COPPER CHELATION INHIBITS ANGIOGENESIS AND MODULATES THE OXIDATIVE IMBALANCE IN A MODEL OF ENDOMETRIOSIS

CONFORTI,ROCÍO AYELEM ; DELSOUC MARÍA BELÉN; VITALE DAIANA LUJÁN ; ALANIZ LAURA ; ZABALA ANA SOFIA ; ZAPATA FLORENCIA ; VALLCANERAS SANDRA SILVINA ; CASAIS MARILINA

Congreso; Reunión Conjunta SAIC-SAI-AAFE-NANOMED; 2021

COPPER CHELATION INHIBITS ANGIOGENESIS AND MODULATES THE OXIDATIVE IMBALANCE IN AMODEL OF ENDOMETRIOSIS Rocío Ayelem1,2, Delsouc María Belén1,2, Vitale Daiana Luján3,4, Alaniz Laura3,4, Zabala Ana Sofia1,2, Zapata Florencia1, Vallcaneras Sandra Silvina1,2, Casais Marilina1,2. 1Laboratorio de Biología de la Reproducción (LaBiR), Facultad de Química, Bioquímica y Farmacia, UniversidadNacional de San Luis (UNSL), San Luis, Argentina. 2InstitutoMultidisciplinario de Investigaciones Biológicas de San Luis(IMIBIO-SL), CONICET, San Luis, Argentina. 3Laboratorio deMicroambiente Tumoral, Centro de Investigaciones Básicasy Aplicadas (CIBA), Universidad Nacional del Noroeste dela Provincia de Buenos Aires (UNNOBA), Buenos Aires, Argentina. 4Centro de Investigaciones y Transferencia del Noroeste de la Provincia de Buenos Aires (CITNOBA), Universidad Nacional del Noroeste de la Provincia de Buenos Aires(UNNOBA)-Universidad Nacional de San Antonio de Areco(UNSAdA)-CONICET, Buenos Aires, Argentina.Email: ro.conforti64@gmail.comEndometriosis (EDT) is an estrogen-dependent disease that affects5-15% of reproductive-aged women. It is characterized by the growthof endometrial-like tissue outside the uterine cavity and often causes chronic pelvic pain and subfertility. Currently, EDT has no cure,and there is an unmet need for new treatment options. Angiogenesisis essential for the growth of endometriotic implants because it ensures an adequate supply of oxygen and nutrients and the removalof waste products. Elevated copper (Cu) levels have been linked toEDT. Cu is required by many enzymes, some involved in the antioxidant system. In cancer, this metal promotes angiogenesis, tumor progression, and oxidative stress. Therefore, our objective was toevaluate the effect of Cu chelation with ammonium tetrathiomolybdate (TM) on angiogenesis and oxidative stress in endometriotic-like lesions. Sixteen female C57BL/6 mice were divided into twoexperimental groups: EDT and EDT+TM. The EDT induction wasperformed by autologous uterine tissue transplantation to the intestinal mesentery. The EDT+TM group received 0.30 mg of TM/dayin their drinking water for two weeks from the postoperative 15thday. Bodyweight and hematocrit were periodically monitored. Endometriotic-like lesions were collected one month after the pathology was induced to analyze the expression of angiogenic markers(RTqPCR), the presence of endothelial cells (immunofluorescence),and oxidative stress (spectrophotometric methods). Treatment withTM induced anti-angiogenic effects by decreasing the number ofblood vessels (p