New natural therapies assessment for the treatment of endometriosis.

RICCI A; OLIVARES C; BILOTAS M; MERESMAN G; BARAÑAO RI

Montpellier

Congreso; 11th World Endometriosis Congress; 2011

World Endometriosis Society

Endometriosis (EDT) is one of the most common gynecological diseases in women of reproductive age. Medical therapies are aimed at down-regulating the ovarian estrogen production using GnRH agonists, progestins, androgenic agents or oral contraceptives. However, side effects limit their long-term use. Objective: The aim of this work was to evaluate the effect of 2 natural compounds in vivo, in a murine model of EDT: epigallocatechin 3-gallate (EGCG), which constitutes approximately 60% of the catechins in green tea, and resveratrol (Res), a phytoalexin found naturally in grapes, peanuts, blueberries and many other plants. Both polyphenols has been related to antiangiogenic, antioxidant and antiinflammatory effects. Methods: EDT was surgically induced to 60 female BALB/c mice of 2 months age. After 15 days, 10 animals were randomly assigned per group and treatments were initiated: Res I (10mg/kg); Res II (25mg/kg); Control (Res vehicle); EGCG I (20mg/kg); EGCG II (100mg/kg); Control (EGCG vehicle). Res was administered daily by intraperitoneal injection and EGCG by esophageal gavage. After 1 month of treatment, animals were sacrificed by cervical dislocation. Then peritoneal fluid was collected and endometrioric-like lesions were counted, measured and removed. Paraffin sections were used to assess apoptosis and cellular proliferation levels by Terminal Deoxynucleotidil Transferase-Mediated dUTP Nick End Labeling (TUNEL) and immunohistochemistry for Proliferating Cell Nuclear Antigen (PCNA) respectively. Vascular endothelial growth factor (VEGF) levels were evaluated in the peritoneal fluid by enzyme-linked immunoassay (ELISA). Statistical comparisons were performed using Kruskal?Wallis nonparametric analysis of variance test and Dunn?s multiple comparison post-test. Results: Both doses of EGCG were able to reduced the number of developed lesions (p<0.05) and their size (I p<0.05 and II p<0.01 vs. Control). However, only Res II reduced lesions size (p<0.01 vs. Control). The number of established lesions observed per mouse was not affected by Res treatment. On the other hand, EGCG and Res caused a similar significant reduction of PCNA positive cells (I p<0.05 and II p<0.01 vs. Controls), whereas TUNEL positive cells were increased with both EGCG doses (I p<0.05 and II p<0.01 vs. Control) but only with Res II (p<0.01 vs. Control). Furthermore, it has been shown that EGCG reduced peritoneal VEGF levels (I p<0.001 and II p<0.05 vs. Control) unlike to Res which increased it (I p<0.001 and p<0.01 vs. Control). Conclusions: Our data suggest that Res and EGCG have an inhibitory effect on endometriotic-like lesions development by reducing proliferative levels and increasing the apoptotic ones. It is important to observe that treatments which begin the 15th day post-surgery have the purpose of evaluating their effect on the development of the already established lesions and not punctually on their establishment. However, the power of a treatment could be reflected on the total reduction of the size and therefore have an effect on the mean of the number of established lesions. These findings are promising and support further investigation of these compounds as novel strategies for treating EDT. Besides, the fact to confirm beneficial effects in EDT by these 2 polyphenols would support the chance to provide natural compounds to patients in long-term treatment.