Clotrimazole is effective for the regression of endometriotic implants in a Wistar rat experimental model of endometriosis

• Published in: Molecular and cellular endocrinology 2018-11, Vol.476, p.17-26
• Main Authors: Machado, Daniel Escorsim, Perini, Jamila Alessandra, de Mendonça, Erika Menezes, Branco, Jessica Ristow, Rodrigues-Baptista, Karina Cristina, Alessandra-Perini, Jessica, Espíndola-Netto, Jair Machado, dos Santos, Thiago Alves, Coelho, Wagner Santos, Nasciutti, Luiz Eurico, Sola-Penna, Mauro, Zancan, Patricia
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Biomarkers - metabolism; Cell Proliferation - drug effects; Cell Survival - drug effects; Clotrimazole; Clotrimazole - adverse effects; Clotrimazole - pharmacology; Clotrimazole - therapeutic use; Disease Models, Animal; Down-Regulation - drug effects; Endometriosis - drug therapy; Endometriosis - pathology; Endometriosis treatment; Endometrium - blood supply; Endometrium - drug effects; Endometrium - pathology; Female; Inflammatory; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - pathology; Prostheses and Implants; Rats, Wistar
• ISSN: 0303-7207; 1872-8057
• DOI: 10.1016/j.mce.2018.04.005

The present work aimed to evaluate molecular, angiogenic and inflammatory changes induced by clotrimazole (CTZ) on endometriosis lesions. For this, thirty female Wistar rats with surgically implanted autologous endometrium were treated with CTZ or vehicle (200 mg/kg) via esophageal gavage for 15 consecutive days. CTZ treatment significantly decreased the growth and the size of the implants, and histological examination indicated regression and atrophy, with no toxicity to the animals. The levels of the angiogenic markers VEGF and VEGFR-2 were significantly decreased in CTZ group. The treatment also promotes a reduction on PGE2 and TNF-α levels. All these effects involve the amelioration of ERK1/2, Akt, AMPK and PERK signaling upon CTZ treatment. In conclusion, CTZ promoted an overall amelioration of endometriosis in a rat model due to the anti-angiogenic properties of the drug. Therefore, our results support the proposal of a clinical trial using CTZ for the treatment of endometriosis. [Display omitted] •Clotrimazole promotes the regression of endometriotic lesions in a rat model.•Clotrimazole decreases inflammatory markers in endometriotic lesions.•The angiogenic markers VEGF and VEGFR-2 are decreased after clotrimazole treatment.•Regression of endometriotic lesions promoted by clotrimazole involves MAPK, Akt, AMPK and endoplasmic reticulum stress.