Department of Chemistry, Missouri University of Science & Technology, Rolla, MO, USA.
Free Radic Res. 2020 May;54(5):319-329. doi: 10.1080/10715762.2020.1763332. Epub 2020 May 22.
Tiopronin (MPG) is a thiol antioxidant drug that has been explored as a treatment for various oxidative stress-related disorders. However, many of its antioxidant capabilities remain untested in well-validated cell models. To more thoroughly understand the action of this promising pharmaceutical compound against acute oxidative challenge, A549 human lung carcinoma cells were exposed to -butyl hydroperoxide (BHP) and treated with MPG. Analyses of cell viability, intracellular glutathione (GSH) levels, and the prevalence of reactive oxygen species (ROS) and mitochondrial superoxide were used to examine the effects of MPG on BHP-challenged cells. MPG treatment suppressed intracellular ROS and mitochondrial superoxide and prevented BHP-induced GSH depletion and apoptosis. These results indicate that MPG is effective at preserving redox homeostasis against acute oxidative insult in A549 cells if present at sufficient concentrations during exposure to oxidants such as BHP. The effects of treatment gleaned from this study can inform experimental design for future work on the therapeutic potential of MPG.
硫普罗宁(MPG)是一种巯基抗氧化药物,已被探索用于治疗各种与氧化应激相关的疾病。然而,其许多抗氧化能力在经过充分验证的细胞模型中仍未得到测试。为了更全面地了解这种有前途的药物化合物对急性氧化应激的作用,用 - 丁基过氧化物(BHP)处理 A549 人肺癌细胞并同时用 MPG 处理。通过分析细胞活力、细胞内谷胱甘肽(GSH)水平以及活性氧(ROS)和线粒体超氧化物的发生情况,来检测 MPG 对 BHP 挑战细胞的影响。MPG 处理可抑制细胞内 ROS 和线粒体超氧化物的产生,并防止 BHP 诱导的 GSH 耗竭和细胞凋亡。这些结果表明,如果在暴露于 BHP 等氧化剂期间存在足够浓度的 MPG,它可有效维持 A549 细胞的氧化还原平衡,对抗急性氧化损伤。本研究中得出的治疗效果可为 MPG 的治疗潜力的未来研究提供实验设计依据。