Molecular and Cellular Biochemistry

, Volume 290, Issue 1–2, pp 97–101 | Cite as

Assessment of protein oxidation in women using raloxifene

  • Ü. Korucuoğlu
  • B. Çiftçi
  • Ö. Gülbahar
  • A. Biri
  • T. Nas
  • R. Gürsoy
  • A. Aricioğlu


Objectives. To assess the oxidative effects of raloxifene use in postmenopausal women by investigating protein carbonyl levels in the plasma.

Methods. Nineteen osteoporotic postmenopausal women treated with raloxifene for 12 months were included in the study. Another seventeen postmenopausal women matched for age and postmenopausal years, without any medication were chosen as a control group. Protein carbonyl levels were determinated as oxidative stress markers by the use of Levine's method in the plasma of these women.

Results. Serum protein carbonyl levels of postmenopausal women treated with raloxifene (1.27 ± 0.32 nmol/mg protein) were significantly lower than the control group (2.18 ± 0.27 nmol/mg protein) (p < 0.05).

Conclusions. Oxidative stress has been found responsible for several diseases including cancer. Protein carbonyl levels, which are the products of protein oxidation, are one of the indicatives of oxidative stress. Therefore, the decline in protein carbonyl levels in this study revealed the decreasing oxidative stress. According to our results, it might be interpreted that raloxifene does not cause oxidative stress, and it may even have protective effects in long-term use.


oxidative stress raloxifene carbonyl group 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lewis JS, Jordan VC: Selective estrogen receptor modulators (SERMs): Mechanisms of anticarcinogenesis and drug resistance. Mutation Research 591: 247–263, 2005PubMedGoogle Scholar
  2. 2.
    Katznellenbongen BS, Katznellenbongen JA: Defining the ‘S’ in SERM's. Science 295: 2380–2381, 2002CrossRefGoogle Scholar
  3. 3.
    Herrington DM, Howard TD, Hawkins GA, Reboussin DM, Xu J, Zheng SL, Brosnihan KB, Meyers DA, Bleecker ER: Estrogen-receptor polymorphisms and effects of estrogen replacement on high-density lipoprotein cholesterol in women with coronary disease. N Engl J Med 346: 967–974, 2002PubMedCrossRefGoogle Scholar
  4. 4.
    Bryant HU, Wilson PK, Adrian MD, Cole HW, Philips DL, Dodge JA, Grese TA, Sluka JP, Glasebrook AL: Selective estrogen receptor modulators: pharmacological profile in the rat uterus. J Soc Gynecol Invest 3: 152A, 1996CrossRefGoogle Scholar
  5. 5.
    Del Rio D, Stewart AJ, Pellegrini N: A review of recent studies on malondialdehyde as toxic molecule and biological marker of oxidative stress. Nutr Metab Cardiovasc Dis 15: 316–328, 2005PubMedCrossRefGoogle Scholar
  6. 6.
    Berlett BS, Stadtman ER: Protein oxidation in aging, disease and oxidative stress. J Biol Chem 272: 20313–20316, 1997PubMedCrossRefGoogle Scholar
  7. 7.
    Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R: Protein carbonyl groups as biomarkers of oxidative stress. Review. Clinica Chimica Acta 329: 23–38, 2003CrossRefGoogle Scholar
  8. 8.
    Grune T, Reinheckel T, Davies KJA: Degradation of oxidized proteins in K562 human hematopoietic cells by proteasome. J Biol Chem 271: 15504–15509, 1996PubMedCrossRefGoogle Scholar
  9. 9.
    Siems WG, Zollner H, Grune T, Esterbauer H: Metabolic fate of 4-hydroxynonenal in hepatocytes: 1,4-dihydroxynonene is not the main product. J Lipid Res 38: 612–622, 1997PubMedGoogle Scholar
  10. 10.
    Pantke U, Volk T, Schmutzler M, Kox WJ, Site N, Grune T: Oxidized proteins as a marker of oxidative stress during coronary heart surgery. Free Radic Biol Med 27: 1080–1086, 1999PubMedCrossRefGoogle Scholar
  11. 11.
    Garibaldi S, Aragno I, Odetti P, Marinari UM: Relationships between protein carbonyls, retinol, and tocopherols level in human plasma. Biochem Molec Biol Int 34: 729–736, 1994PubMedGoogle Scholar
  12. 12.
    Stadtman ER, Starke-Reed PE, Oliver CN, Carney JM, Floyd RA: Protein modification in aging. EXS 62: 64–72, 1992PubMedGoogle Scholar
  13. 13.
    Hoppe G, Ravandi A, Herrera D, Kuksis A, Hoff HF: Oxidation products of cholesteryl linoleate are resistant to hydrolysis in macrophages, form complexes with proteins, and are present in human atherosclerotic lesions. J Lipid Res 38: 1347–1360, 1997PubMedGoogle Scholar
  14. 14.
    Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn B, Shaltiel S, Stadtman ER: Determination of carbonyl content in oxidatively modified proteins. Meth Enzymol 186: 464–478, 1990PubMedCrossRefGoogle Scholar
  15. 15.
    Arteaga E, Villaseca P, Bianchi M, Rojas A, Marshall G: Raloxifene is a better antioxidant of low-density lipoprotein than estradiol or tamoxifen in postmenopausal women in vitro. Menopause: The Journal of The North American Menopause Society 10: 142–146, 2003Google Scholar
  16. 16.
    Wassmann S, Laufs U, Stamenkovic,D et al.: Raloxifene Improves Endothelial Dysfunction in Hypertension by Reduced Oxidative Stress and Enhanced Nitric Oxide Production. Circulation 105: 2083–2091, 2002PubMedCrossRefGoogle Scholar
  17. 17.
    Lowry OH, Roseberg NJ, Farr AL, Randell RJ: Protein measurement with Folin phenol reagent. J Biol Chem 193: 265–275, 1951PubMedGoogle Scholar
  18. 18.
    Ames BN, Shigenaga MK, Hagen TM: Oxidants, antioxi-dants, and degenerative diseases of aging. Proc Natl Acad Sci USA 90: 7915–7922, 1993PubMedCrossRefGoogle Scholar
  19. 19.
    Cross OE, Halliwell B, Borish ET, Pryor W, Ames BN, Saul RL, McCord JM, Harmad D: Davis Conference: oxygen radicals and human disease. Ann Intern Med 107: 526–545, 1987Google Scholar
  20. 20.
    Yalcin A, Kanit L, Durmaz G, Sargin S, Terek CH, Tanyolac B: Altered level of apurinic/apyrimidinic endonuclease redox factor-1 (Ape/Ref-1) mRNA in the hippocampus of ovariectomized rats treated by raloxifene against kainic acid. Clinical and Experimental Pharmacology and Physiology 32: 611–614, 2005PubMedCrossRefGoogle Scholar
  21. 21.
    Biewenga E, Cabell L, Audesirk T: Estradiol and raloxifene protect cultured SN4741 neurons against oxidative stress. Neuroscience letters 373: 179–183, 2005PubMedCrossRefGoogle Scholar
  22. 22.
    Arteaga E, Villaseca P, Bianchi M, Rojas A, Marshall G: Raloxifene is a better antioxidant of low-density lipoprotein than estradiol or tamoxifen in postmenopausal women in vitro. Menopause: The Journal of The North American Menopause Society 10: 142–146, 2003Google Scholar
  23. 23.
    Blasbichler M, Arakil-Aghajanian A, Sinzinger H: Raloxifene does not prevent fibrinogen oxidation in vitro. Med Sci Monit 11: PI1–4, 2005PubMedGoogle Scholar
  24. 24.
    Gomez-Zubeldia MA, Corrales S, Arbues J, Nogales AG, Millan JC: Influence of estradiol and gestagens on oxidative stress in the rat uterus. Gynecol Oncol 86: 250–258, 2002PubMedCrossRefGoogle Scholar
  25. 25.
    Clemons M, Goss P: Estrogen and the risk of breast cancer. N Engl J Med 344: 276–285, 2001PubMedCrossRefGoogle Scholar
  26. 26.
    Magnusson C, Baron JA, Correia N: et al. Breast cancer risk following long term estrogen and estrogen-progestin replacement therapy. Int J Cancer 81: 339–344, 1999PubMedCrossRefGoogle Scholar
  27. 27.
    Early Breast Cancer Trialists' Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351: 1451–1467, 1998CrossRefGoogle Scholar
  28. 28.
    Greaves P, Goonetilleke R, Nunn G, Topham J, Orton T: Two-year carcinogenicity study of tamoxifen in Alderley Park Wistar-derived rats. Cancer Res 53: 3919–3924, 1993PubMedGoogle Scholar
  29. 29.
    Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, Norton L, Jordan VC: The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple outcomes of raloxifene evaluation. J Am Med Assoc 281: 2189–2197, 1999CrossRefGoogle Scholar

Copyright information

© Springer Science + business Media, Inc. 2006

Authors and Affiliations

  • Ü. Korucuoğlu
    • 1
  • B. Çiftçi
    • 1
  • Ö. Gülbahar
    • 2
  • A. Biri
    • 1
  • T. Nas
    • 1
  • R. Gürsoy
    • 1
  • A. Aricioğlu
    • 2
  1. 1.Department of Obstetrics and GynecologyGazi University Faculty of MedicineAnkaraTurkey
  2. 2.Department of Medical BiochemistryGazi University Faculty of MedicineAnkaraTurkey

Personalised recommendations