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THE ROLE OF SELECTİVE ESTROGEN MODULATOR BAZEDOXIFENE IN THE TREATMENT OF ENDOMETRIOSIS IN A RAT MODEL

Year 2013, Volume: 10 Issue: 39, 1604 - 1608, 01.07.2013

Abstract

Aim: The only factor that is proved on the pathogenesis of endometriosis is estrogen. The aim of this study is to investigate the effect of bazedoxifene, a third generation selective estrogen receptor modulator, on the endometriotic implants in the rat endometriosis model by using histopathological examination and immunohistochemical assays.Materials and Method: This randomized, placebocontrolled, experimental study was conducted in the Animal Research Laboratory at Ankara Education and Research Hospital. The study was performed on 20 Wistar female albino rats. Experimental endometriosis model was constituted with implantation of autologous endometrial tissue on the right side of the pelvic wall. The endometriotic implants were examined by second laparatomy after 30 days, and the rats were divided randomly into two groups. Group 1 received 3 mg/ kg Bazedoxifene n =10 per oral, once a day, for 30 more days. Group 2 n =10 was the control group and did not receive any medical treatment. After 30 days of treatment period, the third laparatomy was performed, endometriotic lesions volumes were measured, and endometriotic foci were extracted for histopatological and immunohistochemical evaluation. Histopathological scoring was evaluated according to preservation of epithelial layer. In addition, endometrial implants were evaluated immunohistochemically for VEGF, MMP-2 and MMP-9. Results: The volumes of the lesions were smaller in the group which was treated with bazedoxifene than the ones in the control group which was statistically significant p

References

  • Sidell N, Han SW, Parthasarathy S. Regulation and modulation of abnormal immune responses in endometriosis. Ann N Y Acad Sci 2002;955:159–73. 2. Wheeler JM, Malinak LR. Recurrent endometriosis: incidence, management, and prognosis. Am J Obstet Gynecol 1983; 146(3):247-53.
  • Taylor E, Williams C. Surgical treatment of endometriosis: location and patterns of disease at reoperation. Fertil Steril 2010; 93:57-61.
  • Kulak J Jr, Fischer C, Komm B, Taylor HS. Treatment with bazedoxifene, a selective estrogen receptor modulator, causes regression of endometriosis in a mouse model. Endocrinology 152(8):3226-32. 2011doi: 10.1210/en.2010-1010. Epub 2011 May 17.
  • Komm BS, Kharode YP, Modine PV, Harris HA, Miller CP, Lyttle CR. Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity. Endocrinology 2005;146:3999-4008.
  • Ronkin S, Northington R, Baracat E, et al. Endometrial effects of bazedoxifene acetate, a novel selective estrogen receptor modulator, in postmenopausal women. Obstet Gynecol 2005;105(6):1397-404.
  • Morello KC, Wurz GT, DeGregorio MW. Pharmacokinetics of selective estrogen receptor modulators. Clin Pharmacokinet 2003;42:361-72.
  • Chris P. Spencer, MD, Edward P. Morris and Janice M. Selective estrogen receptor modulators: Women’s panacea for the next millennium? Am J Obstet Gynecol 1999; 180: 763-70.
  • Maeda K, Ohkura S, Tsukamura H. Physiology of the reproduction. In: Krinke GJ, editor. The laboratory rat (Handbook of experimental animals) London:Academic Press; 2000.p.148-149
  • Yao Z, Shen X, Capodanno I, et al: Validation of rat endometriosis model by using raloxifene as a positive control for the evaluation of novel SERM compounds. J Invest Surg 2005;18:177–83.
  • Oba G, Aslan S, Yılmaz M. Gebelik ve siklus dönemlerinin belirlenmesi ama-cıyla ratlarda vajinal sitolojinin kullanılması. Ankara Üniv Vet Fak Derg 2001;48:51-7.
  • Osteen KG, Igarashi TM, Bruner-Tran KL. Progesterone action in the human endometrium: induction of a unique tissue environment which limits matrix metalloproteinase (MMP) expression. Front Biosci 2003 Jan 1;8:d78 86.
  • D’Hodge TM, Hill JA. Endometriosis. In Novak Gynecology 12th ed. Williams and Wilkins Baltimore 1996; 26: 887- 914.

SELEKTİF ESTROJEN RESEPTÖR MODÜLATÖRÜ OLAN BAZEDOKSİFENİN RAT MODELİNDE OLUŞTURULAN ENDOMETRİOZİS TEDAVİSİNDEKİ ROLÜ

Year 2013, Volume: 10 Issue: 39, 1604 - 1608, 01.07.2013

Abstract

Amaç: Endometriozisin gelişiminde rol aldığı kesin olarak gösterilmiş tek faktör östrojendir. Bu çalışmanın amacı; ratlarda deneysel olarak oluşturulan endometriozis modelinde, üçüncü jenerasyon selektif östrojen reseptör modülatörü olan bazedoksifenin endometriotik odaklar üzerindeki etkisini histopatolojik ve immünohistokimyasal yöntemler kullanarak araştırmaktır. Gereçler ve Yöntem: Bu randomize, plasebo kontrollü, deneysel araştırma Ankara Eğitim ve Araştırma Hastanesi Deney Hayvanları Laboratuvar’ında yürütülmüştür. Araştırma için 20 adet Wistar Albino türü dişi rat kullanılmıştır. Otolog endometrial dokunun sağ pelvik yan duvara implante edilmesiyle ratlarda deneysel endometriozis modeli oluşturulmuştur. Otuz günlük iyileşme periodundan sonra endometriozis odakları ikinci laparatomiyle değerlendirilmiş ve ratlar randomize olarak iki gruba ayrılmıştır. Tedavi grubu olan Grup I ' e n =10 3 mg/kg Bazedoksifen oral olarak günde bir kez otuz gün boyunca verilmiştir. Kontrol grubu olan Grup II ' ye n =10 ise herhangi bir medikal tedavi verilmemiştir. Otuz gün sonra üçüncü laparatomi gerçekleştirilerek tedavi ve kontrol gruplarındaki endometriotik odaklar çevre dokuyla birlikte histolojik ve immünohistokimyasal inceleme için çıkarılıp patolojik incelemeye gönderilmiştir. Histopatolojik skor epitelyal tabakanın korunması esasına göre değerlendirilmiştir. İlaveten endometrial implantların, VEGF, MMP-2 ve MMP-9 için immünohistokimyasal incelemeleri de yapılmıştır.Bulgular: Tedavi alan grup ile kontrol grubunun endometriotik lezyon hacimleri karşılaştırıldığında tedavi alan grupta kontrol grubuna göre lezyon hacimlerinin anlamlı olarak düşük olduğu saptanmıştır. p

References

  • Sidell N, Han SW, Parthasarathy S. Regulation and modulation of abnormal immune responses in endometriosis. Ann N Y Acad Sci 2002;955:159–73. 2. Wheeler JM, Malinak LR. Recurrent endometriosis: incidence, management, and prognosis. Am J Obstet Gynecol 1983; 146(3):247-53.
  • Taylor E, Williams C. Surgical treatment of endometriosis: location and patterns of disease at reoperation. Fertil Steril 2010; 93:57-61.
  • Kulak J Jr, Fischer C, Komm B, Taylor HS. Treatment with bazedoxifene, a selective estrogen receptor modulator, causes regression of endometriosis in a mouse model. Endocrinology 152(8):3226-32. 2011doi: 10.1210/en.2010-1010. Epub 2011 May 17.
  • Komm BS, Kharode YP, Modine PV, Harris HA, Miller CP, Lyttle CR. Bazedoxifene acetate: a selective estrogen receptor modulator with improved selectivity. Endocrinology 2005;146:3999-4008.
  • Ronkin S, Northington R, Baracat E, et al. Endometrial effects of bazedoxifene acetate, a novel selective estrogen receptor modulator, in postmenopausal women. Obstet Gynecol 2005;105(6):1397-404.
  • Morello KC, Wurz GT, DeGregorio MW. Pharmacokinetics of selective estrogen receptor modulators. Clin Pharmacokinet 2003;42:361-72.
  • Chris P. Spencer, MD, Edward P. Morris and Janice M. Selective estrogen receptor modulators: Women’s panacea for the next millennium? Am J Obstet Gynecol 1999; 180: 763-70.
  • Maeda K, Ohkura S, Tsukamura H. Physiology of the reproduction. In: Krinke GJ, editor. The laboratory rat (Handbook of experimental animals) London:Academic Press; 2000.p.148-149
  • Yao Z, Shen X, Capodanno I, et al: Validation of rat endometriosis model by using raloxifene as a positive control for the evaluation of novel SERM compounds. J Invest Surg 2005;18:177–83.
  • Oba G, Aslan S, Yılmaz M. Gebelik ve siklus dönemlerinin belirlenmesi ama-cıyla ratlarda vajinal sitolojinin kullanılması. Ankara Üniv Vet Fak Derg 2001;48:51-7.
  • Osteen KG, Igarashi TM, Bruner-Tran KL. Progesterone action in the human endometrium: induction of a unique tissue environment which limits matrix metalloproteinase (MMP) expression. Front Biosci 2003 Jan 1;8:d78 86.
  • D’Hodge TM, Hill JA. Endometriosis. In Novak Gynecology 12th ed. Williams and Wilkins Baltimore 1996; 26: 887- 914.
There are 12 citations in total.

Details

Primary Language Turkish
Journal Section Research Article
Authors

Senem Mine Keskin This is me

Hacer Cavidan Gülerman This is me

Özlem Moraloğlu

Özlem Uzunlar This is me

Şebnem Özyer This is me

Ayla Aktulay This is me

Muzaffer Çaydere This is me

Publication Date July 1, 2013
Published in Issue Year 2013 Volume: 10 Issue: 39

Cite

Vancouver Keskin SM, Gülerman HC, Moraloğlu Ö, Uzunlar Ö, Özyer Ş, Aktulay A, Çaydere M. SELEKTİF ESTROJEN RESEPTÖR MODÜLATÖRÜ OLAN BAZEDOKSİFENİN RAT MODELİNDE OLUŞTURULAN ENDOMETRİOZİS TEDAVİSİNDEKİ ROLÜ. JGON. 2013;10(39):1604-8.