Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model

YILDIRIM, Gazi; FIÇICIOĞLU, Cem; YEŞİLDAĞLAR, Narter; ÖZKAN, Ferda; KOCADAL ÇETİNKAYA, Nilüfer; YILMAZ, Bayram; Attar, Rukset

Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model

Nilüfer KOCADAL ÇETİNKAYA, (Yeditepe Üniversitesi, Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabilim Dalı, İstanbul, Türkiye)

Rukset ATTAR, (Yeditepe Üniversitesi, Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabilim Dalı, İstanbul, Türkiye)

Gazi YILDIRIM, (Yeditepe Üniversitesi, Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabilim Dalı, İstanbul, Türkiye)

Cem FIÇICIOĞLU, (Yeditepe Üniversitesi, Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabilim Dalı, İstanbul, Türkiye)

Narter YEŞİLDAĞLAR, (Yeditepe Üniversitesi, Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabilim Dalı, İstanbul, Türkiye)

Ferda ÖZKAN, (Yeditepe Üniversitesi, Tıp Fakültesi, Patoloji Anabilim Dalı, İstanbul, Türkiye)

Bayram YILMAZ (Yeditepe Üniversitesi, Tıp Fakültesi, Psikiyatri Anabilim Dalı, İstanbul, Türkiye)

Journal of the Turkish-German Gynecological Association

14 0

Yıl: 2013 Cilt: 14 Sayı: 2 Sayfa Aralığı: 81 - 86 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model

Öz:

Amaç: Ooferektomize sıçan endometriozis modelinde melatoninin endometriotik odaklar üzerine etkisini incelemeyi amaçladık Gereç ve Yöntemler: Bu çalışma prospektif, randomize, kontrollü, deneysel bir çalışmadır. Çalışma Yeditepe Üniversitesi Deneysel Araştırma Merkezinde (YÜDETAM) yapıldı. Deneysel çalışmamıza 22 adet dişi, gebe olmayan, nulligravid Spraque-Dawley albino sıçan dahil edildi. Ooferektomize edilen sıçanlarda cerrahi olarak endometriozis oluşturuldu. Sıçanlar iki gruba ayrıldı: kontrol grubu ve melatonin grubu. Melatonin grubunda 2 hafta boyunca sıçanlara melatonin (20 mg/ kg/gün) tedavisi verildi. Endometriotik regresyonu değerlendirmek için operasyonlar yapıldıktan sonra melatonin tedavisi sonlandırıldı. Rekürrens oranlarını değerlendirmek için altıncı haftanın sonunda nekropsiler yapıldı. Endometriotik odakların hacim ve histopatolojik skorları değerlendirildi. Bulgular: Endometriotik lezyonların hacimleri melatonin grubunda anlamlı derecede azaldı. Ayrıca, melatonin grubu kendi içerisinde incelendiğinde endometriotik lezyonların hacimlerinin anlamlı derecede azaldı ve histopatolojik skorları anlamlı derecede arttı. Sonuç: Melatonin sıçanlarda endometriotik odakların gerilemesine ve histopatolojik skorların iyileşmesine neden olur. (J Turkish-German Gynecol Assoc 2013; 14: 81-6)

Anahtar Kelime:

Konular: Kadın Hastalıkları ve Doğum

Melatonin tedavisi ooferektomize sıçanlar endometriozis modelinde endometriotik odaklarda gerilemeye yol açar

Öz:

Objective: We aimed to determine the effects of melatonin treatment on endometrial implants in an oopherectomized rat endomeriosis model.Material and Methods: This study is a prospective, randomised,controlled experimental study. It was carried out at the Experimenal Research Center of Yeditepe University (YUDETAM). Twenty-two,emale, non-pregnant, nulligravid Spraque-Dawley albino rats werencluded in our study. Endometriosis was surgically induced in oopherectomized rats. Rats were randomised into two groups: controlgroup and melatonin group. In the melatonin group, rats were treatedwith melatonin (20 mg/kg/day) for two weeks. After the operationswere performed to assess the regression of the endometriotic lesions,melatonin treatment was stopped. At the end of the sixth week nec-ropsies were performed to assess the rate of recurrence. The volumeand histopathological scores of endometriotic foci were examined.Results: Volumes of the endometriotic lesions significantly decreased in the melatonin group. Also, when the melatonin group wasanalysed within itself, endometriotic lesion volumes decreased andhistopathological scores increased significantly.Conclusion: Melatonin causes regression of the endometriotic lesions in rats and improvement in their histopathological scores.(J Turkish-German Gynecol Assoc 2013; 14: 81-6)

Anahtar Kelime:

Konular: Kadın Hastalıkları ve Doğum

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

Olive DL, Schwartz LB. Endometriosis. N Engl J Med 1993; 328: 1759-69.
Witz CA. Current concepts in the pathogenesis of endometriosis. Clin Obstet Gynecol 1999; 42: 566-85.
Sampson JA. Peritoneal endometriosis due to the menstrual dis- semination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 1927; 14: 422-69.
Blumenkrantz MJ, Gallagher N, Bashore RA, Tenckhoff H. Retrograde menstruation in women undergoing chronic peritoneal dialysis. Obstet Gynecol 1981; 57: 667-70.
Halme J, Hammond MG, Hulka JF, Raj SG, Talbert LM. Retrograde menstruation in healthy women and in patients with endometrio- sis. Obstet Gynecol 1984; 64: 151-4.
Houston DE, Noller KL, Melton LJ 3rd, Selwyn BJ, Hardy RJ. Incidence of pelvic endometriosis in Rochester, Minnesota, 1970- 1979. Am J Epidemiol 1987; 125: 959-69.
Kjerulff KH, Erickson BA, Langenberg PW. Chronic gynecological conditions reported by US women: findings from the National Health Interview Survey, 1984 to 1992. Am J Public Health 1996; 86: 195-9.
Berkkanoglu M, Arici A. Immunology and endometriosis. Am J Reprod Immunol 2003; 50: 48-59.
Gupta S, Agarwal A, Krajcir N, Alvarez JG. Role of oxidative stress in endometriosis. Reprod Biomed Online 2006; 13: 126-34.
Van Langendonckt A, Casanas-Roux F, Donnez J. Iron overload in the peritoneal cavity of women with pelvic endometriosis. Fertil Steril 2002; 78: 712-8.
Ota H, Igarashi S, Hatazawa J, Tanaka T. Immunohistochemical assessment of superoxide dismutase expression in the endome- trium in endometriosis and adenomyosis. Fertil Steril 1999; 72: 129-34.
Ota H, Igarashi S, Kato N, Tanaka T. Aberrant expression of glutathi- one peroxidase in eutopic and ectopic endometrium in endome- triosis and adenomyosis. Fertil Steril 2000; 74: 313-8.
Szczepanska M, Kozlik J, Skrzypczak J, Mikolajczyk M. Oxidative stress may be a piece in the endometriosis puzzle. Fertil Steril 2003; 79: 1288-93.
Polak G, Koziol-Montewka M, Gogacz M, Tarkowski R, Kotarski J. Total antioxidant status of peritoneal fluid in infertile women. Europ J Obstet Gynecol Reprod Biol 2001; 94: 261-3.
Matrisian LM. Metalloproteinases and their inhibitors in matrix remodeling. Trends Genet 1990; 6: 121-5.
Birkedal-Hansen H, Moore WG, Bodden MK, Windsor LJ, Birkedal- Hansen B, DeCarlo A, et al. Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 1993; 4: 197-250.
Nagase H. Activation mechanisms of matrix metalloproteinases. Biol Chem 1997; 378: 151-60.
Hulboy DL, Rudolph LA, Matrisian LM. Matrix metalloproteinases as mediators of reproductive function. Mol Hum Reprod 1997; 3: 27-45.
Sillem M, Prifti S, Neher M, Runnebaum B. Extracellular matrix remodelling in the endometrium and its possible relevance to the pathogenesis of endometriosis. Hum Reprod Update 1998; 4: 730-5.
Collette T, Maheux R, Mailloux J, Akoum A. Increased expression of matrix metalloproteinase-9 in the eutopic endometrial tissue of women with endometriosis. Hum Reprod 2006; 21: 3059-67.
Cox KE, Piva M, Sharpe-Timms KL. Differential regulation of matrix metalloproteinase-3 gene expression in endometriotic lesions compared with endometrium. Biol Reprod 2001; 65: 1297-303.
Uzan C, Cortez A, Dufournet C, Fauvet R, Siffroi JP, Daraï E. Eutopic endometrium and peritoneal, ovarian and bowel endometriotic tissues express a different profile of matrix metalloproteinases -2, -3 and -11, and of tissue inhibitor metalloproteinases-1 and -2. Virchows Arch 2004; 445: 603-9.
Pustovrh MC, Jawerbaum A, Capobianco E, White V, Martínez N, López-Costa JJ, et al. Oxidative stress promotes the increase of matrix metalloproteinases-2 and -9 activities in the feto-placental unit of diabetic rats. Free Radic Res 2005; 39: 1285-93.
Mori K, Shibanuma M, Nose K. Invasive potential induced under long-term oxidative stress in mammary epithelial cells. Cancer Res 2004; 64: 7464-72.
Rajagopalan S, Meng XP, Ramasamy S, Harrison DG, Galis ZS. Reactive oxygen species produced by macrophage-derived foam cells regulate the activity of vascular matrix metalloproteinases in vitro. Implications for atherosclerotic plaque stability. J Clin Invest 1996; 98: 2572-9.
Arumugam K, Yip YC. De novo formation of adhesions in endome- triosis: the role of iron and free radical reactions. Fertil Steril 1995; 64: 62-4.
Alpay Z, Saed GM, Diamond MP. Female infertility and free radi- cals: potential role in adhesions and endometriosis. J Soc Gynecol Invest 2006; 13: 390-8.
Portz DM, Elkins TE, White R, Warren J, Adadevoh S, Randolph J. Oxygen free radicals and pelvic adhesion formation: I. Blocking oxygen free radical toxicity to prevent adhesion formation in an endometriosis model. Int J Fertil 1991; 36: 39-42.
Arendt J, Melatonin and the mammalian pineal gland, Chapman & Hall, London, 1995.
Pevet P, Bothorel B, Slotten H, Saboureau M. The chronobiotic properties of melatonin. Cell Tissue Res 2002; 309: 183-91.
Reiter RJ, Tan DX, Maldonado MD. Melatonin as an antioxidant: physiology versus pharmacology. J Pineal Res 2005; 39: 215-6.
Tan DX, Reiter RJ, Manchester LC, Yan MT, El-Sawi M, Sainz RM, et al. Chemical and physical properties and potential mechanisms: melatonin as a broad-spectrum antioxidant and free radical scav- enger. Curr Top Med Chem 2002; 2: 181-97.
Reiter RJ, Calvo JR, Karbownik M, QiW, Tan DX. Melatonin and its relation to the immune system and inflammation. Ann NY Acad Sci 2000; 917: 376-86.
Paul S, Sharma AV, Mahapatra PD, Bhattacharya P, Reiter RJ, Swarnakar S. Role of melatonin in regulating matrix metallopro- teinase-9 via tissue inhibitors of metalloproteinase-1 during protec- tion against endometriosis. J Pineal Res 2008; 44: 439-49.
Yildirim G, Attar R, Ozkan F, Kumbak B, Ficicioglu C, Yesildaglar N. The effects of letrozole and melatonin on surgically induced endo- metriosis in a rat model: a preliminary study. Fertil Steril 2010; 93: 1787-92.
Demirbag S, Cetinkursun S, Tasdemir U, Ozturk H, Pekcan M, Yesildaglar N. Comparison of hyaluronate/carboxymethylcellulose membrane and ME for prevention of adhesion formation in a rat model. Hum Reprod 2005; 20: 2021-4.
Attar R, Yildirim G, Kumbak B, Fıçıcıoglu C, Demirbag S, Yesildaglar N. Efficacy of melatonin and hyaluronate/carboxymethylcellulose membrane in preventing adhesion re-formation following adhe- siolysis in the rat uterine model. J Obstet Gynaecol Res 2011; 37: 125-31.
Vernon MW, Wilson EA. Studies on the surgical induction of endo- metriosis in the rat. Fertil Steril 1985; 44: 684-94.
Lebovic DI, Kir M, Casey CL. Peroxisome proliferator-activated receptor-gamma induces regression of endometrial explants in a rat model of endometriosis. Fertil Steril 2004; 82: 1008-13.
Uygur D, Aytan H, Zergeroglu S, Batioglu S. Leflunomidean immu- nomodulator induces regression of endometrial explants in a rat model of endometriosis. J Soc Gynecol Investig 2006; 13: 378-83.
Keenan JA, Williams-Boyce PK, Massey PJ, Chen TT, Caudleb MR, Bukovsky A. Regression of endometrial explants in a rat model of endometriosis treated with the immune modulators loxoribine and levamisole. Fertil Steril 1999; 72: 135-41.
Ballweg M. Impact of endometriosis on womens health: compara- tive historical data show that the earlier the onset, the more severe the disease. Best Pract Res Clin Obstet Gynecol 2009; 18: 201-18.
Simoens S, Hummelshoj L, DHooghe T. Endometriosis: cost esti- mates and methodological perspective. Hum Reprod Update 2007; 13: 394-404.
Soares SR, Martínez-Varea A, Hidalgo-Mora JJ, Pellicer A. Pharmacologic therapies in endometriosis: a systematic review. Fertil Steril 2012; 98: 529-55.
Hughes E, FedorkowD, Collins J, Vandekerckhove P. Ovulation sup- pression for endometriosis. Cochrane Database Syst Rev 2003; 3: CD000155.
Koc O, Gunduz B, Topcuoglu A, Bugdayci G, Yilmaz F, Duran B. Effects of pinealectomy and melatonin supplementation on endo- metrial explants in a rat model. Eur J Obstet Gynecol Reprod Biol 2010; 153: 72-6.
Guney M, Oral B, Karahan N, Mungan T. Regression of endometrial explants in a rat model of endometriosis treated with melatonin. Fertil Steril 2008; 89: 934-42.
Paul S, Bhattacharya P, Das Mahapatra P, Swarnakar S. Melatonin protects against endometriosis via regulation of matrix metallopro- teinase-3 and an apoptotic pathway. J Pineal Res 2010; 49: 156-68.
Yesildaglar N, Yildirim G, Attar R, Karateke A, Ficicioglu C, Yilmaz B. Exposure to industrially polluted water resulted in regressed endometriotic lesions and enhanced adhesion formation in a rat endometriosis model: a preliminary study. Fertil Steril 2010; 93: 1722-4.

APA	KOCADAL ÇETİNKAYA N, Attar R, YILDIRIM G, FIÇICIOĞLU C, YEŞİLDAĞLAR N, ÖZKAN F, YILMAZ B (2013). Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model. , 81 - 86.
Chicago	KOCADAL ÇETİNKAYA Nilüfer,Attar Rukset,YILDIRIM Gazi,FIÇICIOĞLU Cem,YEŞİLDAĞLAR Narter,ÖZKAN Ferda,YILMAZ Bayram Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model. (2013): 81 - 86.
MLA	KOCADAL ÇETİNKAYA Nilüfer,Attar Rukset,YILDIRIM Gazi,FIÇICIOĞLU Cem,YEŞİLDAĞLAR Narter,ÖZKAN Ferda,YILMAZ Bayram Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model. , 2013, ss.81 - 86.
AMA	KOCADAL ÇETİNKAYA N,Attar R,YILDIRIM G,FIÇICIOĞLU C,YEŞİLDAĞLAR N,ÖZKAN F,YILMAZ B Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model. . 2013; 81 - 86.
Vancouver	KOCADAL ÇETİNKAYA N,Attar R,YILDIRIM G,FIÇICIOĞLU C,YEŞİLDAĞLAR N,ÖZKAN F,YILMAZ B Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model. . 2013; 81 - 86.
IEEE	KOCADAL ÇETİNKAYA N,Attar R,YILDIRIM G,FIÇICIOĞLU C,YEŞİLDAĞLAR N,ÖZKAN F,YILMAZ B "Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model." , ss.81 - 86, 2013.
ISNAD	KOCADAL ÇETİNKAYA, Nilüfer vd. "Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model". (2013), 81-86.

APA	KOCADAL ÇETİNKAYA N, Attar R, YILDIRIM G, FIÇICIOĞLU C, YEŞİLDAĞLAR N, ÖZKAN F, YILMAZ B (2013). Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model. Journal of the Turkish-German Gynecological Association, 14(2), 81 - 86.
Chicago	KOCADAL ÇETİNKAYA Nilüfer,Attar Rukset,YILDIRIM Gazi,FIÇICIOĞLU Cem,YEŞİLDAĞLAR Narter,ÖZKAN Ferda,YILMAZ Bayram Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model. Journal of the Turkish-German Gynecological Association 14, no.2 (2013): 81 - 86.
MLA	KOCADAL ÇETİNKAYA Nilüfer,Attar Rukset,YILDIRIM Gazi,FIÇICIOĞLU Cem,YEŞİLDAĞLAR Narter,ÖZKAN Ferda,YILMAZ Bayram Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model. Journal of the Turkish-German Gynecological Association, vol.14, no.2, 2013, ss.81 - 86.
AMA	KOCADAL ÇETİNKAYA N,Attar R,YILDIRIM G,FIÇICIOĞLU C,YEŞİLDAĞLAR N,ÖZKAN F,YILMAZ B Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model. Journal of the Turkish-German Gynecological Association. 2013; 14(2): 81 - 86.
Vancouver	KOCADAL ÇETİNKAYA N,Attar R,YILDIRIM G,FIÇICIOĞLU C,YEŞİLDAĞLAR N,ÖZKAN F,YILMAZ B Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model. Journal of the Turkish-German Gynecological Association. 2013; 14(2): 81 - 86.
IEEE	KOCADAL ÇETİNKAYA N,Attar R,YILDIRIM G,FIÇICIOĞLU C,YEŞİLDAĞLAR N,ÖZKAN F,YILMAZ B "Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model." Journal of the Turkish-German Gynecological Association, 14, ss.81 - 86, 2013.
ISNAD	KOCADAL ÇETİNKAYA, Nilüfer vd. "Melatonin treatment results in regression of endometriotic lesions in an ooferectomized rat endometriosis model". Journal of the Turkish-German Gynecological Association 14/2 (2013), 81-86.