BibTex RIS Cite

Estrogen modulating effects of resveratrol in female rats

Year 2016, Volume: 29 Issue: 2, 95 - 101, 01.04.2016
https://doi.org/10.5472/MMJoa.2902.06

Abstract

Objectives: This study investigates the estrogen-like effects of resveratrol (RES) in female rats.Materials and Methods: In this two-step study on estrogenlike activity of RES, immature female rats (21 days old) were used in the first step and pubertal female rats (28 days old) with primary ovarian failure (POF) induced by 4-vinylcyclohexene diepoxide (VCD) were used in the second step. Possible agonistic and/or antagonistic effects of RES were investigated by using several parameters including the ratios of uterine/body weights (UBW), uterine dry/wet weights (UDWW) and body weight increase (BW%), bone density measurement, serum estradiol and vitamin D levels and histological evaluation.Results: In immature rats, RES resulted in an increase in UBW equal to that produced by 17 alpha-ethinyl estradiol (17alphaEE). The minimum effective dose for RES was 10 mg/kg. This effect was not decreased by tamoxifen but was significantly antagonized by fulvestrant. Similarly, tamoxifen did not abolish the effects ofRES completely in rats with POF. However, in rats with VCDinduced POF, tamoxifen resulted in lower UBW values and estradiol levels were significantly higher in 17alphaEE-treated, RES+tamoxifen-treated and 17 beta-estradiol (17betaE)-treated rats compared to control animals.Conclusion: The dose of RES may be important in terms of estrogenic activity and even RES may modulate the effects of estrogen.Keywords: Estrogen, Resveratrol, 4-vinylcyclohexene diepoxide, Primary ovarian failure

References

  • Jiang H, Zhang L, Kuo J, et al. Resveratrol-induced apoptotic death in human U251 glioma cells. Mol Cancer Ther 2005; 4:554-61. doi: 10.1158/1535-7163.MCT-04-0056
  • Frémont L. Biological effects of resveratrol. Life Sci 2000;66:663-73. doi:10.1016/S0024-3205(99)00410-5
  • Wolter F, Ulrich S, Stein J. Molecular mechanisms of the chemopreventive effects of resveratrol and its analogs in colorectal cancer. J Nutr 2004;134:3219-22.
  • Gehm BD, McAndrews JM, Chien P-Y, Jameson JL. Resveratrol, a polyphenolic compound found in grapes and wine, is agonist for estrogen receptor. Proc Natl Acad Sci USA 1997; 94:14138-43. doi:10.1073/pnas.94.25.14138
  • Turner RT, Evans GL, Zhang M, Maran A, Sibonga JD. Is resveratrol an estrogen agonist in growing rats? Endocrinology 1999;140:50-4. doi: 10.1210/endo.140.1.6460
  • Lu R, Serrero G. Resveratrol, a natural product derved from grape, exhibits antiestrogenic activity and inhibits the growth of human breast cancer cells. J Cell Physiol 1999;179:297-304. doi: 10.1002/(SICI)1097-4652(199906)179:3<297::AIDJCP7>
  • 0.CO;2-P
  • Bhat KP, Pezzuto JM. Resveratrol exhibits cytostatic and antiestrogenic properties with human endometrial adenocarcinoma (Ishikawa) cells. Cancer Res 2001; 61:6137-44.
  • Eppenberger U, Woslkowski K, Kung W. Pharmacological and biological properties of droloxifene, a new antiestrogen. Am J Clin Oncol 1991; 14: 5-14.
  • Hoyer PB, Sipes IG. Development of an animal model for ovotoxicity using, 4-vinyl cyclohexene: a case study. Birth Defects Res B Dev Reprod Toxicol 2007; 80:113-25.doi: 10.1002/bdrb.20103
  • Kappeler CJ, Hoyer PB. 4-vinylcyclohexene diepokside: a model chemical for ovotoxicity. Syst Biol Reprod Med 2012; 58: 57-62. doi: 10.3109/19396368.2011.648820.
  • Ke HZ, Paralkar VM, Grasser WA, et al. Effects of CP-336,156, a new nonsteroidal estrogen agonist/antagonist, on bone, serum cholesterol, uterus, and body composition in rat models. Endocrinology 1998; 139: 2068-76. doi: 10.1210/endo.139.4.5902
  • Muhammad FS, Goode AK, Kock ND, et al. Effects of 4-vinylcyclohexene diepoxide on peripubertal and adult Sprague-Dawley Rats: Ovarian, Clinical and Pathological Outcomes. Comparative Medicine 2009; 59:46-59.
  • Odum J, Tinwell H, Van Miller J, Joiner R, Ashby J. The uterotropic activity of nonylphenol in the rat is not mediated by aromatase enzyme induction. Toxicology Letters 2001; 118:165-69. doi: 10.1016/S0378-4274(00)00293-9
  • Oseni T, Patel R, Pyle J, Jordan VC. Selective Estrogen Receptor Modulators and Phytoestrogens. NIH Public Access 2008; 74;1656-65. doi: 10.1055/s-0028-1088304
  • Heather B, Patisaul HB, Whitten P. Dietary phytoestrogens.
  • In: Naz RK, editor. Endocrine disruptors:effects on male and female reproductive systems. 2nd ed. Boca Raton 2004, CRC Press: 135-75.
  • Assikis VJ, Neven P, Jordan VC, Vergote I. A realistic clinical perspective of tamoxifen and endometrial carcinogenesis. Eur J Cancer 1996 32A:1464-76. doi: 10.1016/0959-8049(96)00184-0
  • Moutsatsou P. The spectrum of phytoestrogens in nature:our knowledge is expanding . Hormones 2007; 6:173-93.
  • Bhat KP, Lantvit D, Christov K, Mehta RG, Moon RC, Pezzuto JM. Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models. Cancer Res 2001;61:7456-63.
  • Bowers JL, Tyulmenkov VV, Jernigan SC, Klinge JM. Resveratrol acts as mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology 2000;141:3657-67. doi: 10.1210/endo.141.10.7721
  • Cuccıolla V, BorrielloA, Oliva A, Patrizia G, Zappia V, Della Ragione F. Resveratrol: From basic science to clinic. Cell Cycle 2007; 6: 2495-510. doi: 10.4161/cc.6.20.4815
  • Dundar Y, Ozatik Y, Ozatik O, et al. Synthesis and biological evaluation of the salicylamide and salicylic acid derivatives as anti-estrogen agents. Med Chem 2012; 8:481-90. :10.2174/1573406411208030481
  • Leonard SS, Xia C, Jiang BH, et al. Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem Biophys Res Commun 2003; 309:1017-26. doi:10.1016/j.bbrc.2003.08.105
  • Cao Z, Li Y. Potent induction of cellular antioxidants and phase 2 enzymes by resveratrol in cardiomyocytes: protection against oxidative and electrophilic injury. Eur J Pharmacol 2004;489(1-2):39-48. doi:10.1016/j.ejphar.2004.02.031
  • Li Y, Cao Z, Zhu H. Upregulation of endogeneous antioxidants and phase 2 enzymes by red wine polyphenol, resveratrol in cultured aortic smooth muscle cells leads to cytoprotection against oxidative and electrophilic stres. Pharmacol Res 2006;53:6-15. doi:10.1016/j.phrs.2005.08.002
  • Kasdallah-Grissa A, Mornagui B, Aouani E, et al. Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stres in rat liver. Life Sci 2007; 80:1033-39. doi:10.1016/j.lfs.2006.11.044
  • Ajmo JM, Liang X, Rogers CQ, Pennock B, You M. Resveratrol alleviates alcholic fatty liver in mice. Am J Physiol Gastrointes Liver Physiol 2008; 295:833-42. doi:10.1152/ajpgi.90358.2008.
  • Lohff JC, Christian PJ, Marion SL, Arrandale A, Hoyer PB. Characterization of cyclicity and hormonal profile with impending ovarian failure in a novel chemical-induced Mouse model of perimenopause. Comparative Medicine 2006;55:523-7.

Estrogen modulating effects of resveratrol in female rats

Year 2016, Volume: 29 Issue: 2, 95 - 101, 01.04.2016
https://doi.org/10.5472/MMJoa.2902.06

Abstract

Objectives: This study investigates the estrogen-like effects of resveratrol (RES) in female rats.Materials and Methods: In this two-step study on estrogenlike activity of RES, immature female rats (21 days old) were used in the first step and pubertal female rats (28 days old) with primary ovarian failure (POF) induced by 4-vinylcyclohexene diepoxide (VCD) were used in the second step. Possible agonistic and/or antagonistic effects of RES were investigated by using several parameters including the ratios of uterine/body weights (UBW), uterine dry/wet weights (UDWW) and body weight increase (BW%), bone density measurement, serum estradiol and vitamin D levels and histological evaluation.Results: In immature rats, RES resulted in an increase in UBW equal to that produced by 17 alpha-ethinyl estradiol (17alphaEE). The minimum effective dose for RES was 10 mg/kg. This effect was not decreased by tamoxifen but was significantly antagonized by fulvestrant. Similarly, tamoxifen did not abolish the effects ofRES completely in rats with POF. However, in rats with VCDinduced POF, tamoxifen resulted in lower UBW values and estradiol levels were significantly higher in 17alphaEE-treated, RES+tamoxifen-treated and 17 beta-estradiol (17betaE)-treated rats compared to control animals.Conclusion: The dose of RES may be important in terms of estrogenic activity and even RES may modulate the effects of estrogen.Keywords: Estrogen, Resveratrol, 4-vinylcyclohexene diepoxide, Primary ovarian failure

References

  • Jiang H, Zhang L, Kuo J, et al. Resveratrol-induced apoptotic death in human U251 glioma cells. Mol Cancer Ther 2005; 4:554-61. doi: 10.1158/1535-7163.MCT-04-0056
  • Frémont L. Biological effects of resveratrol. Life Sci 2000;66:663-73. doi:10.1016/S0024-3205(99)00410-5
  • Wolter F, Ulrich S, Stein J. Molecular mechanisms of the chemopreventive effects of resveratrol and its analogs in colorectal cancer. J Nutr 2004;134:3219-22.
  • Gehm BD, McAndrews JM, Chien P-Y, Jameson JL. Resveratrol, a polyphenolic compound found in grapes and wine, is agonist for estrogen receptor. Proc Natl Acad Sci USA 1997; 94:14138-43. doi:10.1073/pnas.94.25.14138
  • Turner RT, Evans GL, Zhang M, Maran A, Sibonga JD. Is resveratrol an estrogen agonist in growing rats? Endocrinology 1999;140:50-4. doi: 10.1210/endo.140.1.6460
  • Lu R, Serrero G. Resveratrol, a natural product derved from grape, exhibits antiestrogenic activity and inhibits the growth of human breast cancer cells. J Cell Physiol 1999;179:297-304. doi: 10.1002/(SICI)1097-4652(199906)179:3<297::AIDJCP7>
  • 0.CO;2-P
  • Bhat KP, Pezzuto JM. Resveratrol exhibits cytostatic and antiestrogenic properties with human endometrial adenocarcinoma (Ishikawa) cells. Cancer Res 2001; 61:6137-44.
  • Eppenberger U, Woslkowski K, Kung W. Pharmacological and biological properties of droloxifene, a new antiestrogen. Am J Clin Oncol 1991; 14: 5-14.
  • Hoyer PB, Sipes IG. Development of an animal model for ovotoxicity using, 4-vinyl cyclohexene: a case study. Birth Defects Res B Dev Reprod Toxicol 2007; 80:113-25.doi: 10.1002/bdrb.20103
  • Kappeler CJ, Hoyer PB. 4-vinylcyclohexene diepokside: a model chemical for ovotoxicity. Syst Biol Reprod Med 2012; 58: 57-62. doi: 10.3109/19396368.2011.648820.
  • Ke HZ, Paralkar VM, Grasser WA, et al. Effects of CP-336,156, a new nonsteroidal estrogen agonist/antagonist, on bone, serum cholesterol, uterus, and body composition in rat models. Endocrinology 1998; 139: 2068-76. doi: 10.1210/endo.139.4.5902
  • Muhammad FS, Goode AK, Kock ND, et al. Effects of 4-vinylcyclohexene diepoxide on peripubertal and adult Sprague-Dawley Rats: Ovarian, Clinical and Pathological Outcomes. Comparative Medicine 2009; 59:46-59.
  • Odum J, Tinwell H, Van Miller J, Joiner R, Ashby J. The uterotropic activity of nonylphenol in the rat is not mediated by aromatase enzyme induction. Toxicology Letters 2001; 118:165-69. doi: 10.1016/S0378-4274(00)00293-9
  • Oseni T, Patel R, Pyle J, Jordan VC. Selective Estrogen Receptor Modulators and Phytoestrogens. NIH Public Access 2008; 74;1656-65. doi: 10.1055/s-0028-1088304
  • Heather B, Patisaul HB, Whitten P. Dietary phytoestrogens.
  • In: Naz RK, editor. Endocrine disruptors:effects on male and female reproductive systems. 2nd ed. Boca Raton 2004, CRC Press: 135-75.
  • Assikis VJ, Neven P, Jordan VC, Vergote I. A realistic clinical perspective of tamoxifen and endometrial carcinogenesis. Eur J Cancer 1996 32A:1464-76. doi: 10.1016/0959-8049(96)00184-0
  • Moutsatsou P. The spectrum of phytoestrogens in nature:our knowledge is expanding . Hormones 2007; 6:173-93.
  • Bhat KP, Lantvit D, Christov K, Mehta RG, Moon RC, Pezzuto JM. Estrogenic and antiestrogenic properties of resveratrol in mammary tumor models. Cancer Res 2001;61:7456-63.
  • Bowers JL, Tyulmenkov VV, Jernigan SC, Klinge JM. Resveratrol acts as mixed agonist/antagonist for estrogen receptors alpha and beta. Endocrinology 2000;141:3657-67. doi: 10.1210/endo.141.10.7721
  • Cuccıolla V, BorrielloA, Oliva A, Patrizia G, Zappia V, Della Ragione F. Resveratrol: From basic science to clinic. Cell Cycle 2007; 6: 2495-510. doi: 10.4161/cc.6.20.4815
  • Dundar Y, Ozatik Y, Ozatik O, et al. Synthesis and biological evaluation of the salicylamide and salicylic acid derivatives as anti-estrogen agents. Med Chem 2012; 8:481-90. :10.2174/1573406411208030481
  • Leonard SS, Xia C, Jiang BH, et al. Resveratrol scavenges reactive oxygen species and effects radical-induced cellular responses. Biochem Biophys Res Commun 2003; 309:1017-26. doi:10.1016/j.bbrc.2003.08.105
  • Cao Z, Li Y. Potent induction of cellular antioxidants and phase 2 enzymes by resveratrol in cardiomyocytes: protection against oxidative and electrophilic injury. Eur J Pharmacol 2004;489(1-2):39-48. doi:10.1016/j.ejphar.2004.02.031
  • Li Y, Cao Z, Zhu H. Upregulation of endogeneous antioxidants and phase 2 enzymes by red wine polyphenol, resveratrol in cultured aortic smooth muscle cells leads to cytoprotection against oxidative and electrophilic stres. Pharmacol Res 2006;53:6-15. doi:10.1016/j.phrs.2005.08.002
  • Kasdallah-Grissa A, Mornagui B, Aouani E, et al. Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stres in rat liver. Life Sci 2007; 80:1033-39. doi:10.1016/j.lfs.2006.11.044
  • Ajmo JM, Liang X, Rogers CQ, Pennock B, You M. Resveratrol alleviates alcholic fatty liver in mice. Am J Physiol Gastrointes Liver Physiol 2008; 295:833-42. doi:10.1152/ajpgi.90358.2008.
  • Lohff JC, Christian PJ, Marion SL, Arrandale A, Hoyer PB. Characterization of cyclicity and hormonal profile with impending ovarian failure in a novel chemical-induced Mouse model of perimenopause. Comparative Medicine 2006;55:523-7.
There are 29 citations in total.

Details

Subjects Clinical Sciences
Other ID JA65PF97UZ
Journal Section Review Makaleler
Authors

Fikriye Yasemin Özatik This is me

Kevser Erol This is me

Orhan Özatik This is me

Publication Date April 1, 2016
Published in Issue Year 2016 Volume: 29 Issue: 2

Cite

APA Özatik, F. Y., Erol, K., & Özatik, O. (2016). Estrogen modulating effects of resveratrol in female rats. Marmara Medical Journal, 29(2), 95-101. https://doi.org/10.5472/MMJoa.2902.06
AMA Özatik FY, Erol K, Özatik O. Estrogen modulating effects of resveratrol in female rats. Marmara Med J. April 2016;29(2):95-101. doi:10.5472/MMJoa.2902.06
Chicago Özatik, Fikriye Yasemin, Kevser Erol, and Orhan Özatik. “Estrogen Modulating Effects of Resveratrol in Female Rats”. Marmara Medical Journal 29, no. 2 (April 2016): 95-101. https://doi.org/10.5472/MMJoa.2902.06.
EndNote Özatik FY, Erol K, Özatik O (April 1, 2016) Estrogen modulating effects of resveratrol in female rats. Marmara Medical Journal 29 2 95–101.
IEEE F. Y. Özatik, K. Erol, and O. Özatik, “Estrogen modulating effects of resveratrol in female rats”, Marmara Med J, vol. 29, no. 2, pp. 95–101, 2016, doi: 10.5472/MMJoa.2902.06.
ISNAD Özatik, Fikriye Yasemin et al. “Estrogen Modulating Effects of Resveratrol in Female Rats”. Marmara Medical Journal 29/2 (April 2016), 95-101. https://doi.org/10.5472/MMJoa.2902.06.
JAMA Özatik FY, Erol K, Özatik O. Estrogen modulating effects of resveratrol in female rats. Marmara Med J. 2016;29:95–101.
MLA Özatik, Fikriye Yasemin et al. “Estrogen Modulating Effects of Resveratrol in Female Rats”. Marmara Medical Journal, vol. 29, no. 2, 2016, pp. 95-101, doi:10.5472/MMJoa.2902.06.
Vancouver Özatik FY, Erol K, Özatik O. Estrogen modulating effects of resveratrol in female rats. Marmara Med J. 2016;29(2):95-101.