Carbocisteine Protects Against Emphysema Induced by Cigarette Smoke Extract in Rats

Hanaoka, Masayuki; Droma, Yunden; Chen, Yan; Agatsuma, Toshihiko; Kitaguchi, Yoshiaki; Voelkel, Norbert F.; Kubo, Keishi

doi:10.1378/chest.10-0920

Cited by 34 publications

(37 citation statements)

References 25 publications

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“…This effect may be linked to the reduced adherence of bacterial pathogens to airway epithelial cells (Rahman and Macnee 2012) and to the downregulation of ICAM-1, a receptor for the major group of rhinovirus (Yasuda et al 2006). Moreover, carbocysteine inhibiting cell apoptosis and promoting the reversal of the imbalance of proteolytic and anti-proteolytic enzyme activities protects against the development of CSEinduced emphysema in rats (Hanaoka et al 2011). To counteract oxidative stress, cells enlist a battery of antioxidant systems, and carbocysteine in a lung "epithelial-like" cell line (WI-26VA4) (Garavaglia et al 2008) induces an increase in the chloride and GSH anionic fluxes, along with an increase in GSH permeability.…”

Section: Discussionmentioning

confidence: 99%

Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

Pace

Ferraro

Vincenzo

et al. 2013

Cell Stress and Chaperones

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Cigarette smoke extracts (CSE) induce oxidative stress, an important feature in chronic obstructive pulmonary disease (COPD), and oxidative stress contributes to the poor clinical efficacy of corticosteroids in COPD patients. Carbocysteine, an antioxidant and mucolytic agent, is effective in reducing the severity and the rate of exacerbations in COPD patients. The effects of carbocysteine on CSE-induced oxidative stress in bronchial epithelial cells as well as the comparison of these antioxidant effects of carbocysteine with those of fluticasone propionate are unknown. The present study was aimed to assess the effects of carbocysteine (10 −4 M) in cell survival and intracellular reactive oxygen species (ROS) production (by flow cytometry) as well as total glutathione (GSH), heme oxygenase-1 (HO-1), nuclearrelated factor 2 (Nrf2) expression and histone deacetylase 2 (HDAC-2) expression/activation in CSE-stimulated bronchial epithelial cells (16-HBE) and to compare these effects with those of fluticasone propionate (10 −8 M). CSE, carbocysteine or fluticasone propionate did not induce cell necrosis (propidium positive cells) or cell apoptosis (annexin Vpositive/propidium-negative cells) in 16-HBE. CSE increased ROS production, nuclear Nrf2 and HO-1 in 16-HBE. Fluticasone propionate did not modify intracellular ROS production, GSH and HDCA-2 but reduced Nrf2 and HO-1 in CSE-stimulated 16-HBE. Carbocysteine reduced ROS production and increased GSH, HO-1, Nrf2 and HDAC-2 nuclear expression/activity in CSE-stimulated cells and was more effective than fluticasone propionate in modulating the CSEmediated effects. In conclusion, the present study provides compelling evidences that the use of carbocysteine may be considered a promising strategy in diseases associated with corticosteroid resistance.

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Section: Discussionmentioning

confidence: 99%

Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

Pace

Ferraro

Vincenzo

et al. 2013

Cell Stress and Chaperones

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“…CSE was prepared as reported previously [29]. Briefly, one cigarette without filters (Marlboro; Philip Morris International Inc; New York City, New York) was burned, and the smoke was passed, using a vacuum pump, through a glass Cambridge filter (Cambridge Filter Japan, Ltd; Tokyo, Japan) with 0.20-μm pores for removing the particles and bacteria into a vessel containing phosphate-buffered saline (PBS) (1 mL per one cigarette).…”

Section: Methodsmentioning

confidence: 99%

Sirt1 expression is associated with CD31 expression in blood cells from patients with chronic obstructive pulmonary disease

et al. 2016

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BackgroundCigarette smoke induced oxidative stress has been shown to reduce silent information regulator 1 (Sirt1) levels in lung tissue from smokers and patients with COPD patients. Sirt1 is known to inhibit endothelial senescence and may play a protective role in vascular cells. Endothelial progenitor cells (EPCs) are mobilized into circulation under various pathophysiological conditions, and are thought to play an important role in tissue repair in chronic obstructive lung disease (COPD). Therefore, Sirt1 and EPC-associated mRNAs were measured in blood samples from patients with COPD and from cultured CD34+ progenitor cells to examine whether these genes are associated with COPD development.MethodsThis study included 358 patients with a smoking history of more than 10 pack-years. RNA was extracted from blood samples and from CD34+ progenitor cells treated with cigarette smoke extract (CSE), followed by assessment of CD31, CD34, Sirt1 mRNA, miR-34a, and miR-126-3p expression by real-time RT-PCR.ResultsThe expression of CD31, CD34, Sirt1 mRNAs, and miR-126-3p decreased and that of miR-34a increased in moderate COPD compared with that in control smokers. However, no significant differences in these genes were observed in blood cells from patients with severe COPD compared with those in control smokers. CSE significantly decreased Sirt1 and increased miR-34a expression in cultured progenitor cells.ConclusionSirt1 expression in blood cells from patients with COPD could be a biomarker for disease stability in patients with moderate COPD. MiR-34a may participate in apoptosis and/or senescence of EPCs in smokers. Decreased expression of CD31, CD34, and miR-126-3p potentially represents decreased numbers of EPCs in blood cell from patients with COPD.

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“…Overexpression of placenta growth factor (PlGF) by titanium dioxide nanoparticles (Chen et al, 2006) or PlGF transgenes (Tsao et al, 2004;Tseng et al, 2004) may contribute to the pathogenesis of pulmonary emphysema. The use of antioxidants protects against CS extract-induced emphysema in rats by reducing chronic inflammation, oxidative stress, apoptosis of lung structural cells, alveolar enlargement, and parenchymal destruction (Hanaoka et al, 2011). Lovastatin can reduce tissue myeloperoxidase content, bronchoalveolar lavage leukocyte accumulation, proinflammatory cytokine release, and NADPH oxidase expression in the ischaemia/reperfusion lung (Naidu et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Dietary Monascus adlay supplements facilitate suppression of cigarette smoke-induced pulmonary endoplasmic reticulum stress, autophagy, apoptosis and emphysema-related PLGF in the rat

Tsai

Chien

2013

Food Chemistry

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Carbocisteine Protects Against Emphysema Induced by Cigarette Smoke Extract in Rats

Cited by 34 publications

References 25 publications

Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells

Sirt1 expression is associated with CD31 expression in blood cells from patients with chronic obstructive pulmonary disease

Dietary Monascus adlay supplements facilitate suppression of cigarette smoke-induced pulmonary endoplasmic reticulum stress, autophagy, apoptosis and emphysema-related PLGF in the rat

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