Institute for Nutritional Science, Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
J Neurochem. 2007 Dec;103(6):2690-700. doi: 10.1111/j.1471-4159.2007.04954.x.
Hydroxytyrosol (HTS) is a natural polyphenol abundant in olive oil. Increasing evidence indicates HTS has beneficial effect on human health for preventing various diseases. In the present study, we investigated the protective effects of HTS on acrolein-induced toxicity in human retinal pigment epithelial cell line, ARPE-19, a cellular model of smoking- and age-related macular degeneration. Acrolein, a major component of the gas phase cigarette smoke and also a product of lipid peroxidation in vivo, at 75 μmol/L for 24 h caused significant loss of cell viability, oxidative damage (increase in oxidant generation and oxidative damage to proteins and DNA, decrease in antioxidants and antioxidant enzymes, and also inactivation of the Keap1/Nrf2 pathway), and mitochondrial dysfunction (decrease in membrane potential, activities of mitochondrial complexes, viable mitochondria, oxygen consumption, and factors for mitochondrial biogenesis, and increase in calcium). Pre-treatment with HTS dose dependently and also time dependently protected the ARPE-19 cells from acrolein-induced oxidative damage and mitochondrial dysfunction. A short-term pre-treatment with HTS (48 h) required > 75 μmol/L for showing protection while a long-term pre-treatment (7 days) showed protective effect from 5 μmol/L on. The protective effect of HTS in this model was as potent as that of established mitochondria-targeting antioxidant nutrients. These results suggest that HTS is also a mitochondrial-targeting antioxidant nutrient and that dietary administration of HTS may be an effective measure in reducing and or preventing cigarette smoke-induced or age-related retinal pigment epithelial degeneration, such as age-associated macular degeneration.
羟基酪醇 (HTS) 是橄榄油中丰富的天然多酚。越来越多的证据表明，HTS 对预防各种疾病具有有益的人体健康作用。在本研究中，我们研究了 HTS 对丙烯醛诱导的人视网膜色素上皮细胞系 ARPE-19 毒性的保护作用，ARPE-19 是吸烟和年龄相关性黄斑变性的细胞模型。丙烯醛是气相香烟的主要成分，也是体内脂质过氧化的产物，在 75μmol/L 下孵育 24 小时会导致细胞活力显著丧失、氧化损伤（增加氧化剂生成和蛋白质及 DNA 的氧化损伤，降低抗氧化剂和抗氧化酶，以及 Keap1/Nrf2 通路失活）和线粒体功能障碍（膜电位下降，线粒体复合物活性、存活线粒体、耗氧量和线粒体生物发生的因素下降，钙增加）。HTS 剂量依赖性和时间依赖性预处理可防止 ARPE-19 细胞发生丙烯醛诱导的氧化损伤和线粒体功能障碍。HTS 的短期预处理（48 小时）需要 >75μmol/L 才能显示保护作用，而长期预处理（7 天）则从 5μmol/L 开始显示保护作用。在该模型中，HTS 的保护作用与已建立的靶向线粒体抗氧化营养素相当。这些结果表明，HTS 也是一种靶向线粒体的抗氧化营养素，膳食中添加 HTS 可能是减少和/或预防香烟烟雾诱导或年龄相关性视网膜色素上皮变性（如年龄相关性黄斑变性）的有效措施。
