Evaluating the therapeutic potential of ammonium tetrathiomolybdate in experimental endometriosis

CONFORTI, R; DELSOUC MB; CASAIS M

Congreso; IV Reunión Conjunta de Sociedades de Biología de la República Argentina. 9-15/09, modalidad virtual; 2020

Endometriosis (EDT) is an estrogen-dependent chronic gynecological disease that affects 10-15% of women of reproductive age. It is characterized by the growth of endometriotic-like tissue outside the uterine cavity, causing microbleeds and producing a constant inflammatory-oxidative focus. This pathology still has no cure and the most used current treatments (hormonal) can have side effects. Trace metals play an important role in the pathogenesis of EDT. Our research group reported a positive correlation between copper (Cu) levels in peritoneal fluid and endometriotic-like lesions volume induced in mice. There are also reports of elevated Cu in samples from patients with EDT by other authors. This metal is a key component in many essential enzymes, acting as a limiting factor in tumor progression, metastasis, and angiogenesis, as well as being able to enhance estrogenic action. Therefore, our objective was to investigate the therapeutic potential of Ammonium Tetrathiomolybdate (TM, Cu chelator) in EDT. For this purpose, we used an experimental model of EDT employing two-month-old female C57BL/6 mice. For surgical induction of endometriotic-like lesions, the right uterine horn was removed from the animal, divided longitudinally, cut into three square pieces of approximately 4 mm2 each, which were then sutured in the intestinal mesentery. Three experimental groups were used: 1) Sham, placebo surgery; 2) EDT and 3) EDT+TM (n=7 animals per experimental group). The EDT+TM group received 0.70 mg of TM/day/mouse in their drinking water for 3 weeks, starting on day 8 postoperatively. After one month of induced pathology, mice were sacrificed. The lesions were identified, counted, measured with caliper in two perpendicular diameters for volume evaluation, weighed, and stored at -80 °C. Peritoneal fluid was also collected for the determination of estradiol by chemiluminescence. Data were statistically analyzed using Student´s t-test and one-way ANOVA followed by Tukey´s test (a p-value