Estrogen modulating effects of resveratrol in female rats

95 - 101, 15.05.2016

Fikriye Özatık Kevser Erol Orhan Özatik

https://doi.org/10.5472/MMJoa.2902.06

Cited By: 1

Öz

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 of

RES 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.

Anahtar Kelimeler

Estrogen, Resveratrol, 4-vinylcyclohexene diepoxide, Primary ovarian failure

Resveratrolün dişi sıçanlarda oluşturduğu estrojen modülatörü etkileri

Öz

Amaç: Çalışmamızda resveratrol (RES)’ün dişi sıçanlarda oluşturduğu estrojenik etkilerin incelenmesi amaçlanmıştır. Gereç ve Yöntem: Çalışmamızın ilk aşamasında, RES’ün, immatür (21 günlük) dişi sıçanlarda, 2. aşamasında 4-vinilsiklohekzen diepoksid (VCD) enjeksiyonu ile primer over yetmezliği (POY) oluşturulan puberte dönemindeki (28 günlük) dişi sıçanlarda oluşturduğu estrojenik etkileri incelenmiştir. RES’ün agonist ve/veya antagonist etkileri çeşitli parametreler kullanılarak araştırılmıştır. Bu parametreler uterus ağırlığı/vücut ağırlığı oranları(UA/VA), uterus kuru ağırlığı/uterus yaş ağırlığı oranları (UKA/UYA), VA artış oranları, kemik dansitometresi, serum estradiol ve vitamin D değerleri ve histolojik değerlendirmedir. Bulgular: İmmatür sıçanlarda UA/VA oranları değerlendirmesinde RES, UA/VA oranını 17 alfa-etinil estradiol (17alfaEE)’e benzer bir şekilde arttırmıştır. En düşük anlamlı etki 10 mg/kg RES dozunda görülmüştür. Bu etki tamoksifen ile azalmazken fulvestrant ile anlamlı bir şekilde antagonize edilmiştir. POY oluşturulmuş dişi sıçanlarda da tamoksifen, RES’ün etkilerini tamamen ortadan kaldırmamıştır. UA/VA değerleri açısından POY geliştirilmiş sıçanlarda VCD+RES10mg/kg+tamoksifen verilen grubun ortalama değerlerinin, VCD+RES 10mg/kg verilen grubun ortalama değerlerinden daha düşüktür. POY geliştirilmiş sıçanlarda estradiol değerleri incelendiğinde, VCD+17alfaEE, sıçanlarda VCD+RES 10mg/kg+tamoksifen ve VCD+17 betaestradiol (17betaE) verilen gruplarda estradiol değerlerinin kontrol değerlerine göre anlamlı derecede arttığı gözlenmektedir. Sonuç: Çalışmamızın sonucuna göre estrojenik aktivite açısından RES’ün dozu önemli bir faktör olabilir ve RES’ün estrojen modülatörü olarak etki ettiği söylenebilir

Anahtar Kelimeler

Estrojen, Resveratrol, 4-vinilsikloheksen diepoksid, Primer over yetmezliği

Kaynakça

• 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::AID- JCP7>3.0.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: 10.1016/09598049(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.