Atalay EKİN, Emre MAT, Levent DERELİ, Volkan TURAN, Cenk GEZER, Murat Ulukuş ULUKUŞ, Çağnur ULUKUŞ, Erol TAVMERGEN, Ulas SOLMAZ

DENEYSEL SIÇAN ENDOMETRİOZİS MODELİNDE BİR İMMUNMODÜLATÖR OLAN PENTOKSİFİLİNİN ADEZYON SKORU ÜZERİNE ETKİSİ

İmmün sistem değişikliklerinin etkin olduğu endometrioziste, bir immunmodulatör olan pentoksifilinin sıçan endometriozis modelinde adezyon skoru üzerine olan etkilerini araştırmaktır. Çalışmamızda 50 adet gebe olmayan, olgun, dişi, Wistar albino sıçanı kullanıldı. Sıçanlar 10’ arlı beş ayrı gruba, rastgele dağıtıldılar. Gruplar; kontrol grubu, intraperitoneal İP yüksek doz pentoksifilin grubu 25 mg/kg , İP düşük doz pentoksifilin grubu 12,5 mg/kg , subkutan SK yüksek doz pentoksifilin grubu 25 mg/kg ve SK düşük doz pentoksifilin grubu 12,5 mg/kg olarak oluşturuldu. Cerrahi müdahaleden dört hafta sonra, vertikal orta hat insizyon yapıldı. Batın içerisindeki adezyonun genişliği, lokalizasyonu ve tipi kaydedildi. Adezyonlar ciddiyetine göre 4 gruba ayrıldı. İP yüksek doz, İP düşük doz, SK yüksek doz ve SK düşük doz pentoksifilin tedavisi yapılan gruplar tek tek, kontrol grubu ile karşılaştırıldığında, tedavi verilen gruplarda kontrol grubuna göre adezyon skoru istatistiksel anlamlı olarak düşük bulundu p = 0.037, p = 0.018, p = 0.033, p = 0.024, sırasıyla . Bununla birlikte tedavi grupları tek bir grup altında toplanıp kontrol grubu ile karşılaştırıldığında da tedavi grubunda adezyon skorunun istatistiksel olarak anlamlı bir şekilde düşük olduğu görüldü p = 0.022 . Endometriozisin patofizyolojisi henüz tam olarak aydınlatılamamıştır, ancak eldeki verilere göre inflamatuar komponenti kuvvetli bir hastalıktır. Bu çalışmada, bir immunmodülatör olan pentoksifilinin adezyon skorunu azalttığı sonucuna vardık

Anahtar Kelimeler:

endometriozis, pentoksifilin, immunmodulatör, adezyon, cerrahi

THE IMMUNOMODULATORY EFFECT OF PENTOXIFYLLINE ON THE ADHESION SCORE IN RAT ENDOMETRIOSIS MODEL

To investigate the effects of pentoxifylline as an immunomodulator on adhesion scores in endometriosis, the disease that inflammatory changes play a major role in the pathogenesis.A total of 50 non-pregnant, mature, female Wistar albino rats were included in the present study. The rats were randomly separated into 5 groups: group I control, group II Intraperitoneal IP high dose 25 mg/kg pentoxifylline administered, group III IP low dose 12.5 mg/kg pentoxifylline administered, group IV subcutaneous SC high dose pentoxifylline administered, and group V SC low dose pentoxifylline administered. Four weeks after the surgical intervention, midline vertical abdominal incisions were performed to explore the width, localisation, and type of the intraabdominal adhesions.When each treatment group IP high dose, IP low dose, SC high dose, SC low dose compared to the control group separately; the adhesion scores were significantly lower p = 0.037, p = 0.018, p = 0.033, p = 0.024, respectively . Besides, when all of the rats were divided into two groups as: treatment group regardless of the treatment type and control group, the adhesion scores were also significantly low in the treatment group p = 0.022 . The pathophysiology of endometriosis is not yet clear, however according to the available data it has a strong inflammatory component. In this study it was demonstrated that the immunomodulator pentoxifylline lowered the adhesion scores

Keywords:

endometriosis, pentoxifylline, immunomodulator, adhesion, surgery,

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) Houston DE, Noller K, Melton LJ and Selwyn BJ. The epidemiology of pelvic endometriosis. Clinical Obstetrics and Gynecology. 1988; 31(4): 787- 800.
) Missmer SA and Cramer DW. The epidemiology of endometrioisis. Obstet Gynecol Clin North AM. 2003; (1): 1- 19.
) Aytan H, Caglar P, Uygur D, Zeteroglu S, Batioglu S. Effect of immunmodulator leflunamide on the induction endometriosis in experimental rat model. Fertil Steril. 2007; 87(3): 699- 702.
) Balasch J, Creus M, Fabregues F, Carmona F, Martinez-Roman S, Manau D, et al. Pentoxifylline versus plecebo in the treatment of infertility associated with minimal or mild endometriosis: a pilot randomized clinical trial. Hum Reprod. 1997; 12(9): 50.
) Sulliva GW, Carper HT, Novick WJ, Mandel GL. Inhibition of the inflamatory action of IL- 1 and TNF on neutrophil by pentoxifylline. Infect Immunun. 1988; (7): 1722.
) YovichJm, Ediringhe WR, Cummins JM, Yovich JL. Influence of pentoxifylline in pelvic peritoneal macrophages. Fertil Steril. 1986; 46: 715.
) Vernon MW, Wilson EA. Studies on the surgical induction of endometriosis in therat. Fertil Steril. ; 44(5): 684- 94. ) Lebovic DI, Kir M, Casey CL. Peroxisome productor- activatedreceptor-gamaa induces regression of endometrial explants in a rat model of endometriosis. Fertil Steril. 2004; (82 Suppl 3): 1008- 13.
) Saltzman AK, Olson TA, Mohanraj T, Carson L, Ramakrishnan S. Prevention of postoperative adhesions by an antibody to vaskular permability factor/vascularendothelial growth factor in a murine model. Am J Obstet Gynecol. 1996; 174(5): 1502- 6.
) Nothnick WB, D’Hooghe TM. Medical management of endometriosis: novel targets and approaches towards the development of future treatment regimes. Gynecol Obstet Invest. 2003; 55(4): 189- 98.
) Hiil JA, Faris HMP, Schiff I, Anderson DJ. Characterization of leukocyte subpopulations in the peritoneal fluid of women with endometriosis. Fertil Steril. 1988; 50(2): 216-22.
) Kanter M, Gul A, Meral İ, Koc A, Erdogan E. Morphological quantitative changes in the number of lympocytes, macrophages and plasma cells in the uterus and lymphnodes of rats exposed to systemic administration of BCG. Tohoku J. ExpMed. ;199(4): 219- 28. ) Ingelmo JM, Quereda F, Acien P. Intraperitoneal and subcutaneous treatment of experimental endometriosis with recombinant human interferon- alpha-2b in amurine model. Fertil Steril. 1999; 71(5): 11.
) Keenan JA, Williams-Boyce PK, Massey PJ, Chen TT, Caudle MR, Bukovsky A. Regression of endometrial explans in a rat model of endometriosis treated with the immunemodulators loxoribine and levamisole. Fertil Steril. 1999; 72(1): 135- 41.
) Steinleitner A, Lambert H, Serpa N, Suarez M, Roy S. Immunomodulation in the treatment of endometriosis-associated subfertility: use of pentoxifylline to reverse the inhibition of fertilization by surgically induced endometriosis in a rodent model. Fertil Steril. 1991; 56(5): 975- 79.