Cigarette Smoke Inhalation Research Articles

Behavioral and histological characterization of the effects of cigarette smoke inhalation and withdrawal in rats

The aims of the study are to assess some effects of smoking for 3 months and of withdrawal of male weaned rats on anxiety, locomotor activity, and depression using common behavioral tests such as the marble burying, open field, and forced swim tests. Somatic signs of abstinence and histological effects were also studied. The rats present changes of the aforementioned behaviors as well as histological alterations of the lungs.

Bufei Jianpi Granules Reduce Quadriceps Muscular Cell Apoptosis by Improving Mitochondrial Function in Rats with Chronic Obstructive Pulmonary Disease.

Background Cell apoptosis is an important mechanism underlying skeletal muscle dysfunction in chronic obstructive pulmonary disease (COPD) patients, and mitochondrial dysfunction is recognized as a central aspect contributing to skeletal muscle deterioration. Bufei Jianpi granules have been confirmed effective for improving motor function in COPD patients, but the specific mechanism for this improved function remains unknown. This study explored the mechanisms by which Bufei Jianpi granules improve cell apoptosis and mitochondrial dysfunction in COPD. Methods Sprague-Dawley rats were randomized into control, model, Bufei Jianpi, and aminophylline groups. A stable COPD rat model was induced with respective repeated cigarette smoke inhalation and intragastric bacterial infection, and rats were sacrificed after 20 weeks; the quadriceps muscle was harvested from each rat. Skeletal muscle mitochondria were extracted for measurements of mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore openings (mPTPs). ATP levels were determined with a firefly luciferase-based ATP assay kit. The rates of cell apoptosis were determined by the transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) method. Cyto C and caspase-3 mRNA and protein levels were measured by qPCR and western blotting. Results ATP, MMP, and mPTPs were markedly decreased in COPD rats, while cell apoptosis, caspase-3, and Cyto C were increased (P<0.01). All aforementioned parameters were improved in treatment groups (P<0.05). ATP, MMP, and mPTPs were significantly higher in the Bufei Jianpi group than in the aminophylline group, while cell apoptosis, caspase-3, and Cyto C were lower (P<0.05). Conclusions Bufei Jianpi granules can inhibit mitochondrial dysfunction and cell apoptosis in peripheral muscles, which might be the mechanism involved in improving skeletal muscle function in COPD patients.

Short-term regulation of the hepatic activities of cytochrome P450 and glutathione S-transferase by nose-only cigarette smoke exposure in mice

The present study aimed to determine the effects of cigarette smoke on the regulation of hepatic cytochrome P450 (CYP) and glutathione S-transferase (GST) enzymes in male BALB/c mice exposed to nose-only cigarette smoke for 4 days. There were no significant increases in serum liver injury markers (alanine aminotransferase and aspartate aminotransferase) or oxidative stress (total antioxidant capacity, malondialdehyde, and glutathione disulfide/reduced glutathione) following cigarette smoke exposure, but malondialdehyde was elevated in the bronchoalveolar lavage fluid of smoke-exposed mice. Additionally, the hepatic microsomal protein levels of Cyp1a and Cyp2b, and the activities of ethoxyresorufin O-deethylase, pentoxyresorufin O-depenylase, and chlorzoxazone 6-hydrxylase, were elevated in smoke-exposed mice. Interestingly, the hepatic activities of GST toward 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene, and ethacrynic acid, but not cumene hydroperoxide were enhanced by cigarette smoke exposure, which was consistent with the increased expression levels of mu- and pi-class GSTs, but not alpha-class GSTs, observed in immunoblot analyses. These findings indicate that the short-term inhalation of cigarette smoke induces drug-metabolizing enzymes such as CYP1A, CYP2B, and mu/pi-class GSTs in the absence of hepatic injury and oxidative stress. Furthermore, smoking may alter hepatic drug metabolism, as well as the disposition and toxicity of xenobiotics, including some therapeutic drugs and cigarette smoke constituents.

Enhancing tristetraprolin activity reduces the severity of cigarette smoke-induced experimental chronic obstructive pulmonary disease.

ObjectiveChronic obstructive pulmonary disease (COPD) is a progressive disease that causes significant mortality and morbidity worldwide and is primarily caused by the inhalation of cigarette smoke (CS). Lack of effective treatments for COPD means there is an urgent need to identify new therapeutic strategies for the underlying mechanisms of pathogenesis. Tristetraprolin (TTP) encoded by the Zfp36 gene is an anti‐inflammatory protein that induces mRNA decay, especially of transcripts encoding inflammatory cytokines, including those implicated in COPD.MethodsHere, we identify a novel protective role for TTP in CS‐induced experimental COPD using Zfp36aa/aa mice, a genetically modified mouse strain in which endogenous TTP cannot be phosphorylated, rendering it constitutively active as an mRNA‐destabilising factor. TTP wild‐type (Zfp36 +/+) and Zfp36aa/aa active C57BL/6J mice were exposed to CS for four days or eight weeks, and the impact on acute inflammatory responses or chronic features of COPD, respectively, was assessed.ResultsAfter four days of CS exposure, Zfp36aa/aa mice had reduced numbers of airway neutrophils and lymphocytes and mRNA expression levels of cytokines compared to wild‐type controls. After eight weeks, Zfp36aa/aa mice had reduced pulmonary inflammation, airway remodelling and emphysema‐like alveolar enlargement, and lung function was improved. We then used pharmacological treatments in vivo (protein phosphatase 2A activator, AAL(S), and the proteasome inhibitor, bortezomib) to promote the activation and stabilisation of TTP and show that hallmark features of CS‐induced experimental COPD were ameliorated.ConclusionCollectively, our study provides the first evidence for the therapeutic potential of inducing TTP as a treatment for COPD.

Testing Differential Associations Between Smoking and Chronic Disease Across Socioeconomic Groups: Pooled Data From 15 Prospective Studies.

For the same quantity of cigarettes smoked, relative to more affluent people, socioeconomically disadvantaged people have higher levels of smoking biomarkers. This may be ascribed to inhaling cigarette smoke more deeply and more frequently and/or choosing higher tar-containing brands. We investigated whether this increased tobacco load, as captured using cotinine measurements, is associated with a greater risk of mortality in lower social groups. We used Cox proportional hazards models stratified by socioeconomic position to calculate hazard ratios in a pooled sample of 15 English and Scottish prospective cohort studies (N = 81,476). During a mean (SD) follow-up of 10.3 (4.4) years, 8234 deaths occurred. Risk of total mortality (hazard ratio; 95% confidence interval) for smokers relative to never-smokers in the high (2.5; 2.1, 3.1), intermediate (2.1; 1.8, 2.4), and low (2.0; 1.9, 2.2) educational groups did not differ markedly (P for interaction=0.61). Similar findings emerged when using cause-specific outcomes and occupational social class and housing tenure as socioeconomic indices. Contrary to our hypothesis, we found no indication that chronic disease mortality associated with smoking was higher in disadvantaged people.

Resveratrol reverses the negative effect of smoking on peri-implant repair in the tibia of rats.

Innovative approaches capable to improve peri-implant bone repair are relevant in the presence of smoking, a risk factor for healing around implants. This study investigated the effect of resveratrol (RESV) on peri-implant repair, and its influence on bone-related markers in rats submitted to cigarette smoking inhalation (CSI). One titanium implant was inserted in each tibiae of rats assigned to CSI+RESV (n:18); CSI+placebo (n:18); and non-CSI (n:18). One implant was removed for counter torque, and the peri-implant tissue was collected for mRNA quantification of BMP-2, OPN, Runx2, Lrp-5, Osx, β-catenin, Dkk1, OPG, and RANKL. The other tibia was submitted to microCT to measure: bone volume, bone porosity, trabecular spacing, trabecular thickness, and bone-implant contact (BIC). No differences were detected between counter torque in CSI+RESV and non-CSI group (p>0.05), whereas CSI+placebo group presented lower values when compared to the others (p<0.05). RESV improved the BIC in CSI rats without differences when compared to non-CSI group (p>0.05), whereas CSI+placebo showed reduced BIC when compared to the other groups (p<0.05). RESV reduced RANKL/OPG and Lrp-5 levels and increased β-catenin in CSI rats when compared to CSI+placebo (p<0.05). Although further investigations should be considered using oral models of dental implants, within the limits of the present study, it was concluded that RESV reverses the negative effects of smoking in the peri-implant repair, benefiting the modulation of bone-related markers.

Resveratrol attenuates oxidative stress during experimental periodontitis in rats exposed to cigarette smoke inhalation.

This study aimed at investigating the effect of the systemic administration of resveratrol (RESV) on oxidative stress during experimental periodontitis in rats subjected to cigarette smoke inhalation. Experimental periodontitis (EP) was induced in 26 male Wistar rats by the insertion of a ligature around one of the first mandibular and maxillary molars. The animals were assigned randomly to the following groups: cigarette smoke inhalation (CSI; 3 times/d, 8minutes/d)+resveratrol (10mg/Kg), that is, SMK+RESV (n=13) and cigarette smoke inhalation+placebo, that is, SMK+PLAC (n=13). The substances were administered daily for 30days (19days prior and 11days following EP induction), and then, the animals were euthanized. The maxillary specimens were processed for morphometric analysis of bone loss, and the tissue surrounding the first maxillary molars was collected for mRNA quantification of Sirtuin 1 (SIRT1) by real-time PCR. The gingival tissues surrounding the mandibular first molars were collected for quantification of superoxide dismutase 1 (SOD1) and nicotinamide adenine dinucleotide phosphatase oxidase (NADPH) using an ELISA assay. Reduced bone loss was demonstrated in animals in the SMK+RESV group as compared to those in the SMK+PLAC (P<0.05) group on the basis of morphometric analysis. Resveratrol promoted higher levels of SIRT and SOD (P<0.05) as well as reduced levels of NADPH oxidase (P<0.05) were found in tissues derived from animals in the SMK+RESV group when compared to those in the SMK+PLAC group. Resveratrol is an efficient therapeutic agent that reduces exacerbation of bone loss found in animals with EP that were also exposed to smoke. The results suggest that its effects could be mediated, at least in part, by its antioxidant and anti-inflammatory properties which attenuate the effects of oxidative stress on EP in the presence of cigarette smoke.

Utilizing Ion Mobility to Identify Isobaric Post-Translational Modifications: Resolving Acrolein and Propionyl Lysine Adducts by TIMS Mass Spectrometry.

Protein post-translational modifications provide critical proteomic details towards elucidating mechanisms of altered protein function due to toxic exposure, altered metabolism, or disease pathogenesis. Lysine propionylation is a recently described modification that occurs due to metabolic alterations in propionyl-CoA metabolism and sirtuin depropionylase activity. Acrolein is a toxic aldehyde generated through exogenous and endogenous pathways, such as industrial exposure, cigarette smoke inhalation, and non-enzymatic lipid peroxidation. Importantly, lysine modifications arising from propionylation and acroleination can be isobaric - indistinguishable by mass spectrometry - and inseparable via reverse-phase chromatography. Here, we present the novel application of trapped ion mobility spectrometry (TIMS) to resolve such competing isobaric lysine modifications. Specifically, the PTM products of a small synthetic peptide were analyzed using a prototype TIMS - time-of-flight mass spectrometer (TIMS-TOF). In that the mobilities of these propionylated and acroleinated peptides differ by only 1%, a high-resolution mobility analysis is required to resolve the two. We were able to achieve more than sufficient resolution in the TIMS analyzer (~170), readily separating these isobars.

Effect of orthodontic force associated with cigarette smoke inhalation in healthy and diseased periodontium. A histometric and immunohistochemistry analysis in rats.

The aim of the present study is to evaluate the effect of orthodontic forces in healthy or diseased periodontium of rats submitted/not submitted to cigarette smoke inhalation. Fifty-six male Wistar rats were allocated into two groups of conditions: smoking and non-smoking. Each group was divided into the following subgroups: control (C), orthodontic tooth movement (OTM), ligature-induced periodontitis (P) and P+OTM (POTM), with n=14 each. Periodontitis was induced in the lower first molar by cotton ligature, and a 4mm closed stainless steel spring was used for orthodontic movement. Animals were exposed to the smoke of 10 cigarettes for 8minutes, 3 times a day for 60days before P induction and OTM. Evaluation parameters were macroscopic analysis of dental movement, bone loss and bone density. In addition, the receptor activator of nuclear factor-kappaB (RANK) immunostaining and RANK ligand/osteoprotegerin ratio in the furcation region were assessed. There was no statistically significant difference between groups, ie, smoking and non-smoking conditions (P=.338). Bone loss intragroup analysis between the P and POTM groups was not significant in smoking (P=1) and non-smoking (P=.5) conditions; both were different from OTM and C in each condition. Regarding bone density, POTM and P were significant to C (P<.05). The POTM group was significant to the P and C (P=.001) regarding dental movement. The RANK ligand/osteoprotegerin ratio in the non-smoking condition was higher in P and POTM compared to C and OTM and to P and POTM in the smoking condition. RANK immunostaining was significant in the smoking condition for the P and POTM groups (P<.05). Within the limitations of the present study, it was concluded that cigarette smoke inhalation had no influence on the evaluated groups, even with the presence of low levels of nicotine, carbon monoxide and tar. The POTM groups did not present greater bone loss compared to P groups, thus periodontal disease is essential for bone loss.

GAMBARAN TINGKAT PENGETAHUAN KELUARGA TENTANG BAHAYA PEROKOK PASIF DI DUSUN JARANAN PANGGUNGHARJO SEWON BANTUL TAHUN 2015

The effects of cigarette smoking are not only borne by those who smoke, but also felt by passive smokers. Passive smokers are more inhale of cigarrette smoke with more particles of a substance. The data of Susenas shows the prevalence of passive smokers in Indonesia amounted to 48,9% or 97.560.002 inhabitans, which consist of 31,88% in men and 66% in women. Surveys shows that more than 90% of active smokers have admitted to smoking in home when they were together with other family members.This research aims to know the description of family's level knowledge about the danger of passive smoker in Dusun Jaranan Panggungharjo Sewon Bantul. The research method used was descriptive survey. The research was done in 2015. The research location was in the village of Jaranan, Panggungharjo Sewon Bantul, Yogyakarta. Subjects of this research were members of the family in Jaranan, Panggungharjo, Sewon Bantul who become passieve smokers with productive age (15 – 64 years old) as many as 71 people. This research used proportional random sampling. The research instrument was a questionnaire of 30 statements. Data were analyzed using frequency distribution. In this research showed that 64,7% of respondent were aged over 31 years, 43,6% of respondent had a recent education junior high school,54,92% were housewifes, 93,36% of respondent got the smoke at home, and 64,78% of respondent were inhaled cigarette smoke average &lt;1 hour. From data processing obtained results of the research showed family's level knowledge about the danger of passive smoker was good by 51 respondent (71,8%), qiute as much as 20 respondent (28,2%), and no respondent who had less knowledge level. The description of family's level knowledge about the danger of passive smoker in Dusun Jaranan Panggungharjo Sewon Bantul was in good categories (71,8%). Key word : family, knowledge, the dangers of passive smokers

Orally administered nicotine effects on rat urinary bladder proliferation and carcinogenesis

Tobacco smoking is a major risk factor for human cancers including urinary bladder carcinoma. Cigarette smoke inhalation in mice and orally administered nicotine in rats and mice increased urothelial cell proliferation. Nicotine, a major component of smoke, induced cell proliferation in multiple cell types in vitro. In the present study, the enhancing effects of nicotine on F344 rat bladder carcinogenesis induced by N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were examined. Nicotine administered in drinking water for 32 weeks following 4 weeks of BBN treatment significantly increased the incidence and number of urothelial carcinomas dose-dependently. Ki67 and pSTAT3 labeling indices and expression of nicotinic acetylcholine receptor alpha 7 (nAChRα7) in non-tumor bladder urothelial lesions were significantly increased by nicotine, but the TUNEL assay for apoptosis showed no increase. In a 4 week study, inhibitors of nicotinic acetylcholine receptor decreased nicotine-induced urothelial simple hyperplasia and Ki67 labeling index in the bladder and kidney pelvis at a single cytotoxic dose of nicotine (40 ppm). Urothelial cytotoxicity with regenerative proliferation was observed by light and scanning electron microscopy. In vitro, nicotine was not cytotoxic to rat or human immortalized urothelial cells (do not express nicotine receptors) below millimolar concentrations, nor in human RT4, T24 or UMUC3 urothelial carcinoma cells (express nicotine receptors). However, nicotine slightly, but statistically significantly, increased cell proliferation at micromolar concentrations in human urothelial carcinoma cells. These data suggest that nicotine enhances urinary bladder carcinogenesis by inducing cytotoxicity with regenerative proliferation. The possible role of direct mitogenesis, involving nAChR and STAT3 signaling and of nicotine receptors requires further investigation at non-cytotoxic doses of nicotine.

Protective role of nebivolol in cadmium-induced hepatotoxicity via downregulation of oxidative stress, apoptosis and inflammatory pathways

Cadmium (Cd) intoxication in human occurs through inhalation of cigarette smoke and ingestion of contaminated water and food. We investigated the role of nebivolol (NEB) in Cd induced hepatotoxicity. In our study; NEB was given as (10 mg/kg/d) orally to rats for 6 weeks, in the presence or absence of hepatotoxicity induced by oral administration of Cd (7 mg/kg/d) for 6 weeks. Levels of serum liver enzyme biomarkers; alanine transaminase (ALT), aspartate transaminase (AST) and serum total antioxidant capacity (TAC) were measured. In addition; mean arterial pressure and total cholesterol levels were measured. Hepatic superoxide dismutase (SOD) and malondialdehyde (MDA) were detected. Hepatic histopathological features, inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) immunoexpressions were evaluated. Tumor necrosis factor alpha (TNF-α) and B-cell lymphoma-2 (Bcl-2) mRNA gene expressions were detected using real time-PCR (rt-PCR). Our results showed marked increase in all measured parameters except SOD, TAC, eNOS immunoexpression and Bcl2 mRNA gene expression which decreased in Cd induced hepatotoxicity group. NEB showed marvelous protective effect against Cd induced changes. NEB decreased liver enzymes (ALT and AST), mean arterial pressure, total cholesterol levels, MDA, iNOS immunoexpression and TNF-α gene expression but significantly increased SOD, TAC, eNOS immunoexpression and Bcl-2 gene expression. Moreover; NEB markedly improved the histopathological changes induced by Cd. These findings prove the antioxidant, anti-apoptotic and anti-inflammatory properties of NEB and its protective role in Cd induced hepatotoxicity.

Reflex bronchoconstriction evoked by inhaled nicotine aerosol in guinea pigs: role of the nicotinic acetylcholine receptor.

Inhaled cigarette smoke stimulated vagal bronchopulmonary C fibers via an action of nicotine on neuronal nicotinic acetylcholine receptor (nAChR). Recent studies have reported that nicotine at high concentrations can also activate the transient receptor potential ankyrin 1 receptor (TRPA1) expressed in these sensory nerves. This study was performed to characterize the airway response to inhaled nicotine aerosol and to investigate the relative roles of nAChR and TRPA1 in this response. Guinea pigs were anesthetized and mechanically ventilated; one tidal volume of nicotine aerosol (2% solution) was diluted by an equal volume of air and delivered directly into the lung via a tracheal cannula in a single breath. Our results showed the following: 1) Inhalation of nicotine aerosol triggered an immediate and pronounced bronchoconstriction; the increase in total pulmonary resistance reached a peak of 588 ± 205% (mean ± SE) in 10-40 s, which gradually returned to baseline after 1-5 min. 2) Pretreatment with either atropine (iv) or mecamylamine (aerosol) almost completely abolished the nicotine-induced bronchoconstriction; the mecamylamine pretreatment did not block the bronchoconstriction and bradycardia evoked by electrical stimulation of the distal end of one sectioned vagus nerve, indicating its minimal systemic effects. 3) Pretreatment with HC-030031, a selective TRPA1 antagonist, abolished the bronchoconstriction induced by allyl isothiocyanate, a selective TRPA1 agonist, but did not attenuate the nicotine-evoked bronchoconstriction. In conclusion, inhalation of a single breath of nicotine aerosol evoked acute bronchoconstriction mediated through the cholinergic reflex pathway. This reflex response was triggered by activation of nAChR, but not TRPA1, located in airway sensory nerves. NEW & NOTEWORTHY Recent reports revealed that nicotine at high concentration activated transient receptor potential ankyrin 1 receptor (TRPA1) expressed in vagal bronchopulmonary sensory nerves. This study showed that inhalation of a single breath of nicotine aerosol consistently evoked acute bronchoconstriction that was mediated through the cholinergic reflex pathway and triggered by activation of nicotinic acetylcholine receptor, but not TRPA1, located in these nerves. This is new and important information considering the recent rapid and alarming rise in the prevalence of e-cigarette use for nicotine inhalation.

Household smoking and breastfeeding duration among Hong Kong Chinese women: a prospective cohort study

BackgroundMaternal smoking or the inhalation of ambient cigarette smoke remains an important public health problem that affects child health with potential lifelong consequences. Hong Kong is one of the most densely populated cities in the world, and living with extended family members is common. Many pregnant women are exposed to secondhand smoke from household and family members. Thus, the aim of this study was to examine the effect of maternal, paternal, and other household smokers on the duration of breastfeeding in Hong Kong. MethodsThis analysis was based on a prospective cohort study. From Oct 11, 2011, to May 31, 2012, mother–infant pairs were recruited during the postnatal hospital admission from four geographically distributed public hospitals in Hong Kong. Participants were Cantonese-speaking Hong Kong residents who gave birth to a full-term, singleton infant, who intended to breastfeed, and had no serious medical or obstetric complications. Exclusion criteria were admission to the special care nursery for more than 48 h after birth or admission to the neonatal intensive care unit. Data were collected directly from participants during postnatal hospitalisation and after discharge through telephone follow-up. In-hospital data collection included basic demographic details, maternal and infant data, and in-hospital feeding data. Follow-up data included infant feeding status at 1, 2, 3, 6, 9, and 12 months post partum or until breastfeeding was stopped. Participants were asked whether they smoked during pregnancy, whether their partner or husband smoked, and whether any other family members living in the same household smoked. Smoking was then categorised as total number of smokers living in the same household (zero, one, or two or more). The primary outcome was the duration of any and exclusive breastfeeding up to 12 months post partum. The study was approved by the Institutional Review Board of the University of Hong Kong/Hospital Authority Hong Kong West Cluster and from all study hospitals. Informed written consent was obtained from each participant. FindingsWe recruited a total of 1277 mother–infant pairs admitted to the obstetric units of four public hospitals in Hong Kong and followed them up by telephone up to 12 months post partum. After further exclusion of 37 (3%) participants with no further contact after hospitalisation, 1240 mother–infant pairs were successfully followed up. Of the mothers, 806 (65%) reported no smokers in the household, 337 (27%) reported one smoker in the household, and 95 (8%) reported two or more smokers in the household. We noted a pattern of increasing number of smokers living in the household associated with progressively shorter duration of any and exclusive breastfeeding. However, the effect of number of smokers living in the household on the overall duration of exclusive breastfeeding was not statistically significant. A Kaplan-Meier survival curve showed that the number of smokers living in the household was associated with progressively shorter duration of any breastfeeding. When compared with mothers who reported no smokers in the family, those exposed to two or more family members that smoked were almost 40% more likely to stop any breastfeeding (adjusted hazard ratio 1·37, 95% CI 1·06–1·76) within 12 months. InterpretationWe found that mothers exposed to a greater number of smokers in the household had a significantly higher risk of breastfeeding cessation. Practitioners can assess the smoking patterns of pregnant women and their family members and provide smoking cessation education and support to this high-risk group. Future research is needed to identify the physiological factors associated with smoking on breastfeeding practices. FundingHealth and Medical Research Fund; Food and Health Bureau of the Hong Kong Government.

Effects of Omega-3 Polyunsaturated Fatty Acids to The Serum Level of Interleukin-8, Percentage of Forced Expiratory Volume in 1 Second (%FEV1), and COPD Assesment Test Scores in Stable COPD Patients

Backgorund: Cigarette smoke inhalation and the other exposure can cause of airway inflammatory and it was the most cause of chronic obstruction pulmonary desease (COPD) pathogenesis. The airway inflammatory will release cytokines proinflammation, one of them was interleukin (IL)-8. Omega-3 polyunsaturated fatty acids (PUFA) have anti-inflammatory effect and its can decrease cytokines production in COPD pathogenesis. &#x0D; Methods: This study aimed to analyze effects of omega 3 PUFAs on serum IL-8, %FEV1, and CAT score in stable COPD patients. Clinical trials of experimental with pretest and posttest designs were conducted of 32 stable COPD patients came to clinic in Dr. Moewardi Hospital Surakarta from December 2016 until February 2017. Samples were taken by consecutive sampling. Subjects were divided into two groups include the treatment group (n=16) received standard COPD therapy omega 3 PUFA 600mg/day and the control group (n=16) received only standard COPD therapy for 28 days.&#x0D; Results: There were significant difference (P=0.0001) towards decreased of serum IL-8 between treatment group (-3.56+5.32pg/ml) and control group (8.90+9.98pg/ml), increase difference were no significantly of %VEP1 value (P=0.473) between treatment group (7.02+7.17pg/ml) and control group (5.32+5.97pg/ml), decrease difference of CAT scores significantly (P=0.0001) between treatment group (-16.13+3.03pg/ml) and control group (-4.75+4.17pg/ml).&#x0D; Conclusions: Omega-3 PUFA may decrease airway inflammation with decrease serum IL-8 level significantly, increase of %FEV1 no significantly and improve the clinical symptoms of stable COPD by decreased CAT scores significantly in stable COPD patients. (J Respir Indo. 2017; 37(4): 265-77)

Cigarette smoke induces rat testicular injury via mitochondrial apoptotic pathway.

An understanding of the causative mechanisms of the harmful effects of cigarette smoke on the male reproductive system remains incomplete. Here, we investigated three different inhaled cigarette smoke doses over five different exposure durations to identify how the testis is affected. The effects of cigarette smoke exposure on testicular germ cells were characterized by morphological changes and a significant elevation in the number of apoptotic cells. Caspase 3 activation increased dramatically after cigarette smoke exposure, accompanied by significant time-dependent expression of the pro-apoptotic proteins Bak (B cell lymphoma/leukemia 2 [Bcl-2] homologous antagonist killer), Bcl2l11 (a BH3 domain-only protein related to Bcl-2), Apaf1 (Apoptotic protease-activating factor-1), and Caspase 9. Conversely, the abundance of anti-apoptotic Bcl2l2 decreased. Taken together, our findings suggest that extensive inhalation of cigarette smoke damages testicular germ cells through the induction of the mitochondrial apoptotic pathway through the Bcl-2 protein family.

Evaluation of a naLastnameetric hydroxiapatite covered implant surface. In vivo study in rats submitted to cigarette smoke inhalation

Evaluation of a naLastnameetric hydroxiapatite covered implant surface. In vivo study in rats submitted to cigarette smoke inhalation

Airway Epithelial Barrier Dysfunction in Chronic Obstructive Pulmonary Disease: Role of Cigarette Smoke Exposure.

The epithelial lining of the airway forms the first barrier against environmental insults, such as inhaled cigarette smoke, which is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). The barrier is formed by airway epithelial junctions, which are interconnected structures that restrict permeability to inhaled pathogens and environmental stressors. Destruction of the epithelial barrier not only exposes subepithelial layers to hazardous agents in the inspired air, but also alters the normal function of epithelial cells, which may eventually contribute to the development of COPD. Of note, disruption of epithelial junctions may lead to modulation of signaling pathways involved in differentiation, repair, and proinflammatory responses. Epithelial barrier dysfunction may be particularly relevant in COPD, where repeated injury by cigarette smoke exposure, pathogens, inflammatory mediators, and impaired epithelial regeneration may compromise the barrier function. In the current review, we discuss recent advances in understanding the mechanisms of barrier dysfunction in COPD, as well as the molecular mechanisms that underlie the impaired repair response of the injured epithelium in COPD and its inability to redifferentiate into a functionally intact epithelium.

Impact of resveratrol on bone repair in rats exposed to cigarette smoke inhalation: histomorphometric and bone-related gene expression analysis

This study investigated the effect of resveratrol on bone healing and its influence on the gene expression of bone-related markers in rats exposed to cigarette smoke. Two calvarial defects were created in each of 60 rats, which were assigned equally (n=20) to three groups: (1) resveratrol (10mg/kg)+smoke exposure (SMK+RESV); (2) placebo+smoke exposure (SMK+PLA); or (3) placebo+no smoke exposure (NS+PLA). Substances were administered daily for 30days following surgery. Smoke inhalation was started 7days before surgery and continued for 30days after surgery. One defect was processed for histomorphometric analysis and the other was used for mRNA quantification of bone-related gene expression by qPCR. The remaining defect was smaller in the SMK+RESV (2.27±0.61mm, P=0.0003) and NS+PLA (2.17±0.74mm, P=0.0005) groups than in the SMK+PLA group (3.12±0.47mm). Higher levels of Runx2 were observed in the NS+PLA group than in the smoke exposure groups (vs. SMK+PLA, P=0002; vs. SMK+RESV, P=0.052); levels of Lrp-5 were also higher in the no smoke exposure group (vs. SMK+RESV, P=0.009; vs. SMK+PLA, P=0.003). Resveratrol therapy decreased RANKL/OPG expression when compared to placebo (SMK+RESV vs. SMK+PLA, P=0.017). Dkk1 levels were decreased in the SMK+RESV group when compared to the SMK+PLA (P=0.006) and NS+PLA groups (P=0.005). In conclusion, resveratrol optimizes the repair of critical-sized bone defects, up-regulating the gene expression of important bone remodelling markers in rats exposed to cigarette smoke inhalation.

Polysaccharide from Ephedra sinica Stapf inhibits inflammation expression by regulating Factor-β1/Smad2 signaling

Mahuang, a famous traditional Chinese medicine, is widely used for the treatment of common cold and inflammatory diseases in China. We investigated the protective effects of polysaccharide from Ephedra sinica Stapf (ESP-B4) against airway and pulmonary inflammation. Animal model was made in SD rats via intratracheal instillation of Lipopolysaccharides (LPS) on day1 and 14 and inhalation of Cigarette Smoke (CS) for 4 weeks. ESP-B4 was administered by oral gavage for 2 weeks. We studied the number of inflammatory cells in serum, production of TNF-α, IL-6, IL-8 and MMP-9 in lung homogenization buffer, and the expression of TGF-β1, P-Smad2 and P-Smad3 in lung tissue. In vitro, model was made in A549 cells with LPS and cigarette smoke extract. We investigated the levels of TNF-α, IL-6 and IL-8, and the expression of TGF-β1, P-Smad2, P-Smad3 and Smad7. Our results revealed that ESP-B4 lowered the recruitment of inflammatory cells; and decreased the production of TNF-α, IL-6, IL-8 and MMP-9, significantly reduced the expression of TGF-β1, P-Smad2 and P-Smad3, increased the expression of Smad7. These results indicated that ESP-B4 reduced airway and pulmonary inflammation by regulating inflammatory cytokines and the TGF-β1/Smad2 pathway, thus providing a potential treatment for chronic obstructive pulmonary diseases (COPD).