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 µg/ml) for 10–30 min and then exposed to H₂O₂ (1–4 mM) for two additional hours at 37 °C, 5% at CO₂, the intracellular peroxide production, reflected by dichloro-fluorescein (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 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).

Key words

A549 cells - Anti-oxidant activity - DNA damage - Erdosteine metabolite I - Genotoxicity

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