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

França PRC, Patricia Ribeiro de Carvalho França, João Pedro Barros de Paiva, João Pedro Barros Paiva, Paiva JPB, Rosângela Ribeiro de Carvalho, Carvalho RR, Rosangela Ribeiro de Carvalho, Cláudia P. Figueiredo, Claudia Pinto Figueiredo, Figueiredo CP, Sirois P, Pierre Sirois, Pierré Sirois, Patrícia Dias Fernandes, Patricia Dias Fernandes
Peptides · 2024 · vol. 181 , pp. 171294 · doi:10.1016/j.peptides.2024.171294 · PMID:39265809 · W4402419989
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R-954, a bradykinin B1 receptor antagonist, demonstrated therapeutic potential in a preclinical model of endometriosis by reducing disease severity.

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Abstract

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-1β, interleukin-6, tumor necrosis factor). However, only R-954 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 anti-inflammatory 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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Condition tags

endometriosis

MeSH descriptors

Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists Bradykinin B1 Receptor Antagonists

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