title: Protective effect of erdosteine metabolite I against hydrogen peroxide-induced oxidative DNA-damage in lung epithelial cells.
abstract: It has been shown that the mucolytic agent erdosteine (N-carboxymethylthio-acetyl-homocysteine thiolactone, CAS 84611-23-4) has anti-inflammatory and anti-oxidant properties, and an active metabolite I (MET I) containing pharmacologically active sulphydryl group has been found to have a free radical scavenging activity. The aim of this study was to assess the ability of erdosteine metabolite I to protect A549 human lung adenocarcinoma cell against hydrogen peroxide (H2O2)-mediated oxidative stress and oxidative DNA damage. When A549 cells were pre-treated with the active metabolite I (2.5-5-10 microg/ml) for 10-30 min and then exposed to H2O2 (1-4 mM) for two additional hours at 37 degrees C, 5% at CO2, the intracellular peroxide production, reflected by dichlorofluorescein (DCF) fluorescence, decreased in a concentration-dependent manner. Furthermore, using a comet assay as an indicator for oxidative DNA damage, it was found that the metabolite I prevented damage to cells exposed to shortterm H2O2 treatment. The data suggest that this compound is effective in preventing H2O2-induced oxidative stress and DNA damage in A549 cells. The underlying mechanisms involve the scavenging of intracellular reactive oxygen species (ROS).
authors.affiliation: Department of Pharmacology, Chemotherapy and Medical Toxicology, School of Medicine, University of Milan, Milan, Italy. laura.marabini@unimi.it
authors.forename: Laura
authors.initials: L
authors.lastname: Marabini
authors.forename: Rossella
authors.initials: R
authors.lastname: Calò
authors.forename: Pier Carlo
authors.initials: PC
authors.lastname: Braga
mesh_terms: D000975:Antioxidants; D045744:Cell Line, Tumor; D002470:Cell Survival; D020552:Comet Assay; D004249:DNA Damage / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors* / Q000633:toxicity; D007202:Indicators and Reagents; D008168:Lung / Q000166:cytology* / Q000187:drug effects; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013864:Thioglycolates / Q000378:metabolism / Q000494:pharmacology*; D013876:Thiophenes / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D007202:Indicators and Reagents; D016877:Oxidants; D017382:Reactive Oxygen Species; D013864:Thioglycolates; D013876:Thiophenes; C048498:erdosteine; D006861:Hydrogen Peroxide