Ulipristal Asetatın Ratlarda Oluşturulan Cerrahi Endometriozise Etkisi

Yıl 2022, Cilt: 2 Sayı: 3, 15 - 19, 22.12.2022

Mehmet Nuri Duran Hacı Öztürk Şahin Nihal Kılınç Bülent Demir

https://doi.org/10.58252/artukluder.1180091

Öz

Amaç: Ulipristal Asetat'ın ratlarda oluşturulan endometriozis odakları üzerindeki etkisinin araştırılması hedeflendi.
Gereç ve Yöntem: Çalışma, yaklaşık 280 gram ağırlığında 12 haftalık ratlarla yürütüldü. Otolog endometriozis modeli oluşturulduktan sonra, ulipristal asetat almayan gruba günlük oral salin, ulipristal asetat verilen gruba ise 4 hafta süreyle 0.5 mg/kg (0.125 mg/rat/gün) oral yolla verildi. Histopatolojik ve immünohistokimyasal değerlendirmeler için ektopik endometriyal dokular çıkarıldı. Boyama Hematoksilen-Eozin, Ki-67 ve Siklooksijenaz-2 ile yapıldı.
Bulgular: Ektopik endometrium yüzey epitelinin Hematoksilen-Eozin Boyama skoru ulipristal asetat negatif grubunda 2,5 puan, ulipristal asetat pozitif grubunda 0,5 puan olarak bulundu. İmmünhistokimyasal değerlendirmede ektopik endometriyal yüzey epitelinin Ki-67 pozitifliği ulipristal asetat negatif grubunda %71.2, ulipristal asetat pozitif grubunda ise %31,7 olarak bulundu. Siklooksijenaz-2 pozitifliği ulipristal asetat negatif grubunda %67, ulipristal asetat pozitif grubunda ise %27 olarak tespit edildi.
Sonuçlar: Hematoksilen-Eozin boyaması, ulipristal asetat negatif grubunun 2.5 (iyi-orta derecede korunmuş epitel) ve ulipristal asetat pozitif grubunun 0.5 (epitel nadiren var veya yok) olduğunu ortaya koydu. Ulipristal asetat pozitif grubunda Ki-67 ve Siklooksijenaz-2 immünohistokimyasal pozitiflik yüzdesinin ulipristal asetat negatif grubuna göre istatistiksel olarak anlamlı düzeyde azaldığı bulundu. Bu konuda daha fazla literatür verisine ihtiyaç vardır.

Anahtar Kelimeler

Rat model, ulipristal asetat, Endometriozis, COX-2, Ki-67

The Effect of Ulipristal Acetate on Surgical Endometriosis Created in Rats

Öz

Objective: The effect of Ulipristal Acetate on endometriosis foci created in rats was investigated.
Methods: The study was conducted with 12-week-old rats weighing approximately 280 grams. After creating an autologous endometriosis model, the group that did not receive ulipristal acetate negative was administered with oral saline daily, and the group given ulipristal acetate positive was administered with 0.5 mg/kg (0.125 mg/rat/day) orally for 4 weeks. Ectopic endometrial tissues were removed for histopathological and immunohistochemical evaluations. Staining was performed with Hematoxylin Eosin, Ki-67, and Cyclooxygenase-2.
Results: The Hematoxylin-Eosin Staining score of the ectopic endometrium surface epithelium was found to be 2.5 points in the ulipristal acetate negative group, and 0.5 points in the ulipristal acetate positive group. In the immunohistochemical evaluation, Ki-67 positivity of the ectopic endometrial surface epithelium was found to be 71.2% in the ulipristal acetate negative group vs. 31.7% in the ulipristal acetate positive group. Cyclooxygenase-2 positivity was detected as 67% in the ulipristal acetate negative group vs. 27% in the ulipristal acetate positive group.
Conclusions: Hematoxylin-Eosin staining revealed that ulipristal acetate negative group was 2.5 (well-moderately preserved epithelium), and the ulipristal acetate positive group was 0.5 (epithelium was rarely present or absent). It was found that the percentage of Ki-67 and Cyclooxygenase-2 immunohistochemical positivity was decreased in the ulipristal acetate positive group compared to the ulipristal acetate negative group at a statistically significant level. More literature data are needed on this subject.

Anahtar Kelimeler

Rat model, Ulipristal acetate, Endometriosis, COX-2, Ki-67

Kaynakça

• Giudice LC, Kao LC. Endometriosis. The Lancet. 2004;364(9447):1789-1799.
• Bulun SE, Yilmaz BD, Sison C, et al. Endometriosis. Endocrine Reviews. 2019;40(4):1048-1079.
• Meuleman C, Vandenabeele B, Fieuws S, Spiessens C, Timmerman D, D’Hooghe T. High prevalence of endometriosis in infertile women with normal ovulation and normospermic partners. Fertility and Sterility. 2009;92(1):68-74.
• Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstetrics and Gynecology Clinics of North America. 1997;24(2):235-258.
• Chaichian S. It is the time to treat endometriosis based on pathophysiology. Journal of Reproduction & Infertility. 2019;20(1):1-2.
• Ferrero S, Barra F, Leone Roberti Maggiore U. Current and emerging therapeutics for the management of endometriosis. Drugs. 2018;78(10):995-1012.
• Chwalisz K, Garg R, Brenner RM, Schubert G, Elger W. Selective progesterone receptor modulators (SPRMs): a novel therapeutic concept in endometriosis. Annals of the New York Academy of Sciences. 2002;955:373-393,396-406.
• Huniadi CA, Pop OL, Antal TA, Stamatian F. The effects of ulipristal on Bax/Bcl-2, cytochrome C, Ki-67 and cyclooxygenase-2 expression in a rat model with surgically induced endometriosis. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2013;169(2):360-365.
• Scholzen T, Gerdes J. The Ki-67 protein: from the known and the unknown. Journal of Cellular Physiology. 2000;182(3):311-322.
• Ota H, Igarashi S, Sasaki M, Tanaka T. Distribution of cyclooxygenase-2 in eutopic and ectopic endometrium in endometriosis and adenomyosis. Human Reproduction. 2001;16(3):561-566.
• Noble LS, Takayama K, Zeitoun KM, et al. Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells. The Journal of Clinical Endocrinology & Metabolism. 1997;82(2):600-606.
• Jarzabek K, Koda M, Walentowicz-Sadlecka M, Grabiec M, Laudanski P, Wolczynski S. Altered expression of ERs, aromatase, and COX2 connected to estrogen action in type 1 endometrial cancer biology. Tumour Biology : The Journal of the International Society for Oncodevelopmental Biology and Medicine. 2013;34(6):4007-4016.
• Özkul T. Deney Hayvanlarının Kullanımında Genel Mevzuat, Düzenleme ve Kurallar. Ankara: Derman Medical Publishing; 2006:1-4.
• Thatte U, Puri K, Suresh K, Gogtay N. Declaration of Helsinki, 2008: Implications for stakeholders in research. Journal of Postgraduate Medicine. 2009;55(2):131.
• Keenan JA, Williams-Boyce PK, Massey PJ, Chen TT, Caudle MR, Bukovsky A. Regression of endometrial explants in a rat model of endometriosis treated with the immune modulators loxoribine and levamisole. Fertility and Sterility. 1999;72(1):135-141.
• Sanketh DS, Kumari K, Rao RS, et al. Expression of Ki-67, p53, α-SMA and COX-2 in lichen planus and related lesions: A pilot study. Journal of Oral Biology and Craniofacial Research. 2019;9(2):230-235.
• Singh SS, Evans D, Mcdonald S, Senterman M, Strickland S. Ulipristal acetate prior to surgery for endometriosis. Reproductive Sciences. 2020;27:1707–1714.
• Singh SS, Suen MWH. Surgery for endometriosis: Beyond medical therapies. Fertility and Sterility. 2017;107(3):549-554.
• Wagenfeld A, Saunders PTK, Whitaker L, Critchley HOD. Selective progesterone receptor modulators (SPRMs): Progesterone receptor action, mode of action on the endometrium and treatment options in gynecological therapies. Expert Opinion on Therapeutic Targets. 2016;20(9):1045-1054.
• Rozenberg S, Praet J, Pazzaglia E, Gilles C, Manigart Y, Vandromme J. The use of selective progestin receptor modulators (SPRMs) and more specifically ulipristal acetate in the practice of gynaecology. The Australian & New Zealand Journal of Obstetrics & Gynaecology. 2017;57(4):393-399.
• Dolmans M, Donnez J, Fellah L. Uterine fibroid management: Today and tomorrow. Journal of Obstetrics and Gynaecology Research. 2019;45(7):1222-1229.
• Donnez J, Tatarchuk TF, Bouchard P, et al. Ulipristal acetate versus placebo for fibroid treatment before surgery. The New England Journal of Medicine. 2012;366(5):409-420.
• Conway F, Morosetti G, Camilli S, et al. Ulipristal acetate therapy increases ultrasound features of adenomyosis: A good treatment given in an erroneous diagnosis of uterine fibroids. Gynecological Endocrinology. 2019;35(3):207-210.
• Donnez J, Arriagada P, Marciniak M, Larrey D. Liver safety parameters of ulipristal acetate for the treatment of uterine fibroids: a comprehensive review of the clinical development program. Expert Opinion on Drug Safety. 2018;17(12):1225-1232.