Staniek Katrin, Rosenau Thomas, Gregor Wolfgang, Nohl Hans, Gille Lars
Research Institute for Biochemical Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Veterinärplatz 1, A-1210 Vienna, Austria.
Biochem Pharmacol. 2005 Nov 1;70(9):1361-70. doi: 10.1016/j.bcp.2005.07.030.
alpha-Tocopherol is the most important lipophilic antioxidant of the chromanol type protecting biomembranes from lipid peroxidation (LPO). Therefore, alpha-tocopherol and its derivatives are frequently used in the therapy or prevention of oxygen radical-derived diseases. In the present study, novel chromanol-type antioxidants (twin-chromanol, cis- and trans-oxachromanol) as well as the well-known short-chain analogue of alpha-tocopherol, pentamethyl-chromanol, were tested for their antioxidative potency in rat heart mitochondria (RHM). Our experiments revealed that the bioenergetic parameters of mitochondria were not deteriorated in the presence of chromanols (up to 50 nmol/mg protein). Exposure of RHM to cumene hydroperoxide and Fe2+ (final concentrations 50 microM each), inducing LPO, significantly affected their bioenergetic parameters which were determined in the presence of glutamate and malate (substrates of mitochondrial complex I). Alterations of the bioenergetic parameters were partially prevented in a concentration-dependent manner by preincubating RHM with antioxidants before adding the radical-generating system. In the lower concentration range, twin-chromanol turned out to be more efficient than pentamethyl-chromanol, both being far more protective than cis- and trans-oxachromanol. Measurement of protein-bound SH groups and thiobarbituric acid-reactive substances revealed that this protective effect was due to their antioxidative action. Furthermore, HPLC measurements of alpha-tocopherol and alpha-tocopheryl quinone in rat liver mitochondria demonstrated an alpha-tocopherol-sparing effect of twin-chromanol. In conclusion, new chromanol-type antioxidants, especially twin-chromanol, were able to improve bioenergetic and biochemical parameters of mitochondria exposed to oxidative stress.
α-生育酚是色满醇类型中最重要的亲脂性抗氧化剂，可保护生物膜免受脂质过氧化作用（LPO）的影响。因此，α-生育酚及其衍生物常用于治疗或预防氧自由基相关疾病。在本研究中，对新型色满醇类抗氧化剂（双色满醇、顺式和反式氧杂色满醇）以及著名的α-生育酚短链类似物五甲基色满醇在大鼠心脏线粒体（RHM）中的抗氧化能力进行了测试。我们的实验表明，在色满醇存在的情况下（高达50 nmol/mg蛋白质），线粒体的生物能量参数并未恶化。将RHM暴露于异丙苯过氧化氢和Fe2+（最终浓度均为50 μM）中，诱导脂质过氧化，显著影响了它们在谷氨酸和苹果酸（线粒体复合体I的底物）存在下测定的生物能量参数。在添加自由基生成系统之前，通过将RHM与抗氧化剂预孵育，生物能量参数的改变以浓度依赖的方式得到了部分预防。在较低浓度范围内，双色满醇比五甲基色满醇更有效，两者的保护作用都远强于顺式和反式氧杂色满醇。对蛋白质结合的SH基团和硫代巴比妥酸反应性物质的测量表明，这种保护作用是由于它们的抗氧化作用。此外，对大鼠肝脏线粒体中α-生育酚和α-生育酚醌的HPLC测量表明双色满醇具有α-生育酚节省效应。总之，新型色满醇类抗氧化剂，尤其是双色满醇，能够改善暴露于氧化应激下的线粒体的生物能量和生化参数。
