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, 10⁻⁹M) of either estradiol, tibolone, 3α-hydroxytibolone, 3β-hydroxytibolone, Δ⁴-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 10⁻⁹M of steroids. Using 10⁻⁸M 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 10⁻⁷M, 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.

• Antioxidant effect
• estradiol
• superoxide anion inhibition
• tibolone
• tibolone metabolites

Acknowledgements

The authors wish to express their gratitude to Organon International Ltd. for their technical, material and methodological support and for providing us with the different metabolites of tibolone, to Balázs Gérecz for his administrative and technical support and to Krisztina Nagy for her devoted efforts in solving technical problems in laboratory work.

Declaration of interest

This study was sponsored by Organon International Ltd. and Maecenator Foundation.