Koren Erez, Zverev Igor, Ginsburg Isaac, Kohen Ron
Department of Pharmaceutics, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
Biomed Pharmacother. 2008 Mar;62(3):179-88. doi: 10.1016/j.biopha.2007.12.012. Epub 2008 Jan 14.
Low molecular weight antioxidants (LMWA) supplements are a popular and routine approach to assist the cell and the whole organism to cope with increasing oxidative stress. Numerous experiments have been conducted in which exogenous antioxidants were supplemented to cells, animals and humans to prevent and delay pathological disorders associated with reactive oxygen species. Recently, many meta-analysis publications have demonstrated the failure of this approach and in some cases even showed an increase in the severity of the disease and all-cause mortality. The reasons for the lack of success are not fully understood and the concept of antioxidant therapy is questionable. We suggest a new explanation concerning the way antioxidants function in the living cells that can elucidate some of the conflicting data published. The aim of this study was to examine the hypothesis that the overall antioxidant capacities of cells in culture remains constant and since the cells tightly regulate this antioxidant network, supplementation with exogenous antioxidants cannot enhance the total antioxidant capacity of the cells. This assumption was examined in HaCaT, Hep3B, PC3 and Caco-2 cells using several types of antioxidant supplements. It has been shown that while the levels of the specific administrated antioxidant increased significantly intracellularly, the overall antioxidant capacity of the cells as evaluated by various methods did not increase, and in some cases, even decreased. These results support the hypothesis and demonstrate that the total antioxidant capacity of these cells in culture is kept under tight regulation and cannot be enhanced by exogenous LMWA.
低分子量抗氧化剂（LMWA）补充剂是一种常用的常规方法，用于帮助细胞和整个生物体应对不断增加的氧化应激。已经进行了大量实验，在细胞、动物和人类中补充外源性抗氧化剂，以预防和延缓与活性氧相关的病理紊乱。最近，许多荟萃分析出版物表明这种方法并不成功，在某些情况下甚至显示疾病严重程度和全因死亡率有所增加。缺乏成功的原因尚未完全了解，抗氧化剂疗法的概念也值得怀疑。我们提出了一种关于抗氧化剂在活细胞中发挥作用方式的新解释，这可以阐明一些已发表的相互矛盾的数据。本研究的目的是检验以下假设：培养细胞的总体抗氧化能力保持恒定，并且由于细胞严格调节这个抗氧化网络，补充外源性抗氧化剂不能提高细胞的总抗氧化能力。使用几种类型的抗氧化剂补充剂在HaCaT、Hep3B、PC3和Caco-2细胞中检验了这一假设。结果表明，虽然特定给予的抗氧化剂在细胞内的水平显著增加，但通过各种方法评估的细胞总体抗氧化能力并未增加，在某些情况下甚至下降。这些结果支持了这一假设，并表明这些培养细胞的总抗氧化能力受到严格调节，外源性低分子量抗氧化剂不能增强其能力。
