Skip to main content
SpringerLink
Log in

Comparison of ex vivo inhibitory effect between 2-hydroxyestradiol and its 17-sulfate on rat hepatic microsomal lipid peroxidation

  • Articles
  • Published:
Lipids

Abstract

Two endogenous antioxidants that are speculated to be defense substances against preeclampsia, 2-hydroxyestradiol (2-OH-E2) and its 17-sulfate, 2-hydroxyestradiol 17-sulfate (2-OH-E2-17-S), were administered to rats to compare their inhibitory effects on hepatic microsomal lipid peroxidation, and the lipid peroxides were determined in NADPH- and ascorbic acid-dependent systems. The two catechols showed a strong inhibitory effect on lipid peroxidation in both systems, and the effect was dose dependent. However, a large difference was observed in their inhibition patterns. After administration of 2-OH-E2, the effect appeared immediately and decreased gradually with time. In contrast, the effect of 2-OH-E2-17-S appeared some time after administration and persisted for a longer time. Both catechols also showed a striking difference in their dynamics. After administration, 2-OH-E2 was detected in the blood together with its metabolites, 2-methoxyestradiol and 2-methoxyestrone, and they disappeared immediately. In contrast, 2-OH-E2-17-S was present in the blood for a longer time together with its O-methylated product, 2-methoxyestradiol 17-sulfate, but disappeared from liver microsomes within 2 h after administration. The results imply no occurrence of a direct inhibition effect of 2-OH-E2-17-S.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

2-OH-E1 :

2-hydroxyestrone

2-OH-E2 :

2-hydroxyestradiol

2-OMe-E1 :

2-methoxyestrone

2-OMe-E2 :

2-methoxyestradiol

4-OMe-E2 :

4-methoxyestradiol

2-OH-E2-17-S:

2-hydroxyestradiol 17-sulfate

2-OMe-E2-17-S:

2-methoxyestradiol 17-sulfate

4-OMe-E2-17-S:

4-methoxyestradiol 17-sulfate

AsA:

ascorbic acid

COMT:

catechol O-methyl transferase

TBA:

2-thiobarbituric acid

References

  1. Hubel, C.A., Roberts, J.M., Taylor, R.N., Musci, T.J., Rogers, G.M., and McLaughlin, M.K. (1989) Lipid Peroxidation in Pregnancy: New Perspectives on Preeclampsia, Am. J. Obstet. Gynecol. 161, 1025–1034.

    PubMed  CAS  Google Scholar 

  2. Tanaka, A., Morikawa, H., Yamasaki, M., and Mochizuki, M. (1996) Lipid Metabolism and Endothelial Cell Dysfunction in Women with Preeclampsia, Folia Endocrinol. 72, 85–94.

    CAS  Google Scholar 

  3. Komura, S., Ohishi, N., and Yagi, K. (1996) Catecholestrogen as a Natural Antioxidant, Ann. N.Y. Acad. Sci. 786, 419–429.

    PubMed  CAS  Google Scholar 

  4. Kono, S., Merriam, G.R., Brandon, D., Loriaux, D.L., and Lipsett, M.B. (1982) Radioimmunoassay and Metabolism of the Catechol Estrogen 2-Hydroxyestradiol, J. Clin. Endocrinol. Metab. 54, 150–154.

    PubMed  CAS  Google Scholar 

  5. Takanashi, K., Watanabe, K., and Yoshizawa, I. (1993) Conversion of Estradiol 17-Sulfate to Its 2- and 4-Hydroxylated Catechols by Human Placental Microsomes, Biol. Pharm. Bull. 16, 217–219.

    PubMed  CAS  Google Scholar 

  6. Takanashi, K., Watanabe, K., and Yoshizawa, I. (1995) On the Inhibitory Effect of C17-Sulfoconjugated Catecholestrogens upon Lipid Peroxidation of Rat Liver Microsomes, Biol. Pharm. Bull. 18, 1120–1125.

    PubMed  CAS  Google Scholar 

  7. Kashiwagi, T., Yasuda, J., Yamamoto, T., Honjo, H., Takanashi, K., and Yoshizawa, I. (1999) Serum 2-Hydroxyestradiol 17-Sulphate in Pregnancy, Endocr. J. 46, 453–458.

    PubMed  CAS  Google Scholar 

  8. Takanashi, K., Honma, T., Kashiwagi, T., Honjo, H., and Yoshizawa, I. (2000) Detection and Measurement of Urinary 2-Hydroxyestradiol 17-Sulfate, the Potential Placental Antioxidant During Pregnancy, Clin. Chem. 46, 373–378.

    PubMed  CAS  Google Scholar 

  9. Watanabe, K., Kimura, R., and Yoshizawa, I. (1986) Synthesis and High-Performance Liquid Chromatography of 3,4-Guaiacol Estrogen Sulfates, Chem. Pharm. Bull. 34, 2231–2235.

    CAS  Google Scholar 

  10. Buege, J.A., and Aust, S.D. (1978) Microsomal Lipid Peroxidation, Methods Enzymol. 52, 302–310.

    Article  PubMed  CAS  Google Scholar 

  11. Takanashi, K., Watanabe, K., Itoh, S., Kamada, M., Honma, T., and Yoshizawa, I. (1995) HPLC Separation of Ring D Conjugated Estrogens, Bunseki Kagaku 44, 793–796.

    CAS  Google Scholar 

  12. Heyns, W., Baelen, H.V., and DeMoor, P. (1967) Study of Steroid-Protein Binding by Means of Competitive Adsorption: Application to Cortisol Binning in Plasma, Clin. Chim. Acta 18, 361–370.

    Article  CAS  Google Scholar 

  13. Watanabe, K., Takanashi, K., and Yoshizawa, I. (1989) Plasma Estradiol 17-Sulfate and 2-Hydroxyestradiol 17-Sulfate Levels and Their Metabolic Clearance Rates in Rats, J. Steroid Biochem. 32, 823–827.

    Article  PubMed  CAS  Google Scholar 

  14. Ball, P., Emons, G., Kayser, H., and Teichmann, J. (1983) Metabolic Clearance Rates of Catechol Estrogens in Rats, Endocrinology 113, 1781–1783.

    PubMed  CAS  Google Scholar 

  15. Dunn, J.F., Merriam, G.R., Eil, C., Kono, S., Loriaux, D.L., and Nisula, B.C. (1980) Testosterone-Estradiol Binding Globulin Binds to 2-Methoxyestradiol with Greater Affinity Than to Testosterone, J. Clin. Endocrinol. Metab. 51, 404–406.

    PubMed  CAS  Google Scholar 

  16. Kono, S., Merriam, G.R., Brandon, D.D., Loriaux, D.L., Lipsett, M.B., and Fujino, T. (1983) Radioimmunoassay and Metabolic Clearance Rate of Catecholestrogens, 2-Hydroxyestrone and 2-Hydroxyestradiol in Man, J. Steroid Biochem. 19, 627–633.

    Article  PubMed  CAS  Google Scholar 

  17. Ball, P., and Knuppen, R. (1980) Catecholestrogens, Acta Endocrinol. 93 (Suppl. 232), 1–127.

    Google Scholar 

  18. Hoffman, A.R., Paul, S.M., and Axelrod, J. (1980) The Enzymatic Formation of Catechol Estrogens from 2-Methoxyestrogens by Rat Liver Microsomes, Endocrinology 107, 1192–1197.

    Article  PubMed  CAS  Google Scholar 

  19. Ball, P., Stubenrauch, G., and Knuppen, R. (1977) Metabolism of 2-Methoxy- and 4-Methoxyoestrone in Man in vivo, J. Steroid Biochem. 8, 989–993.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Hokkaido College of Pharmacy, 7-1 Katsuraoka-cho, 047-0264, Otaru, Hokkaido, Japan

    Kaori Takanashi, Yasunori Osanai, Takahiro Kyo & Itsuo Yoshizawa

Authors
  1. Kaori Takanashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yasunori Osanai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takahiro Kyo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Itsuo Yoshizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Itsuo Yoshizawa.

About this article

Cite this article

Takanashi, K., Osanai, Y., Kyo, T. et al. Comparison of ex vivo inhibitory effect between 2-hydroxyestradiol and its 17-sulfate on rat hepatic microsomal lipid peroxidation. Lipids 38, 847–854 (2003). https://doi.org/10.1007/s11745-003-1135-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11745-003-1135-4

Keywords

Search

Navigation