Clotrimazole reduces endometriosis and the estrogen concentration by downregulating aromatase

in Reproduction
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  • 1 Laboratório de Pesquisa de Ciências Farmacêuticas (LAPESF), Unidade de Farmácia, Centro Universitário Estadual da Zona Oeste (UEZO), Rio de Janeiro, Rio de Janeiro, Brasil
  • 2 Programa de Ciências Morfológicas (PCM), Instituto de Ciências Biomédicas (ICB), Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Rio de Janeiro, Brasil
  • 3 Programa de Pós-Graduação em Saúde Pública e Meio Ambiente, Escola Nacional de Saúde Pública (ENSP), Fundação Osvaldo Cruz (Fiocruz), Rio de Janeiro, Rio de Janeiro, Brasil
  • 4 Laboratório de Enzimologia e Controle do Metabolismo (LabECoM), Departamento de Biotecnologia Farmacêutica (BioTecFar), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Rio de Janeiro, Brasil
  • 5 Laboratório de Oncobiologia Molecular (LabOMol), Departamento de Biotecnologia Farmacêutica (BioTecFar), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Rio de Janeiro, Brasil

Correspondence should be addressed to D E Machado; Email: danielescorsim@yahoo.com.br
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This study aimed to analyse the effects of clotrimazole (CTZ) on estrogen production pathway in endometriosis progression. Experimental endometriosis was induced by autologous transplantation in female Wistar rats, and then the rats were treated with clotrimazole (200 mg/kg) or vehicle, both orally and intraperitoneally, for 15 consecutive days. Serum estrogen levels and vaginal smear analyses were performed and ERα (estrogen receptor alpha) and CYP19 (cytochrome P450 aromatase) levels in the endometriotic lesions were analysed morphologically and immunohistochemically. The clotrimazole group presented a reduction in serum estrogen levels, which were not influenced by the estrous cycle of the animals. The expression of ERα and CYP19 in endometriotic lesions was also reduced in the clotrimazole group compared to the control group. Moreover, clotrimazole treatment decreased the size of the lesions, as confirmed by histological examination, which showed glandular atrophy for both routes of administration. These results suggest that clotrimazole interferes with the estrogen production pathway by downregulating CYP19 and, therefore, reducing serum estrogen levels. Thus, the drug decreases endometriotic lesion size and consequently disease progression.

 

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Sept 2018 onwards Past Year Past 30 Days
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