Sino-German Laboratory for Molecular Medicine, Key Laboratory for Clinical Cardiovascular Genetics of Ministry of Education, Cardiovascular Institute & Fu Wai Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China.
Chin Med J (Engl). 2009 Nov 5;122(21):2652-6.
The use of doxorubicin (DOX) is limited by its dose-dependent cardiotoxicity. Reactive oxygen species (ROSs) play an important role in the pathological process of DOX-induced cardiotoxicity. The aim of this study was to evaluate the protective effect of chrysoeriol, a flavone compound, against DOX-induced apoptosis and death in H9c2 cells and to find out its preliminary mechanism.
We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, Hoechst33258 staining and measurement of lactate dehydrogenase (LDH) release to evaluate the protective effect of chrysoeriol against DOX-induced apoptosis and death in H9c2 cells. To find out the mechanism of this protective effect, we observed the immunofluorescence of intracellular ROS and measured the activities of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Furthermore, we evaluated the effect of chrysoeriol on the antitumor activity of DOX in HeLa cells with MTT assay.
The results of MTT assay, Hoechst 33258 staining and measurement of LDH release showed that chrysoeriol significantly reduced doxorubicin-induced apoptosis and cell death. Chrysoeriol at a dose of 20 microg/ml notably reduced intracellular ROS, decreased the concentration of MDA in the supernatant of DOX-treated H9c2 cells and increased SOD and GPx activities to their normal levels. Further study showed that the addition of chrysoeriol did not affect the antitumor activity of DOX.
Chrysoeriol could potentially serve as a novel cardioprotective agent against DOX-induced cardiotoxicity without affecting the antitumor activity of DOX.
多柔比星（DOX）的使用受到其剂量依赖性心脏毒性的限制。活性氧（ROS）在 DOX 诱导的心脏毒性的病理过程中发挥重要作用。本研究旨在评估白杨素（一种黄酮类化合物）对 H9c2 细胞中 DOX 诱导的细胞凋亡和死亡的保护作用，并找出其初步机制。
我们使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H-四唑溴盐（MTT）测定法、Hoechst33258 染色和乳酸脱氢酶（LDH）释放测定法来评估白杨素对 H9c2 细胞中 DOX 诱导的细胞凋亡和死亡的保护作用。为了找出这种保护作用的机制，我们观察了细胞内 ROS 的免疫荧光，并测定了丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）的活性。此外，我们通过 MTT 测定法评估了白杨素对 HeLa 细胞中 DOX 抗肿瘤活性的影响。
MTT 测定法、Hoechst33258 染色和 LDH 释放测量结果表明，白杨素显著减少了 DOX 诱导的细胞凋亡和死亡。白杨素在 20μg/ml 的剂量下明显减少了细胞内 ROS，降低了 DOX 处理的 H9c2 细胞上清液中 MDA 的浓度，并增加了 SOD 和 GPx 的活性使其恢复正常水平。进一步的研究表明，添加白杨素并不影响 DOX 的抗肿瘤活性。
白杨素可能作为一种新型的 DOX 诱导心脏毒性的心脏保护剂，而不影响 DOX 的抗肿瘤活性。
