title: Comparative cytoprotective effects of carbocysteine and fluticasone propionate in cigarette smoke extract-stimulated bronchial epithelial cells.
abstract: 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), nuclear-related 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 V-positive/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 CSE-mediated 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.
authors.affiliation: Institute of Biomedicine and Molecular Immunology, National Research Council-Palermo, Palermo, Italy, pace@ibim.cnr.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pace
authors.forename: Maria
authors.initials: M
authors.lastname: Ferraro
authors.forename: Serena
authors.initials: S
authors.lastname: Di Vincenzo
authors.forename: Chiara
authors.initials: C
authors.lastname: Cipollina
authors.forename: Stefania
authors.initials: S
authors.lastname: Gerbino
authors.forename: Diego
authors.initials: D
authors.lastname: Cigna
authors.forename: Valentina
authors.initials: V
authors.lastname: Caputo
authors.forename: Rossella
authors.initials: R
authors.lastname: Balsamo
authors.forename: Luigi
authors.initials: L
authors.lastname: Lanata
authors.forename: Mark
authors.initials: M
authors.lastname: Gjomarkaj
mesh_terms: D000730:Androstadienes / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002233:Carbocysteine / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D000068298:Fluticasone; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D056464:Histone Deacetylase 2 / Q000378:metabolism; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009336:Necrosis; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014026:Nicotiana / Q000737:chemistry*
chemical_list: D000730:Androstadienes; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D002233:Carbocysteine; D000068298:Fluticasone; D051547:Heme Oxygenase-1; D056464:Histone Deacetylase 2; D005978:Glutathione