Fertility and Sterility
Volume 93, Issue 8 , Pages 2674-2679, 15 May 2010

A selective cyclooxygenase-2 inhibitor suppresses the growth of endometriosis with an antiangiogenic effect in a rat model

  • Daniel Escorsim Machado, M.Sc.

      Affiliations

    • Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária–Ilha do Fundão, Rio de Janeiro, Brazil
    • ,
  • Plínio Tostes Berardo, M.D., Ph.D.

      Affiliations

    • Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária–Ilha do Fundão, Rio de Janeiro, Brazil
    • ,
  • Richardt Gama Landgraf, Ph.D.

      Affiliations

    • Departamento de Ciências Biológicas, Universidade Federal de São Paulo, Campus Diadema, São Paulo, Brazil
    • ,
  • Patrícia Dias Fernandes, Ph.D.

      Affiliations

    • Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
    • ,
  • Celia Palmero, M.Sc.

      Affiliations

    • Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária–Ilha do Fundão, Rio de Janeiro, Brazil
    • ,
  • Leandro Miranda Alves, Ph.D.

      Affiliations

    • Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária–Ilha do Fundão, Rio de Janeiro, Brazil
    • ,
  • Maurício Simões Abrao, M.D., Ph.D.

      Affiliations

    • Departamento de Obstetrícia e Ginecologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
    • ,
  • Luiz Eurico Nasciutti, Ph.D.

      Affiliations

    • Programa de Pesquisa em Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária–Ilha do Fundão, Rio de Janeiro, Brazil
    • Corresponding Author InformationReprint requests: Luiz Eurico Nasciutti, Ph.D., Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Cidade Universitária–Ilha do Fundão, 21941-590 Rio de Janeiro, RJ, Brazil (FAX: 55-21-2562-6483).

Received 2 July 2009; received in revised form 17 November 2009; accepted 17 November 2009. published online 07 January 2010.

Objective

To analyze the antiangiogenic effects of the selective cyclooxygenase-2 (COX-2) inhibitor parecoxib on the growth of endometrial implants in a rat model of peritoneal endometriosis.

Design

Pharmacologic interventions in an experimental model of peritoneal endometriosis.

Setting

Research laboratory in the Federal University of Rio de Janeiro.

Animal(s)

Twenty female Sprague-Dawley rats with experimentally induced endometriosis.

Intervention(s)

After implantation and establishment of autologous endometrium onto the peritoneum abdominal wall, rats were randomized into groups and treated with parecoxib or the vehicle by IM injection for 30 days.

Main Outcome Measure(s)

Vascular density, the expression of vascular endothelial growth factor (VEGF) and its receptor Flk-1, the distribution of activated macrophages, the expression of COX-2, and the prostaglandin concentration in the endometriotic lesions treated with parecoxib were analyzed.

Result(s)

The treatment significantly decreased the implant size, and histologic examination indicated mostly atrophy and regression. A reduction in microvessel density and in the number of macrophages, associated with decreased expression of VEGF and Flk-1, also were observed. The treatment group showed a low concentration of prostaglandin E2.

Conclusion(s)

These results suggest that the use of COX-2 selective inhibitors could be effective to suppress the establishment and growth of endometriosis, partially through their antiangiogenic activity.

Key Words: Angiogenesis, COX-2 inhibitor, endometriosis, PGE2, vascularization, VEGF

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 D.E.M. has nothing to disclose. P.T.B. has nothing to disclose. R.G.L. has nothing to disclose. P.D.F. has nothing to disclose. C.P. has nothing to disclose. L.M.A. has nothing to disclose. M.S.A. has nothing to disclose. L.E.N. has nothing to disclose.

 Supported by the National Council for Scientific and Technological Development (CNPq), and the Carlos Chagas Filho Rio de Janeiro State Foundation for the Support of Research (FAPERJ).

PII: S0015-0282(09)04117-X

doi:10.1016/j.fertnstert.2009.11.037

Fertility and Sterility
Volume 93, Issue 8 , Pages 2674-2679, 15 May 2010

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