Effects of Provinol and Its Combinations with Clinically Used Antiasthmatics on Airway Defense Mechanisms in Experimental Allergic Asthma

Kazimierová, Ivana; Jošková, Marta; Pecháňová, Oľga; Šutovská, Martina; Fraňová, Soňa

doi:10.1007/5584_2014_75

Cited by 5 publications

(3 citation statements)

References 21 publications

(20 reference statements)

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“…Exposure to vaporised e-cigarette vapour had no effects on NHBE cell viability, determined by LDH assays (see online supplementary figure S3A). Ciliary beating serves as one of the main defence functions of the airways 24. Cells exposed to nicotine-containing e-cigarette vapours had significantly reduced CBF 8 hours after exposure (5.2±0.5 Hz vs 2.6±1 Hz; p=0.01; p<0.05; figure 6B).…”

Section: Resultsmentioning

confidence: 99%

Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner

García-Arcos

Geraghty

Baumlin

et al. 2016

Thorax

261

263

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BackgroundThe use of electronic (e)-cigarettes is increasing rapidly, but their lung health effects are not established. Clinical studies examining the potential long-term impact of e-cigarette use on lung health will take decades. To address this gap in knowledge, this study investigated the effects of exposure to aerosolised nicotine-free and nicotine-containing e-cigarette fluid on mouse lungs and normal human airway epithelial cells.MethodsMice were exposed to aerosolised phosphate-buffered saline, nicotine-free or nicotine-containing e-cigarette solution, 1-hour daily for 4 months. Normal human bronchial epithelial (NHBE) cells cultured at an air-liquid interface were exposed to e-cigarette vapours or nicotine solutions using a Vitrocell smoke exposure robot.ResultsInhalation of nicotine-containing e-cigarettes increased airway hyper-reactivity, distal airspace enlargement, mucin production, cytokine and protease expression. Exposure to nicotine-free e-cigarettes did not affect these lung parameters. NHBE cells exposed to nicotine-containing e-cigarette vapour showed impaired ciliary beat frequency, airway surface liquid volume, cystic fibrosis transmembrane regulator and ATP-stimulated K+ ion conductance and decreased expression of FOXJ1 and KCNMA1. Exposure of NHBE cells to nicotine for 5 days increased interleukin (IL)-6 and IL-8 secretion.ConclusionsExposure to inhaled nicotine-containing e-cigarette fluids triggered effects normally associated with the development of COPD including cytokine expression, airway hyper-reactivity and lung tissue destruction. These effects were nicotine-dependent both in the mouse lung and in human airway cells, suggesting that inhaled nicotine contributes to airway and lung disease in addition to its addictive properties. Thus, these findings highlight the potential dangers of nicotine inhalation during e-cigarette use.

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Section: Resultsmentioning

confidence: 99%

Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner

García-Arcos

Geraghty

Baumlin

et al. 2016

Thorax

261

263

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“…Similarly to sperm cilia, tracheal ciliary epithelium is controlled by intracellular cAMP levels. In a recent animal study was confirmed that the ciliary beat frequency in tracheal epithelial cells is significantly higher, when ovalbumin-sensitized guinea pigs were treated with systemic theophylline at the dose of 10 mg/kg/day (Kazimierováet al, 2015). This suggests direct involvement of PDE inhibition in ameliorating the impaired defense mechanisms caused by sensitization and challenging the animals with ovalbumin, used to mimic the asthma-like conditions (airway hyperresponsiveness associated with eosinophilic inflammation).…”

Section: Non-selective Pde Inhibitorsmentioning

confidence: 87%

Respiratory Cilia as a Therapeutic Target of Phosphodiesterase Inhibitors

2020

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Mucociliary clearance is an essential airway defense mechanism dependent predominantly on the proper ciliary function and mucus rheology. The crucial role of cilia is evident in`a variety of respiratory diseases, as the ciliary dysfunction is associated with a progressive decline in lung function over time. The activity of cilia is under supervision of multiple physiological regulators, including second messengers. Their role is to enable a movement in coordinated metachronal waves at certain beat frequency. Ciliary function can be modulated by various stimuli, including agents from the group of beta 2 agonists, cholinergic drugs, and adenosine triphosphate (ATP). They trigger cilia to move faster in response to elevated cytoplasmic Ca 2+ originated from intracellular sources or replenished from extracellular space. Well-known cilia-stimulatory effect of Ca 2+ ions can be abolished or even reversed by modulating the phosphodiesterase (PDE)-mediated breakdown of cyclic adenosine monophosphate (cAMP) since the overall change in ciliary beating has been dependent on the balance between Ca 2+ ions and cAMP. Moreover, in chronic respiratory diseases, high ATP levels may contribute to cAMP hydrolysis and thus to a decrease in the ciliary beat frequency (CBF). The role of PDE inhibitors in airway cilia-driven transport may help in prevention of progressive loss of pulmonary function often observed despite current therapy. Furthermore, administration of selective PDE inhibitors by inhalation lowers the risk of their systemic effects. Based on this review we may conclude that selective (PDE1, PDE4) or dual PDE inhibitors (PDE3/4) increase the intracellular level of cyclic nucleotides in airway epithelial cells and thus may be an important target in the development of new inhaled mucokinetic agents. Further research is required to provide evidence of their effectiveness and feasibility regarding their cilia-modulating properties.

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“…As per Pennoc, sRaw is a parameter calculated from the phase shift between nasal and thoracic respiratory flows, using the HSE respiratory software PULMODYN PENNOCK. Changes in the thoracic and nasal airflow were provoked according to a method described by Kazimierová et al (Kazimierová et al, 2015). Briefly, the animals were exposed for thirty seconds to histamine aerosol at concentration 10 -6 mol/L.…”

Section: The Evaluation Of Airway Smooth Muscle Reactivity In Vivomentioning

confidence: 99%

Effect of inhaled and oral n-acetylcysteine on airway defense mechanism

Pappová

Kazimierová

Kočmálová

2017

European Pharmaceutical Journal

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Aim:N-acetylcysteine is the prototype of mucolytic agents. The aim of this study was to evaluate the acute and chronic effect of inhaled and oral N-acetylcysteine on airway reactivity, cough reflex and ciliary beat frequency and parameters of mentioned defense mechanisms were assessed in physiological conditions.Methods:An experiment was performed using healthy guinea pigs treated with inhaled (0.6 M; 5min) and oral N-acetylcysteine (20 mg/kg), administrated either acutely as a single dose or chronically during 7 days. The cough reflex and specific airway resistance were assessed byin vivomethod, using a double chamber plethysmograph box. The ciliary beat frequency was evaluated inin vitroconditions on tracheal brushed samples using light microscope coupled to high speed video camera.Results:Inhaled and oral N-acetylcysteine, either administrated as a single dose or during 7 days, have shown a tendency to decrease sensitivity of the cough reflex and increase the airway reactivity. Acute administration of inhaled and oral N-acetylcysteine had no statistically relevant effect on the ciliary beat frequency, whereas chronic administration of both inhaled and oral N-acetylcysteine led to a marked reduction in the ciliary beat frequency.Conclusion: Chronic administration of oral and inhaled N-acetylcysteine had a negative impact on the ciliary beat frequency, which represents one of the key factors determining the rate of mucociliary clearance. Thus, administration of N-acetylcysteine is less likely to increase the expulsion of mucus by ciliary movement. In addition, the observed tendency of inhaled and oral N-acetylcysteine to increase the airway reactivity may limit its use in conditions with severe airflow obstruction.

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Effects of Provinol and Its Combinations with Clinically Used Antiasthmatics on Airway Defense Mechanisms in Experimental Allergic Asthma

Cited by 5 publications

References 21 publications

Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner

Chronic electronic cigarette exposure in mice induces features of COPD in a nicotine-dependent manner

Respiratory Cilia as a Therapeutic Target of Phosphodiesterase Inhibitors

Effect of inhaled and oral n-acetylcysteine on airway defense mechanism

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