Cao Zhuoxiao, Li Yunbo
Department of Pharmaceutical Sciences, St. John's University College of Pharmacy and Allied Health Professions, 8000 Utopia Parkway, Jamaica, NY 11439, USA.
Eur J Pharmacol. 2004 Apr 5;489(1-2):39-48. doi: 10.1016/j.ejphar.2004.02.031.
Resveratrol is known to be protective against oxidative cardiovascular disorders. However, the underlying mechanisms remain unclear. This study was undertaken to determine if resveratrol could increase endogenous antioxidants and phase 2 enzymes in cardiomyocytes, and if such increased cellular defenses could provide protection against oxidative and electrophilic cell injury. Incubation of cardiac H9C2 cells with low micromolar resveratrol resulted in a significant induction of a scope of cellular antioxidants and phase 2 enzymes in a concentration- and/or time-dependent fashion. To investigate the protective effects of the resveratrol-induced cellular defenses on oxidative and electrophilic cell injury, H9C2 cells were first incubated with resveratrol, and then exposed to xanthine oxidase (XO)/xanthine, 4-hydroxy-2-nonenal or doxorubicin. We observed that resveratrol pretreatment afforded a marked protection against the above agent-mediated cytotoxicity in H9C2 cells. Moreover, the resveratrol pretreatment led to a great reduction in XO/xanthine-induced intracellular accumulation of ROS. Taken together, this study demonstrates that resveratrol induces antioxidants and phase 2 enzymes in cardiomyocytes, which is accompanied by increased resistance to oxidative and electrophilic cell injury.
众所周知，白藜芦醇对氧化型心血管疾病具有保护作用。然而，其潜在机制仍不清楚。本研究旨在确定白藜芦醇是否能增加心肌细胞内源性抗氧化剂和Ⅱ相酶，以及这种增强的细胞防御是否能提供针对氧化性和亲电性细胞损伤的保护作用。用低微摩尔浓度的白藜芦醇孵育心脏H9C2细胞，导致一系列细胞抗氧化剂和Ⅱ相酶以浓度和/或时间依赖性方式显著诱导。为了研究白藜芦醇诱导的细胞防御对氧化性和亲电性细胞损伤的保护作用，首先用白藜芦醇孵育H9C2细胞，然后将其暴露于黄嘌呤氧化酶（XO）/黄嘌呤、4-羟基-2-壬烯醛或阿霉素中。我们观察到，白藜芦醇预处理对上述试剂介导的H9C2细胞毒性提供了显著的保护作用。此外，白藜芦醇预处理导致XO/黄嘌呤诱导的细胞内活性氧积累大幅减少。综上所述，本研究表明白藜芦醇可诱导心肌细胞中的抗氧化剂和Ⅱ相酶，同时增强对氧化性和亲电性细胞损伤的抵抗力。
