title: Antioxidant effect of the active metabolites of tibolone.
abstract: Certain steroidal compounds have an antioxidant effect in humans. Our aim was to test whether the synthetic steroid tibolone and its metabolites are also able to display such a property. For this, granulocytes from healthy men and women were incubated for two hours with different concentrations (10(-7), 10(-8), 10(-9 )M) of either estradiol, tibolone, 3α-hydroxytibolone, 3β-hydroxytibolone, Δ(4)-tibolone, 3α-sulfated-tibolone, 3α-17β-disulfated-tibolone, 3β-sulfated-tibolone or 3β-17β-disulfated-tibolone. Superoxide anion generation of neutrophils was measured by photometry. Results of different steroids were given as percentages of their controls. A more simple superoxide generating system, the xanthine-xanthine oxidase reaction was also tested. We found that granulocyte superoxide production did not differ from the control using 10(-9 )M of steroids. Using 10(-8 )M concentration: estradiol (80.9 ± 2.5%); 3β-sulfated-tibolone (83.3 ± 4.7%); 3β-17β-disulfated-tibolone (81.0 ± 4.2%) caused a significant decrease in superoxide production, compared to the control. In addition at 10(-7 )M, 3β-hydroxytibolone and 3α-sulfated-tibolone also showed antioxidant effects. In the xanthine-xanthine oxidase system estradiol (67.4 ± 1.0%), 3α-sulfated-tibolone (85.8 ± 5.3%), 3α-17β-disulfated-tibolone (71.9 ± 2.5%), 3β-sulfated-tibolone (73.9 ± 5.0%), and 3β-17β-disulfated-tibolone (65.8 ± 3.4%) caused a significant decrease in superoxide production. Conclusively, although tibolone itself did not show significant antioxidant capacity, most of its active metabolites have antioxidant effects.
authors: 2nd Department of Internal Medicine, Faculty of Medicine .
authors: Julia
authors: J
authors: Stark
authors: Szabolcs
authors: S
authors: Varbiro
authors: Miklos
authors: M
authors: Sipos
authors: Zsolt
authors: Z
authors: Tulassay
authors: Levente
authors: L
authors: Sara
authors: Ildiko
authors: I
authors: Adler
authors: Elek
authors: E
authors: Dinya
authors: Zoltan
authors: Z
authors: Magyar
authors: Bela
authors: B
authors: Szekacs
authors: Istvan
authors: I
authors: Marczell
authors: Helenius J
authors: HJ
authors: Kloosterboer
authors: Karoly
authors: K
authors: Racz
authors: Gabor
authors: G
authors: Bekesi
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000378:metabolism*; D020847:Estrogen Receptor Modulators / Q000378:metabolism / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D006098:Granulocytes / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009652:Norpregnenes / Q000378:metabolism / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D020847:Estrogen Receptor Modulators; D004967:Estrogens; D009652:Norpregnenes; D013481:Superoxides; C027385:tibolone
keywords: Antioxidant effect; estradiol; superoxide anion inhibition; tibolone; tibolone metabolites