Skip to main content
SpringerLink
Log in

Protective Effects of Colchicine in an Experimental Rat Endometriosis Model: Histopathological Evaluation and Assessment of TNF-α Levels

  • Original Article
  • Published:
Reproductive Sciences Aims and scope Submit manuscript

Abstract

Objective: Endometriosis is an estrogen-dependent chronic inflammatory disease observed in reproductive period. The aim of the present study is to assess the efficacy of colchicine, widely used to treat many inflammatory diseases, in an experimental rat endometriosis model. Study Design: Experimental endometriosis was constituted with implantation of autogenous endometrial tissue. Rats were divided randomly into 2 groups as colchicine group (n = 8) and control group (n =8). Although oral 0.1 mg/kg colchicine was administered 4 weeks to the colchicine group, the same amount of saline solution was administered to the control group. Before and after 30 days of treatment period, peritoneal and tissue tumor necrosis factor α (TNF-α), the volumes and histopathological properties of the implants were evaluated. Results: Although the implant volume decreased significantly in the colchicine group (89.2 ± 13.4 mm3 to 35.2 ± 4.5 mm3, P < .05), the implant volume increased in the control group (85.1 ± 14.2 mm3 to 110.3 ± 10.5 mm3, P < .05). When compared to the control group, the colchicine group had significantly lower histopathologic sores (1.4 ± 0.2 vs 2.6 ± 0.4, P < .001). Although peritoneal fluid TNF-α levels were significantly decreased in the colchicine group (45.2 ± 5.3 pg/mL vs 12.1 ± 5.2 pg/mL, P < .001), the peritoneal fluid TNF-α levels were significantly increased in the control group after the treatment (44.2 ± 3.5 pg/mL vs 61.3 ± 12.2 pg/mL; P < .001). Tissue TNF-α levels were significantly lower in the colchicine group when compared to the control group (45.4 ± 8.6 pg/mL vs 71.3 ± 11.2 pg/mL; P < .001). Conclusion: Colchicine resulted in regression of endometrial implant volumes in experimental rat endometriosis model and decreased peritoneal and tissue TNF-α levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Benagiano G, Brosens I. Who identified endometriosis? Fertil Steril. 2011;95(1):13–16.

    Article  PubMed  Google Scholar 

  2. Olive DL, Schwartz LB. Endometriosis. N Engl J Med. 1993;328(24):1759–1769.

    Article  CAS  PubMed  Google Scholar 

  3. Yilmaz N, Ozaksit G, Keskin R, et al. The effect of formoterol on peritoneal VEGF levels in rats with endometriosis. Cytokine. 2012;58(1):47–49.

    Article  CAS  PubMed  Google Scholar 

  4. Acien P, Velasco I. Endometriosis: a disease that remains enigmatic. ISRN Obstetr Gynecol. 2013;2013:242149.

    Google Scholar 

  5. Eskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am. 1997;24(2):235–258.

    Article  CAS  PubMed  Google Scholar 

  6. Prevalence and anatomical distribution of endometriosis in women with selected gynaecological conditions: results from a multicentric Italian study. Gruppo italiano per lo studio dell’endometriosi. Hum Reprod. 1994;9(6):1158–1162.

    Article  Google Scholar 

  7. 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. Fertil Steril. 2009;92(1):68–74.

    Article  PubMed  Google Scholar 

  8. Kennedy S, Bergqvist A, Chapron C, et al. ESHRE guideline for the diagnosis and treatment of endometriosis. Hum Reprod. 2005;20(10):2698–2704.

    Article  PubMed  Google Scholar 

  9. Treatment of pelvic pain associated with endometriosis. Fertil Steril. 2008;90(5 suppl):S260–S269.

    Google Scholar 

  10. Kyama CM, Mihalyi A, Simsa P, et al. Non-steroidal targets in the diagnosis and treatment of endometriosis. Curr Med Chem. 2008;15(10):1006–1017.

    Article  CAS  PubMed  Google Scholar 

  11. Sampson JA. Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation. Am J Pathol. 1927;3(2):93–110. 143.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Oosterlynck DJ, Cornillie FJ, Waer M, Vandeputte M, Koninckx PR. Women with endometriosis show a defect in natural killer activity resulting in a decreased cytotoxicity to autologous endometrium. Fertil Steril. 1991;56(1):45–51.

    Article  CAS  PubMed  Google Scholar 

  13. Ferguson BR, Bennington JL, Haber SL. Histochemistry of muco-substances and histology of mixed mullerian pelvic lymph node glandular inclusions. Evidence for histogenesis by mullerian metaplasia of coelomic epithelium. Obstet Gynecol. 1969;33(5):617–625.

    CAS  PubMed  Google Scholar 

  14. Nap AW, Groothuis PG, Demir AY, Evers JL, Dunselman GA. Pathogenesis of endometriosis. Best Pract Res Clin Obstet Gynaecol. 2004;18(2):233–244.

    Article  PubMed  Google Scholar 

  15. Soares SR, Martinez-Varea A, Hidalgo-Mora JJ, Pellicer A. Pharmacologic therapies in endometriosis: a systematic review. Fertil Steril. 2012;98(3):529–555.

    Article  CAS  PubMed  Google Scholar 

  16. Wu MY, Ho HN. The role of cytokines in endometriosis. Am J Reprod Immunol. 2003;49(5):285–296.

    Article  PubMed  Google Scholar 

  17. Schlesinger N, Schumacher R, Catton M, Maxwell L. Colchicine for acute gout. Cochrane Database Syst Rev. 2006(4):CD006190.

  18. Lidar M, Livneh A. Familial Mediterranean fever: clinical, molecular and management advancements. Netherlands J Med. 2007;65(9):318–324.

    CAS  Google Scholar 

  19. Cronstein BN, Terkeltaub R. The inflammatory process of gout and its treatment. Arthritis Res Ther. 2006;8(suppl 1):S3.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Niel E, Scherrmann JM. Colchicine today. Joint Bone Spine. 2006;73(6):672–678.

    Article  CAS  PubMed  Google Scholar 

  21. Vernon MW, Wilson EA. Studies on the surgical induction of endometriosis in the rat. Fertil Steril. 1985;44(5):684–694.

    Article  CAS  PubMed  Google Scholar 

  22. do Amaral VF, Dal Lago EA, Kondo W, Souza LC, Francisco JC. Development of an experimental model of endometriosis in rats. Revista do Colegio Brasileiro de Cirurgioes. 2009;36(3):250–255.

    Article  PubMed  Google Scholar 

  23. Islimye M, Kilic S, Zulfikaroglu E, Topcu O, Zergeroglu S, Batioglu S. Regression of endometrial autografts in a rat model of endometriosis treated with etanercept. Eur J Obstet Gynecol Reprod Biol. 2011;159(1):184–189.

    Article  CAS  PubMed  Google Scholar 

  24. Burney RO. The genetics and biochemistry of endometriosis. Curr Opin Obste Gynecol. 2013;25(4):280–286.

    Article  Google Scholar 

  25. Koninckx PR, Kennedy SH, Barlow DH. Endometriotic disease: the role of peritoneal fluid. Hum Reprod Update. 1998;4(5):741–751.

    Article  CAS  PubMed  Google Scholar 

  26. Sikora J, Mielczarek-Palacz A, Kondera-Anasz Z. Role of natural killer cell activity in the pathogenesis of endometriosis. Curr Med Chem. 2011;18(2):200–208.

    Article  CAS  PubMed  Google Scholar 

  27. Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril. 2001;75(1):1–10.

    Article  CAS  PubMed  Google Scholar 

  28. Eisermann J, Gast MJ, Pineda J, Odem RR, Collins JL. Tumor necrosis factor in peritoneal fluid of women undergoing laparoscopic surgery. Fertil Steril. 1988;50(4):573–579.

    Article  CAS  PubMed  Google Scholar 

  29. Richter ON, Dorn C, Rosing B, Flaskamp C, Ulrich U. Tumor necrosis factor alpha secretion by peritoneal macrophages in patients with endometriosis. Arch Gynecol Obstet. 2005;271(2):143–147.

    Article  CAS  PubMed  Google Scholar 

  30. Ravelli RB, Gigant B, Curmi PA, et al. Insight into tubulin regulation from a complex with colchicine and a stathmin-like domain. Nature. 2004;428(6979):198–202.

    Article  CAS  PubMed  Google Scholar 

  31. Wilson L, Panda D, Jordan MA. Modulation of microtubule dynamics by drugs: a paradigm for the actions of cellular regulators. Cell Struct Fund. 1999;24(5):329–335.

    Article  CAS  PubMed  Google Scholar 

  32. Terkeltaub RA. Colchicine update: 2008. Semin Arthritis Rheum. 2009;38(6):411–419.

    Article  CAS  PubMed  Google Scholar 

  33. Sharpe KL, Zimmer RL, Griffin WT, Penney LL. Polypeptides synthesized and released by human endometriosis differ from those of the uterine endometrium in cell and tissue explant culture. Fertil Steril. 1993;60(5):839–851.

    Article  CAS  PubMed  Google Scholar 

  34. Altintas D, Kokcu A, Kandemir B, Cetinkaya MB, Tosun M. Efficacy of imiquimod, an immunomodulatory agent, on experimental endometriosis. Fertil Steril. 2008;90(2):401–405.

    Article  CAS  PubMed  Google Scholar 

  35. Aytan H, Caglar P, Uygur D, Zergeroglu S, Batioglu S. Effect of the immunomodulator leflunomide on the induction of endometriosis in an experimental rat model. Fertil Steril. 2007;87(3):698–701.

    Article  PubMed  Google Scholar 

  36. Ceyhan ST, Onguru O, Fidan U, et al. Comparison of aromatase inhibitor (letrozole) and immunomodulators (infliximab and etanercept) on the regression of endometriotic implants in a rat model. Eur J Obstet Gynecol Reprod Biol. 2011;154(1):100–104.

    Article  CAS  PubMed  Google Scholar 

  37. Yasar O, Iskender C, Kaymak O, Taflan Yaman S, Uygur D, Danisman N. Retrospective evaluation of pregnancy outcomes in women with familial Mediterranean fever. J Matern Fetal Neonatal Med. 2014;27(7):733–736.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Mustafa Kemal University Medical School, Mustafa Kemal Üniversitesi Tıp Fakültesi, Kadın Hastalıkları ve Doğum Anabilim Dalı, 31100, Hatay, Turkey

    Raziye Keskin Kurt MD, Atilla Karateke MD, Ayşe Güler Okyay MD, Dilek Benk Silfeler MD & Ali Ulvi Hakverdi MD

  2. Department of Pharmacology, Mustafa Kemal University Medical School, Hatay, Turkey

    Neslihan Pinar MD

  3. Department of Pathology, Dışkapı Eğitim ve Araştırma Hastanesi, Ankara, Turkey

    Aynur Albayrak MD

  4. Department of Biochemistry, Dışkapı Eğitim ve Araştırma Hastanesi, Ankara, Turkey

    Seyda Özdemir MD

Authors
  1. Raziye Keskin Kurt MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Neslihan Pinar MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Atilla Karateke MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ayşe Güler Okyay MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dilek Benk Silfeler MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Aynur Albayrak MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Seyda Özdemir MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ali Ulvi Hakverdi MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Raziye Keskin Kurt MD.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kurt, R.K., Pinar, N., Karateke, A. et al. Protective Effects of Colchicine in an Experimental Rat Endometriosis Model: Histopathological Evaluation and Assessment of TNF-α Levels. Reprod. Sci. 22, 258–263 (2015). https://doi.org/10.1177/1933719114542029

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1177/1933719114542029

Keywords

Search

Navigation