Filipe Paulo, Silva Artur M S, Seixas Raquel S G R, Pinto Diana C G A, Santos Alvaro, Patterson Larry K, Silva João N, Cavaleiro José A S, Freitas João P, Mazière Jean-Claude, Santus René, Morlière Patrice
Faculdade de Medicina de Lisboa, Clínica de Dermatologia, 1699 Lisboa, Portugal.
Biochem Pharmacol. 2009 Mar 15;77(6):957-64. doi: 10.1016/j.bcp.2008.11.023. Epub 2008 Nov 27.
It is shown that the relationship between the alkyl chain length of 3-alkyl-3',4',5,7 tetrahydroxyflavones (FnH) bearing alkyl chains of n=1, 4, 6, 10 carbons and their capacity to counter oxidative damage varies markedly with the nature of the biological system. In Cu(2+)-induced lipid peroxidation of low-density lipoprotein (LDL), the less hydrophobic short-chain F1H and F4H are probably located in the outer layer of LDL and parallel the reference flavonoid antioxidant, quercetin (Q) as effective inhibitors of lipid peroxidation. A marked inhibition of haemolysis induced in red blood cells (RBC) suspensions by the membrane-permeant oxidant, tert-butylhydroperoxide (t-BuOOH), is observed with F4H and F6H present at concentration in the micromolar range. However, F10H the most hydrophobic FnH is even more effective than Q against both haemolysis and lipid peroxidation as measured by malondialdehyde (MDA) equivalents. In oxidation of RBC by H(2)O(2,) at least 50 times more F6H and F10H than by t-BuOOH are required to only partly inhibit haemolysis and MDA production. The F1H, F4H and Q are found rather inactive under these conditions. At concentrations in the micromolar range, a marked protection against the cytotoxic effects of the t-BuOOH-induced oxidative stress in human skin NCTC 2544 keratinocytes is also exhibited by the four FnH antioxidants and is comparable to that of Q. Thus, the four FnH species under study may be considered as potent antioxidants which manifest complementary anti-oxidative actions in biological systems of markedly different complexity.
结果表明，具有n = 1、4、6、10个碳原子烷基链的3 - 烷基 - 3'，4'，5，7 - 四羟基黄酮（FnH）的烷基链长度与其对抗氧化损伤的能力之间的关系，会因生物系统的性质而显著不同。在铜离子（Cu(2+)）诱导的低密度脂蛋白（LDL）脂质过氧化过程中，疏水性较低的短链F1H和F4H可能位于LDL的外层，并且作为脂质过氧化的有效抑制剂，其作用与参考类黄酮抗氧化剂槲皮素（Q）相当。在红细胞（RBC）悬浮液中，由膜渗透性氧化剂叔丁基过氧化氢（t - BuOOH）诱导的溶血受到显著抑制，当F4H和F6H的浓度处于微摩尔范围时即可观察到这种抑制作用。然而，疏水性最强的F10H在对抗溶血和脂质过氧化方面比Q更有效，脂质过氧化通过丙二醛（MDA）当量来衡量。在过氧化氢（H(2)O(2)）氧化红细胞的过程中，与t - BuOOH相比，至少需要50倍以上的F6H和F10H才能部分抑制溶血和MDA的产生。在这些条件下，F1H、F4H和Q的活性较低。在微摩尔浓度范围内，四种FnH抗氧化剂对叔丁基过氧化氢诱导的人皮肤NCTC 2544角质形成细胞氧化应激的细胞毒性作用也表现出显著的保护作用，且与Q相当。因此，所研究的四种FnH可被视为有效的抗氧化剂，它们在复杂性明显不同的生物系统中表现出互补的抗氧化作用。
