Takanashi K, Watanabe K, Yoshizawa I
Hokkaido College of Pharmacy, Japan.
Biol Pharm Bull. 1995 Aug;18(8):1120-5. doi: 10.1248/bpb.18.1120.
The antioxidant effect of C17-sulfoconjugated catechol estrogens was examined under ascorbic acid- or NADPH-dependent lipid peroxidation in rat liver microsomes and compared with that of various estrogens and alpha-tocopherol. Among the estrogens tested, a free catechol estrogen such as 4-hydroxyestradiol showed the strongest effect, followed by 2-hydroxyestradiol, 2-methoxyestradiol and estradiol. Next to these steroids, 2-hydroxyestradiol 17-sulfate, followed by 4-methoxyestradiol, 4-hydroxyestradiol 17-sulfate and estrone also showed a strong inhibitory effect, which was greater than that of alpha-tocopherol. Among the C17-sulfates, the guaiacols (2- and 4-methoxyestradiol 17-sulfate) showed a slightly lower effect than alpha-tocopherol, but estradiol 17-sulfate had almost no effect. The antioxidant activity observed in phenolic or guaiacol steroids was considered to be attributed to the catechols produced by their 2- (or 4-)hydroxylation or their O-demethylation, respectively, during the incubation. This was confirmed by identification of the catechols produced from phenolic or guaiacol estrogens and even from the estrogen C3-sulfates. The mechanism of the inhibition by catechols on lipid peroxidation was speculated to involve their activity as radical scavengers, because of their strong reducing activity for 1,1-diphenyl-2-picrylhydrazyl. The above results suggest that C17-sulfoconjugated catechol estrogens (2- and 4-hydroxyestradiol 17-sulfate), although with slightly lower activity than their free catechols, are promising endogenous antioxidants. The physiological role of these estrogen conjugates during pregnancy is discussed.
在大鼠肝微粒体中，在抗坏血酸或NADPH依赖性脂质过氧化条件下检测了C17 - 硫酸共轭儿茶酚雌激素的抗氧化作用，并与各种雌激素和α - 生育酚的抗氧化作用进行了比较。在所测试的雌激素中，游离儿茶酚雌激素如4 - 羟基雌二醇显示出最强的作用，其次是2 - 羟基雌二醇、2 - 甲氧基雌二醇和雌二醇。在这些类固醇之后，2 - 羟基雌二醇17 - 硫酸盐，其次是4 - 甲氧基雌二醇、4 - 羟基雌二醇17 - 硫酸盐和雌酮也显示出很强的抑制作用，其作用大于α - 生育酚。在C17 - 硫酸盐中，愈创木酚（2 - 和4 - 甲氧基雌二醇17 - 硫酸盐）的作用略低于α - 生育酚，但雌二醇17 - 硫酸盐几乎没有作用。在酚类或愈创木酚类固醇中观察到的抗氧化活性被认为分别归因于它们在孵育过程中通过2 - （或4 - ）羟基化或O - 去甲基化产生的儿茶酚。从酚类或愈创木酚雌激素甚至雌激素C3 - 硫酸盐产生的儿茶酚的鉴定证实了这一点。由于儿茶酚对1,1 - 二苯基 - 2 - 苦基肼有很强的还原活性，推测其对脂质过氧化的抑制机制涉及其作为自由基清除剂的活性。上述结果表明，C17 - 硫酸共轭儿茶酚雌激素（2 - 和4 - 羟基雌二醇17 - 硫酸盐）虽然活性略低于其游离儿茶酚，但有望成为内源性抗氧化剂。本文还讨论了这些雌激素共轭物在怀孕期间的生理作用。
