Effect of estradiol and selected antiestrogens on pro- and antioxidant pathways in mammalian uterus.
In this study, we examined the effect of 17 beta-estradiol and selected antiestrogens on uterine NADPH-oxidase activity, superoxide dismutase (SOD) activity, hydride (H.-), dienyl radical and O2 -radical generation, and membrane fluidity. NADPH oxidase activity was positively modulated in estradiol-treated animals and negatively regulated in animals that received injections of AF-45, RU-39411, tamoxifen, or ICI-182780. The SOD activity was markedly reduced in estradiol-treated animals when compared with the control animals. A positive modulation of SOD activity was observed upon treatment with AF45, RU39411, tamoxifen, and ICI 182780, though the potency varied among the individual test compounds. We observed detectable H(.-)-radical generation as evidenced from MNP H.- adduct formation in the uterine cell preparations from untreated control animals. Estradiol produced a tremendous augmentation in the superoxide radical profiles in uterine cell preparations compared to the control levels. All the other compounds that were tested significantly lowered the superoxide levels in the test set-up. AF-45, RU-39411, tamoxifen, and ICI-182780 induced varying orders of suppression of H(.-)-radical generation in the test subjects. There was a significant enhancement in membrane fluidity, hydride radical levels, and dienyl radical generation in the estradiol-treated group. All the antiestrogens did not exhibit a similar action on these parameters. RU-39411 exhibited antiestrogen-like activity in modulating hydride levels and membrane fluidity, whereas it stimulated dienyl radical generation. Thus our tests showed that the selected antiestrogens failed to show estrogen-like activity in these assays. It appears that estradiol exerts feedback control over pro- and antioxidant pathways and that markers of oxidative status could be used as a measure to evaluate the antiestrogenic activity of estradiol agonists/antagonists.
Jain
S
S
School of Life Sciences, Devi Ahilya University, Indore, India.
Saxena
D
D
Kumar
P G
PG
Koide
S S
SS
Laloraya
M
M
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D005260:Female; D005609:Free Radicals; D051379:Mice; D019255:NADPH Oxidases / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides; D014599:Uterus / Q000187:drug effects / Q000378:metabolism*
D000975:Antioxidants; D020847:Estrogen Receptor Modulators; D005609:Free Radicals; D013481:Superoxides; C060411:RU 39411; D004958:Estradiol; D013482:Superoxide Dismutase; D019255:NADPH Oxidases