Mandziuk Slawomir, Baj Tomasz, Sieniawska Elwira, Dudka Jaroslaw, Gieroba Renata, Iwan Magdalena, Glowniak Kazimierz
Department of Oncological Pneumology and Alergology, Medical University of Lublin , Poland .
Drug Chem Toxicol. 2015 Jan;38(1):1-8. doi: 10.3109/01480545.2014.893443. Epub 2014 Mar 3.
The delayed cardiomyopathy caused by doxorubicin - an chemotherapeutic drug with broad spectrum of anticancer activity - is mainly triggered by oxidative stress. The aim of this study was to assess an effect of Mutellina purpurea methanolic extract fraction and other antioxidants of plant origin: rutin, quercetin and chlorogenic acid (all 1 mg% w/v) on oxidative stress and morphological changes induced by doxorubicin in cardiomyocytes H9c2. Mitochondrial oxidative stress in cardiomyocytes induced by 1 µM doxorubicin was evidenced by MitoTracker and RedoxSensor Red CC-1 dyes. Moreover, cardiomyocytes morphological changes and cell viability were evaluated. The tested fraction slightly reduced mitochondrial ROS fluorescence, similar to quercetin. Chlorogenic acid revealed concentration dependent prooxidative and antioxidative properties in the applied H9c2 model. The evaluation of the protective effect of tested compounds on doxorubicin-induced cytotoxicity was based on the examination of induced oxidative stress and morphology changes. The protective effect was described in the following order: rutin > chlorogenic acid (0.5 µM) > LH8 and quercetin. According to the MTT test, rutin seems to be the most promising compound that should be tested in a future studies.
阿霉素(一种具有广泛抗癌活性的化疗药物)引起的迟发性心肌病主要由氧化应激引发。本研究的目的是评估紫背天葵甲醇提取物组分以及其他植物源抗氧化剂:芦丁、槲皮素和绿原酸(均为1mg% w/v)对阿霉素诱导的H9c2心肌细胞氧化应激和形态变化的影响。用MitoTracker和RedoxSensor Red CC-1染料证实了1µM阿霉素诱导的心肌细胞线粒体氧化应激。此外,还评估了心肌细胞的形态变化和细胞活力。受试组分与槲皮素相似,能轻微降低线粒体ROS荧光。在应用的H9c2模型中,绿原酸表现出浓度依赖性的促氧化和抗氧化特性。基于对诱导的氧化应激和形态变化的检测,评估受试化合物对阿霉素诱导的细胞毒性的保护作用。保护作用按以下顺序排列:芦丁>绿原酸(0.5µM)>LH8和槲皮素。根据MTT试验,芦丁似乎是最有前景的化合物,应在未来研究中进行测试。