On the inhibitory effect of C17-sulfoconjugated catechol estrogens upon lipid peroxidation of rat liver microsomes.
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.
Hokkaido College of Pharmacy, Japan.
K
K
Takanashi
K
K
Watanabe
I
I
Yoshizawa
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001241:Aspirin / Q000378:metabolism; D015764:Bepridil / Q000031:analogs & derivatives / Q000737:chemistry; D001713:Biphenyl Compounds; D002393:Estrogens, Catechol / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005609:Free Radicals; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D010851:Picrates; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013455:Sulfur / Q000737:chemistry
D000975:Antioxidants; D001713:Biphenyl Compounds; D002393:Estrogens, Catechol; D005609:Free Radicals; D010851:Picrates; D009249:NADP; D013455:Sulfur; D015764:Bepridil; C004931:1,1-diphenyl-2-picrylhydrazyl; D001241:Aspirin