Yoshida Yasukazu, Saito Yoshiro, Hayakawa Mieko, Habuchi Yoko, Imai Yasuharu, Sawai Yoshiyuki, Niki Etsuo
Human Stress Signal Research Center, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka, Japan.
Lipids. 2007 May;42(5):439-49. doi: 10.1007/s11745-007-3037-5. Epub 2007 Mar 15.
Lipid peroxidation has gained renewed attention with increasing evidence showing its biological role in producing toxic compounds and cellular signaling mediators. The assessment of lipid peroxidation levels in vivo is difficult partly because lipids are oxidized by different oxidants by different mechanisms to give versatile types of products, which may undergo metabolism and secondary reactions. In the present study, total hydroxyoctadecadienoic acids (tHODE) and 7alpha- and 7beta-hydroxycholesterol (t7-OHCh) from 44 healthy human subjects were assessed as biomarkers after reduction with sodium borohydride followed by saponification with potassium hydroxide comparing with the prevailing standard 8-isoprostaglandin F(2alpha) (t8-iso-PGF(2alpha)). The average concentrations of tHODE, total 8-isoprostaglandin F(2alpha) (t8-iso-PGF(2alpha)), t7alpha-OHCh, and t7beta-OHCh were 203, 0.727, 87.1, and 156 nmol/l plasma and 1,917, 12.8, 1,372, and 3,854 nmol/l packed erythrocytes, respectively. The ratios of tHODE and t7-OHCh to the parent substrates were 194 and 3,519 micromol tHODE/mol linoleates and 40.9 and 686 micromol t7-OHCh/mol cholesterol in plasma and erythrocytes, respectively. It was found that (1) t7-OHCh in blood was unexpectedly high, as high as or even higher than tHODE, (2) the amounts of tHODE was more than 100 fold higher than t8-iso-PGF(2alpha) (3) the level of lipid oxidation products in erythrocytes was higher than that in plasma, and (4) lipid peroxidation products level tended to increase while antioxidant level decrease with age. These products may be used as potential biomarker for assessment of lipid peroxidation and oxidative stress in vivo.
随着越来越多的证据表明脂质过氧化在产生有毒化合物和细胞信号介质方面的生物学作用，它再次受到关注。体内脂质过氧化水平的评估很困难，部分原因是脂质会被不同的氧化剂通过不同的机制氧化，从而产生多种类型的产物，这些产物可能会经历代谢和二次反应。在本研究中，对44名健康人类受试者的总羟基十八碳二烯酸（tHODE）以及7α-和7β-羟基胆固醇（t7-OHCh）进行了评估，评估方法是先用硼氢化钠还原，然后用氢氧化钾皂化，之后将其作为生物标志物与现行标准8-异前列腺素F2α（t8-iso-PGF2α）进行比较。血浆中tHODE、总8-异前列腺素F2α（t8-iso-PGF2α）、t7α-OHCh和t7β-OHCh的平均浓度分别为203、0.727、87.1和156 nmol/L，红细胞中分别为1917、12.8、1372和3854 nmol/L。血浆和红细胞中tHODE和t7-OHCh与母体底物的比率分别为194和3519 μmol tHODE/mol亚油酸酯以及40.9和686 μmol t7-OHCh/mol胆固醇。研究发现：（1）血液中的t7-OHCh意外地高，与tHODE相当甚至更高；（2）tHODE的量比t8-iso-PGF2α高100多倍；（3）红细胞中脂质氧化产物的水平高于血浆中的水平；（4）脂质过氧化产物水平倾向于随着年龄增长而增加，而抗氧化剂水平则下降。这些产物可作为评估体内脂质过氧化和氧化应激的潜在生物标志物。
