It has been shown that the mucolytic agent erdosteine (N- carboxymethylthioacetyl-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 μg/ml) for 10-30 min and then exposed to H 2O2(1-4 mM) for two additional hours at 37°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 short-term H2O2treatment. 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).
Protective effect of erdosteine metabolite I against hydrogen peroxide-induced oxidative DNA-damage in lung epithelial cells / L. Marabini, R. Calò, P. Braga. - In: ARZNEIMITTEL-FORSCHUNG. - ISSN 0004-4172. - 61:12(2011 Dec), pp. 700-706.
Protective effect of erdosteine metabolite I against hydrogen peroxide-induced oxidative DNA-damage in lung epithelial cells
L. MarabiniPrimo
;P. BragaUltimo
2011
Abstract
It has been shown that the mucolytic agent erdosteine (N- carboxymethylthioacetyl-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 μg/ml) for 10-30 min and then exposed to H 2O2(1-4 mM) for two additional hours at 37°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 short-term H2O2treatment. 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).Pubblicazioni consigliate
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