R-954, a bradykinin B1 receptor antagonist, as a potential therapy in a preclinical endometriosis model

被引:0
|
作者
Franca, Patricia Ribeiro de Carvalho [1 ]
de Paiva, Joao Pedro Barros [1 ]
de Carvalho, Rosangela Ribeiro [2 ]
Figueiredo, Claudia Pinto [3 ]
Sirois, Pierre [4 ]
Fernandes, Patricia Dias [1 ]
机构
[1] Univ Fed Rio de Janeiro, Lab Farmacol Dor & Inflamacao, Inst Ciencias Biomed, Programa Pesquisa Descoberta Farmacos, Rua Cesar Pernetta S-N. CCS,predio novo do ICB, BR-21941902 Rio De Janeiro, Brazil
[2] Fiocruz MS, Lab Ambiental Toxicol, Ave Brasil 4036, Manguinho, Brazil
[3] Univ Fed Rio de Janeiro, Fac Farm, Rio De Janeiro, Brazil
[4] Laval Univ, CHUL Res Ctr, Quebec City, PQ, Canada
关键词
Bradykinin; Bradykinin receptor 1 antagonist; Endometriosis; R-954; KININ RECEPTORS; PATHOGENESIS;
D O I
10.1016/j.peptides.2024.171294
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Endometriosis is a gynecological condition characterized by the growth of endometrium-like tissues outside of the uterine cavity. Currently available drugs are efficacious in treating endometriosis-related pain, however it's not a targeted treatment. The aim of this work is to evaluate the effects of R-954, a bradykinin B1 receptor antagonist, in a murine model of endometriosis. The model was induced in animals through autologous transplantation of part of the uterine horn. After 51 days, it was observed that implants developed into endometriotic lesions. The administration of R-954 or progesterone, for 15 consecutive days, prevented the progression of cyst development, reduced the size and weight of the cysts. Both treatments also reduced cellular infiltrate and production of inflammatory mediators (interleukin-1 beta, interleukin-6, tumor necrosis factor). However, only R954 decreased angiogenic factors (VEGF and VEGF receptor). In addition, treatment with the antagonist did not interfere in the females' estrous cycle, as well as prevented gestational losses (reduction in the number of intermediate resorptions in pregnant females with endometriosis). Data suggested that R-954 has antiinflammatory and anti-angiogenic effects; does not influence the estrous cycle; and prevents the number of gestational losses suggesting it as a good candidate for endometriosis treatment.
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页数:8
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