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.