ON THE INHIBITORY EFFECT OF C-17-SULFOCONJUGATED CATECHOL ESTROGENS UPON LIPID-PEROXIDATION OF RAT-LIVER MICROSOMES

The antioxidant effect of C-17-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 ste roids, 2-hydroxyestradiol 17-sulfate, followed by 4-methoxyestradiol, 4-hydroxyestradiol 17-sulfate and estrone also showed a strong inhibit ory effect, which was greater than that of alpha-tocopherol. Among the C-17-sulfates, the guaiacols (2- and 4-methoxyestradiol 17-sulfate) s howed a slightly lower effect than alpha-tocopherol, but estradiol 17- sulfate had almost no effect. The antioxidant activity observed in phe nolic: or guaiacol steroids was considered to be attributed to the cat echols produced by their 2- (or 4-)hydroxylation or their O-demethylat ion, respectively, during the incubation. This was confirmed by identi fication of the catechols produced from phenolic or guaiacol estrogens and even from the estrogen C-3-sulfates. The mechanism of the inhibit ion by catechols on lipid peroxidation was speculated to involve their activity as radical scavengers, because of their strong reducing acti vity for 1,1-diphenyl-2-picrylhydrazyl. The above results suggest that C-17-sulfoconjugated catechol estrogens (2- and 4-hydroxyestradiol 17 -sulfate), although with slightly lower activity than their free catec hols, are promising endogenous antioxidants. The physiological role of these estrogen conjugates during pregnancy is discussed.