Jauslin Matthias L, Vertuani Silvia, Durini Elisa, Buzzoni Lisa, Ciliberti Nunzia, Verdecchia Sara, Palozza Paola, Meier Thomas, Manfredini Stefano
Santhera Pharmaceuticals, Hammerstrasse 47, Liestal 4410, Switzerland.
Mol Cell Biochem. 2007 Aug;302(1-2):79-85. doi: 10.1007/s11010-007-9429-2. Epub 2007 May 3.
Friedreich Ataxia (FRDA), the most frequent inherited ataxia, is not only characterized by progressive gait and limb ataxia, but in most cases is also accompanied by a severe hypertrophic cardiomyopathy. This life threatening symptom can be ameliorated by the administration of idebenone, a short chain quinone antioxidant, supporting additional evidence that oxidative stress plays a major role in the pathogenesis of this disease. In this study we analyze the combinatorial effect of different antioxidants on cell viability of FRDA fibroblasts and of RAT-1 immortalized fibroblasts exposed to oxidative stress. We find that an equimolar mixture of idebenone and vitamin E is more potent than each of the compound alone. Increased potency was also obtained with a novel synthetic antioxidant (Fe-Aox29) combining the active groups from both idebenone and vitamin E. These results indicate, that idebenone and vitamin E might act synergistically to counteract oxidative stress in fibroblasts from FRDA patients.
弗里德赖希共济失调（FRDA）是最常见的遗传性共济失调，不仅表现为进行性步态和肢体共济失调，而且在大多数情况下还伴有严重的肥厚性心肌病。这种危及生命的症状可通过给予艾地苯醌（一种短链醌类抗氧化剂）得到改善，这进一步证明氧化应激在该疾病的发病机制中起主要作用。在本研究中，我们分析了不同抗氧化剂对暴露于氧化应激的FRDA成纤维细胞和RAT-1永生化成纤维细胞活力的联合作用。我们发现，艾地苯醌和维生素E的等摩尔混合物比单独的每种化合物更有效。一种结合了艾地苯醌和维生素E活性基团的新型合成抗氧化剂（Fe-Aox29）也具有增强的效力。这些结果表明，艾地苯醌和维生素E可能协同作用以对抗FRDA患者成纤维细胞中的氧化应激。
