Shao Zuo-Hui, Vanden Hoek Terry L, Xie Jingtian, Wojcik Kim, Chan Kim Chai, Li Chang-Qing, Hamann Kimm, Qin Yimin, Schumacker Paul T, Becker Lance B, Yuan Chun-Su
Tang Center for Herbal Medicine Research, Emergency Resuscitation Research Center, and Department of Medicine, Pritzker School of Medicine, University of Chicago, Chicago, IL, USA.
Cardiovasc Toxicol. 2003;3(4):331-9. doi: 10.1385/ct:3:4:331.
Grape seed proanthocyanidin extract (GSPE), a polyphenolic compound with antioxidant properties, may protect against cardiac ischemia and reperfusion injury. However, its potential toxicity at higher doses is unknown. The authors tested the effects of GSPE on reactive oxygen species (ROS) generation, cell survival, lactate dehydrogenase (LDH) release, and caspase- 3 activity using chick cardiomyocytes incubated with GSPE at 5, 10, 50, 100, or 500 micrograms/mL in medium for 8 h. Exposure to increasing concentrations of GSPE (100 or 500 micrograms/mL) resulted in an increase in ROS generation and cell death as measured by propidium iodide uptake and LDH release. Caspase-3 activity was significantly increased fourfold in cells exposed to GSPE 500 micrograms/ mL compared to controls; this was abolished by the selective caspase-3 inhibitor Ac-Asp-Gln-Thr-Asp-H (50 microM), which also significantly reduced the cell death resulting from GSPE (500 micrograms/mL). The antioxidant N-acetylcysteine (NAC, 100 microM) reduced cell death induced by GSPE (500 micrograms/mL) but failed to attenuate caspase-3 activation. Collectively, the authors conclude that higher doses of GSPE could cause apoptotic cell injury via effector caspase-3 activation and subsequent induction of ROS generation. Consumers may take higher doses of dietary supplements in the belief that natural herbs have no major side effects. This study demonstrates that dosages of GSPE should be optimized to avoid potential harmful pro-oxidant effects.
葡萄籽原花青素提取物（GSPE）是一种具有抗氧化特性的多酚类化合物，可能对心脏缺血再灌注损伤具有保护作用。然而，其高剂量时的潜在毒性尚不清楚。作者使用在培养基中分别与5、10、50、100或500微克/毫升GSPE孵育8小时的鸡心肌细胞，测试了GSPE对活性氧（ROS）生成、细胞存活、乳酸脱氢酶（LDH）释放和半胱天冬酶-3活性的影响。随着GSPE浓度的增加（100或500微克/毫升），通过碘化丙啶摄取和LDH释放测量，ROS生成增加，细胞死亡增多。与对照组相比，暴露于500微克/毫升GSPE的细胞中半胱天冬酶-3活性显著增加了四倍；选择性半胱天冬酶-3抑制剂Ac-Asp-Gln-Thr-Asp-H（50微摩尔）可消除这种增加，该抑制剂还显著减少了由GSPE（500微克/毫升）导致的细胞死亡。抗氧化剂N-乙酰半胱氨酸（NAC，100微摩尔）减少了GSPE（500微克/毫升）诱导的细胞死亡，但未能减弱半胱天冬酶-3的激活。总体而言，作者得出结论，高剂量的GSPE可通过效应半胱天冬酶-3激活和随后诱导ROS生成导致凋亡性细胞损伤。消费者可能会因认为天然草药没有重大副作用而服用更高剂量的膳食补充剂。本研究表明，应优化GSPE的剂量以避免潜在的有害促氧化作用。
