence of e-cigarette use (vaping) increasing worldwide, there are concerns about children's exposure to secondhand vapor.ObjectiveTo compare nicotine absorption among children who are (1) exposed to secondhand tobacco smoke only or (2) exposed to secondhand vapor only with (3) those exposed to neither.Design, setting, and participantsThe US Continuous National Health and Nutrition Examination Survey (NHANES) is a repeat cross-sectional survey. Participants are interviewed in their homes and, several days after, visit a mobile examination center to provide biological specimens. This study uses data from a nationally representative sample of US households from 2017 to 2020. Participants were children aged 3 to 11 years with serum cotinine levels incompatible with current firsthand nicotine use (ie, <15 μg/L). The final analysis was conducted on January 9, 2024.ExposuresReported exposure to secondhand smoke or vapor indoors in the past 7 days (only secondhand smoke, only secondhand vapor, or neither). Covariates included age, sex, ethnicity, family income, body weight, and height.Main outcomes and measuresThe primary outcome was serum cotinine concentration, an objective biomarker of nicotine absorption. Geometric mean cotinine levels and 95% CIs were calculated using log-normal tobit regression, accounting for the complex survey design and weights.ResultsThe mean (SD) age of the 1777 children surveyed was 7.4 (2.6) years, 882 (49.6%) were female, and 531 (29.9%) had family incomes below the poverty level. Nicotine absorption, as indexed by serum cotinine level, was highest among children only exposed to secondhand smoke (0.494 μg/L μg/L; 95% CI, 0.386-0.633 μg/L), followed by those exposed only to secondhand vapor (0.081 μg/L; 95% CI, 0.048-0.137 μg/L), equating to 83.6% (95% CI, 71.5%-90.5%; P < .001) lower nicotine absorption. Among children with no reported secondhand exposure, the geometric mean cotinine level was 0.016 μg/L (95% CI, 0.013-0.021 μg/L), or 96.7% (95% CI, 95.6%-97.6%; P < .001) lower than for those with exposure to secondhand smoke. Results were similar after covariate adjustment.Conclusions and relevanceIn this cross-sectional study of US children, nicotine absorption was much lower in children who were exposed to secondhand vapor vs secondhand smoke, but higher than in those exposed to neither. These findings suggest that switching from smoking to vaping indoors may substantially reduce, but not eliminate, children's secondhand exposure to nicotine and other noxious substances.
| S-EPMC11240186 | biostudies-literature