Marabini Laura, Calò Rossella, Braga Pier Carlo
Department of Pharmacology, Chemotherapy and Medical Toxicology, School of Medicine, University of Milan, Milan, Italy.
Arzneimittelforschung. 2011;61(12):700-6. doi: 10.1055/s-0031-1300590.
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).
已表明黏液溶解剂厄多司坦（N - 羧甲基硫代乙酰 - 高半胱氨酸硫内酯，CAS 84611 - 23 - 4）具有抗炎和抗氧化特性，并且已发现含有具有药理活性巯基的活性代谢物I（MET I）具有自由基清除活性。本研究的目的是评估厄多司坦代谢物I保护A549人肺腺癌细胞免受过氧化氢（H2O2）介导的氧化应激和氧化性DNA损伤的能力。当A549细胞用活性代谢物I（2.5 - 5 - 10微克/毫升）预处理10 - 30分钟，然后在37℃、5%二氧化碳条件下再暴露于H2O2（1 - 4毫摩尔）两小时时，由二氯荧光素（DCF）荧光反映的细胞内过氧化物生成以浓度依赖方式降低。此外，使用彗星试验作为氧化性DNA损伤的指标，发现代谢物I可防止短期H2O2处理对细胞造成的损伤。数据表明该化合物可有效预防A549细胞中H2O2诱导的氧化应激和DNA损伤。潜在机制涉及细胞内活性氧（ROS）的清除。
