Yoshida Yasukazu, Niki Etsuo
National Institute of Advanced Industrial Science and Technology (AIST), Human Stress Signal Research Center, 1-8-31 Midorigaoka, Ikeda 563-8577, Japan.
Biofactors. 2006;27(1-4):195-202. doi: 10.1002/biof.5520270117.
The biological role of lipid peroxidation products has continued to receive a great deal of attention not only for the elucidation of pathological mechanisms but also for their practical application to clinical use as bio-markers. In the last fifty years, lipid peroxidation has been the subject of extensive studies from the viewpoints of mechanisms, dynamics, product analysis, involvement in diseases, inhibition, and biological signaling. Lipid hydroperoxides are formed as the major primary products, however they are substrates for various enzymes and they also undergo various secondary reactions. In this decade, F2-isoprostanes from arachidonates and neuroprostanes from docosahexanoates have been proposed as bio-markers. Although these markers are formed by a free radical-mediated oxidation, the yields from the parent lipids are minimal. Compared to these markers, hydroperoxy octadecadienoates (HPODE) from linoleates and oxysterols from cholesterols are yielded by much simpler mechanisms from more abundant parent lipids in vivo. Recently, the method in which both free and ester forms of hydroperoxides and ketones as well as hydroxides of linoleic acid and cholesterol are measured as total hydroxyoctadecadienoic acid (tHODE) and 7-hydroxycholesterol (t7-OHCh), respectively, was proposed. The concentrations of tHODE and t7-OHCh determined by GC-MS analysis from physiological samples were much higher than that of 8-iso-prostagrandin F(2alpha). In addition to this advantage, hydrogen-donor activity of antioxidants in vivo could be determined by the isomeric-ratio of HODE (9- and 13-(Z,E)-HODE/9- and 13-(E,E)-HODE).
脂质过氧化产物的生物学作用一直备受关注，这不仅体现在对病理机制的阐释上，还体现在其作为生物标志物在临床应用中的实际价值。在过去的五十年里，脂质过氧化从机制、动力学、产物分析、与疾病的关联、抑制作用以及生物信号传导等多个角度，都成为了广泛研究的对象。脂质氢过氧化物是主要的初级产物，然而它们是多种酶的底物，并且还会经历各种二级反应。在这十年间，源自花生四烯酸的F2 -异前列腺素和源自二十二碳六烯酸的神经前列腺素被提议作为生物标志物。尽管这些标志物是由自由基介导的氧化反应形成的，但母体脂质的生成量极少。与这些标志物相比，体内亚油酸生成的氢过氧化十八碳二烯酸（HPODE）和胆固醇生成的氧化甾醇是通过更为简单的机制，从更为丰富的母体脂质中产生的。最近，有人提出了一种方法，即分别将氢过氧化物和酮的游离及酯形式以及亚油酸和胆固醇的氢氧化物作为总羟基十八碳二烯酸（tHODE）和7 -羟基胆固醇（t7 - OHCh）进行测定。通过气相色谱 - 质谱分析从生理样本中测定的tHODE和t7 - OHCh浓度，远高于8 -异前列腺素F(2α)的浓度。除了这一优势外，体内抗氧化剂的氢供体活性可以通过HODE的异构体比例（9 -和13 -（Z,E）- HODE / 9 -和13 -（E,E）- HODE）来确定。
