Takanashi Kaori, Osanai Yasunori, Kyo Takahiro, Yoshizawa Itsuo
Hokkaido College of Pharmacy, Otaru, Hokkaido 047-0264, Japan.
Lipids. 2003 Aug;38(8):847-54. doi: 10.1007/s11745-003-1135-4.
Two endogenous antioxidants that are speculated to be defense substances against preeclampsia, 2-hydroxyestradiol (2-OH-E2) and its 17-sulfate, 2-hydroxyestradiol 17-sulfate (2-OH-E2-17-S), were administered to rats to compare their inhibitory effects on hepatic microsomal lipid peroxidation, and the lipid peroxides were determined in NADPH- and ascorbic acid-dependent systems. The two catechols showed a strong inhibitory effect on lipid peroxidation in both systems, and the effect was dose dependent. However, a large difference was observed in their inhibition patterns. After administration of 2-OH-E2, the effect appeared immediately and decreased gradually with time. In contrast, the effect of 2-OH-E2-17-S appeared some time after administration and persisted for a longer time. Both catechols also showed a striking difference in their dynamics. After administration, 2-OH-E2 was detected in the blood together with its metabolites, 2-methoxyestradiol and 2-methoxyestrone, and they disappeared immediately. In contrast, 2-OH-E2-17-S was present in the blood for a longer time together with its O-methylated product, 2-methoxyestradiol 17-sulfate, but disappeared from liver microsomes within 2 h after administration. The results imply no occurrence of a direct inhibition effect of 2-OH-E2-17-S.
两种内源性抗氧化剂，即推测为子痫前期防御物质的2-羟基雌二醇（2-OH-E2）及其17-硫酸盐2-羟基雌二醇17-硫酸盐（2-OH-E2-17-S），被给予大鼠以比较它们对肝微粒体脂质过氧化的抑制作用，并在NADPH和抗坏血酸依赖系统中测定脂质过氧化物。这两种儿茶酚在两个系统中均对脂质过氧化表现出强烈的抑制作用，且该作用呈剂量依赖性。然而，观察到它们的抑制模式存在很大差异。给予2-OH-E2后，作用立即出现并随时间逐渐降低。相反，2-OH-E2-17-S的作用在给药一段时间后出现并持续较长时间。两种儿茶酚在其动态变化方面也表现出显著差异。给药后，在血液中检测到2-OH-E2及其代谢产物2-甲氧基雌二醇和2-甲氧基雌酮，它们立即消失。相反，2-OH-E2-17-S与其O-甲基化产物2-甲氧基雌二醇17-硫酸盐一起在血液中存在较长时间，但在给药后2小时内从肝微粒体中消失。结果表明2-OH-E2-17-S不存在直接抑制作用。
