Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology, Zurich, CH-8093, Switzerland.
Department of Biological Sciences, Macquarie University, Sydney, 2109, Australia.
Arch Biochem Biophys. 2019 Oct 15;674:108107. doi: 10.1016/j.abb.2019.108107. Epub 2019 Sep 16.
Many theoretical and experimental studies have shown that the principal initial biological targets of free radicals are nucleic acids, lipids and proteins. The reaction normally generates carbon-centered radicals which can propagate molecular damage either directly or after formation of new reactive species following reaction with oxygen. Overall damage prevention is therefore best achieved by repair of the carbon radicals before they initiate further reactions. Recent studies have shown that the repair cannot be achieved by normal levels of the endogenous antioxidants glutathione, ascorbate or urate. Since their concentrations are well regulated and cannot be enhanced by oral intake, we have investigated the effectiveness of flavonoids and other polyphenols as potential carbon radical repair agents, because their levels in vivo can be significantly enhanced by diet. Pulse radiolysis measurements of the rate constants of repair of amino acid radicals by several polyphenols showed reversible formation of radical-polyphenol adducts 100-1000 times faster than previously reported for the bimolecular stoichiometric reactions of flavonoids i.e. with rate constants in the order of 10 Ms. Adduct formation depended only on the presence of a carbon-centered radical and an aromatic moiety in the reactants, without the involvement of redox reactions at the phenolic groups. Formation of adducts lowered the reactivity of the radicals. Our results suggest that flavonoids, polyphenols and many of their metabolites can effectively reduce the damaging potential of carbon radicals at concentrations achievable in vivo by diets rich in fruits and vegetables.
许多理论和实验研究表明，自由基的主要初始生物靶标是核酸、脂质和蛋白质。该反应通常会生成碳中心自由基，这些自由基可以直接或在与氧反应后形成新的反应性物质后，进一步引发分子损伤。因此，通过在碳自由基引发进一步反应之前对其进行修复，是实现整体损伤预防的最佳方法。最近的研究表明，内源性抗氧化剂谷胱甘肽、抗坏血酸或尿酸无法实现正常水平的修复。由于它们的浓度受到良好的调节，并且不能通过口服摄入来增强，因此我们研究了类黄酮和其他多酚作为潜在碳自由基修复剂的有效性，因为它们在体内的水平可以通过饮食显著增强。几种多酚修复氨基酸自由基的脉冲辐解速率常数的测量结果表明，自由基-多酚加合物的形成可逆，比以前报道的类黄酮的双分子化学计量反应快 100-1000 倍，即反应常数在 10 Ms 范围内。加合物的形成仅取决于反应物中碳中心自由基和芳基部分的存在，而不涉及酚基团的氧化还原反应。加合物的形成降低了自由基的反应性。我们的结果表明，类黄酮、多酚和它们的许多代谢物可以在富含水果和蔬菜的饮食中达到体内可实现的浓度，有效降低碳自由基的破坏性潜力。
