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Erschienen in: Archives of Gynecology and Obstetrics 3/2012

01.09.2012 | Reproductive Medicine

Therapeutic efficiency of Atosiban, an oxytocin receptor blocking agent in the treatment of experimental endometriosis

verfasst von: Yavuz Simsek, Onder Celik, Abdullah Karaer, Mehmet Gul, Ercan Yılmaz, Onder Koc, Cemil Colak, Sehnaz Zengin, Nasuhi Engin Aydin

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 3/2012

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Abstract

Purpose

The current study investigated the potential therapeutic efficiency of atosiban, an oxytocin receptor antagonist, in an experimental endometriosis model.

Methods

Endometriosis was surgically induced in 35 female rats during estrus. Four weeks after this procedure, relaparotomy was performed. The viability and dimensions of the endometriosis foci were recorded. Rats were then randomly divided into three groups. In the first group (n = 8), a daily dose of 0.2 ml 0.9 % NaCl was injected intraperitoneally (i.p.) (control cases). In the second and third groups (n = 8 and n = 8), 0.5 mg/kg/day i.p. atosiban and 1 mg/day i.p. diltiazem were given, respectively. At the end of the treatment, laparotomy was performed, and the dimensions of the endometriosis foci were recorded. The endometrial implants were processed for histological and immunohistochemical studies. The volumes of endometriotic implants were measured, and immunohistochemical analyses were performed, and compared between the groups.

Results

After the treatment with atosiban, volumes of endometriotic implants decreased significantly. Proliferating cell nuclear antigen expression levels were significantly reduced in the atosiban and diltiazem groups compared with the control group.

Conclusions

In a rat endometriosis model, atosiban, an agent used for the first time for the medical treatment of endometriosis, has shown significant therapeutic efficiency.
Literatur
1.
Zurück zum Zitat Vignali M, Infantino M, Matrone R, Chiodo I, Somigliana E, Busacca M et al (2002) Endometriosis: novel etiopathogenetic concepts and clinical perspectives. Fertil Steril 78(4):665–678PubMedCrossRef Vignali M, Infantino M, Matrone R, Chiodo I, Somigliana E, Busacca M et al (2002) Endometriosis: novel etiopathogenetic concepts and clinical perspectives. Fertil Steril 78(4):665–678PubMedCrossRef
2.
Zurück zum Zitat Giudice LC, Kao LC (2004) Endometriosis. Lancet 13–19;364(9447):1789–1799 Giudice LC, Kao LC (2004) Endometriosis. Lancet 13–19;364(9447):1789–1799
3.
Zurück zum Zitat Matarese G, De Placido G, Nikas Y, Alviggi C (2003) Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease? Trends Mol Med 9(5):223–228PubMedCrossRef Matarese G, De Placido G, Nikas Y, Alviggi C (2003) Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease? Trends Mol Med 9(5):223–228PubMedCrossRef
4.
Zurück zum Zitat Olivares C, Bilotas M, Buquet R, Borghi M, Sueldo C, Tesone M et al (2008) Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis. Hum Reprod 23(12):2701PubMedCrossRef Olivares C, Bilotas M, Buquet R, Borghi M, Sueldo C, Tesone M et al (2008) Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis. Hum Reprod 23(12):2701PubMedCrossRef
5.
Zurück zum Zitat Celik O, Hascalik S, Elter K, Tagluk ME, Gurates B, Aydin NE (2008) Combating endometriosis by blocking proteasome and nuclear factor-kappaB pathways. Hum Reprod 23(11):2458–2465PubMedCrossRef Celik O, Hascalik S, Elter K, Tagluk ME, Gurates B, Aydin NE (2008) Combating endometriosis by blocking proteasome and nuclear factor-kappaB pathways. Hum Reprod 23(11):2458–2465PubMedCrossRef
7.
Zurück zum Zitat Asselin E, Goff AK, Bergeron H, Fortier MA (1996) Influence of sex steroids on the production of prostaglandins F2 alpha and E2 and response to oxytocin in cultured epithelial and stromal cells of the bovine endometrium. Biol Reprod 54(2):371–379PubMedCrossRef Asselin E, Goff AK, Bergeron H, Fortier MA (1996) Influence of sex steroids on the production of prostaglandins F2 alpha and E2 and response to oxytocin in cultured epithelial and stromal cells of the bovine endometrium. Biol Reprod 54(2):371–379PubMedCrossRef
8.
Zurück zum Zitat Danet-Desnoyers G, Wetzels C, Thatcher WW (1994) Natural and recombinant bovine interferon tau regulate basal and oxytocin-induced secretion of prostaglandins F2 alpha and E2 by epithelial cells and stromal cells in the endometrium. Reprod Fertil Dev 6(2):193–202PubMedCrossRef Danet-Desnoyers G, Wetzels C, Thatcher WW (1994) Natural and recombinant bovine interferon tau regulate basal and oxytocin-induced secretion of prostaglandins F2 alpha and E2 by epithelial cells and stromal cells in the endometrium. Reprod Fertil Dev 6(2):193–202PubMedCrossRef
9.
Zurück zum Zitat Mechsner S, Bartley J, Loddenkemper C, Salomon DS, Starzinski-Powitz A, Ebert AD (2005) Oxytocin receptor expression in smooth muscle cells of peritoneal endometriotic lesions and ovarian endometriotic cysts. Fertil Steril 83:1220–1231PubMedCrossRef Mechsner S, Bartley J, Loddenkemper C, Salomon DS, Starzinski-Powitz A, Ebert AD (2005) Oxytocin receptor expression in smooth muscle cells of peritoneal endometriotic lesions and ovarian endometriotic cysts. Fertil Steril 83:1220–1231PubMedCrossRef
10.
Zurück zum Zitat Bussolati G, Cassoni P (2001) Editorial: the oxytocin/oxytocin receptor system-expect the unexpected. Endocrinology 142(4):1377–1379PubMedCrossRef Bussolati G, Cassoni P (2001) Editorial: the oxytocin/oxytocin receptor system-expect the unexpected. Endocrinology 142(4):1377–1379PubMedCrossRef
11.
Zurück zum Zitat Zeitoun KM, Bulun SE (1999) Aromatase: a key molecule in the pathophysiology of endometriosis and a therapeutic target. Fertil Steril 72(6):961–969PubMedCrossRef Zeitoun KM, Bulun SE (1999) Aromatase: a key molecule in the pathophysiology of endometriosis and a therapeutic target. Fertil Steril 72(6):961–969PubMedCrossRef
12.
Zurück zum Zitat Gross GH (1977) A technique for sustained synchronization of hamster estrous cycles by hormonal means. Horm Behav 9:23–31PubMedCrossRef Gross GH (1977) A technique for sustained synchronization of hamster estrous cycles by hormonal means. Horm Behav 9:23–31PubMedCrossRef
13.
Zurück zum Zitat Vernon MW, Wilson EA (1985) Studies on the surgical induction of endometriosis in the rat. Fertil Steril 44:684–694PubMed Vernon MW, Wilson EA (1985) Studies on the surgical induction of endometriosis in the rat. Fertil Steril 44:684–694PubMed
14.
Zurück zum Zitat Kannan V, Gadamsetty D, Rose M, Maria S, Mustafa I, Khedkar A et al (2010) Quantitative determination of oxytocin receptor antagonist atosiban in rat plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 1;878(15–16):1069–1076 Kannan V, Gadamsetty D, Rose M, Maria S, Mustafa I, Khedkar A et al (2010) Quantitative determination of oxytocin receptor antagonist atosiban in rat plasma by liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 1;878(15–16):1069–1076
15.
Zurück zum Zitat Downing SJ, Edwards D, Hollingsworth M (1987) Diltiazem pharmacokinetics in the rat and relationship between its serum concentration and uterine and cardiovascular effects. Br J Pharmacol 91(4):735–745PubMedCrossRef Downing SJ, Edwards D, Hollingsworth M (1987) Diltiazem pharmacokinetics in the rat and relationship between its serum concentration and uterine and cardiovascular effects. Br J Pharmacol 91(4):735–745PubMedCrossRef
16.
Zurück zum Zitat Iseri SO, Sener G, Saglam B, Gedik N, Ercan F, Yegen BC (2005) Oxytocin protects against sepsis-induced multiple organ damage: role of neutrophils. J Surg Res 126:73–81PubMedCrossRef Iseri SO, Sener G, Saglam B, Gedik N, Ercan F, Yegen BC (2005) Oxytocin protects against sepsis-induced multiple organ damage: role of neutrophils. J Surg Res 126:73–81PubMedCrossRef
17.
Zurück zum Zitat Cetinel S, Hancioğlu S, Sener E, Uner C, Kiliç M, Sener G et al (2010) Oxytocin treatment alleviates stress-aggravated colitis by a receptor-dependent mechanism. Regul Pept 25(160):146–152CrossRef Cetinel S, Hancioğlu S, Sener E, Uner C, Kiliç M, Sener G et al (2010) Oxytocin treatment alleviates stress-aggravated colitis by a receptor-dependent mechanism. Regul Pept 25(160):146–152CrossRef
18.
Zurück zum Zitat Dusunceli F, Iseri SO, Ercan F, Gedik N, Yegen C, Yegen BC (2008) Oxytocin alleviates hepatic ischemia-reperfusion injury in rats. Peptides 29:1216–1222PubMedCrossRef Dusunceli F, Iseri SO, Ercan F, Gedik N, Yegen C, Yegen BC (2008) Oxytocin alleviates hepatic ischemia-reperfusion injury in rats. Peptides 29:1216–1222PubMedCrossRef
19.
Zurück zum Zitat Tuğtepe H, Sener G, Biyikli NK, Yüksel M, Cetinel S, Gedik N et al (2007) The protective effect of oxytocin on renal ischemia/reperfusion injury in rats. Regul Pept 140:101–108PubMedCrossRef Tuğtepe H, Sener G, Biyikli NK, Yüksel M, Cetinel S, Gedik N et al (2007) The protective effect of oxytocin on renal ischemia/reperfusion injury in rats. Regul Pept 140:101–108PubMedCrossRef
20.
Zurück zum Zitat Leyendecker G, Kunz G, Noe M, Herbertz M, Mall G (1998) Endometriosis: a dysfunction and disease of the archimetra. Hum Reprod Update 4(5):752–762PubMedCrossRef Leyendecker G, Kunz G, Noe M, Herbertz M, Mall G (1998) Endometriosis: a dysfunction and disease of the archimetra. Hum Reprod Update 4(5):752–762PubMedCrossRef
21.
Zurück zum Zitat Kunz G, Noe M, Herbertz M, Leyendecker G (1998) Uterine peristalsis during the follicular phase of the menstrual cycle: effects of oestrogen, antioestrogen and oxytocin. Hum Reprod Update 4(5):647–654PubMedCrossRef Kunz G, Noe M, Herbertz M, Leyendecker G (1998) Uterine peristalsis during the follicular phase of the menstrual cycle: effects of oestrogen, antioestrogen and oxytocin. Hum Reprod Update 4(5):647–654PubMedCrossRef
22.
Zurück zum Zitat Leyendecker G, Kunz G, Herbertz M, Beil D, Huppert P, Mall G et al (2004) Uterine peristaltic activity and the development of endometriosis. Ann N Y Acad Sci 1034:338–355PubMedCrossRef Leyendecker G, Kunz G, Herbertz M, Beil D, Huppert P, Mall G et al (2004) Uterine peristaltic activity and the development of endometriosis. Ann N Y Acad Sci 1034:338–355PubMedCrossRef
23.
Zurück zum Zitat Salamanca A, Beltran E (1995) Subendometrial contractility in menstrual phase visualised by transvaginal sonography in patients with endometriosis. Fertil Steril 64:193–195PubMed Salamanca A, Beltran E (1995) Subendometrial contractility in menstrual phase visualised by transvaginal sonography in patients with endometriosis. Fertil Steril 64:193–195PubMed
24.
Zurück zum Zitat Bulun SE, Fang Z, Imir G, Gurates B, Tamura M, Yilmaz B et al (2004) Aromatase and endometriosis. Semin Reprod Med 22(1):45–50PubMedCrossRef Bulun SE, Fang Z, Imir G, Gurates B, Tamura M, Yilmaz B et al (2004) Aromatase and endometriosis. Semin Reprod Med 22(1):45–50PubMedCrossRef
25.
Zurück zum Zitat Bilotas M, Meresman G, Stella I, Sueldo C, Barañao RI (2010) Effect of aromatase inhibitors on ectopic endometrial growth and peritoneal environment in a mouse model of endometriosis. Fertil Steril 15;93(8):2513–2518 Bilotas M, Meresman G, Stella I, Sueldo C, Barañao RI (2010) Effect of aromatase inhibitors on ectopic endometrial growth and peritoneal environment in a mouse model of endometriosis. Fertil Steril 15;93(8):2513–2518
26.
Zurück zum Zitat Nawathe A, Patwardhan S, Yates D, Harrison GR, Khan KS (2008) Systematic review of the effects of aromatase inhibitors on pain associated with endometriosis. BJOG 115(7):818–822PubMedCrossRef Nawathe A, Patwardhan S, Yates D, Harrison GR, Khan KS (2008) Systematic review of the effects of aromatase inhibitors on pain associated with endometriosis. BJOG 115(7):818–822PubMedCrossRef
27.
Zurück zum Zitat Miyake A (1992) Roles of calcium ion in reproductive physiology. Acta Obstetrica et Gynaecologica Japonica 44(8):976–981PubMed Miyake A (1992) Roles of calcium ion in reproductive physiology. Acta Obstetrica et Gynaecologica Japonica 44(8):976–981PubMed
28.
Zurück zum Zitat Gorczynska E, Handelsman DJ (1991) The role of calcium in follicle-stimulating hormone signal transduction in Sertoli cells. J Biol Chem 266(35):23739–23744PubMed Gorczynska E, Handelsman DJ (1991) The role of calcium in follicle-stimulating hormone signal transduction in Sertoli cells. J Biol Chem 266(35):23739–23744PubMed
29.
Zurück zum Zitat Morad F, Elsayed EM, Mahmoud SM (1997) Inhibition of steroid sex hormones release in rats by two Ca2+ channel blockers. Pharmacol Res 35(3):177–180PubMedCrossRef Morad F, Elsayed EM, Mahmoud SM (1997) Inhibition of steroid sex hormones release in rats by two Ca2+ channel blockers. Pharmacol Res 35(3):177–180PubMedCrossRef
Metadaten
Titel
Therapeutic efficiency of Atosiban, an oxytocin receptor blocking agent in the treatment of experimental endometriosis
verfasst von
Yavuz Simsek
Onder Celik
Abdullah Karaer
Mehmet Gul
Ercan Yılmaz
Onder Koc
Cemil Colak
Sehnaz Zengin
Nasuhi Engin Aydin
Publikationsdatum
01.09.2012
Verlag
Springer-Verlag
Erschienen in
Archives of Gynecology and Obstetrics / Ausgabe 3/2012
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-012-2390-7

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